The present invention relates to profiles for attaching rigid plates, especially photovoltaic modules, to a roof and to a method and system for attaching photovoltaic modules to a roof structure with the help of profiles.

Roofs are an ideal place to install photovoltaic modules. Rigid Si photovoltaic modules are very well known but are difficult to handle (they are heavy) and require expensive heavy frames to install them on the roof.
To make a.o. a commercial (i.e. essentially flat) roof watertight, it is well known to use a polymeric or a bituminous waterproofing membrane as a top layer of the roof (commercial buildings). In the case of a roof having on its top a waterproofing membrane, many penetrations of this membrane will generally be required to install the frames for the rigid Si photovoltaic modules. All these penetrations may lead to leakage and to cold bridges (leading to condensation inside the roof structure). Moreover not all roof structures are suited to carry heavy frames, which will catch the wind (sail effect). On a pitched roof this is also not aesthetical.
U.S. Pat. No. 5,505,788 describes a support system of spacers (profiles) and/or insulation panels supporting PV modules. The spacers or panels supporting the PV modules are loosely laid on the waterproofing membrane. They are interlocked but need to be further secured on the roof against wind up-lift forces by pavers at their perimeter. With such system, the slope of the modules (tilt angle) is anyway limited due to the wind up-lift resistance and due to shading issue (the modules are close to each other because their substrate or support must be "interlocking"; therefore modules installed with a high tilt angle will cast shadow on the modules behind). The weight of the pavers may further be incompatible with the load bearing capacity of many commercial buildings.
U.S. Pat. No. 6,729,081 describes a light weight photovoltaic module which is self-adhesive and can in principle be glued onto the waterproofing membranes in a cost effective way and without the use of fasteners which perforate the waterproofing membrane and the insulation panels. Gluing operations are however quite delicate on the roof. The (self-) adhesive may be further not compatible with the existing waterproofing membrane. Gluing of such photovoltaic modules directly onto the waterproofing membrane will also block or at least much reduce the water vapor permeability of the waterproofing membrane, leading potentially to condensation problems inside the roof structure and/or to damages to the photovoltaic cells and/or to internal delamination of the encapsulating layers of the photovoltaic modules.
Another way to obtain a roof with flexible photovoltaic modules attached onto it is to use, as waterproofing membrane, a waterproofing membrane with factory laminated flexible light weight photovoltaic modules on top of it. Such waterproofing membranes are produced by companies like SIT (Solar Integrated) in the USA or by Alwitra in Germany. They consist of several elongated modules supplied e.g. by United Solar Ovonic (Uni-Solar modules) glued in parallel to the polymeric waterproofing membrane. The several Uni-Solar modules are connected in serial under the waterproofing membrane. The connections / soldering are protected (encapsulated) by cast polyamide or cast epoxy or cast polyurethane resin or by similar system. Such photovoltaic waterproofing membranes and systems are described e.g. in DE 29824045 U1 and WO2004066324 A2.
The known photovoltaic waterproofing membranes suffer from several drawbacks:                Risk of formation of creases during installation because of the differential internal tensions.        the modules are very easy to steal.        Internal tension as a result of thermal cycli (sun-night) due to the poor matching of the coefficients of dilatation of the modules and of the polymeric films, sheets and glues.        The water vapor permeability trough the sheet is partly blocked resulting into:                    Increased condensation into the insulation panels.            Increased risk of delamination of the internal layers of the photovoltaic modules.                        a higher temperature of the photovoltaic module compared to an installation on a not insulated substrate. and the temperature inside the building will be increased.        These membranes are difficult to install as the insulation panels have to be partly cut out (carved) to encompass the connection and cables.        Difficulty to access the connections (which are under the welded membranes when installed, meaning that the membrane has to be cut).        The choice of the insulation material is limited to such with high reaction to fire.        Parts of the waterproofing membrane cannot be covered with photovoltaic modules.        They are expensive because they are produced in two steps (production of the PV modules in the first step and lamination in a second step).
These photovoltaic waterproofing membranes may also be installed on top of the existing waterproofing membrane, as a panel, by welding them on the existing waterproofing membrane.
Water may accumulate between the photovoltaic panel and the waterproofing membrane. This may lead to development of micro-organisms which will attack/damage the waterproofing membrane (especially with plasticzed poly vinyl chloride (P-PVC)) and/or the module.
Thus, it is an object of the present invention to propose a safe (fire-, wind-, strain-safe) and practical system to attach photovoltaic modules on a roof without the drawbacks of the existing systems.
Especially, the system shall preserve water vapor permeability of the roof and reduce the photovoltaic module temperature and exposition to humidity, extending its durability and avoiding exceeding the critical 85° C. at the adhesive level even in the South of Europe.
The above mentioned objects are achieved by using soft profiles with rigid inserts for fixing photovoltaic modules to a roofing structure and by a method of fixing comprising the steps of providing a rigid substrate to which photovoltaic modules are attached, providing profiles, fixing them on the roofing structure and attaching the modules to the profile. The problems are further solved by a system for attaching these photovoltaic modules to a roofing membrane. To simplify matters the description will refer to photovoltaic modules it being understood that the profiles, method and system of the invention are suited to attach any kind of rigid plate or mounting frame or tracking system on a roof.
The method and system according to the invention improves the durability of the photovoltaic modules, the durability of the glues and connections, the durability of the roofing membranes and reduces the heating cost and/or electricity consumption for air conditioning.
The modules and method according to the invention will reduce the risk of proliferation of micro-organisms which may damage roofing membranes. It will limit the strain, e.g. due to wind up-lift, material shrinkage (loss of plasticizer), material swelling (water take-up) and by dilatation, on the modules and connections. It can be made theft-proof, allowing
to easily remove the modules with a suitable tool, while avoiding unwanted removal by thieves.
The object of the present invention is solved in particular by attaching, preferably by gluing, typically inexpensive photovoltaic modules/cells, possibly with improved formulation and composition of their back sheet, on a rigid metal sheet or on an optionally glass reinforced plastic sheet (composite sheet). Then, these rigid metal sheets or these preferably glass reinforced plastic sheets are fastened on the roof to the (partly) soft profiles with rigid inserts, said profiles being beforehand attached, preferably heat welded on the waterproofing membrane. The profiles have to be soft at least at their membrane facing side because otherwise temperature changes and other stresses could lead to damages of the membrane like creases or cracks. Alternativaly, instead of fastening the rigid metal sheets or the preferably glass reinforced plastic sheets with the help of rigid insert, the upper part of the profile may be rigid and play the role of the insert.
According to the invention the modules are installed with the help of profiles. To this end, profiles are attached to the roof by one of welding, glueing and mechanical fixing means like nails, screws or hook and loop. The waterproofing membrane (and modules) are preferably sealed with the profiles. The profiles can take the form of singular molds, e.g. cup-shaped. Alternatively the profiles can take the form of strips with legs provided on the modules, e.g. as part of the rigid sheet, the rigid sheet being possibly equipped at its rear side with feet (profiles or cup-shaped).
Preferably, soft profiles with a rigid (e.g. metallic) insert are welded/glued to a previously (also years earlier) installed waterproofing membrane. The profiles are preferably equipped with flaps to ease welding, to improve sealing to the waterproofing membrane and to spread wind up-lift forces. The rigid, metal or preferably glass reinforced plastic sheet of the photovoltaic modules is attached (e.g. with stainless steel screws or with clips or with glues like MS (modified silicone) polymers) on the upper (rigid) part of the profile or to the insert (with screws drilling through the plastic profile). Profiles/rails or punctual fasteners/clamps may be used to attach the modules, depending on the geometry of the PV modules. It will be recognized that these methods consisting of attaching the rigid metal or glass reinforced plastic sheets with the photovoltaic modules, to profiles attached to the waterproofing membrane, do not require to perforate the waterproofing membrane.
Self drilling screws (corrosion resistant like stainless steel screws) are preferred and well known in the art. The screws (self-drilling or not) may also be long enough to attach the waterproofing membrane to the roof substrate. In this case the metal or rigid glass reinforced plastic sheets advantageously replace the pressure repartition plate of the classical mechanical fasteners. The welded profile should in this case be a "filled" (not hollow) profile to keep the roof watertight as the waterproofing membrane is in this particular embodiment, perforated.
Sealing means like rubber patches (EPDM, butyl, . . . ) and/or silicone beads, preferably butyl sealing patches may be used to improve the waterproofing and the corrosion resistance of the connection (screws+metal sheet) between the metal sheet/rigid plastic sheet and the profiles/inserts. The upper part of the profile is, if necessary, designed to be compatible with these butyl patches. Thermo-resistant rigid PVC (e.g. wood composites) as upper part (for soft PVC base) is for instance adequate.
Preferably the profile has flaps at its bottom to allow for a sealing of the profile with the waterproofing membrane. The flaps can be of the same, a similar or some other material(s) than the profile. The flaps are preferably made from a material compatible with the material of the waterproofing membrane, i.e. weldable thereto. They are in one preferred variant made from the same or a similar material and more preferred integrally with the profile. They can also be made from a different material, e.g. when the material of the profile differs from that of the waterproofing membrane. The flaps may be sealed to the membrane by welding or glueing, preferably they can be sealed by welding.
The flaps can also serve the purpose of attaching the profile to the waterproofing membrane and/or the roof. In one variant they preferably carry a hook and loop fastener. The second, corresponding part of the hook and loop fastener is attached to the waterproofing membrane or the roof and the profile attached by pressing both parts of the fastener onto each other. The profile can take the from of a strip in this variant. In another preferred variant the flaps are weldable to the membrane. With the help of flaps one can also attach a e.g. PVC profile to a e.g. bituminous waterproofing membrane. The flaps are made from a material weldable to the membrane and are attached and/or sealed to the profile. The profile can then be welded to the membrane with the help of the flaps.
The upper part of the profile may be discontinuous/interrupted (extrusion flow periodically interrupted for the upper part or upper part of the profile periodically cut out) to be more cost effective, more flexible (with less stress by dilatation and allowing for attachment to curved roofs), to better fit e.g. with corrugation or ribs or folded edges of metal substrate and to ease the introduction of a metallic insert. Such profiles may be produced as follow: During the extrusion process of the profile, the flow of the part of the profile above the flaps part may be interrupted or the part of the profile above the flaps part may be periodically cut out (e.g. by a moving knife system after the die) and the scraps recycled. The rigid part of the profile is interrupted every length of less than 1 m, typically of less than 50 cm. The interruption of the upper part of the profile should match the size (width) of the rigid sheets to be fastened onto the profile. In case of use of hollow profiles with inserts, the use of "interrupted profiles" will additionally help to introduce the insert into the profile. If the profile has a rigid top part, the interruption will additionally solve the problem of dilatation of the rigid top part (with the related stresses). The interruption can be foreseen for the whole height of the profile in the case of profiles with flaps, so that the profile is reduced to a strip between the fixing areas. The interruption can also relate to part of the profile height. The remaining height of the profile can advantageously be utilized during fixing the profile to a roofing structure since a welding machine can be constructed to be guided by the remaining height of the profile.
In one mode the invention provides waterproofing membrane in the form of a polymeric watertight flexible sheet with integrated hollow polymeric profiles. The sheet with the integrated profiles is preferably produced in a one step extrusion process, by combining flat die extrusion and extrusion of profiles. Useful techniques, especially regarding the extrusion of profiles, tubes and cables (sheathing), injection of blowing air into tubes, etc are extensively described in the literature e.g. in "Les matières plastiques: Structure, Propriétés, Mise en Oeuvre, Norme. Editions de I'usine".
It is also possible to lay the metallic inserts (preferably a rectangular insert) on the waterproofing sheet. To avoid damage to the waterproofing sheet, e.g. double face self-adhesives sealing strips may be laid between the sheet and inserts at least at the ends of the inserts (protection against sharp edges). Strips of sheets like waterproofing sheets (possibly reinforced) are then laid and possibly glued around the metallic inserts, with flaps welded to the waterproofing sheet. The strips form a profile with welded flaps around the metallic inserts. The metallic inserts may contain a sealing foam. Sealing strips may be glued between inserts and sheets to improve sealing performances in case of perforation of the profile, insert and waterproofing sheet by mechanical fasteners.
In an especially preferred embodiment the invention provides a system of profiles comprising soft polymeric profiles with a rigid insert for fixing to a waterproofing sheet and secondary profiles for attaching and arranging photovoltaic modules. The secondary profiles are attached to the profiles in an angle, preferably approximately rectangular to the first profiles. This system increases the flexibility of arrangement of the photovoltaic modules on the roof.
The secondary profiles may be part of the frames or sheets of the PV modules (module with flaps) or installed separately. These profiles can have any appropriate shape and length. Preferably they are metallic or from another rigid material. The length is advantageously chosen so that at least two photovoltaic modules can be attached to one secondary profile, preferably the length is such that it covers the whole area in which photovoltaic modules are intended to be installed. Suitable forms of the secondary profiles are a U-shape or a T-shape or a L-shaped, or a rectangle shape, which provide flat parts for fixing of the secondary profiles to the polymeric profiles and rims/edges for attaching the photovoltaic modules (or their mounting frames). The arrangement and distance of the secondary profiles is adapted to the size of the photovoltaic modules. The angle between the polymeric and the secondary profiles can be chosen as desired. It is advantageous to choose an angle that brings the photovoltaic modules in an optimal orientation relative to the sun, i.e. approximately southwards. Of course, orientation of the building and other circumstances like objects blocking the sunlight from a certain direction have to be taken into account. The profiles must also be installed to allow rain water to escape.
Attaching of the photovoltaic modules is facilitated according to the invention. Since the secondary profiles have no sealing function, the fixing means for the modules may be much simpler. Positioning is also easier due to the length of the secondary profiles providing an extended area for fixing. This will prevent stresses on the roofing structure, too. Any fixing means known per se may be used to attach the photovoltaic modules to the secondary profiles. Communicating forms for clicking the modules, suitably with its frame onto the profiles, screws, bolts and so on may be used. Preferably the photovoltaic modules are laid on the secondary profiles and attached to them with fasteners and metallic profiles or clamps or hinges. The photovoltaic modules may be mounted to the secondary profiles in the factory (e.g. by a flaps system with hinges). The fasteners may perforate the secondary and also the polymeric profiles. Self drilling stainless steel screws are preferred, especially for aluminum inserts. Hinges, profiles/rails or punctual fasteners/clamps may be used to attach the modules, depending on the geometry of the photovoltaic modules. To increase electricity production, the modules may be installed on the roof with an angle with the sheet and polymeric profiles, i.e. the surface of the module is not parallel to the surface of the roof. Especially in this case, the rigid inserts (FIG. 1c) or the secondary profiles (FIG. 1b) should preferably have a length of more than 2 m, preferably of more than 3 m to obtain a load repartition effect (ski effect) on the roof against the tilting forces of the wind.
For a very strong connection (high wind load) of the secondary profiles and/or PV modules to the roof structure, it is possible to perforate the soft polymeric profiles, inserts and waterproofing sheet with adequate screws to connect the secondary profiles and/or PV modules to the roof structure. In this case, the polymeric profiles must be connected to the waterproofing sheet in a 100% durable watertight way to avoid water infiltration.
If the waterproofing sheet is an existing waterproofing sheet (i.e. the waterproofing sheet has been previously installed on an existing roof), the soft profiles will be attached (e.g. welded) on the existing roof on site. In this case, it is preferred not to perforate the waterproofing sheet with the mechanical fasteners which are required to secure the PV modules or secondary profiles onto the roof. Indeed, it is very difficult to obtain a totally defect free connection (i.e. a watertight connection without some little infiltrations) between the soft profiles and the waterproofing sheet, as a result of dirt and several pollutants which adhere to the existing waterproofing sheet. It has been surprisingly discovered anyway that the polymeric profiles, preferably with soft flaps, spread efficiently the wind up-lift forces on the waterproofing sheet and assure a strong although soft (no damage to the waterproofing sheet by dilatation-contraction cycli) connection of the PV modules and/or secondary profiles to the roof. In most of the case, the PV modules and/or secondary profiles need only to be attached to the polymeric profiles and inserts. The fasteners don't need to perforate the waterproofing sheet.
The photovoltaic modules which are useful for this invention may consist of any type of photovoltaic cells and contain, between the metallic back-electrode and the transparent front-electrode, as active material (junctions) e.g.: a-Si, tandem cell (a-Si, a-Si or a-Si, microcrystalline silicon, . . . ), triple junction a-Si/a-SiGe/a-SiGe, Organic PhotoVoltaic (OPV), CIGS, and/or Cadmium Telluride thin films. The photovoltaic modules which are useful for this invention may be with or without frame. Thermal solar modules may also be attached to the roof with the profiles and systems of this invention.
Typically, the cells are e.g. built or transferred on a metallic foil (stainless steel, copper, . . . ) or a plastic film (PET, PEN, Polyimide, . . . ) with the right texture, as known per se. This foil or film is here also called the substrate of the cell.
For achieving low-cost mass production, the cells are usually built on plastic films and serial connected in strips of around 5 to 25 mm, like e.g. described in WO 98/13882 (for example by lift-up, laser, etching and silk printing of Ag paste processes, . . . ). These types of cells and serial connections, while being cost effective, withstand only little strain and will be sensitive to storms and to usual stresses during e.g. works on the roof, etc. especially if the photovoltaic modules are built (encapsulated) only with plastic films or foils (low rigidity compared to metal) and installed according to the previous art (DE 29824045 U1 and WO2004066324 A2) and/or on relatively soft insulation panels.
The cells may also be built on stainless steel foil, typically 40 cm wide and 120 μm thick. The typically 120 μm foil is cut in rectangles of typically 40 cm*30 cm and connected in serial with metal strips and encapsulated to obtain a photovoltaic module. Such modules are less sensitive to strain. They are available e.g. from Uni-Solar (United Solar Ovonic). The production process is more expensive and needs by-pass diodes to function properly (shadow effect). It may bring higher lightning risk and electrical break-down risk. A dielectric film (PET, PA . . . ) is required.
Since the present invention aims to provide cost effective and safe photovoltaic roof solutions, the photovoltaic modules should preferably but not mandatory contain cost effective cells.
Typically the photovoltaic modules attached to the rigid metal or preferably glass fiber reinforced plastic sheet according to this invention have from the top (sky face) to the bottom (roof face) the following composition (connections not described):    a) A transparent front sheet preferably of fluoropolymer (typically 50 to 200 μm of ETFE, FEP, PVDF/acrylic . . . , containing required stabilizer and preferably long lasting UV absorbers) generally surface treated to improve adhesion of layer b)    b) A transparent adhesive layer (EVA, ionomers, etc.; total thickness 100 to 1500 μm) or layers which are flexible and impact resistant but usually have poor fire resistance.    c) A plastic or metallic film/foil which carries the active layers (TCO-photovoltaic junction-back electrode) on top of it, if relevant, with serial connections.    d) A back layer comprising:            an adhesive layer or coextruded layers (tie-layer/TPO/tie-layer), preferably opaque and if required flame retarded, to provide adhesion of the plastic or metallic cell substrate (c) to the lower metal or rigid plastic sheet (back sheet). The flame retardant is preferably on base of halogen flame retardants (e.g. Saytex 8010®) with Sb2O3, acting in the gas phase (flame retardants releasing substances which "poison" the combustion in the gas phase). Adhesive layers or tie layers may be EVA films or hot-melts, tie layers on base of polyolefin copolymers with acrylic acid (EAA) or grafted with maleic anhydride, epoxy glues, PUR glues, etc, and will be chosen by the man skilled in the art to obtain good adhesion between the cell substrate film and the coated metal sheet or rigid plastic sheet.        Optionally a dielectric film may be included.            e) A lower metal foil (Aluminum, Epoxy coated steel, . . . ) or rigid plastic sheet (glass reinforced PP, Polyester, Epoxy, . . . ).
Alternatively, the photovoltaic modules according to this invention may also have from the top (sky face) to the bottom (roof face) the following composition (connections not described):    a) A transparent, typically 4 mm thick, tempered glass    b) A transparent adhesive layer (EVA, ionomers, . . . ; total thickness 200 to 1500 μm) or layers which are flexible and impact resistant.    c) Rigid Silicium cells (typically 300 μm thick) or a plastic or metallic foil which carries the active layers (TCO-photovoltaic junction-back electrode) on top of it.    d) A back layer comprising:    e) An adhesive layer or coextruded layers (tie-layer/TPO/tie-layer) preferably opaque and flame retarded, to provide adhesion of the silicium or plastic or metallic cell substrate (c) to the lower metal or rigid plastic sheet (back sheet).    f) Optionally a dielectric film may be included.    g) A lower metal (Aluminum, Epoxy coated steel, . . . ) or glass (with frame) or rigid plastic sheet (glass reinforced PP, Polyester, Epoxy, . . . ) or a metal frame with classical backsheet (Tedlar/aluminium/PET, etc. . . . ) preferably with flaps. The module may be rigidified and protected against "edge damage" by an Aluminium protective frame. Such modules are mounted and fixed to a mounting frame with e.g. rigid flaps to provide a tilt angle on the roof. Such mounting frames are known per se. The modules with their frames and flaps are then attached on the soft profile with insert as described.
Layers a), b) and c) may also be instead thin film photovoltaic cells deposited on glass, like a-Si cells.
The encapsulating layers are wider and longer than the cells in both cases, to reduce oxygen and water ingress to the cells along the edges. Sealing beads may be further used to obtain a maximal protection against humidity and oxygen allowing the use of oxygen and moisture sensitive cells, being understood that the adhesive layers include also barriere films.
The lamination on the rigid (coated) metal or glass reinforced plastic sheet may be done according to any known suitable method and with appropriate adhesives, but preferably during the vacuum lamination/encapsulation process of the cells. The metal or plastic sheet may be equipped at this stage with e.g. rigidifying profiles or cup-shape pieces at the rear of the sheet (to avoid excessive deflection when installed on the roof).
More details about light weight flexible photovoltaic cells and modules (and the process of laminating them in e.g. a vacuum laminator) can be found in numerous patents and patent applications like EP 0769 818 A2, WO 2006/089044, WO 98/13882, and in the patents from the following companies: Konarka (Organic photovoltaic and Graetzel cells and modules), VHF—Flexcell (a-Si:H cells and modules), Helianthos/AKZO NOBEL (a-Si:H cells and modules), Powerfilm (Iowa Thin Film) (a-Si:H cells and modules), Canon, (a-Si:H cells and modules), Fugi, (a-Si:H cells and modules), United Solar Ovonic, (a-Si:H and triple junction cells and modules).
Metal sheets suitable as rigid sheet for this invention may be typically:                0.5 to 2 mm single sheet metal profile, as made from Al55/Zn45 type coated steel (Aluzinc, Galvalume, Galval, Zincalume), AZ185 with e.g. epoxy coating        0.5 to 2 mm Aluminium sheets (possibly coated to further improve corrosion resistance in agressive environments)The metal sheet may be partly corrugated to improve its flexural rigidity. Coatings to improve the adhesion of the metal sheets with polymeric films may be PVC-Vac, PUR, Epoxy, Acrylic, etc. based coatings.
Rigid glass reinforced plastic sheets may be:                Glass reinforced flame retarded PP, preferably corona treated and/or with a primer (e.g. chlorinated polyolefin),        Flame retarded epoxy or unsaturated polyester glass fiber composites
The color of the sheets is preferably white (IR reflecting) except if the sheet is used to heat water. In the latter case the sheet is preferably dark coloured.
Adequate glue for adhesion of the rigid metal or plastic sheet to the photovoltaic module (=layers a) to d)) is easily selected by the man skilled in the art. Acrylic/epoxy adhesives may be used to pre-coat the metal sheets.
The waterproofing membranes and composition of profiles used for this invention are known per se. Conventional sheets and compositions for sheets and profiles are useful and may consist of any material which is suitable for roofs. The material must be resistant to weathering and in particular to UV light (except when the material is fully protected by the metal or preferably glass reinforced sheets), be watertight and resistant to temperature variations.
Common materials are soft (modified) polyolefins (polyethylene, chlorinated polyethylene, polypropylene, ethylene propylene rubber, copolymers of ethylene and vinyl acetate and their mixtures, etc.), EPDM (ethylene propylene diene monomer), TPV (thermoplastic vulcanistes like Santoprene®), PIB (polyisobutylene), ECB (ethylene copolymer bitumen), plasticized PVC (phthalate plasticizer, polyadipates plasticizers, Elvaloy® types resin, PVC-grafted on EVA or polyacrylate, etc.), bitumen, and blends of two or more of these. The sheets and profiles may consist of several layers (obtained e.g. by coextrusion). For the layer to adhere to metallic inserts, functionalized polymers may be used containing in their back-bone and/or as side chains functionalities like maleic anhydrides and/or acrylic acids functionalities. Parts of profiles and/or sheets which are perforated may have a e.g. inner layer containing super-absorbing polymeric particulates, possibly at the nano-scale. When perforated, such e.g. inner-layer will seal the leakage.
The sheets are commonly reinforced with polyester scrim (typically 3*3, 1100 dTex) and/or glass fleece (typically 50 g/m2) and may have a polyester backing to attach the sheet to the insulation panels. The sheets are preferably also fire resistant, either as a property of the material used or by addition of suitable fire retardants. The sheets further contain pigments and possibly UV light and thermal stabilizers and may be coated by protective varnishes or barrier coatings (against plasticizer migration . . . ).
The profiles have similar composition as the waterproofing membranes. They may have an upper part which is more rigid. For instance, if the base part is soft PVC (plasticized PVC (P-PVC)), the rigid part may be rigid U-PVC (with additives to increase its softening temperature and fibers to increase the pull-out value of the screws). On TPO profiles (e.g. based on Hifax CA 10 A), a glass reinforced PP (impact modified) may be used. Screws/clamps will be fastened in this upper part possibily along groves.
Expancel® from AKZO or other well known blowing agents may be used to produce a foam core for the profiles, if desired. e.g. PUR foam and/or mechanicals means may also be used in the field to seal the profiles.
Therefore, and as example, if the waterproofing membrane is a P-PVC waterproofing membrane, the profile will be based on P-PVC with possibly a coextruded upper layer of rigid PVC (glass reinforced, . . . ) optimized to increase the pull-out value of the screws/clamps.
Compared to the previous art, the invention offers the following advantages:                Improved reaction to fire when the modules are attached on a metal sheet and therefore completely separated from the waterproofing membrane by this metallic fire barrier sheet, which further works as a heat sink and therefore greatly limits fire propagation.        Possibility to achieve outstanding reaction to fire when layers d) contain enough halogenated flame retardant, allowing for the use of a thick protective transparent EVA adhesive layer b)        No folds or creases into the module during installation.        Low strain of the cells (including barriers layers) and interconnections during storms and other mechanical stresses        The modules are difficult to steal as the modules can mechanically be fastened with special screws (anti-theft screws)        There is ventilation under the module and therefore:                    The temperature of the module in use is lower which means in principle a higher electricity production and certainly a higher durability.            Lower temperature of the waterproofing (WP) membrane which means lower need of electricity for air conditioning and better aging of the waterproofing membrane (protected part)                        The ventilation under the module can easily be closed to achieve when desired annealing of a-Si modules.        Less risk that the modules will get submerged by water (3 cm above the WP membrane)        Low risk of condensation and formation of vapor at elevated temperature under the modules (less corrosion of the contacts and less damage to the cells by elevated temperature vapor) due to the ventilation        better encapsulation (protection against moisture and oxygen) of the cells (e.g. by metal and glass)        No risk of formation of creases in use (high dimensional stability of the metal sheet and separation from the waterproofing membrane and moving insulation panels) and reduced risk of delamination between substrate and module or inside the modules (better aging resistance of the adhesive between metal sheet and module as no water vapor at high pressure may damage the adhesive)        Higher durability of the photovoltaic modules as the surface temperature of the modules is reduced        Possibility to fully cover (protect) large sections of the plastic roof with the photovoltaic module panels of this invention while keeping (enough) water vapor permeability        Possibly lower cost of installation of the waterproofing membrane as the rigid metal or glass reinforced plastic sheet (with long screws or mechanical fasteners) may be used to attach the waterproofing membrane (perforated) to the roof surface in a rigid way. The waterproofing membrane may even be first fastened to the roof structure with parallel rows of mechanical fasteners (perforating the membrane) or with bars. These rows or bars are then covered by the profiles (instead of usual strips) and sealed by welding the flaps of the profiles to the waterproofing membrane. The PV modules (their substrate, secondary profiles, etc.) are then fastened to the profiles, without need of perforation of the waterproofing membrane.        Lower risk to reach module and adhesive temperature in excess of 85° C., which is the critical temperature for self-adhesive glues and for many useful glues/adhesive films (e.g. Ethylene Acrylic Acid copolymers).        Ease of installation and of control/replacement of cables and electrical connections        Ease of installation of protective elements for cables, etc (it is possible to perforate with screws the rigid metal or plastic sheet, without perforation of the waterproofing membrane)        Protection against weathering of cables and electrical connections (they may be attached under the photovoltaic panels)        No development of micro-organisms (plasticizer extraction) thanks to the ventilation of the space between the waterproofing membrane and the modules        No perforation of the roof required        The profiles, at the roofing sheet side, are soft so no cracks will form due to dilatation of the profiles in the waterproofing membrane        In case of a full plastic module, the lightning risk is reduced        The building is kept cooler (less electricity consumption for air conditioning)        Possibility to use the space between the metallic base of the modules, the profiles and the insulated waterproofing membrane to install thermal solar water heating systems.        Possibility to attach all the modules together with anti-theft screws: theft of modules becomes very difficult.        Possibility to install curved metallic profiles along the edges of the area of the roof covered by modules: limitation of lightning risk and of theft.
The photovoltaic system remains light weight (<15 kg/m2) compared to crystalline silicon modules with their mounting frames and/or the ski effect allows spreading the load on the roof surface.

This patent is subject to a terminal disclaimer.


A communication system for video information apparatus for carrying out a communication between a video information apparatus and a peripheral apparatus arranged so that a communication is repeatedly carried out at a period synchronized with a signal of a vertical period having a constant phase relation relative to a vertical synchronizing signal.

1. Field of the Invention
This invention relates to bidirectional communication between a single master apparatus and a plurality of slave apparatus and, more particularly but not exclusively, to a method and apparatus for communication between video information apparatus, such as VTR (video tape recorder) or video disc player, and peripheral apparatus, such as tuner, a timer, a video camera, editing apparatus, a computer and so on.
2. Description of the Prior Art
Recently, in order to enhance the enjoyment of video equipment, a video information system has been developed, which comprises a VTR as master apparatus and a plurality of peripheral or slave apparatus, such as .Iadd.a video .Iaddend.camera, a television tuner unit, a timer unit and .Iadd.editing .Iaddend.apparatus. In such a system, the communication of control data, such as a mode signal and various other control signals, between the VTR and each peripheral apparatus becomes a significant problem.
In a system for bidirectional communication between a VTR used as master apparatus and a plurality of peripheral apparatus each used as a slave apparatus, it is important that the number of communication lines be reduced as much as possible. This becomes increasingly important as the number of slave apparatus is increased.
A bidirectional communication system having at the side of the master apparatus only two communication lines one of which is a transmission communication line and the other of which is a reception communication line has much to recommend it. Alternatively, a bidirectional communication system having only one communication line may be employed.
The assignee of the present application has previously proposed a bidirectional communication system using only one communication line (see copending U.S. patent application Ser. No. 06/732,004, filed May 6, 1985, and assigned to the assignee of the present application).
In this previously proposed system, a communication interval formed of a plurality of master and slave transmission areas that are arranged in a time division manner is taken as one block, and this block is repeated cyclically. The time control for communication is provided exclusively by the master apparatus. The number of slave apparatus transmission areas is equal to the number of slave apparatus.
Even when two communication lines (master apparatus transmission line and slave apparatus transmission line) are used, seen from the side of the slave apparatus the transmission lines appear as one. Accordingly, when the communication is carried out cyclically as described above, the transmissions from the several slave apparatus are effected in the respective transmission areas in a time division manner.
However, since transmission areas are provided for all of the plurality of slave apparatus in a time division manner, as the number of slave apparatus increases, the total transmission period becomes very long.
Since each slave apparatus does not always request the master apparatus to transmit video information, if a transmission area is provided for each of the plurality of slave apparatus as described above, an unoccupied or useless transmission area occurs, resulting in low time efficiency.
On the other hand, it frequently happens that a mode signal, a control signal and a command signal are communicated between the video information apparatus and the peripheral apparatus, for example, between the VTR and the video camera and the editing apparatus, in order that the two apparatus may be operated in synchronism with each other.
In the prior art, a communication of this kind is performed regardless of its time relation to an input signal or a reproduced video signal. For example, when a mode is changed, commands such as "playback mode next", "stop mode next" and so on are transmitted and received.
Particularly, when a communication is carried out only in a necessary case, as when the mode is changed as described above, if a miscommunication or erroneous communication occurs, the present mode remains erroneous at least until the next communication is made for changing the mode.
Further, since it is not known in advance exactly when the transmission data will arrive at the peripheral apparatus, the peripheral apparatus must be always in an interruptible state and always in a communicable state, so that the software therefor is difficult to write.
As to the video information apparatus, since it is not known in advance exactly when the command or the like will arrive from the peripheral apparatus, the software therefor is also difficult to write.
For this reason, it may be concluded that the communication should be carried out cyclically. However, if the cycle or period is free-running and not synchronized with a video signal or in a fixed time relation to the latter, various problems occur.
For example, it has recently been proposed that data such as a time code including a frame number, a field number and the like be multiplexed on a video signal and then recorded. In such case, when the time codes are communicated, if the communication between the VTR and the peripheral apparatus is carried out over a period longer than, for example, the vertical period, the communication surpasses the frame number or field number of the time code at a certain time, producing a dropout in the time code input.
Furthermore, it the period of the communication is not synchronized with the video signal, when the command (for example) "set recording mode two fields from now" is issued in a communication between the VTR and the editing apparatus, the time "two fields from now" cannot be determined uniquely. This makes the software therefor very difficult to write.

Communication system for video information apparatus


According to the present invention, a resist resin having in its structure a specific bridged-bond-containing aliphatic ring, and a resist composition comprising the same are provided. By using this resist composition, a resist pattern excellent in both transparency against short-wavelength light and dry-etching resistance can be formed by alkali development with high resolution.

In manufacturing processes of electronic components such as LSIs, fine patterning techniques utilizing photolithography have conventionally been adopted. Namely, a resist solution is firstly coated onto the surface of a substrate or the like to form a resist film; and the resist film is subjected to pattern-wise exposure to light, and then to treatments such as development by an alkaline developer to form a resist pattern. Subsequently, the bare surface of the substrate or the like is dry-etched by utilizing this resist pattern as an anti-etching mask to form minute lines and openings, and the remaining resist is finally removed by means of ashing.
Therefore, the resist herein used is generally required to have high dry-etching resistance. From this point of view, resists containing aromatic compounds have widely been used. Specifically, there have been developed a large number of resists containing, as base resins, novolak resins that are alkali-soluble.
On the other hand, in line with the trend toward high-density, high-integration LSIs and the like, the above-described fine patterning techniques have been improved in recent years so that patterning can be attained at the level of sub-half micron order; and this tendency toward fine patterning is expected to be more remarkable. Indeed, the wavelengths of light sources for use in photolithography are being made shorter; and it is now attempted to form fine resist patterns by using ArF excimer laser light (wavelength 193 nm), or a 5-fold higher harmonic wave of a YAG laser (wavelength 218 nm).
However, the resists containing, as base resins, resins containing aromatic compounds, which have commonly been used heretofore, have such a peculiarity that benzene nucleus contained in the compounds show high light absorption against the above-described short-wavelength light. Therefore, when it is tried to form a resist pattern, it is difficult to allow light to fully reach the substrate side of a resist film when the film is exposed to light. It has thus been difficult to form, with high sensitivity and high accuracy, patterns excellent in shape.
Under such circumstances, there is a strong demand for the development of highly transparent resist resins suitable also for photolithography which uses ArF excimer laser light, or a 5-fold higher harmonic wave of a YAG laser.
From this viewpoint, those resists containing alicyclic compounds in place of aromatic compounds are now attracting attention. Japanese Patent Laid-Open Patent Publication No. 39665/1992, for instance, describes the following example: alkali-solubility is imparted to a resist which is excellent in both dry-etching resistance and transparency against short-wavelength light and which comprises a compound containing adamantane that is a bridged-bond-containing alicyclic compound, by copolymerizing the resist and another acrylic compound; and a resist pattern is formed by alkali development, by the use of this alkali-solubility-imparted resist.
As shown in Japanese Patent Laid-Open Publication No. 199467/1995, there is known a resist material containing, as tricyclodecanyl structure, an alicyclic compound having 5-membered rings, which is one of bridged-bond-containing alicyclic compounds.
However, in the case where a resist pattern is formed by means of alkali development by the use of a resist containing such an alicyclic compound, various problems will be brought about. This is because the alicyclic structure such as adamantane skeleton has extremely high hydrophobicity, so that the difference in alkali-solubility between this alicyclic structure and a group which imparts alkali solubility to the resist is great.
For example, the predetermined area of the resist film cannot be uniformly dissolved and removed by development, so that the lowering of resolution is brought about. Moreover, the lowering of resolution is also caused due to the swelling of the resist pattern that occurs after development, and the resist film is cracked or undergoes surface roughening because even the area of the resist film that is supposed to remain after development is partly dissolved. Further, the separation of the resist pattern is often caused due to the penetration of an alkaline solution into the resist film-substrate interface. Furthermore, phase separation between the part having the alicyclic structure and the group which imparts alkali solubility, such as carboxylic acid moiety, tends to proceed in the polymer, so that it is difficult to obtain a homogeneous resist solution. In addition, such a resist solution shows poor coating performance.
In order to reduce the hydrophobicity of these alicyclic compounds, the introduction of a polar group such as COOH or OH group into the alicyclic compounds has been proposed (Japanese Patent Laid-Open Publications No. 83076/1998, No. 252324/1995 and No. 221519/1997). It has been confirmed that the solubility is considerably improved in all of these compounds.
However, the structure of these alicyclic compounds is such that COOH or OH group is combined with secondary or primary carbon atom of the aliphatic ring, so that this COOH or OH group tends to secondarily react with other substituents in the resists. Moreover, these compounds have low glass transition temperatures, so that they tend to bring about the lowering of resolution, and the swelling of the pattern after development.
An object of the present invention is therefore to provide, by overcoming the aforementioned problems, a resist resin which can be a component of a resist composition having high transparency against short-wavelength light and high dry-etching resistance, capable of forming a resist pattern excellent in adhesion and resolution by means of alkali development.
Another object of the present invention is to provide the above-described resist composition.
A further object of the present invention is to provide a pattern forming process using the resist composition.


Thermoplastic compositions having improved mechanical characteristics and particularly an improved impact resistance, especially when measured on test pieces having high thickness, comprising:. (A) an impact resistant vinyl aromatic graft copolymer containing an amount comprised between 0.1 and 2% by weight of an ethylenically unsaturated compound having a carboxylic group or one of its derivatives in the molecule; and PA1 (B) a polyamide resin.

As known, impact resistant vinyl aromatic copolymers are obtained by bulk or bulk-suspension polymeryzation of olefinic rubber solutions, such as ethylenepropylene (EPM) or ethylene-propylene-non conjugated diene (EPDM) solutions, in a vinyl aromatic monomer alone or in blend with other polymerizable ethylenically unsaturated monomers.
Styrene-acrylonitrile copolymers grafted on olefinic rubbers (AES) show a very good impact resistance but their low thermoresistance makes them unsuitable for particular applications where temperatures of 120.degree.-160.degree. C. are used, or for manufacturing products which come into contact with parts heated at such temperatures.
It is known that a way of improving those missing property of AES copolymers is to provide a blend with other polymers having a good thermoresistance such as for example a polyamide. In fact, such resin shows a good elongation, high energy absorption, especially in ball drop tests, and a very good thermoresistance; however, the high notch sensitivity and water absorbtion constitute a significant limitation for the use of these resins. Moreover, polyamides are seldom compatible with the impact resistant vinyl aromatic copolymers, therefore, the interfaces between the domains of the blend components represent very weak areas along which the breaking of the material takes place.
In order to make polyamides compatible with impact resistant vinyl aromatic copolymers, it was proposed in the published German patent Application N. 3, 120, 803 to use a compatibilizer constituted by a styrene copolymer containing from 2 to 50% by weight of carboxylic acid and/or reactive anhydride groups. The compatibilizing copolymer described in that reference has a molecular weight between 500 and 20.000; in particular 500 and 7.000, preferably between 800 and 2.000.
The so obtained mixtures have improved impact strength (IZOD) properties which, however, are not completely satisfactory for several applications.
According to the published European patent Application No. 202214, the impact strength of the polyamide compositions can be improved by preparing a blend comprising:
a) 5-79.5% by weight of a composition grafted on rubber consisting of graft copolymer of 15-85% by weight of at least one monomer selected from the group consisting of C.sub.1 -C.sub.4 alkyl methacrylate, C.sub.1 -C.sub.4 alkyl acrylate, metha-acrylonitrile and acrylonitrile and of 85-15% by weight of a vinyl aromatic monomer, wherein the monomers are polymerized in the presence of and grafted on a rubber substrate having a glass transition temperature below 0.degree. C., wherein the percentage by weight of rubber is from 5 to 80% and the percentage by weight of graft copolymer is from 95 to 20%;
b) 94.5-20% by weight of a polyamide, and
c) 0.5-60% by weight of a compatibilizing copolymer comprising a copolymerized, functionalized monomer able to react with the polyamide, wherein the functionalized monomer concentration is comprised between 0.05 and 4% mol., with respect to the copolymer.
However, the so obtained compositions, do not have an optimal combination of properties for all of the applications in they can be used.
In particular, an increase in impact strength can be obtained by using an excess of impact resistant vinyl aromatic polymer with respect to the polyamide resin; however, this increase is at the cost of the thermoresistance. Therefore the obtained products can't be processed at a temperature over 120.degree.-140.degree. C. On the contrary, by increasing the polyamide resin content, the thermoresistance of the composition increases, however, it is achieved at the cost of the impact strength.

Thermoplastic compositions based on a vinyl aromatic graft copolymer and a polyamide


An encapsulating resin composition is provided, which gives a cured product having heat resistance, light resistance, and flexibility equivalent to those of silicone resins and having a refractive index of 1.57 or greater which is larger than that of epoxy resins. The encapsulating resin composition contains: a high refractive index acrylic-based or methacrylic-based monomer having a refractive index of 1.55 or greater; and a nonfunctional fluorene compound. In a preferred form, each of the high refractive index acrylic-based or methacrylic-based monomer and the nonfunctional fluorene compound has a 9,9-bisphenylfluorene skeleton.

1. Field of the Invention
The present invention relates to a resin composition for encapsulating light-emitting devices and to a light-emitting device module encapsulated with the resin composition.
2. Description of the Related Art
Light-emitting devices such as LEDs (Light-Emitting Diodes) have low power consumption, are small in size, and are lightweight, and light-emitting devices encapsulated with resin are used in various types of lamps. In recent years, both blue and white LEDs have been developed, and the luminance of LEDs has also increased. Accordingly, the applications of LEDs have been rapidly expanding and include forming a backlight light source for liquid crystal display panels, forming a light source for illumination, and forming signal lamps. Furthermore, the application of LEDs to the headlamps of automobiles is also being developed.
Traditionally, bisphenol A glycidyl ether type epoxy resins are used as an encapsulating resin for light-emitting devices such as LEDs. However, with the increase in luminance of LEDs, both the heat resistance and light resistance (particularly with regard to resistance to both UV and blue light) of such epoxy resins have become insufficient. Therefore, in high-intensity LEDs, UV LEDs, and the like, the encapsulating resin thereof is discolored by the heat or UV light emitted by these LEDs, and this causes a problem in that the luminance of LED modules reduces over time. In order to resolve this problem, highly transparent epoxy resins of improved type and the like have been developed. However, the heat resistance and light resistance of such resins are still not satisfactory. In addition to this, since epoxy resins become hard once cured, a problem arises in that thermal stress may, for example, cause breakages in the wiring or peeling at the junction between an electrode and the wiring in LED modules.
In view of the above, gel-type silicone resins have recently been used in high-intensity type LEDs as they exhibit excellent heat resistance and light resistance, and also exhibit excellent physical flexibility. However, the gel-type silicone resins are two-part type curable resins in which the hydrosilylation reaction is utilized, and hence the gel-type silicone resins have to be used within their pot-life after mixing.
Moreover, since the refractive index of the gel-type silicone resins is lower than that of epoxy resins, the silicone resins have a drawback in that they reduce the light extraction efficiency of the LED modules that include these resins. Specifically, in the most common types of high intensity LED modules, an LED chip is placed face down on a sapphire substrate having a high refractive index (being 1.76), and light is extracted from the sapphire substrate side of the LED module. In order to extract light from the sapphire substrate into an encapsulating resin efficiently, it is preferable that the refractive index of the encapsulating resin be close to the refractive index of sapphire, i.e. 1.76. However, among the various silicone resins used as an encapsulating resin, dimethyl silicone resin has a refractive index of 1.41. In addition to this, diphenyl dimethyl-based and phenyl methyl-based silicone resins, into which a phenyl group is introduced to increase the refractive index thereof, only have a refractive index of approximately 1.51. When an excessively large number of phenyl groups are introduced to a silicone resin in order to increase its refractive index, the viscosity increases too much and the silicon resin therefore becomes unsuitable for pouring into a mold, and the physical flexibility of the cured product of the resultant resin is therefore impaired. Hence, the refractive index of silicone resins used as an encapsulating resin is lower than that of epoxy resins, which have a refractive index in the range of 1.53 to 1.57. Therefore, at present, while silicone resins are used, there is a compromise made with regard to light extraction efficiency in order to still take advantage of their excellent heat resistance, light resistance, and physical flexibility.
Meanwhile, there is an attempt to increase the refractive index of a resin as a whole by adding fine particles having a high refractive index to the resin (see Japanese Patent Application Laid-Open No. 2004-15063). In this case, titanium oxide, zirconium oxide, zinc oxide, and the like are considered to be used as the high refractive index fine particles. However, in order to increase the refractive index of the silicone resins to a desired level using this technique, a relatively high volume percent of, i.e., at least 10 to 40% by volume of the fine particles must be mixed into the silicone resin being used. At such a high mixing ratio, high transparency cannot be obtained, and furthermore, appropriate fluidity cannot be obtained at the time of pouring the silicone resin into a mold. Hence, there has been an attempt to improve the transparency of silicone resins using fine particles called single-nano size particles. However, as the cohesive force of the ultrafine particles of single-nano size is very strong, it is very difficult to uniformly disperse the ultrafine particles within a resin without forming secondary aggregated particles. Therefore, a technology for increasing the refractive index by adding such fine particles has not yet been practically realized. Accordingly, in high-intensity LED modules, a gel-type silicone resin alone is still often used even though the refractive index is compromised.

Encapsulating resin composition and light-emitting device

Sony Chemical & Information Device Corporation


In a frequency dividing circuit, a VD pulse is generated as a vertical synchronization signal on the basis of the bus clock inputted from an external circuit, while in the gate circuit, integral circuit, gate circuit and hold circuit, the frequency of bus clock is detected on the basis of the VD pulse. Moreover, in the PWM circuit, when the frequency of the bus clock is high or low, a shutter drive pulse having the width shorter or longer than that in the related art is generated, respectively. The electronic shutter driver closes the electronic shutter of the CCD imager (charges generated in the CCD imager are discharged) for the period corresponding to the shutter drive pulse. Thereby, the discharging period in the CCD imager is fixed to a constant period without relation to the frequency of the bus clock. Accordingly, an image having adequate luminance can be obtained by the so-called multi-scan type image sensing device.

1. Field of the Invention
The present invention relates to an image sensing device and a method of adjusting a quantity of light and particularly to an image sensing device and a method of adjusting a quantity of light for sensing an image by driving, for example, an imager utilizing a CCD (Charge Coupled Device) with clocks of various frequencies to be inputted externally.
2. Description of Related Art
A so-called multi-scan type image sensing device has been proposed as an apparatus for sensing an image by driving an imager (CCD imager) utilizing a CCD with clocks of various frequencies to be inputted externally.
FIG. 10 shows an example of the structure of such as multi-scan type image sensing device. The light from an object to be picked up is incident to a lens 1 and is then received at the receiving surface of a CCD imager 3 via an iris 1A and a primary colors vertical stripe filter 2. At the light receiving surface of the CCD imager 3, a photosensor, for example, is formed and this photosensor generates charges, through photoelectric conversion, corresponding to the quantity of light received at the light receiving surface. The CCD imager 3 is driven by a driver 14 to sequentially transfer charges generated by the photosensor and moreover to convert such charges into an image signal (analog signal) as an electrical signal. This image signal is supplied to an S/H (Sample/Hold) circuit 5 after level adjustment in an AGC (Automatic Gain Controller) 4.
Here, the CCD imager 3 is designed to generate an image signal corresponding to an image, for example, of 811.times.508 pixels (number of pixels in the horizontal direction.times.number of pixels in the vertical direction) and an image displayed in field units (525/2 scanning lines) by the so-called interlaced scanning.
The S/H circuit 5 samples and holds the image signal from the AGC 4 and outputs such an image signal to an A/D converter 6 depending on the predetermined system clock supplied, for example, from an external apparatus such as a personal computer via a driver 14. The A/D converter 6 converts the image signal sampled and held by the S/H circuit 5 to the digital data of 8 bits, for example, by the A/D converting method depending on the system clock. This digital data is then supplied to a chromaticness simultaneous processing circuit 7. Here, since the light received by a CCD imager 3 is applied via the primary colors stripe filter 2, the color signals corresponding to three primary colors of the red (R), green (G) and blue (B) lights from the CCD imager 3 are outputted as the image signals. In this case, the red, green and blue color signals are outputted, for example, in the sequence of red, green, blue, red, . . . Therefore, the color signals supplied in this sequence are also outputted as the digital data in this sequence through AGC 4, S/H circuit 5 and A/D converter 6. Accordingly, the chromaticness simultaneous processing circuit 7 adjusts the output timing of the color signals of red, green and blue (so-called RGB) and simultaneously outputs such signals as a set of signals.
Namely, the chromaticness simultaneous processing circuit 7 is composed of an R data timing adjusting circuit 7R, a G data timing adjusting circuit 7G and a B data timing adjusting circuit 7B and when those obtained by converting the red, green or blue color signals into digital data with A/D converter 6 are defined respectively as R data, G data or B data, the R data timing adjusting circuit 7R, G data timing adjusting circuit 7G or B data timing adjusting circuit 7B respectively adjust the output timing of R data, G data or B data and simultaneously output respective outputs. These R data, G data and B data are supplied, for example, to external apparatus such as a personal computer and are then rendered for viewing by predetermined image processing.
Meanwhile, the system clock from an external apparatus is supplied, as explained above, not only to the A/D converter 6 and driver 14 but also to a frequency dividing circuit 8. The frequency dividing circuit 8 also has counters 9 to 11 and generates signals for giving various timings by dividing the system clock with the predetermined frequency dividing ratio.
That is, the system clock inputted to the frequency dividing circuit 8 is supplied to a counter 9. The counter 9 counts up the system clock and resets, when the count value becomes 3, the count value and outputs the pulse of the predetermined width (the width, for example, equal to the pulse width of the system clock). The counter 9 repeats the operation explained above. Therefore, the counter 9 outputs the clock (hereinafter referred to as 1/3 system clock) obtained by dividing the frequency of the system clock by 1/3.
The 1/3 system clock is supplied to the chromaticness simultaneous processing circuit 7. In this circuit, the output timings of the R data, G data and B data are adjusted on the basis of this 1/3 system clock. Moreover, this 1/3 system clock is also supplied to a counter 10. In the counter 10, the operation similar to that in the counter 9 is performed and thereby the 1/3 system clock is divided, for example, to 3/910 and is then outputted. Therefore, the counter 10 outputs the clock obtained by dividing the system clock to 1/910 (=1/3.times.3/910).
Here, the period of the clock (obtained by dividing the system clock to 1/910) outputted from the counter 10 corresponds to the length of one line (one horizontal scanning line) of the image signal outputted from the CCD imager 3. Therefore, this clock gives the horizontal scanning period for driving the CCD imager 3 and accordingly it is called as the HD (Horizontal Drive) pulse.
The HD pulse is supplied to a counter 11 and a driver 14. The counter 11 divides the HD pulse, for example, to 2/525 to output to the driver 14 by the operation similar to that in the counter 9.
Here, the period of pulse outputted from the counter 11 corresponds to one field (525/2 lines) of the image signal outputted from the CCD imager 3. Therefore, this pulse gives the vertical scanning period (field period) for driving the CCD imager 3 and accordingly it is called as the VD (Vertical Drive) pulse.
The driver 14 drives the CCD imager 3 depending on the system clock, HD pulse and VD pulse. Moreover, the driver 14 controls the S/H circuit 5 depending on the system clock.
The frequency dividing circuit 8 also generates and outputs the horizontal blanking signal (/H.BLK) and vertical blanking signal (/V.BLK) in addition to the 1/3 system clock, HD pulse, VD pulse. A manual iris adjusting mechanism 51 is operated for adjusting luminance of the image signal outputted from the CCD imager 3. That is, when the manual iris adjusting mechanism 51 is operated, an operation signal corresponding to such operation is supplied to an iris drive circuit 52. The iris drive circuit 52 drives, upon reception of the operation signal from the manual iris adjusting mechanism 51, the iris 1A corresponding to such operation signal. Thereby, the amount of light incident to the CCD imager 3 increases or decreases to adjust the luminance of the image signal outputted from the CCD imager 3.
In such a multi-scan type image sensing device as explained above, if the frequency of the system clock supplied externally is different, accumulation time for charges generated in the CCD imager 3 is also different and therefore the image having adequate luminance cannot be obtained. Namely, when the period of system clock, for example, is extremely longer or shorter, a white image or a black image has been obtained.
Therefore, as a method of obtaining the image having adequate luminance, a method for adjusting an electronic shutter has been proposed, in which the manual iris adjusting mechanism 51 is operated to adjust luminance of the image signal outputted from the CCD imager 3 or to discharge the charges generated in the CCD imager 3. This method, however, has a problem that such adjustment has been required for each change of frequency of the system clock.
Moreover, when the so-called auto-iris has been utilized, it has also been difficult to obtain the image having adequate luminance due to insufficient adjusting range since the adjusting range is usually limited to the range corresponding to the system clock with reference to use of the system clock having the predetermined and fixed period.

Image sensing device and method of adjusting quantity of light


Disclosed are compounds of the Formula I

This invention relates to fused-ring compounds containing an indole. This invention further relates to compounds that selectively bind to the M4 muscarinic receptor. In addition, this invention relates to a method of treating Parkinson""s disease.
Parkinson""s disease (PD) is a progressive neurodegenerative disease characterized by hypokinesia, tremor, and muscular rigidity. It results in a slowing of voluntary movements, a festinating gait, peculiar posture, and general weakness of muscles. There is progressive degeneration within the nuclear masses of the extrapyramidal system, and a characteristic loss of melanin-containing cells from the substantia nigra and a corresponding reduction in dopamine levels in the corpus striatum. The cause of PD is unknown, but it is widely believed that multifactorial genetic and environmental factors are contributors. While the disease can develop at any age, it is most common in adults, and typically afflicts people at about sixty years of age and older. Parkinson""s disease is becoming a particularly serious disease given the aging population.
There are no known cures for PD. The most common treatment has been the administration of levodopa, the precursor to dopamine, whose concentration in the substantia nigra is known to diminish as the disease progresses. Levodopa often produces unpleasant complications, resulting in even more serious health problems that are untreatable.
There are a group of monomeric proteins called muscarinic receptors found throughout the body of animals, including humans. These muscarinic receptors are present in the central nervous system, the peripheral nervous system, and in peripheral organs. There have been five muscarinic receptor subtypes identified, and they are referred to as M1, M2, M3, M4, and M5 receptors. The various receptors are present throughout the body, and the individual subtypes seem to be responsible for different actions. For example, in peripheral tissues, M1 receptors amplify ganglionic neurotransmission. M2 receptors are involved in contractility and heart rate, while M3 receptors mediate contraction of smooth muscles. For muscarinic receptors in brain tissue, the M1 receptors play a role in memory and learning, the M2 receptors influence autonomic functions, and there is evidence that M4 receptors control motor behavior.
Compounds that antagonize muscarinic receptors have been developed for treatment of neurodegenerative diseases such as PD. Because the various muscarinic receptor subtypes are expressed in numerous body tissues, and each subtype appears to control or effect a different bodily function, it would be useful to find compounds that are selective for a single subtype. The M4 subtype is found in high levels in the striatum of the brain and is involved in motor function. Accordingly, compounds that selectively antagonize the M4 receptor would be useful as treatments for PD, without adversely affecting other body functions controlled by the other muscarinic receptor subtypes.
The present invention provides compounds that are useful in a method of selectively antagonizing the M4 muscarinic receptor, the method comprising the administration of an effective amount of such a compound to a subject, preferably mammalian, in need thereof.
The present invention is directed to fused-ring derivatives containing an indole and their use as antagonists of the M4 muscarinic receptor. The compounds of the invention are those having the structure of Formula I:
wherein:
R1 is hydrogen, lower alkyl or COOR7, or aryl, heteroaryl, arylalkyl or heteroarylalkyl optionally substituted with one, two, or three groups independently selected from hydrogen, halogen, lower alkyl, lower alkoxy, hydroxy, cyano, nitro, amino, mono- or dialkylamino, carboxy, alkoxycarbonyl, carbamoyl, sulfamoyl, trifluoromethyl, or alkylthio;
R3 is hydrogen or lower alkyl;
R2, R4, R5, and R6 independently represent hydrogen, halogen, lower alkyl, lower alkoxy, hydroxy, cyano, nitro, amino, mono- or dialkylamino, carboxy, alkoxycarbonyl, carbamoyl, sulfamoyl, trifluoromethyl, or alkylthio;
R7 is hydrogen or lower alkyl;
xe2x80x94may or may not be a bond; and
R8 is hydrogen or oxo.
The instant invention includes pharmaceutical compositions of compounds of Formula 1 and a method of treating PD, the method comprising administering to a patient having PD a therapeutically effective amount of a compound of Formula I.
Also provided is a method of selectively antagonizing the M4 muscarinic receptor, the method comprising administering to a patient in need selectively antagonizing the M4 muscarinic receptor an M4 muscarinic receptor antagonizing amount of a compound of Formula I.
The novel compounds encompassed by the instant invention are those described by the general Formula I set forth above, and the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof
Preferred compounds of Formula I are those in which R1 is COOR7; R2 is lower alkyl or (un)substituted aryl or heteroaryl; R3 is hydrogen; R4 is hydrogen or halogen; R5 is lower alkoxy, alkylthio, lower alkyl, or halogen; R6 is hydrogen; R7 is lower alkyl; and R8 is hydrogen.
More preferred compounds of Formula I are those where R2 are methyl, ethyl, n-propyl, or (un)substituted heteroaryl; R4 is hydrogen or bromo; and R5 is lower alkyl or alkylthio.
In addition to the compounds of Formula I, the invention encompasses compounds of Formula II:
wherein R1, R2, R3, R4, and R5 are as defined above for Formula I.
Preferred compounds of Formula II are those where R1 is COOR7; R2 is lower alkyl or (un)substituted aryl or heteroaryl; R3 is hydrogen; R4 is hydrogen or halogen; R5 is lower alkoxy, alkylthio, lower alkyl, or halogen; and R7 is lower alkyl.
In addition, the invention encompasses compounds of Formula III:
wherein R2, R3, R4, R5, and R6 are as defined above for Formula I.
Preferred compounds of Formula III are those where R2 is lower alkyl or (un)substituted aryl or heteroaryl; R3 is hydrogen; R4 is hydrogen or halogen; R5 is lower alkoxy, alkylthio, lower alkyl, or halogen; R6 is hydrogen; and R7 is lower alkyl.
In addition, the invention encompasses compounds of Formula IV:
Preferred compounds of Formula IV are those in which R1 is COOR7; R2 is lower alkyl or (un)substituted aryl or heteroaryl; R4 is hydrogen or halogen; R5 is lower alkoxy, alkylthio, lower alkyl, or halogen; R6 is hydrogen; and R7 is lower alkyl.
Except as expressly defined otherwise, the following definition of terms is employed throughout this specification.
The terms xe2x80x9calkyl,xe2x80x9d xe2x80x9clower alkyl,xe2x80x9d or xe2x80x9c(C1-C6)-alkylxe2x80x9d mean a straight or branched hydrocarbon having from 1 to 6 carbon atoms and includes, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, and the like. The alkyl group can also be substituted with one or more of the substituents listed below for aryl.
By xe2x80x9calkoxy,xe2x80x9d xe2x80x9clower alkoxy,xe2x80x9d or xe2x80x9c(C1-C6)-alkoxyxe2x80x9d in the present invention is meant straight or branched chain alkoxy groups having 1 to 6 carbon atoms, such as, for example, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, pentoxy, 2-pentyl, isopentoxy, neopentoxy, hexoxy, 2-hexoxy, 3-hexoxy, and 3-methylpentoxy.
The term xe2x80x9chalogenxe2x80x9d includes chlorine, fluorine, bromine, and iodine, and their monovalent radicals.
The term xe2x80x9carylxe2x80x9d means an aromatic carbocyclic group having a single ring (e.g., phenyl), multiple rings (e.g., biphenyl), or multiple condensed rings in which at least one is aromatic (e.g., 1,2,3,4-tetrahydronaphthyl, naphthyl, anthryl, or phenanthryl), unsubstituted or substituted by 1 to 3 substituents selected from alkyl, O-alkyl and S-alkyl, OH, SH, xe2x80x94CN, halogen, 1,3-dioxolanyl, CF3, NO2, NH2, NHCH3, N(CH3)2, NHCO-alkyl, xe2x80x94(CH2)mCO2H, xe2x80x94(CH2)mCO2-alkyl, xe2x80x94(CH2)mSO3H, xe2x80x94NH alkyl, xe2x80x94N(alkyl)2, xe2x80x94CH2)mPO3H2, xe2x80x94(CH2)mPO3(alkyl)2, xe2x80x94(CH2)mSO2NH2, and xe2x80x94(CH2)mSO2NH-alkyl wherein alkyl is defined as above and m is 0, 1, 2, or 3. A preferable aryl group of the present invention is phenyl.
The term xe2x80x9caralkylxe2x80x9d or xe2x80x9carylalkylxe2x80x9d means an alkyl moiety (as defined above) substituted with an aryl moiety (also as defined above).
By heteroaryl (aromatic heterocycle) in the present invention is meant one or more aromatic ring systems of 5-, 6-, or 7-membered rings containing at least one, and up to four heteroatoms selected from nitrogen, oxygen, or sulfur. Such heteroaryl groups include, for example, thienyl, furanyl, thiazolyl, imidazolyl, (is)oxazolyl, pyridyl, pyrimidinyl, (iso)quinolinyl, naphthyridinyl, benzimidazolyl, and benzoxazolyl. The heterocycle is unsubstituted or substituted by 1 to 3 substituents selected from alkyl, O-alkyl and S-alkyl, OH, SH, xe2x80x94CN, halogen, 1,3-dioxolanyl, CF3, NO2, NH2, NHCH3, N(CH3)2, NHCO-alkyl, xe2x80x94(CH2)mCO2H, xe2x80x94(CH2)mCO2-alkyl, xe2x80x94(CH2)mSO3H, xe2x80x94NH alkyl, xe2x80x94N(alkyl)2, xe2x80x94CH2)mPO3H2, xe2x80x94(CH2)mPO3(alkyl)2, xe2x80x94(CH2)mSO2NH2, and xe2x80x94(CH2)mSO2NH xe2x80x94alkyl wherein alkyl is defined as above and m is 0, 1, 2, or 3. A preferable -heteroaryl group of the present invention is 2-, 3-, or 4-pyridine.
The term xe2x80x9cheteroarylalkylxe2x80x9d means an alkyl moiety (as defined above) substituted with an heteroaryl moiety (also as defined above).
The symbol xe2x80x9cxe2x80x94xe2x80x9d means a covalent bond. xe2x80x9cM4 selective bindingxe2x80x9d means that a compound binds to the M4 muscarinic receptor subtype by at least about 20-fold more than to any of the other receptor subtypes (M1, M2, M3, and M5).
The term xe2x80x9cpharmaceutically acceptable salt, ester, amide, and prodrugxe2x80x9d as used herein refers to the amino acid addition salts of the compounds of the present invention which are, within the scope of sound medical judgement, suitable for use in contact with the tissues of patients without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit/risk ratio, and effective for their intended use, as well as the zwitterionic forms, where possible, of the compounds of the invention. The term xe2x80x9csaltsxe2x80x9d refers to the relatively nontoxic, inorganic, and organic acid addition salts of compounds of the present invention. These salts can be prepared in situ during the final isolation and purification of the compounds, or by separately reacting the purified compound in its free base form with a suitable organic or inorganic acid and isolating the salt thus formed. Representative salts include the hydrobromide, hydrochloride, sulfate, bisulfate, nitrate, acetate, oxalate, valerate, oleate, palmitate, stearate, laurate, borate, benzoate, lactate, phosphate, tosylate, citrate, maleate, fumarate, succinate, tartrate, naphthylate mesylate, glucoheptonate, lactiobionate and laurylsulphonate salts, and the like. These may include cations based on the alkali and alkaline earth metals, such as sodium, lithium, potassium, calcium, magnesium, and the like, as well as, nontoxic ammonium, quaternary ammonium and amine cations including, but not limited to ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, ethylamine, and the like. (See, for example, Berge S. M., et al., Pharmaceutical Salts, J. Pharm. Sci., 1977;66:1-19, which is incorporated herein by reference.)
Examples of pharmaceutically acceptable, nontoxic amides of the compounds of this invention include amides derived from ammonia, primary C1-C6 alkyl amines and secondary C1-C6 dialkyl amines wherein the alkyl groups are straight or branched chain. In the case of secondary amines, the amine may also be in the form of a 5- or 6-membered heterocycle containing one nitrogen atom. Amides derived from ammonia, C1-C3 alkyl primary amides and C1-C2 dialkyl secondary amides are preferred. Amides of the compounds of the invention may be prepared according to conventional methods.
The term xe2x80x9cprodrugxe2x80x9d refers to compounds that are rapidly transformed in vivo to yield the parent compound of the above formulas, for example, by hydrolysis in blood. A thorough discussion is provided in T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Vol. 14 of the A.C.S. Symposium Series, and in Bioreversible Carriers in Drug Design ed. Edward B. Roche, American Pharmaceutical Association and Pergamon Press, 1987, both of which are incorporated herein by reference.
In addition, the compounds of the present invention can exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like. In general, the solvated forms are considered equivalent to the unsolvated forms for the purposes of the present invention.
Certain of the compounds of the present invention possess one or more chiral centers and each center may exist in the R or S configuration. The present invention includes all diastereomeric, enantiomeric, and epimeric forms as well as the appropriate mixtures thereof. Additionally, the compounds of the present invention may exist as geometric isomers. The present invention includes all cis, trans, syn, anti, entgegen (E), and zusammen (Z) isomers as well as the appropriate mixtures thereof.
Representative compounds of the invention are shown below in Table 1.
Representative compounds of the present invention, which are encompassed by Formula I include, but are not limited to the compounds in Table 1 and their pharmaceutically acceptable acid or base addition salts, or amide, or prodrugs thereof.
In the methods of the present invention, a compound can be administered either orally, rectally, parenterally (intravenously, intramuscularly, or subcutaneously), intracisternally, intravaginally, intraperitoneally, intravesically, locally (powders, ointments, or drops), or as a buccal or nasal spray.
Compositions suitable for parenteral injection may comprise physiologically acceptable sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, and sterile powders for reconstitution into sterile injectable solutions or dispersions. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents, or vehicles include water, ethanol, polyols (propyleneglycol, polyethyleneglycol, glycerol, and the like), suitable mixtures thereof, vegetable oils (such as olive oil), and injectable organic esters such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surfactants.
These compositions may also contain adjuvants such as preserving, wetting, emulsifying, and dispensing agents. Prevention of the action of microorganisms can be ensured by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, and the like. It may also be desirable to include isotonic agents, for example, sugars, sodium chloride, and the like. Prolonged absorption of the injectable pharmaceutical form can be brought about by the use of agents delaying absorption, for example, aluminum monostearate and gelatin.
Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is admixed with at least one inert customary excipient (or carrier) such as sodium citrate or dicalcium phosphate or (a) fillers or extenders, as for example, starches, lactose, sucrose, glucose, mannitol, and silicic acid; (b) binders, as for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose, and acacia; (c) humectants, as for example, glycerol; (d) disintegrating agents, as for example, agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain complex silicates, and sodium carbonate; (e) solution retarders, as for example paraffin; (f) absorption accelerators, as for example, quaternary ammonium compounds; (g) wetting agents, as for example, cetyl alcohol and glycerol monostearate; (h) adsorbents, as for example, kaolin and bentonite; and (i) lubricants, as for example, talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, or mixtures thereof. In the case of capsules, tablets, and pills, the dosage forms may also comprise buffering agents.
Solid compositions of a similar type may also be employed as fillers in soft- and hard-filled gelatin capsules using such excipients as lactose or milk sugar, as well as high molecular weight polyethyleneglycols, and the like.
Solid dosage forms such as tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells, such as enteric coatings and others well-known in the art. They may contain opacifying agents, and can also be of such composition that they release the active compound or compounds in a certain part of the intestinal tract in a delayed manner. Examples of embedding compositions which can be used are polymeric substances and waxes. The active compounds can also be in microencapsulated form, if appropriate, with one or more of the above-mentioned excipients.
Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs. In addition to the active compounds, the liquid dosage forms may contain inert diluents commonly used in the art, such as water or other solvents, solubilizing agents, and emulsifiers, as for example, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propyleneglycol, 1,3-butyleneglycol, dimethylformamide, oils, in particular, cottonseed oil, groundnut oil, corn germ oil, olive oil, castor oil, and sesame oil, glycerol, tetrahydrofurfuryl alcohol, polyethyleneglycols, and fatty acid esters of sorbitan, or mixtures of these substances, and the like.
Besides such inert diluents, the composition can also include adjuvants, such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents.
Suspensions, in addition to the active compounds, may contain suspending agents, as for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar, and tragacanth, or mixtures of these substances, and the like.
Compositions for rectal administrations are preferably suppositories which can be prepared by mixing the compounds of the present invention with suitable nonirritating excipients or carriers such as cocoa butter, polyethyleneglycol, or a suppository wax, which are solid at ordinary temperatures but liquid at body temperature and therefore, melt in the rectum or vaginal cavity and release the active component.
Dosage forms for topical administration of a compound of this invention include ointments, powders, sprays, and inhalants. The active component is admixed under sterile conditions with a physiologically acceptable carrier and any preservatives, buffers or propellants as may be required. Ophthalmic formulations, eye ointments, powders, and solutions are also contemplated as being within the scope of this invention.
The compounds of the present invention can be administered to a patient at dosage levels in the range of about 0.1 to about 1000 mg/day, and generally from about 5 to about 250 mg/kg/day. For a normal human adult having a body weight of about 70 kg, a dosage in the range of about 0.01 to about 100 mg/kg of body weight per day is sufficient. The specific dosage used, however, can vary. For example, the dosage can depend on a number of factors including the requirements of the patient, the severity of the condition being treated, and the pharmacological activity of the compound being used. The determination of optimum dosages for a particular patient is well-known to those skilled in the art. The term xe2x80x9cpatientxe2x80x9d means humans and other animals.
For use in treating PD, the invention compound is typically part of a pharmaceutical composition and is administered to a patient by methods well-known to those skilled in the art. The invention compound will be present in an amount of about 5% to about 95% by weight of the composition.
The examples presented below are intended to illustrate particular embodiments of the invention, and are not intended to limit the scope of the specification or the claims in any way.
The compounds of Formula I are readily prepared by methods utilizing standard organic chemical reactions. An illustration of the preparation of compounds of the present invention is shown in Scheme 1. R2, R5, and R6 are as defined above for Formula I.
Armed with the disclosure provided herein (particularly the schemes and the synthetic examples that follow) and knowledge common to all who practice in the field, those of ordinary skill in the art will be able to make and use the entire scope of compounds disclosed herein.
Generally, Scheme 1 illustrates a synthetic route to the indole-containing fused ring compounds of the present invention. An ethyl 2-(4-aminophenyl)acetate is iodinated with a reagent such as, for example, iodine monochloride, to afford the corresponding ethyl 2-(4-amino-3-iodophenyl)acetate. This amine is treated with a 3-oxoacetate to produce the desired ethyl 3-(phenylamino)but-2-enoate. Formation of the indole is then achieved upon treatment with a catalyst, such as, for example, palladium acetate. The resulting ethyl 2-[3-(ethoxycarbonyl)indol-5-yl]acetate is saponified with a base such as potassium hydroxide to afford the 2-[3-(ethoxycarbonyl)indol-5-yl]acetic acid. The acid is subsequently converted to the amide by treatment with an amine and a suitable coupling agent, such as, for example, N,Nxe2x80x2-carbonyldiimidazole or dicyclohexylcarbodiimide. Cyclization of the amide (e.g., in the presence of phosphorous oxychloride via the Bischler-Napieralske reaction) affords the dihydroisoquinoline, which is then treated with, for example, oxomethyl 2,2-dimethylpropanoate to produce the corresponding trihydroisoquinoline-2-carbaldehyde-ene. This compound is further cyclized and subsequently reduced to form the 6,11,12,13,12a,6a-hexahydroisoquinolino[2,1-b]pyrrolo[2,3-h]isoquinoline. The R4 group (as found in Formula I) can be present on the starting ethyl 2-(4-aminophenyl)acetate or introduced at various steps of the scheme (such as depicted in Scheme 1), depending on the nature of the group. The indole nitrogen can also be alkylated with various procedures known in the art.
The disclosures in this application of all articles and references, including patents, are incorporated herein by reference.
The invention is illustrated further by the following examples which are not to be construed as limiting the invention in scope or spirit to the specific procedures described in them.
The starting materials and various intermediates may be obtained from commercial sources, prepared from commercially available organic compounds, or prepared using well-known synthetic methods.
Representative examples of methods for preparing intermediates of the invention are set forth below.

Fused ring system containing indole as M4 selective aza-anthracene muscarinic receptor antagonists

Abstract: and pharmaceutically acceptable salts, esters, amides, and prodrugs thereof,

Abstract: wherein

Abstract: R1 is hydrogen, lower alkyl, COOR7, (un)substituted aryl, (un)substituted heteroaryl, (un)substituted arylalkyl, or (un)substituted heteroarylalkyl;

Abstract: R3 is hydrogen or lower alkyl;

Abstract: R7 is hydrogen or lower alkyl; and

Abstract: R8 is hydrogen or oxo.

Abstract: Also provided is a method for selectively antagonizing the M4 muscarinic receptor and a method for treating Parkinson""s disease.


Compounds of formula (I) wherein R1, R4, R8, X and Y as defined herein are provided as useful for the inhibition of certain types of cancer cells, amongst others, breast cancer cells, or for the manufacture of anti-cancer agents.

Cancer is a disease that seriously jeopardizes the health of human beings. Around the globe, about 6 millions people die of cancer every year, with another 10 millions seriously affected by the disease. According to the estimate of the World Health Organization, in the 21st century, cancer will become the "number one killer" of mankind.
In the past several decades, many ways of treating cancer became available, mainly including surgery, radiotherapy, chemotherapy, hormonotherapy, gene therapy, and immunotherapy, among which surgery, radiotherapy and chemotherapy have become the major means. Chemotherapy refers to treating cancer with chemical medication. It is the most rapidly expanding field in the diagnosis and treatment of cancer. A great number of new medicines aiming at different targets are ready for clinical application, and developments in research in mechanism of drug action and pharmacokinetics have made the clinical administration routes and means more fitting for killing tumor cells while protecting the normal tissues.
At present, pharmaceuticals for chemotherapy mainly includes: compounds that affects the biosynthesis of nucleic acid (e.g., 5-fluorouracil, amethopterin, cytarabine, hydroxyurea); compounds that directly destroys DNA and prevents its reproduction, e.g. alkylating agents (e.g., cisplatin and carboplatin); antineoplastic antibiotics (e.g., daunorubicin, mitomycin C) compounds that interferes with the transcription and prevents the synthesis of RNA (e.g., actinomycin D, adriamycin) and other transcription restraining antibiotics; compounds that affects the synthesis of protein (e.g., catharanthines, podophyllotoxins, asparaginase) hormones (e.g., adrenal cortical hormone, estrogen, androgen, tamoxifen, aminoglutethimide). The property of interfering in the polymerization or depolymerization of microtubulin of many natural medicines is regarded as having antineoplastic activity. Historically, research focused on two classes of antimitotic agents. The first class includes compounds that bind reversibly to tubulin and prevent microtubule assembly (e.g., colchicine, vinblastine, combretastatin). The second class of antimicrotubule agents features molecules that prevent microtubule disassembly (e.g., taxotere, epothilone, discodermolide, eleutherobine).
Despite the utility of taxus and vinca alkaloids in the clinic, there are serious limitations to these therapies. On-target toxicity of these agents is associated with the notion that tubulin polymers play a critical role in the non-mitotic cytoskeletal functions in both proliferating and terminally differentiated cells. Microtubules are also essential for axonal transport in neurons. Peripheral neurotoxicity of Paclitaxel™, Docetaxel™ and Vincristine™ has been extensively studied. Although manageable and reversible for the majority of second-generation anti-mitotic drugs, this severe side effect may preclude repeated courses of therapy. Neuropathy continues to be an issue for novel agents in clinical development, for example dolastatin-10. In addition, drug efflux pumps play a role in tumors developing resistance to the tubulin-binding drugs. For example, vinca alkaloids and taxanes are both substrates for the P-gp efflux pump encoded by the multidrug resistance mdr1 gene, resulting in decreased sensitivity to these compounds in vivo. Due to these limitations of the tubulin-binding antimitotic agents, there is ongoing need to identify new subsets of antimicrotubule agents that yield anti-mitotic effect with better specificity and more predictable pharmacology
One major drawback when treating cancer is to achieve selectivity against this type of cancer cells. Most chemotherapy against these types of cancer comprises: anti-estrogen therapy such as tamoxifene, raloxifene and toremifene that are Selective Estrogen Receptor Modulators (SERM) that block estrogen's action on some tissues or organs and acts like estrogen on others. They are used for both pre- and postmenopausal women and considered as the first-line hormone therapy. In addition, there is also fulvestrant that is a pure estrogen receptor antagonist.
Selective aromatase inhibitors such as letrozole, anastrozole and exemestane, and nonselective aromatase inhibitors such as aminoglutethimide and testolactone are blocking the function of the enzyme aromatase, which is needed to convert pre-estrogen into a biologically active form. These molecules block the conversion of a pre-estrogen compound produced by tissues other than the ovaries into estrogen. They are used also in the first- and the second-line therapy for early stage breast cancer as well as for postmenopausal women. In the third-line therapy are found progesterone-like drugs such as megestrol acetate. These drugs are traditionally used in postmenopausal women after tamoxifen no longer works. Finally, there are the Luteinizing Hormone-Releasing Hormone (LHRH)-like drugs such as goserelin and leuprolide acetate that reduce estrogen production by the ovaries and used in premenauposal women in complement with aromatase inhibitors.
There remains a need to discover and synthesize new potent compounds having selective activity against certain types of cancer cells, there by providing highly selective anti-cancer molecules.
Certain substituted 2-imidazolidones have now been found to be specific for certain types of cancer cells.

Substituted 2-imidazolidinones and 2-imidazolones and their use in the treatment of cancer