A crop lifter apparatus has a base member attached to a selected guard finger of a cutting header. A front lifting finger extends forward and downward from the base member at a first angle downward from horizontal, and a rear lifting finger extends rearward and upward from the base member at second angle upward from horizontal, where the second angle is greater than the first angle. A front end of the front lifting finger is at a front vertical location that is a first distance below a top surface of the table, and a rear end of the rear lifting finger is at a rear vertical location that is a second distance above the top surface of the table, and the second distance is at least twice the first distance.

For various reasons crops sometimes are lying so close to the ground that it is difficult to cut them with a conventional harvest header. Some crops are inherently short, while others may be taller, but are prone to fall down when they reach maturity. Heavy rain or hail can also cause crop to be lying close to the ground at harvest time. Such a crop where relatively tall crop plants fall over close to the ground is commonly called a lodged crop.
Typically the knife on cutting headers comprises a knife bar extending along the front lower edge of the header, with a plurality of triangular knife sections attached to the bar such that the apex of the triangle extends forward from the bar. The exposed side edges of the knife sections are sharpened. Guards are attached to the front lower edge of the header and serve to protect the knife sections from breakage when contacting stones and like obstructions. The guards comprise pointed guard fingers extending forward, and the knife moves back and forth along the edge of the header in a slot cut laterally through the guard fingers. In addition to protecting the knife, the guard fingers also enable the knife sections to cut the crop. As the knife section moves back and forth it pushes crop against the sides of those portions of the guard finger that are above and below the slot, shearing the crop stalks.
A conventional knife is a few inches above the ground when the header is in its lowest position, such that very short or downed crop material will pass under the knife and be lost. Many different kinds of "crop lifters", as they have come to be known, have been developed over the last century and more. Typically these crop lifters are attached to the header and/or the forward extending point of the guard finger, and provide an arm of various designs that rides along the ground ahead of the knife. A lifting finger extends at a shallow angle from the front of the arm back and over the knife. As the header moves down the field, the arm rides along the ground and under the downed crop stalks, which then are lifted and pass over the lifting finger to the knife, where they are cut and continue moving onto the header from where they can be passed to the harvester, swatter table, or the like.
U.S. Pat. Nos. 700,029 and 791,022 to Gatermann, U.S. Pat. No. 2,734,332 to Fisher, U.S. Pat. No. 2,892,298 to Chaney, U.S. Pat. No. 2,960,814 to Babcock, and Canadian Patent Number 407,654 to Young disclose a crop lifter that is pivotally attached to the header so as to be able to move up and down to follow the ground. The Babcock and Fisher devices float on the ground, while the others are biased toward the ground by springs. U.S. Pat. No. 4,120,138 to Schumacher illustrates a crop lifter that is fixed to the header instead of pivoting, but is made of spring steel so that same may move up and down to follow the ground.
U.S. Pat. No. 7,650,738 to Dietrich discloses a crop lifter with a bore member that is secured to a guard finger. The bore member defines a bore and the lifting finger extends through the bore such that a forward end thereof extends downward and forward from the bore member at a shallow angle to pass under and raise the crop stalks, and the rearward portion of the lifting finger extends rearward from the bore member and upward at the same shallow angle to a rear end above and rearward of the knife. The shallow angle is fixed at a desired angle that suits the conditions being encountered and can be adjusted.
Once cut, it is most desirable for efficient operation of the harvester mechanisms to deliver the stalks in a smooth orderly now from the knife to a feeding mechanism that conveys the stalks up into the harvester mechanism. Draper type cutting headers have right and left wide conveyor belts that move along the header table perpendicular to the operating travel direction with front edges thereof just behind the knife. The cut crop stalks fall onto the belts and are carried to a middle conveyor belt moving rearward that receives the stalks and carries them rearward into a feeder mechanism that moves them into the harvester mechanism. When cutting upright crop stalks, the stalks fall onto the belts generally parallel to each other, with the heads at the top ends of the stalks together on the inner side of the belts, and are moved smoothly to the middle conveyor belt and head first into the feeder mechanism.
In contrast, auger type cutting headers for harvesters have a large diameter auger extending from one end of the header to the other perpendicular to the operating travel direction. Right hand and left hand auger flighting on corresponding end portions of the auger carry the cut crop stalks to a feeder mechanism generally in the middle of the table. Fingers on the middle portion of the auger grab the stalks and push them rearward into the feeder mechanism. In the auger type header there is some distance between the knife and the outer edges of the auger fighting. When cutting upright crop stalks, the stalks fall against the flighting as they are cut and are moved smoothly to the feeder mechanism with the heads at the top ends of the stalks falling toward the center so that the stalks enter the feeding mechanism head first.
When the crop stalks are tying down close to the ground however, crop lifter are often required to raise the stalks above the knife so same can be cut. These conventional crop lifters only raise the stalks a short distance above the knife, such that they when cut they are still generally lying down. The cut stalks can have heads pointed in all directions and, in an auger type header, once cut they must slide rearward across a width of header table before contacting the auger flighting under generally the rotational center of the auger where outer edges of the fighting are located close to the header table. In some conditions the stalks do not flow smoothly over the table to the auger, but bunch up and move to the auger in lumps, reducing the efficiency of the harvester.
In both auger and draper type headers, with conventional crop lifters raising crop stalks that are lying down, the stalks enter the feeder mechanism oriented in all directions, some sideways, some cut end first, and with only a portion in the desirable head first orientation. Harvester efficiency is reduced compared to a smooth head first flow of crop stalks.


A verifier is provided for assessing unique characteristics exhibits by a user over a period of time. The unique characteristics are captured through various interactions with the user over time using a habit capture system which models the user's characteristics when he or she uses a keyboard, a mouse or a digitizer, among others. When the system is first used, the user is prompted to answer various questions, some of which inquire into personal information. As the user responds, information representative of the user is captured, including keyboard typing patterns, mouse click patterns, misspelling patterns, among others. Data captured by the habit capture system is provided to a verifier which samples the user's characteristics and compares the characteristics of the current user with that stored in a database.

1. Field of the Invention
The invention relates to an apparatus and a method for identity verification, and more particularly, to an apparatus and a method for verifying the identity of a student during one or more computer-based training sessions.
2. Description of the Related Art
The dawn of the microprocessor age has ushered an era with previously unimagined dimensions. Through the enabling technology of the microprocessor, an individual can leverage his or her creative power to perform a wide variety of information-processing tasks that previously had to be assigned to entire departments. Additionally, the networks that made the microprocessor ubiquitous around the world empower the user with a global broadcasting capability. Such technological lever has shifted the traditional power structure from central offices to individuals located in far-flung offices around the world, allowing decisions to be made quicker and more accurately.
The empowerment of the individual by the microprocessor has provided a fundamental and pervasive impact on civilizations. In the past, certain citizens could rely on brute strength as a substitute for formal training or education. However, because a well trained workforce is vital to the growth of nations, the proper training of citizens has significant national implications, for those who fail to train their citizens in technological matters face significant disruptions in their economies, possibly leading to extinction.
As reported in America's popular press, many improvements are needed to sustain the status of America as a world power. In the U.S., higher education remains a labor-intensive service industry made up of fiercely independent and mutually suspicious organizations, each of which jealously guards its expensive and underused facilities. Despite all the tax advantages and private and public subsidies associated with higher education, annual tuition increases have become a hallmark for America's colleges and universities. Furthermore, tuitions are expected to consume ever larger fractions of family budgets, leave so many graduates laden with debt and compel more and more prospective students to select colleges on the basis of cost rather than academic abilities or personal preferences.
Additionally, the U.S. educational system has to overcome a number of other forces that are unrelated to financial burdens. One such force negatively affecting the effectiveness of the school system is the lack of qualified faculties or teachers for classrooms. The U.S. educational system also faces competition in the form of television shows and interactive multimedia games, most of which resort to graphical uses of violence and sex. Given such competition for the students' mind-share, traditional teaching tools such as books and lectures face significant hurdles.
Yet another force that negatively impacts the effectiveness of the educational system is the rigid structure built into our existing educational system. This rigid structure forces students to commute to school, regardless of the relationship of the courses to high traffic time. Additionally, to compensate for the lack of qualified teachers, the average class size has increased. Furthermore, the U.S. educational system rigidly enforces group learning. This herd mentality is sub-optimal, as the more intelligent members of the class are constrained to progress at the average class rate. Thus, the rigidity of our existing educational infrastructure causes a significant amount of time to be wasted in doing things other than learning.
Historically, teachers, professors and educators have for centuries informed and raised awareness of the populace using printed publications such as books and libraries. However, the inexorable march of technology has provided a new arsenal to educators: the computer. Since the sixties, experimental computer-based training systems such as PLATO, executing on Control Data Corporation's mainframes, have appeared. More recently, computer-based educational programs have become available to subscribers and other students with access to a microcomputer and a telephone. Today, existing electronic teaching programs have included video teleconferencing and electronic mail to supplement the more traditional teaching tools such as books. However, the present solutions are not competitive with television shows and interactive multimedia games. Furthermore, due to security issues, present day computer aided instruction systems have been limited to non-credit classes to eliminate the thorny potentials for cheating. Thus, the current solutions require the student to take tests at a central testing facility to minimize incidents of cheating. Although a number of more enlightened universities such as Rice University have deployed an honor code system, such faith in humanity is still not the norm in most universities. Thus, for many universities, requiring students to appear at predetermined test locations is a necessary evil to ensure the sanctity of the grade and the honors bestowed upon the students. This requirement adds unnecessary overhead costs for both the education institution and the student. Furthermore, the requirement reduces the productive time that the student could spend studying instead of taking tests.


A method for forming a capacitor comprises providing a substrate. A bottom electrode material layer is formed on the substrate. A first mask layer is formed on the bottom electrode material layer. A second mask layer is formed on the first mask layer. The second mask layer is patterned to form a patterned second mask layer in a predetermined region for formation of a capacitor. A plurality of hemispherical grain structures are formed on a sidewall of the patterned second mask layer. The first mask layer is etched by using the hemispherical grain structures and the patterned second mask layer as a mask, thereby forming a patterned first mask layer having a pattern. The pattern of the first mask layer is transferred to the bottom electrode material layer. And, a capacitor dielectric layer and a top electrode layer are formed on the bottom electrode material layer to form the capacitor.

1. Field of the Invention
The present invention relates to methods for fabricating semiconductor devices, and in particular to methods for fabricating capacitors.
2. Description of the Related Art
The development trend in the rapidly evolving integrated circuit industry is toward high performance, miniaturization, and high operating speed. Dynamic random access memory (DRAM) fabrication methods have also developed rapidly. More specifically, shrinking design dimensions is a strategic aim. However, as each memory cell shrinks, a capacitor must maintain a certain charge storage capacity, for example more than 25 fF, to ensure reliable operation of the memory cell.
A DRAM cell typically comprises a transistor and a capacitor. The capacitor is formed by disposing a dielectric material between two electrode plates. The capacitance is represented as C=KA/D, wherein K is the dielectric constant of the dielectric material in the capacitor; A is the electrode area; and D is the distance between two electrode plates. To increase capacitance without enlarging the area occupied by the DRAM cell on the wafer, a high-k dielectric material is used to form the dielectric layer between the electrode plates. Alternatively, growth of HSG silicon (hemispherical grained silicon) on the surface of the top and/or bottom electrode plate is used to increase the surface area of the electrode plates. U.S. Pat. No. 6,300,192 by Kim entitled as "METHOD FOR FABRICATING A DRAM CELL CAPACITOR USING HEMISPHERICAL GRAIN (HSG) SILICON", discloses forming HSG silicon on the polysilicon plate by performing a seeding method in a stacked capacitor structure. However, this skill is limited to the bottom electrode material, which must be polysilicon for growth of HSG silicon. As metal is needed for the electrode plate, the conventional technology for increasing the surface area of the electrode plate by growing HSG silicon on the polysilicon electrode is not suitable for use in the manufacturing process. Hence, a new method for increasing the surface area of the electrodes to raise capacitance without additional photolithography mask is needed.

Industrial Technology Research Institute


It has been found that in sol-gel processes utilizing TMAH, it is possible to treat a trimethylamine (TRIMA)-containing solution with hydrogen peroxide to form trimethylamine oxide--(CH.sub.3).sub.3 N.sup.+ --O.sup.- (TRIMAO), a water soluble compound which is less volatile and less odorous than TRIMA, and which is capable of being sent to a standard wastewater treatment plant. The hydrogen peroxide is generally added to the TRIMA-containing solution in a H.sub.2 O.sub.2 :TRIMA ratio of at least 3:1, advantageously at least 10:1. Because of the resultant TRIMAO solution's ability to be sent to a standard wastewater treatment facility, improved productivity and lowered expense of the overall fiber fabrication process are obtained. The invention is also suitable for treatment of triethylamine.

1. Field of the Invention
The invention relates to optical fiber fabrication, in particular the disposal of by-products of such fabrication.
2. Discussion of the Related Art
Glass optical fiber is typically drawn from a solid preform containing an overcladding that surrounds an inner cladding and core. An overcladding tube is generally formed separately from the inner cladding and core, and the components are then brought together to make the preform. The overcladding does not have to meet the demanding purity and uniformity specifications of the core and inner cladding, and some efforts at improving manufacturing efficiency and lowering cost of optical fiber manufacturing processes have therefore focused on the overcladding. These efforts have led to the use of sol-gel processes to form overcladding tubes.
U.S. Pat. No. 5,240,488, the disclosure of which is hereby incorporated by reference, discloses a sol-gel process for production of overcladding tubes. In the process, an aqueous colloidal silica dispersion is used. The dispersion is typically stabilized by addition of a base such as tetramethylammonium hydroxide (TMAH). It is also possible to use tetraethylammonium hydroxide (TEAH). TMAH and TEAH are believed to stabilize silica particles by the following mechanism: Introduction of the TMAH or TEAH solution into a silica dispersion raises the pH value. The silica then takes on a negative surface charge due to ionization of silanol groups present on the surface, in accordance with the following reaction: EQU --Si--OH+OH.sup.- .fwdarw.--Si--O.sup.- +H.sub.2 O.
The negative charge on the silica particles creates mutual repulsion, preventing substantial agglomeration and maintaining the stability of the dispersion. At a later stage in the process, as discussed at Col. 15, lines 39-65 of the '488 patent, a gelling agent such as methyl formate is added to reduce the pH. The methyl formate, through reaction with water and/or base, neutralizes the negatively-charged silica to a degree where gelation is induced.
While processes such as that of the '488 patent produce good results, use of TMAH has caused some inconveniences in large-scale optical fiber fabrication. As shown in the Table in Cols. 11 and 12 of the '488 patent, once a gelled tube is dried, the tube must be heated to drive off volatile organic materials and water. During this heating, the tetramethylammonium salt that is present (e.g., tetramethyl ammonium formate in the reaction of the '488 patent) breaks down to an extent into trimethylamine (TRIMA), which has an undesirable odor, and is volatile and flammable. (TRIEA formed when using TEAH exhibits similar, undesirable properties.) The TRIMA or TRIEA is therefore burned or trapped and subsequently removed. Neither option is desirable, and both require significant off-line treatment that affects the productivity and expense of the overall fabrication process. Additionally, burning is expensive, and may lead to emission of undesirable gases that are removed by expensive emission controls.
Thus, the use of TMAH (or TEAH) in sol-gel overcladding fabrication has the potential to complicate an optical fiber manufacturing process. An easier, less-expensive method for disposing of TRIMA (or TRIEA) is desirable.

Process for treating by-product of optical fiber fabrication


A high frequency semi-isotropic embossed polymer interlayer sheet is disclosed. The embossed polymer interlayer sheet has a first side; a second side opposing the first side; and an embossed surface on at least one of the sides, and a surface texture ratio, Str, (as measured per ISO 25178) of between 0.1 and 0.99. The embossed polymer sheet may have at least 50 roughness peaks per centimeter (R PC, as measured per ASME B46.1 [1985]). The embossed polymer sheet may have a mottle value of less than or equal to 2.5 (as measured by a Clear Mottle Analyzer [CMA]). The embossed polymer sheet may be polyvinyl butyral.

1. Field of the Invention
This disclosure is related to the field of polymer interlayers for multiple layer glass panels and multiple layer glass panels having at least one embossed polymer interlayer sheet. Specifically, this disclosure is related to the field of embossed polymer interlayer sheets of multiple layer glass panels and methods of embossing the polymer interlayer sheets.
2. Description of Related Art
Generally, multiple layer glass panels are comprised of two sheets of glass, or other applicable substrates, with a polymer interlayer sheet or sheets sandwiched there between. The following offers a simplified description of the manner in which multiple layer glass panels are generally produced. First, at least one polymer interlayer sheet is placed between two substrates to create an assembly. It is not uncommon for multiple polymer interlayer sheets to be placed within the two substrates creating a multiple layer glass panel with multiple polymer interlayers. Then, air is removed from the assembly by an applicable process or method known to one of skill in the art; e.g., through nip rollers, vacuum bag or another de-airing mechanism. Following the removal of the air from the assembly, the constituent parts of the assembly are preliminarily press-bonded together by a method known to one of ordinary skill in the art. In a last step, in order to form a final unitary structure, this preliminary bonding is rendered more permanent by a lamination process known to one of ordinary skill in the art such as, but not limited to, autoclaving. Amongst other applications, the resultant laminate glass panels from this process are utilized in architectural windows and in the windows of motor vehicles and airplanes.
Generally, there are a number of possible problems encountered in the art of manufacturing multiple layer glass panels. Two (2) common problems are: de-gassing and optical quality.
De-gassing (also referred to as de-airing) is the removal of the presence of gas or air in a multiple layer glass panel. Gas trapped in a multiple layer glass panel can have a negative or degenerative effect on the optical clarity and adhesion of the panel. During the manufacturing process of laminated multiple layer glass panel constructs, gases can become trapped in the interstitial spaces between the substrates and the one or more polymer interlayers. Generally, this trapped air is removed in the glazing or panel manufacturing process by vacuum de-airing the construct, nipping the assembly between a pair of rollers (also referred to as nip roll de-airing) or by some other method known to those of skill in the art. However, these technologies are not always effective in removing all of the air trapped in the interstitial spaces between the substrates, especially when the polymer interlayer sheet has a smooth surface.
Lamination of a multiple layer glass panel is a multi-step process in which the polymer interlayer sheet(s) and rigid substrates are converted to a combined final form (the multiple layer glass panel or glazing) having desirable performance and optical clarity characteristics. Nip roll de-airing is one technique that is used to evacuate air from the rigid substrate/polymer interlayer/rigid substrate construction prior to the final step in the lamination process of autoclaving. It frequently can be employed to improve autoclave yields in commercial operations. In one embodiment, samples are moved along a conveyor in an oven or several ovens and then forced into and through a pair of rubber rollers with a set gap. The gap is typically set slightly smaller than the thickness of the sample (i.e., the substrate/polymer/substrate construction). The nip rollers typically can range in hardness, for example, from 35 to 75 Durometer Shore A. The conveyor transporting the sample through the oven prior to where the sample is "nipped" heats up the glass. Glass temperatures of the sample can be from 30° C. to over 100° C., as desired. Lower temperatures are often referred to as a "cold" nip roll process. As used herein, when referring to a cold nip roll process, the glass temperature ranges from about 45° C. to about 60° C. (as measured by a contact thermometer or similar device attached to or aimed at the glass, such as with an infrared type thermometer). Once cooled to room temperature, the nipped sample can be evaluated for de-airing quality or uniformity. The nipped sample can then be placed in an autoclave for final finishing. After finishing, the final or finished laminate can be evaluated for mottle and other optical defects.
Generally, the presence of a gas in the interstitial spaces of a multiple layer glass panel takes the form of bubbles in the polymer interlayer sheet(s) or pockets of gas between the polymer interlayer sheet(s) and the substrates. These bubbles and gaseous pockets are undesirable and problematic where the end-product multiple layer glass panel will be used in an application where optical quality is important. Thus, the creation of a solid-phase interlayer essentially free of any gaseous pockets or bubbles is paramount in the multiple layer glass panel manufacturing process.
Not only is it important to create a multiple layer glass panel free of gaseous pockets and bubbles immediately after manufacturing, but it is also important that the glass panel remain free of gaseous pockets and bubbles over its lifetime. It is not an uncommon defect in the art of multiple layer glass panels for dissolved gases to appear (e.g., for bubbles to form) in the panel over time, especially at elevated temperatures and under certain weather conditions and sunlight exposure. Thus, it is also important that, in addition to leaving the laminate production line free from any bubbles or gaseous cavities, that the multiple layer glass panel remain gas-free for a substantial period of time under end-use conditions to fulfill its commercial role.
For the successful production of high quality automotive or architectural multiple layer glass panels, also known as safety glazings, there needs to be an assurance of high yields when combining the initial, individual, polymer sheet(s) with the preferred glass type/part through the entire glass panel manufacturing process. A key part of that process is the autoclave cycle where the multiple layer glass panel structure enters into a pre-final or "pre-press" stage and emerges as a completed entity and saleable part for installation into a vehicle or building. Ensuring the highest autoclave yield possible for the glass panel manufacturer is essential for highest profitability and success because production of multiple layer glass panels is a time-consuming batch process where significant process bottlenecking and highest losses can occur because it is difficult to recycle parts once they have been laminated.
In order to facilitate the de-airing process and to provide acceptable optical quality, particularly in the glass panel, it has become common in the art of multiple layer glass panel manufacturing to emboss one or both sides of the polymer interlayer(s), thereby creating minute raised and depressed portions on the surface of the polymer interlayer. Embossment of the polymer interlayer has been shown to be effective in enhancing the de-airing process, and it is also effective in reducing the occurrence of blocking.
While certain embossing methods and techniques in the manufacture of multiple layer glass panels are known, there are several problems with the different embossing processes previously utilized in the art (referred to herein as "Conventional Processes"). In some Conventional Processes for making polymer interlayer sheets, the polymer sheet was cooled from a polymer sheet melt to form a polymer interlayer sheet, and then the surface of the polymer interlayer sheet was reheated, before the embossing step. Practically, in some methods, this necessitated that the polymer interlayer be fed through multiple sets of rollers in additional production steps before it could be embossed. FIGS. 1 and 2 depict two different Conventional Processes each which utilize multiple cooling, reheating and embossing steps. These additional production steps could significantly add to the costs, energy intake and the overall space required for multiple layer glass panel production.
Often, if both sides of a polymer were embossed in the Conventional Processes, the embossing was generally performed in separate successive steps with separate sets of embossing rollers by running the polymer interlayer sheet between two sets of embossing rollers. Thus, embossing in some Conventional Processes was performed in multiple separate successive stages with different sets of rollers, with each side of the polymer interlayer sheet being embossed in one of the successive stages. FIG. 2 provides a diagram of such a multi-step embossing process.
This multi-stage embossing process is generally required in some Conventional Processes because of the necessity of cooling the polymer interlayer sheet from a melt prior to embossing. As noted previously, in some Conventional Processes, the polymer interlayer sheet is not embossed directly after it leaves the extrusion die while it is still a melt because the molten polymer will stick to the embossing rolls causing a mess and degrading the integrity of the polymer interlayer sheet, rendering it unusable. Accordingly, the polymer interlayer sheet is cooled prior to embossing. However, a completely cooled polymer interlayer sheet is difficult, if not impossible, to emboss, therefore, in some Conventional Processes, after the polymer melt is cooled to a polymer interlayer sheet, the surface of the interlayer sheet must be reheated with the embossing roller (or by some other technique) at the time of embossing. The surface roughness or surface pattern of the embossed polymer interlayer sheet made by this process often has lower retention of the pattern than surface roughness or surface pattern of embossed polymer interlayer sheets of some other processes.
In some Conventional Processes using two embossing steps, the heated embossing roller is combined with a non-embossing roller, such as a rubber roller, which offers greater and more consistent pressure (higher contact force) to the embossing roller system than can be achieved if two metal (e.g., steel) embossing rollers are utilized simultaneously. Thus, if both sides of the polymer interlayer sheet are to be embossed in the Conventional Processes, usually at least two sets of rollers (each set being comprised of an embossing roller and a rubber roller) are utilized.
FIG. 3 depicts another Conventional Process for embossing a polymer interlayer sheet. As shown in FIG. 3, the polymer interlayer sheet is embossed in a step right after leaving the extruder die. The polymer interlayer sheet is embossed at an elevated temperature (that is, it is embossed while it is still a melt). No cooling step is required or utilized to lower the temperature between the steps of extrusion from the extrusion die and embossing. Rather, the polymer melt sheet (as opposed to the cooled and set polymer interlayer sheet) is embossed in a single embossing stage in which the polymer melt sheet is fed from the extrusion die into a single set of two embossing rollers (which in some embodiments are made of steel) directly out of the extrusion die, and both sides of the polymer melt sheet are simultaneously embossed. One side of the polymer melt sheet is embossed by one of the embossing rollers and the other side of the polymer melt sheet is embossed by the other embossing roller.
In some Conventional Processes, the embossed polymer interlayer sheet would perform adequately in the de-airing processes, but the optical clarity or optical properties of the final multiple layer glass panel was not acceptable to laminators due to reduced optical clarity or mottle. In other Conventional Processes, the optical clarity or optical properties of the final multiple layer glass panel was acceptable to laminators, but the embossed polymer interlayer sheet would not perform adequately in the de-airing processes, and de-air uniformity was unacceptable. Finally, in some Conventional Processes, neither the de-airing performance nor the optical quality (or mottle) was adequate. Mottle refers to an objectionable visual defect that manifests itself as graininess or texture in a laminated multiple layer polymer interlayer. Mottle and de-air uniformity will be further described below.
Multiple layer glass panels or laminated safety glazings need to have high optical quality and be free of defects as they are used in many demanding visual applications. It has been found that the quality of the pre-press laminate (the rigid substrate/polymer/rigid substrate construction or the glass/polymer sheet(s)/glass sandwich construction) after initial de-airing, such as cold nip roll de-airing, prior to final lamination is an excellent predictor of how well the panels will behave in the autoclave (that is, how good the final laminate quality will be) and therefore how good or bad the autoclave yield will be, therefore, the pre-press laminates should have certain qualities such as minimum entrapped air, a uniform de-airing appearance and minimization of air pockets or surface texture prior to autoclave finishing steps.
Summarized, the previous embossed polymer interlayer sheets, when laminated in a multiple layer glass panel, did not always provide the combination or balance of desired optical clarity (such as mottle) and optimum de-airing properties (such as de-air uniformity in the cold nip roll process). Stated differently, previous embossed polymer interlayer sheets, as well as some non-embossed polymer interlayer sheets, did not always provide the desired balance of properties, including at least good or acceptable de-airing and good or acceptable optical clarity, while not adversely affecting other properties of either the embossed polymer interlayer sheet or the multiple layer glass panel. This embossed polymer sheets of the invention specifically provide an embossed polymer sheet that has good de-air uniformity in the cold nip roll process and low, commercially acceptable mottle.


A windshield wiper snow removal and deicing device raises a windshield wiper blade away from a windshield, upon which the blade is otherwise maintained in contacting engagement therewith by a wiper biasing spring connected to the wiper arm, such that the blade falls down and impacts the windshield to remove snow and ice accumulated thereon while wiping on the windshield. In a first embodiment, a motor connected to the arm rotates a flap connected thereto to raise the blade above the windshield. In a second embodiment, a cover for a casing attached to the windshield is raised into an idle deployment configuration for engaging the arm and raising the blade above the windshield. In a third embodiment, a body on the arm has a pivoting member to engage an engagement stop on the windshield, with the pivoting member pivoting into a vertical configuration to lift the blade off the windshield.

Driving in inclement winter weather is a hazardous proposition for a wide variety of reasons, not-the least being the need for clear and unobstructed visibility. Blizzards, ice storms and the like induce a good deal of stress to the motor vehicle driver that is only increased by a lack of a clear view of the road ahead. To some extent windshield wipers do a commendable job of keeping the windscreen clear but in extreme weather situations they tend to become clogged with a build-up of ice and frozen rain thereby reducing or eliminating their intended cleaning efficiency. In such instances an imprudent driver may try to remedy the situation by attempting to grope at a moving windshield blade and snap it against the windscreen in the hope of dislodging the accumulating ice while driving. This practice is clearly both impractical and dangerous as the attention of the driver is distracted from the primary task of driving safely and responsibly thus making him a hazard to both himself and others. A more responsible yet not necessarily much safer alternative would be to bring the vehicle to a stop at the side of the road, disembark and manually free the ice or snow from the wipers. The potential danger existing in this solution is that in stopping and exiting the vehicle in extreme weather conditions, the driver puts himself and his vehicle at risk from fellow motorists driving in the same extreme conditions. Ideally, a device that could mechanically and automatically dislodge ice build-up from windshield wiper assemblies without physical human intervention while said vehicle was in motion would be welcome.
Many attempts were made as shown in U.S. Pat. No. 5,749,119 granted to Isaac on May 12, 1998 for a "windshield wiper blade deicer" used to alternately raise the two wiper blades with a motor/shaft assembly when in the stowed non-operating position, and in U.S. Pat. No. 6,381,799 granted to Leutsch et al. on May, 2002 for a "windshield wiper with blade lifting mechanism" located within the wiper mounting bearing housing and used to raise the wiper blade away from the windshield via a ramp cooperating with a rocker arm when the wiper is in the stowed non-operating position. Canadian Patent application No. 2,212,090 of Vanderzweep and published on Mar. 5, 1999 discloses a "windshield wiper lifting device" used to lift the wiper blade when the wiper is not being used (static mode) at the lower end of its displacement path, and eventually, for one embodiment, when the wiper is being used (dynamic mode). All above devices only operate while the wiper blade is not used (static mode) and in the lower most position on the windshield where the blade pushes all the snow it wipes off from the windshield during its return segment of travel path.
US Patent application publication No. 2004/0128787 to Wagner published on Jul. 8, 2004 discloses a "windshield wiper blade slapper apparatus" that includes a solenoid activated push-pull rod connected to the wiper bearing housing and the wiper arm to successively raise and lower the latter during operation of the wiper on the windshield. Although the above apparatus can operate at any position of the wiper blade along its wiping travel path during the use of the wiper, it is relatively complex to install by retrofit on existing wiper blades since it requires special tools and modification of the existing wiper mounting bearing housing, especially in order not to interfere with the existing mechanism allowing for the wiper blade to be manually raised during cleaning and/or maintenance thereof.
Accordingly, there is a need for an improved snow removal and deicing device for windshield wiper.

Snow removal and deicing device for windshield wiper


The present invention relates to compounds having pharmacological activity toward the 5-HT7 receptor. Pharmaceutical compositions and methods for their use in the treatment of CNS disorders are described.

The present invention relates to compounds having pharmacological activity toward the 5-HT7 receptor. Pharmaceutical compositions and methods for their use in the treatment of CNS disorders are described.
The 5-HT7 receptor is the most recent addition to the burgeoning family of 5-HT receptors. 5-HT7 receptors have been cloned from rat, mouse, guinea pig, and human cDNA and exhibit a high degree of interspecies homology, (approximately 95%) but a low sequence homology with other 5-HT receptors ( less than 40%). The pharmacological profile of this receptor is unique yet consistent across species. Thus, high 5-HT7 receptor affinity is observed from 5-CT, 5-HT, 5-MeOT, and methiothepin, moderate affinity for 8-OHDPAT, clozapine, and ritanserin, and low affinity for pindolol, sumatriptan, and buspirone. Recent data have demonstrated the existence of four 5-HT7 splice variants in humans and three in rat (Heidmann, et al., J. Neurochem., 1997, 68, 1372-1381). Preliminary pharmacological comparison of the long (5-HT7a) and short (5-HT7b) forms of the receptor have revealed no substantial differences in receptor binding affinity (Jasper et al., J. Pharmocol., 1997, 120, 298). 5-HT7 receptors are positively coupled to adenylate cyclase when expressed in cell lines, native guinea pig hippocampus, and cultured vascular smooth muscle cells.
The greatest abundance of 5-HT7 mRNA is found in the brain where it is discretely located within thalamus, hypothalamus, and various limbic and cortical regions. Autoradiographic techniques confirm that the distribution of 5-HT7 receptor binding sites in rat and guinea pig brain matches, to a large extent, the mRNA distribution (To, et al., J. Pharmocol., 1995, 115, 107-116).
Preliminary data support that the 5-HT7 receptor may be involved in the pathophysiology of sleep disorders, depression, (Schwartz, et al., Adv. Int. Med. 1993, 38, 81-106) and schizophrenia (Roth, et al., J. Pharmacol. Exp. Ther., 1994, 268, 1403-1410). The 5-HT7 receptor stimulation has caused relaxation of the blood vessels in monkey (Leung, et al. Br. J. Pharmocol., 1996, 117, 926-930), dog (Cushing, et al. J. Pharmocol. Exp. Ther., 1996, 277, 1560-1566) and rabbit (Martin, et al., Br. J. Pharmocol., 1995, 114, 383). Therefore, the therapeutic utility of 5-HT7 receptor ligands requires the discovery of selective therapeutic agents. The present invention discloses novel 5-HT7 receptor antagonists.
Accordingly, one object of the present invention is to provide novel inhibitors of the 5-HT7 receptor or pharmaceutically acceptable salts or prodrugs thereof.
It is another object of the present invention to provide pharmaceutical compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of at least one of the compounds of the present invention or a pharmaceutically acceptable salt or prodrug form thereof.
It is another object of the present invention to provide a method for treating central nervous system disorders comprising administering to a host in need of such treatment a therapeutically effective amount of at least one of the compounds of the present invention or a pharmaceutically acceptable salt or prodrug form thereof.
These and other objects, which will become apparent during the following detailed description, have been achieved by the inventors"" discovery that compounds of formula (I):
or pharmaceutically acceptable salt forms thereof, wherein R1, X, Y, n and A are defined below, are effective 5-HT7 inhibitors.
[1] Thus, in a first embodiment, the present invention provides a novel compound of formula (I):
or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein:
R1 is selected from a C6-10 carbocyclic aromatic residue substituted with 1-3 R1a, and a 5-10 membered aromatic heterocyclic system containing from 1-4 heteroatoms selected from N, O, and S substituted with 0-2 R1a;
R1a is independently selected at each occurrence from halo, xe2x80x94NO2, xe2x80x94CN, xe2x80x94CF3 and xe2x80x94CF2CF3;
X is selected from xe2x80x94S(O)pxe2x80x94, xe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94CH(OH)xe2x80x94, xe2x80x94CH(OC(O)CH3)xe2x80x94, xe2x80x94NR4axe2x80x94, xe2x80x94S(O)2NR4xe2x80x94 and a five membered saturated, partially saturated or unsaturated ring containing 0-2 heteroatoms selected from the group consisting of O and N;
with the proviso that when X is a five membered saturated, partially saturated or unsaturated ring containing 0-2 heteroatoms selected from O and N, R1 may be an unsubstituted C6-10 carbocyclic aromatic residue;
R4 is selected from hydrogen and C1-6 alkyl;
R4a is taken together with R1 to form a 5 or 6-membered fused heterocyclic ring containing 1-2 heteroatoms selected from O or N, and substituted with 1 or 2 carbonyl groups;
Y is C1-3 alkylene;
A is selected from a 5 or 6 membered saturated, partially saturated or unsaturated ring which contains from 0-1 heteroatoms selected from N, O and S substituted with 0-3 R5, napthyl substituted with 0-3 R5, and napthyl fused with ring B substituted with 0-3 R5;
R5 is selected from C1-5 alkyl, halo and xe2x80x94OCH3;
n is selected from 1, 2, and 3; and
p is selected from 0, 1, and 2.
[2] In a preferred embodiment, the present invention provides novel compounds, wherein:
R1 is phenyl substituted with 1-3 R1a;
R1a is selected independently at each occurrence from halo, xe2x80x94CN, xe2x80x94CF3 and xe2x80x94CF2CF3;
X is selected from xe2x80x94S(O)2xe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94NR4axe2x80x94, xe2x80x94C(O)xe2x80x94, isoxazolyl and isoxazolinyl;
R4a is taken together when R1 is phenyl to form a 5 membered fused cyclic urea;
Y is propylene;
A is selected from phenyl substituted with 0-3 R5, napthyl substituted with 0-3 R5 and napthyl fused with ring B substituted with 0-3 R5;
R5 is selected independently at each occurrence from C1-5 alkyl, halo and xe2x80x94OCH3; and
n is selected from 1 and 2.
[3] In a more preferred embodiment, the present invention provides novel compounds, wherein:
R1 is phenyl substituted with 1-3 R1a;
R1a is selected independently at each occurrence from para-halo and meta-fluoro;
X is selected from xe2x80x94S(O)2xe2x80x94, xe2x80x94Sxe2x80x94 and xe2x80x94C(O)xe2x80x94;
Y is propylene;
A is phenyl substituted with 0-2 R5;
R5 is selected independently at each occurrence from C1-5 alkyl, halo and xe2x80x94OCH3; and
n is selected from 1 and 2.
[4] In a further more preferred embodiment, the present invention provides novel compounds, wherein:
R1 is phenyl substituted with 1-3 R1a;
R1a is meta-fluoro;
X is selected from xe2x80x94S(O)2xe2x80x94, xe2x80x94Sxe2x80x94 and xe2x80x94C(O)xe2x80x94;
Y is propylene;
A is phenyl substituted with 0-2 R5;
R5 is selected independently at each occurrence from C1-5 alkyl, halo and xe2x80x94OCH3; and
n is selected from 1 and 2.
[5] In an even further more preferred embodiment, the present invention provides a compound selected from the group:
1,3-Dihydro-2-((4-(4-fluorophenyl)-4-oxobutyl))isoindole,
1,3-Dihydro-2-((4-(4-fluorophenyl)-4-hydroxybutyl)) isoindole,
1,3-Dihydro-2-((4-(4-fluorophenyl)-4-acetoxybutyl)) isoindole,
2-((4-(4-Fluorophenyl)-4-oxobutyl))-1,2,3,4-tetrahydroisoquinoline,
1,3-Dihydro-2-((4-(4-fluorophenyl)-4-oxobutyl)) benz[f]isoindole,
2-((4-(4-Pyridyl)-4-oxobutyl))-1,2,3,4-tetrahydroisoquinoline,
2-((4-(3-Fluorophenyl)-4-oxobutyl))-1,2,3,4-tetrahydroisoquinoline,
1,3-Dihydro-2-((4-(4-fluorophenyl)-4-oxobutyl))-1H-benz[de] isoquinoline,
2-((4-Oxo-4-(2-thienyl)butyl))-1,2,3,4-tetrahydroisoquinoline,
6,7-Dimethoxy-2-((4-(4-fluorophenyl)oxobutyl))-1,2,3,4-tetrahydroisoquinoline,
2-((3-(1,3-Dihydro-2H-benzimidazol-2-one)-1-ylpropyl))-1,2,3,4-tetrahydroisoquinoline,
2-(3-Phenylisoxazol-5-yl)methyl-1,2,3,4-tetrahydroisoquinoline,
(+/xe2x88x92)-2-((3-(4-Fluorophenyl)-2-isoxazolin-5-yl)methyl-1,2,3,4-tetrahydroisoquinoline,
1,3-Dihydro-2-((3-(4-fluorophenoxy)propyl))isoindole,
2-((3-(4-Fluorophenylthio)propyl))-1,2,3,4-tetrahydroisoquinoline,
1,3-Dihydro-2-((3-(4-fluorophenylthio)propyl))isoindole,
1,3-Dihydro-2-((3-(4-fluorophenylsulfonyl)propyl)) isoindole,
2-((3-(4-Fluorophenylsulfonyl)propyl))-1,2,3,4-tetrahydroisoquinoline
2-((3-(3-Fluorophenylthio)propyl))-1,2,3,4-tetrahydroisoquinoline
2-((3-(3-Fluorophenylsulfonyl)propyl))-1,2,3,4-tetrahydroisoquinoline
1,3-Dihydro-2-((4-(4-pyridyl)-4-oxobutyl))isoindole,
1,3-Dihydro-2-((4-(3-pyridyl)-4-oxobutyl))isoindole,
1,3-Dihydro-2-((4-(4-nitrophenyl)-4-oxobutyl))isoindole,
1,3-Dihydro-2-((4-(3-nitrophenyl)-4-oxobutyl))isoindole,
1,3-Dihydro-2-((4-(2-thienyl)-4-oxobutyl))isoindole,
1,3-Dihydro-2-((4-(3-thienyl)-4-oxobutyl))isoindole,
2-((4-(3-Pyridyl)-4-oxobutyl))-1,2,3,4-tetrahydroisoquinoline,
2-( (4-(4-Nitrophenyl)-4-oxobutyl))-1,2,3,4-tetrahydroisoquinoline,
2-((4-(3-Nitrophenyl)-4-oxobutyl))-1,2,3,4-tetrahydroisoquinoline,
2-((4-(3-Thienyl)-4-oxobutyl))-1,2,3,4-tetrahydroisoquinoline,
2-((3-(4-Fluorophenylsulfonyl)propyl))-1,2,3,4-tetrahydroisoquinoline,
2-((3-(4-Pyridylsulfonyl)propyl))-1,2,3,4-tetrahydroisoquinoline,
2-((3-(4-Nitrophenylsulfonyl)propyl) )-1,2,3,4-tetrahydroisoquinoline,
2-((3-(3-Nitrophenylsulfonyl)propyl))-1,2,3,4-tetrahydroisoquinoline,
2-((3-(2-Thienylsulfonyl)propyl))-1,2,3,4-tetrahydroisoquinoline,
2-((3-(3-Thienylsulfonyl)propyl))-1,2,3,4-tetrahydroisoquinoline,
1,3-Dihydro-2-((1-(3-thienylsulfonyl)propyl))isoindole,
1,3-Dihydro-2-((1-(2-thienylsulfonyl)propyl))isoindole,
1,3-Dihydro-2-((1-(4-fluorophenylsulfonyl)propyl)) isoindole,
1,3-Dihydro-2-((1-(3-fluorophenylsulfonyl)propyl)) isoindole,
1,3-Dihydro-2-((1-(4-nitrophenylsulfonyl)propyl)) isoindole,
1,3-Dihydro-2-((1-(3-nitrophenylsulfonyl)propyl)) isoindole,
1,3-Dihydro-2-((1-(4-pyridylsulfonyl)propyl))isoindole, and
1,3-Dihydro-2-((1-(3-pyridylsulfonyl)propyl))isoindole.
[6] In a second embodiment, the present invention provides a novel compound of formula (II):
or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein:
R1 is selected from a C6-10 carbocyclic aromatic residue substituted with 1-3 R1a, and a 5-10 membered aromatic heterocyclic system containing from 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R1a;
R1a is independently selected at each occurrence from (CH2)rOR1d, halo, C1-4 alkyl, (CH2)rxe2x80x94C3-6 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, xe2x80x94CN, xe2x80x94NO2, xe2x80x94OCF3, (CH2)rNR1bR1c, (CH2)rSO2R1d, (CH2)rC(O)OH, (CH2)rC(O)OR1d, (CH2)rOC(O)R1d, (CH2)rC(O)R1d, (CH2)rNR1bC(O)R1c, (CH2)rC(O)NR1bR1c, (CH2)rSR1d, (CH2)rCH(xe2x95x90NR1b)NR1bR1c, (CH2)rSO2NR1bR1c, (CH2)rSO2NR1bR1c, (CH2)r(CF2)rCF3 and (CH2)r-phenyl substituted with 0-3 R1e;
R1b and R1c are independently selected at each occurrence from hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl and (CH2)r-phenyl substituted with 0-3 R1e;
R1d is independently selected at each occurrence from C1-6 alkyl and (CH2)r-phenyl substituted with 0-2 R1e;
R1e is independently selected at each occurrence from H, xe2x80x94(CH2)rOR1e, halo, C1-4 alkyl, CN, NO2, and xe2x80x94CF3;
R1f is selected from hydrogen and C1-5 alkyl;
R1g is C1-5 alkyl;
X is selected from xe2x80x94CR6R7xe2x80x94, xe2x80x94CR2R3xe2x80x94, xe2x80x94C(O)xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94S(O)2xe2x80x94, xe2x80x94S(O)2NR4xe2x80x94 and NR4a;
R4 is selected independently at each occurrence from hydrogen, C1-6 alkyl, (CH2)rxe2x80x94C3-7 cycloalkyl, (CH2)r-aryl, and (CH2)r-heteroaryl;
R4a is taken together with R1 to form a 5 or 6-membered fused heterocyclic ring containing 1-2 heteroatoms selected from O and N, substituted with 1 or 2 carbonyl groups;
R6 is selected independently at each occurrence from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, (CH2)rxe2x80x94C3-6 cycloalkyl, (CH2)r-phenyl, xe2x80x94OH, xe2x80x94OC(O)R6a, C(O)R6a and C(O)OR6a;
R6a is selected independently from C1-6 alkyl, phenyl and benzyl;
R7 is selected from hydrogen and C1-5 alkyl;
A is selected from a 5 or 6 membered saturated, partially saturated or unsaturated ring which contains from 0-1 heteroatoms selected from N, O and S substituted with 0-3 R5, napthyl substituted with 0-3 R5, and napthyl fused with ring B substituted with 0-3 R5;
R5 is selected independently at each occurrence from (CH2)rOR5d, halo, C1-4 alkyl, (CH2)rxe2x80x94C3-6 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, xe2x80x94CN, xe2x80x94NO2, xe2x80x94OCF3, (CH2)rNR5bR5c, (CH2)rSO2R5d, (CH2)rC(O)OH, (CH2)rC(O)OR5d, (CH2)rOC(O)R5d, (CH2)rC(O)R5b, (CH2)rNR5bC(O)R5c, (CH2)rC(O)NR5bR5c, (CH2)rSR5d, (CH2)rCH(xe2x95x90NR5b)NR5bR5c, (CH2)rSO2NR5bR5c, (CH2)rSO2NR5bR5c, (CH2)r(CF2)rCF3 and (CH2)r-phenyl substituted with 0-3 R5e;
R5b and R5c are independently selected at each occurrence from hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, (CH2)r-phenyl;
R5d is independently selected at each occurrence from C1-6 alkyl, phenyl substituted with 0-2 R5e, and benzyl substituted with 0-2 R5e;
R5e is independently selected at each occurrence from hydrogen, xe2x80x94(CH2)rOR5f, halo, C1-4 alkyl, CN, NO2, and xe2x80x94CF3;
R5f is selected from hydrogen and C1-5 alkyl;
R5g is C1-5 alkyl;
n is selected from 1, 2, and 3;
r is selected from 0, 1, and 2.
[7] In a preferred embodiment, the present invention provides novel compounds, wherein:
R1 is phenyl substituted with 1-3 R1a;
R1a is selected from halo, xe2x80x94CN, xe2x80x94CF3 and xe2x80x94CF2CF3;
A is selected from phenyl substituted with 0-3 R5, napthyl substituted with 0-3 R5 and napthyl fused to ring B substituted with 0-3 R5;
X is selected from xe2x80x94C(O)xe2x80x94 and xe2x80x94S(O)2xe2x80x94;
R5 is independently selected at each occurrence from C1-5 alkyl, halo and xe2x80x94OCH3; and
n is selected from 1 and 2.
[8] In a more preferred embodiment, the present invention provides novel compounds, wherein:
R1 is phenyl substituted with 1-2 R1a;
R1a is selected from para-halo and meta-halo;
A is phenyl substituted with 0-3 R5;
X is selected from xe2x80x94C(O)xe2x80x94 and xe2x80x94S(O)2xe2x80x94;
R5 is independently selected at each occurrence from C1-5 alkyl, halo and xe2x80x94OCH3; and
n is selected from 1 and 2.
[9] In a further more preferred embodiment, the present invention provides a compound selected from the group:
2-((1-(4-Fluorophenylsulfonyl)-4-piperidyl))-1,2,3,4-tetrahydroisoquinoline,
2-((1-(3-Fluorophenylsulfonyl)-4-piperidyl))-1,2,3,4-tetrahydroisoquinoline,
2-((1-(3-Fluorophenylsulfonyl)-4-piperidyl))-1,2,3,4-tetrahydroisoquinoline,
2-((1-(4-Pyridylsulfonyl)-4-piperidyl))-1,2,3,4-tetrahydro-isoquinoline,
2-((1-(3-Pyridylsulfonyl)-4-piperidyl))-1,2,3,4-tetrahydro-isoquinoline,
2-((1-(4-Nitrophenylsulfonyl)-4-piperidyl))-1,2,3,4 tetrahydroisoquinoline,
2-((1-(3-Nitrophenylsulfonyl)-4-piperidyl))-1,2,3,4-tetrahydroisoquinoline,
2-((1-(2-Thienylsulfonyl)-4-piperidyl))-1,2,3,4-tetrahydro-isoquinoline,
2-((1-(3-Thienylsulfonyl)-4-piperidyl))-1,2,3,4-tetrahydro-isoquinoline,
1,3-Dihydro-2-((1-(3-thienylsulfonyl)-4-piperidyl)) isoindole,
1,3-Dihydro-2-((1-(2-thienylsulfonyl)-4-piperidyl)) isoindole,
1,3-Dihydro-2-((1-(4-fluorophenylsulfonyl)-4-piperidyl)) isoindole,
1,3-Dihydro-2-((1-(3-fluorophenylsulfonyl)-4-piperidyl)) isoindole,
1,3-Dihydro-2-((1-(4-nitrophenylsulfonyl)-4-piperidyl)) isoindole,
1,3-Dihydro-2-((1-(3-nitrophenylsulfonyl)-4-piperidyl)) isoindole,
1,3-Dihydro-2-((1-(4-pyridylsulfonyl)-4-piperidyl)) isoindole, and
1,3-Dihydro-2-((1-(3-pyridylsulfonyl)-4-piperidyl)) isoindole,
or a pharmaceutically acceptable salt form thereof.
[10] In a third embodiment, the present invention provides for a novel compound of formula (III):
or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein:
R1 is selected from a C6-10 carbocyclic aromatic residue substituted with 1-3 R1a, and a 5-10 membered aromatic heterocyclic system containing from 1-4 heteroatoms selected from N, O and S, substituted with 0-2 R1a;
R1a is independently selected at each occurrence from (CH2)rOR1d, halo, C1-4 alkyl, (CH2)rxe2x80x94C3-6 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, xe2x80x94CN, xe2x80x94NO2, xe2x80x94OCF3, (CH2)rNR1bR1c, (CH2)rSO2R1d, (CH2)rC(O)OH, (CH2)rC(O)OR1d, (CH2)rOC(O)R1d, (CH2)rC(O)R1d, (CH2)rNR1bC(O)R1c, (CH2)rC(O)NR1bR1c, (CH2)rSR1d, (CH2)rCH(xe2x95x90NR1b)NR1bR1c, (CH2)rSO2NR1bR1c, (CH2)rSO2NR1bR1c, (CH2)r(CF2)rCF3 and (CH2)r-phenyl substituted with 0-3 R1e;
R1b and R1c are independently selected at each occurrence from hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl and (CH2)r-phenyl substituted with 0-3 R1e;
R1d is independently selected at each occurrence from C1-6 alkyl and (CH2)r-phenyl substituted with 0-2 R1e;
R1e is independently selected at each occurrence from H, xe2x80x94(CH2)rOR1f, halo, C1-4 alkyl, CN, NO2, and xe2x80x94CF3;
R1f is selected from hydrogen and C1-5 alkyl;
R1g is C1-5 alkyl;
R4 is selected independently at each occurrence from hydrogen, C1-6 alkyl, (CH2)rxe2x80x94C3-7 cycloalkyl, (CH2)r-aryl, and (CH2)r-heteroaryl;
R4a is taken together with R1 to form a 5 or 6- membered fused heterocyclic ring containing 1-2 heteroatoms selected from O and N substituted with 1 or 2 carbonyl groups;
R6 is selected independently at each occurrence from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, (CH2)rxe2x80x94C3-6 cycloalkyl, (CH2)r-phenyl, xe2x80x94OH, xe2x80x94OC(O)R6a, C(O)R6a, C(O)OR6a;
R6a is selected independently from C1-6 alkyl, phenyl and benzyl;
R7 is selected from hydrogen and C1-5 alkyl;
Y is C1-3 alkylene;
A is selected from a 5 or 6 membered saturated, partially saturated or unsaturated ring which contains from 0-1 heteroatoms selected from N, O and S, substituted with 0-3 R5, napthyl substituted with 0-3 R5, and napthyl fused with ring B substituted with 0-3 R5;
R5 is selected independently at each occurrence from (CH2)rOR5d, halo, C1-4 alkyl, (CH2)rxe2x80x94C3-6 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, xe2x80x94CN, xe2x80x94NO2, xe2x80x94OCF3, (CH2)rNR5bR5c, (CH2)rSO2R5d, (CH2)rC(O)OH, (CH2)rC(O)OR5d, (CH2)rOC(O)R5d, (CH2)rC(O)R5b, (CH2)rNR5bC(O)R5c, (CH2)rC(O)NR5bR5c, (CH2)rSR5d, (CH2)rCH(xe2x95x90NR5b) NR5bR5c, (CH2)rSO2NR5bR5c, (CH2)rSO2NR5bR5c, (CH2)r(CF2)rCF3 and (CH2)r-phenyl substituted with 0-3 R5e;
R5b and R5c are independently selected at each occurrence from hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, (CH2)r-phenyl;
R5d is independently selected at each occurrence from C1-6 alkyl, phenyl substituted with 0-2 R5e, and benzyl substituted with 0-2 R5e;
R5e is independently selected at each occurrence from hydrogen, xe2x80x94(CH2)rOR5f, halo, C1-4 alkyl, CN, NO2, and xe2x80x94CF3;
R5f is selected from hydrogen and C1-5 alkyl;
R5g is C1-5 alkyl;
n is selected from 1, 2, and 3;
r is selected from 0, 1, and 2; and
m is selected from 1, 2, and 3.
[11] In a preferred embodiment, the present invention provides for novel compounds, wherein:
R1 is phenyl substituted with 1-3 R1a;
R1a is selected independently at each occurrence from halo, xe2x80x94CN, xe2x80x94CF3 and xe2x80x94CF2CF3;
Y is propylene;
A is selected from phenyl substituted with 0-3 R5, napthyl substituted with 0-3 R5 and napthyl fused to ring B substituted with 0-3 R5;
R5 is selected independently at each occurrence from C1-5 alkyl, halo and xe2x80x94OCH3;
n is selected from 1 and 2; and
m is 1.
[12] In a more preferred embodiment, the present invention provides for novel compounds, wherein:
R1 is phenyl substituted with 1-2 R1a;
R1a is selected from para-halo and meta-halo;
A is phenyl substituted with 0-3 R5;
Y is C1-3 alkylene;
R5 is independently selected at each occurrence from C1-5 alkyl, halo and xe2x80x94OCH3; and
n is selected from 1 and 2; and
m is 1.
[13] In a more preferred embodiment, the present invention provides for novel compounds, wherein:
1,3-Dihydro-2-[3-((2-(4-fluorophenyl)-1,3-dioxolan-2-yl)) propyl]isoindole,
1,3-Dihydro-2-[3-((2-(4-bromophenyl)-1,3-dioxolan-2-yl)) propyl]isoindole,
1,3-Dihydro-2-[3-((2-(4-methylphenyl)-1,3-dioxolan-2-yl)) propyl]isoindole, and
2-[3-((2-(4-Fluorophenyl)-1,3-dioxolan-2-yl))propyl]-1,2,3,4-tetrahydroisoquinoline.
In a fourth embodiment, the present invention provides pharmaceutical compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of at least one of the compounds of the present invention or a pharmaceutically acceptable salt form thereof.
In a fifth embodiment, the present invention provides a method of treating a central nervous system disorder, including sleep disorders, depression and schizophrenia comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula (I), (II) or (III), or a pharmaceutically acceptable salt thereof.
The compounds herein described may have asymmetric centers. Compounds of the present invention containing an asymmetrically substituted atom may be isolated in optically active or racemic forms. It is well known in the art how to prepare optically active forms, such as by resolution of racemic forms or by synthesis from optically active starting materials. Many geometric isomers of olefins, Cxe2x95x90N double bonds, and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention. Cis and trans geometric isomers of the compounds of the present invention are described and may be isolated as a mixture of isomers or as separated isomeric forms. All chiral, diastereomeric, racemic forms and all geometric isomeric forms of a structure are intended, unless the specific stereochemistry or isomeric form is specifically indicated.
The term xe2x80x9csubstituted,xe2x80x9d as used herein, means that any one or more hydrogens on the designated atom is replaced with a selection from the indicated group, provided that the designated atom""s normal valency is not exceeded, and that the substitution results in a stable compound. When a substitent is keto (i.e., xe2x95x90O), then 2 hydrogens on the atom are replaced.
When any variable (e.g., R1a) occurs more than one time in any constituent or formula for a compound, its definition at each occurrence is independent of its definition at every other occurrence. Thus, for example, if a group is shown to be substituted with 0-2 R1a, then said group may optionally be substituted with up to two R1a groups and R1a at each occurrence is selected independently from the definition of R1a. Also, combinations of substituents and/or variables are permissible only if such combinations result in stable compounds.
When a bond to a substituent is shown to cross a bond connecting two atoms in a ring, then such substituent may be bonded to any atom on the ring. When a substituent is listed without indicating the atom via which such substituent is bonded to the rest of the compound of a given formula, then such substituent may be bonded via any atom in such substituent. Combinations of substituents and/or variables are permissible only if such combinations result in stable compounds.
As used herein, xe2x80x9cC1-6 alkylxe2x80x9d, is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms, examples of which include, but are not limited to, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, t-butyl, pentyl, and hexyl; xe2x80x9cAlkenylxe2x80x9d is intended to include hydrocarbon chains of either a straight or branched configuration and one or more unsaturated carbon-carbon bonds which may occur in any stable point along the chain, such as ethenyl, propenyl, and the like.
As used herein, xe2x80x9chaloxe2x80x9d or xe2x80x9chalogenxe2x80x9d refers to fluoro, chloro, bromo, and iodo.
As used herein, xe2x80x9ccarbocyclexe2x80x9d or xe2x80x9ccarbocyclic residuexe2x80x9d is intended to mean any stable 6- or 10-membered monocyclic or bicyclic aromatic compound. Examples of such carbocycles include phenyl, indanyl, indenyl and naphthyl.
As used herein, the term xe2x80x9caromatic heterocyclic systemxe2x80x9d or xe2x80x9caromatic heterocyclexe2x80x9d is intended to mean a stable 5- to 7- membered monocyclic or bicyclic or 7- to 10-membered bicyclic heterocyclic aromatic ring which consists of carbon atoms and from 1 to 4 heterotams independently selected from the group consisting of N, O and S. It is preferred that the total number of S and O atoms in the aromatic heterocycle is not more than 1.
Examples of such aromatic heterocyclic systems include, but are not limited to, pyridyl, pyrimidyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl and indazolyl.
The phrase xe2x80x9cpharmaceutically acceptablexe2x80x9d is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio.
As used herein, xe2x80x9cpharmaceutically acceptable saltsxe2x80x9d refer to derivatives of the disclosed compounds wherein the parent compound is modified by making acid or base salts thereof. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts include the conventional non-toxic salts or the quaternary ammonium salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. For example, such conventional non-toxic salts include those derived from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, nitric and the like; and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic, sulfanilic, 2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isethionic, and the like. The pharmaceutically acceptable salts of the present invention can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, nonaqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington""s Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418, the disclosure of which is hereby incorporated by reference. xe2x80x9cProdrugsxe2x80x9d are intended to include any covalently bonded carriers which release the active parent drug according to formula (I) in vivo when such prodrug is administered to a mammalian subject. Prodrugs of a compound of formula (I) are prepared by modifying functional groups present in the compound in such a way that the modifications are cleaved, either in routine manipulation or in vivo, to the parent compound. Prodrugs include compounds of formula (I) wherein a hydroxy, amino, or sulfhydryl group is bonded to any group that, when the prodrug or compound of formula (I) is administered to a mammalian subject, cleaves to form a free hydroxyl, free amino, or free sulfhydryl group, respectively. Examples of prodrugs include, but are not limited to, acetate, formate and benzoate derivatives of alcohol and amine functional groups in the compounds of formula (I), and the like. Preferred prodrugs are amine prodrugs the amine group is attached to a group selected from OH, C1-4 alkoxy, C6-10 aryloxy, C1-4 alkoxycarbonyl, C6-10 aryloxycarbonyl, C6-10 arylmethylcarbonyl, C1-4 alkylcarbonyloxy C1-4 alkoxycarbonyl, and C6-10 arylcarbonyloxy C1-4 alkoxycarbonyl. More preferred prodrugs are OH, methoxy, ethoxy, benzyloxycarbonyl, methoxycarbonyl, and methylcarbonyloxymethoxycarbonyl.
xe2x80x9cStable compoundxe2x80x9d and xe2x80x9cstable structurexe2x80x9d are meant to indicate a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent.
The compounds of Formula I can be prepared using the reactions and techniques described below. The reactions are performed in a solvent appropriate to the reagents and materials employed and suitable for the transformations being effected. It will be understood by those skilled in the art of organic synthesis that the functionality present on the molecule should be consistent with the transformations proposed. This will sometimes require a judgment to modify the order of the synthetic steps or to select one particular process scheme over another in order to obtain a desired compound of the invention. Preferred methods include, but are not limited to, those described below. All references cited herein are hereby incorporated in their entirety herein by reference.
Some compounds of Formula 1 may be prepared, as shown in Scheme 1, by treatment of an alkylating agent (1-1) with an amine (1-2) in the presence of a base in an appropriate solvent.
Examples of useful alkylating agents (1-1) are those where LG is a good leaving group, such as Cl, Br, I, alkylsulfonate, arylsulfonate, or perhaloalkylsulfonate. Useful bases include, but are not limited to, an excess of amine (1-2) itself, metal carbonates such as K2CO3 or Cs2CO3, metal hydroxides such as NaOH or KOH, hindered alkoxides such as potassium t-butoxide, or non-nucleophilic tertiary organic amines such as N,N-diisopropylethylamine. These bases are required to absorb the acid Hxe2x80x94LG which is liberated during the reaction. Typical solvents include polar aprotic liquids such as DMF or THF, or protic liquids such as alcohols, including ethanol or isopropanol. It is known by those skilled in the art that the rates of alkylations of amines may be enhanced, particularly where LG is Cl or Br, by the addition of a catalytic amount of an iodide salt, such as NaI or KI, typically in the amount of 0.1 to 5 mole percent.
An alternate set of useful amine alkylation conditions utilize an organic solvent which is poorly miscible with water, such as toluene or dichloromethane, and an aqueous solution of the base, particularly metal alkoxides, along with a phase transfer catalyst (PTC). Typical phase transfer catalysts include tetraalkylammonium halides or hydroxides.
Alternatively, amine (1-1) may be initially converted into its conjugate base by treatment with a strong base, such as n-butyllithium, in an inert solvent, typically THF, near or below ambient temperature under an inert atmosphere such as nitrogen or argon. The resulting amine amion is then treated with alkylating agent (1xe2x80x941), which may be introduced in an inert solvent.
In order to achieve useful reaction rates, any of the above reactions of Scheme 1 may require the application of heat from an external source.
The required alkylating agents (1xe2x80x941), when not commercially available, are generally well known to those skilled in the art and are readily prepared by usual methods. In certain instances, it may be advantageous to prepare reagents (1xe2x80x941) in the same reaction vessel to be used for the alkylation without purification or isolation, before addition of the amine (1-2).
Many examples of the needed amine reagents (1-2) are commercially available or are known in the literature. When the desired amine (1-2) is new, a number of literature methods are generally applicable. These include, but are not limited to, reduction of amides or imides with borane (Gawley et al., J. Org. Chem. 1988, 53, 5381) or lithium aluminum hydride (Uffer et al., Helv. Chim. Acta 1948 31, 1397; Moffett, Org. Syn., Coll. Vol. IV 1963, 354).
An alternate sequence for the synthesis of some compounds of Formula 1 is illustrated in Scheme 2.
An imide (2-1) is converted to its conjugate base by treatment with a base in an appropriate silvent, then allowed to react with alkylating agent (1-1) described in Scheme 1. An alkyl imide (2-2) intermediate is formed and isolated. The conjugate base of imide (2-1) may be isolated and purified in some instances, such as by precipitation by a non-polar solvent followed by filtration. Useful bases include metal alkoxides and carbonates. Alternatively, this conjugate base may be generated in situ by mixing with a non-nucleophilic base either before or after the addition of the alkylating agent (1-1).
The alkyl imide intermediate (2-2) is then converted to the amine (1) by treatment with a reducing agent, such as borane or lithium aluminum hydride, in an appropriate solvent, typically THF.
It will be recognized by those skilled in the art that certain functional group substituents on reagents (1-1) or (2-1) may not be compatible with the strongly reducing conditions described in Step 2 of Scheme 2. In such instances, these functional groups may be carried through the reaction sequence in a protected form, then released after the reduction reaction. The choice of protecting groups, and conditions for their introduction and subsequent removal, will be known to those skilled in the art, and are generally as described in Green and Wuts, Protective Groups in Organic Synthesis, 2nd Ed., Wiley and Sons, NY, 1991.
Where convenient, some compounds of Formula (I) may be prepared as shown in Scheme 3.
Here, the functional group Xxe2x80x94H of reagent (3-1) is converted into its nucleophilic conjugate base by treatment with an appropriate base in a useful solvent, and allowed to react with an electrophile (3-2) wherein the leaving group LG, as described above, is connected by linker group Y to the ring nitrogen. The ring nitrogen is rendered in non-nucleophilic form in (3-2) by its incorporation into an amide or imide functional group as shown. The resulting amide or imide adduct (3-3) is then reduced to the desired amine (1) as described in Scheme 2.
The choice of base for the first reaction of Scheme 3 is dependent on the acidity of functional group Xxe2x80x94H of (3-1). Where Xxe2x80x94H of (3-1) is relatively acidic, such as xe2x80x94Sxe2x80x94H, a fairly weak base such as a metal carbonate or hydroxide, is appropriate. For less acidic Xxe2x80x94H such as xe2x80x94Oxe2x80x94H, a stronger base such as metal hydride (e.g. sodium hydride) or alkyllithium will be useful.
The synthesis of the required electrophile (3-2) is by conversion of amide or imide (2-1) to its conjugate base and treatment with bifunctional reagent LGxe2x80x94Yxe2x80x94LG, wherein LG is a leaving group as described above. The two leaving groups may be the same, in which case an excess of the reagent would be employed to statistically ensure monoadduct (3-2), or different, whereby a stoichiometric amount is acceptable and the less reactive LG would remain in (3-2). In some instances the electrophile (3-2) may be prepared in situ and not isolated or purified, but then allowed to react with nucleophile (3-1) as just described. In such an in situ preparation of the electrophile, it may be necessary to preform the conjugate base of reagent (3-1) in a separate reaction vessel, then transfer it into the vessel containing the electrophile.
Another method useful for the preparation of some compounds of Formula 1 is shown in Scheme 4.
Amine (1-2) is condensed with an aldehyde or ketone (4-1) to form an enamine intermediate, which frequently is not isolated but is reduced in situ to form amine adduct (1). Many such reductive amination conditions are well known in the chemical literature by those skilled in the art, and these are not further detailed here.
Another method for the preparation of some members of Formula 1 is given in Scheme 5.
Amine (1-2) is condensed with carboxy compound (5-1) to form amide (5-2). The amide is then treated with a reducing agent, commonly borane or lithium aluminum hydride as described earlier, to generate the desired amine (1).
The carboxy group can be the parent carboxylic acid (Z is OH) in which case a coupling reagent must also be used. Many coupling reagents are known in the literature for forming amide bonds from carboxylic acids and amines; examples include, but are not limited to DCC, HBTU, TBTU, HATU, BOP, PyBOP, and alkyl chloroformates. Some of these coupling reagents, such as alkyl chloroformates, also require the presence of a non-nucleophilic base to consume the acid formed. Appropriate bases for such coupling reactions include tertiary amines such as N,N-diisopropylethylamine, triethylamine, or N-methylmorpholine. Under coupling conditions such as these, the carboxy group is converted into an activated species (Z is a leaving group) which is usually not isolated, but is allowed to react in situ with the amine partner (1-2).
Alternatively to the in situ activation of the carboxylic acid for coupling, the acid can be converted into a relatively stable, activated derivative which is isolable in pure form. Examples of this type include, but are not limited to, formation of an acid halide (X is F, Cl, Br), an N-hydroxysuccinimide ester, or a pentafluorophenyl ester. Carboxylic acid pre-activating methods such as these are well known, especially in the peptide literature.
It will be recognized by those skilled in the art that one type of functional group substituent on a compound of Formula 1 may be converted into another functional group by the appropriate chemical reaction at an advantageous point in the synthetic sequence after the ring nitrogen to carbon bond formation in the Schemes is complete. Of course, such manipulations must be chemically compatible with the newly formed tertiary amine present in the compound of Formula 1.
Typically, the free base amine products of Formula 1, once prepared, are treated with an acid in an appropriate solvent to yield a salt adduct. These salt forms are often advantageous because they generally exhibit improved crystallinity, formulatability, and water solubility relative to the parent amines. Frequently, the salt adducts crystallize directly from the salt formation solvent medium, and can be isolated by filtration. In some cases, a co-solvent, usually of lesser polarity, must be added to induce crystallization.
The following examples further illustrate details for the preparation of the compounds of the present invention, and are not to be construed as limiting the inventors scope. Those skilled in the art will readily understand that known variations of the conditions and processes of the following preparative procedures can alternatively be used to prepare compounds of the present invention. All temperatures are degrees Celsius.


Disclosed are a multi-layer substrate and a manufacture method thereof. The multi-layer substrate of the present invention comprises a surface dielectric layer and at least one bond pad layer. The surface dielectric layer is located at a surface of the multi-layer substrate. The bond pad layer is embedded in the surface dielectric layer to construct the multi-layer substrate with the surface dielectric layer of the present invention. The manufacture method of the present invention forms at least one bond pad layer on a flat surface of a carrier and then forms the surface dielectric layer to cover the bond pad layer where the bond pad layer is embedded therein. After the multi-layer substrate is separated from the carrier, the bond pad layer and the surface dielectric layer construct a flat surface of the multi-layer substrate.

1. Field of the Invention
The present invention generally relates to a multi-layer substrate and manufacture method thereof, and more particularly to a flat surface multi-layer substrate and manufacture method thereof.
2. Description of Prior Art
Miniaturization for electronic productions is an unavoidable trend in this modern world. While the scale of the semiconductor chips is continuously getting smaller, the scale of the related technology for packaging is also inevitably needed to be microminiaturized to follow the scale of the semiconductor chip. Today, because the integration of integrated circuits has been greatly increased, using a multi-layer substrate having high integration for packaging a chip device or an electronic component is necessary to obtain a high performance integration system consequently.
Please refer to FIG. 1, which illustrates a diagram of a multi-layer substrate according to prior art. The surface of the multi-layer substrate is the surface for connecting to a device or an electronic component. Such multi-layer substrate includes a bond pad layer 102, a surface dielectric layer 104 and a solder mask layer 106. The metal layer 108 under the bond pad layer 102 is electrically connected therewithin. According to prior arts, multiple metal layers (not shown) and multiple dielectric layers (not shown) are manufactured by Sequential Lamination method or by Build-up method, but in prior arts, the thickness of the surface dielectric layer 104 is larger then those of the bond pad layer 102 and the metal layer 108.
Generally, the thicknesses of the bond pad layer 102 and the metal layer 108 are only ranged from micrometers to dozens of micrometers, but the thickness of the surface dielectric layer 104 can greatly reach from dozens of micrometers up to 200 micrometers. As shown in FIG. 1, because the metal layer 108 exists under the bond pad layer 102, regardless of the manufacturing method by either the Sequential Lamination method or the Build-up method, the surface dielectric layer 104 having dielectric material layer of a certain thickness will make the bond pad layer on the surface of the multi-layer substrate not flat. As aforementioned, the surface dielectric layer 104 can be thickened up to 200 micrometers and the metal layer 108 is only ranged from micrometers to dozens of micrometers, that the thickness of the dielectric layer 104 is much thicker than that of the metal layer 108. Therefore, in the Sequential Lamination method or the Build-up method of prior arts, some process parameters in the methods may be adjusted to deform the surface dielectric layer 104 to make the flatness thereof into an acceptable range for the package.
However, with greater increase in the integration of integrated circuits, the smaller scale and the electrical performance of the semiconductor chips has to be re-considered. The thicknesses of the bond pad layer 102, the surface dielectric layer 104 and the metal layer 108 have to be smaller accordingly. Decreases of the thicknesses of the bond pad layer 102 and the metal layer 108 are limited for keeping the electrical performance of the transmission signals but decrease of the thickness of the surface dielectric layer 104 seems to be more practicable. PCB industry today has tried to manufacture a surface dielectric layer 104 which is only about ten micrometers. In a practical example, the thickness of the surface dielectric layer 104 comes to such scale of only ten micrometers and the thickness of the metal layer 108 may get smaller as a few micrometers or ten micrometers, whose scale of the thickness become in the same degree, the aforesaid means of deforming the surface dielectric layer 104 will fail to make the flatness thereof into an acceptable range for the package. The surface flatness of the multi-layer substrate inevitably becomes worse.
FIG. 2 illustrates a diagram of a multi-layer substrate connected to a chip device with a Flip-Chip package according to prior art. The multi-layer substrate manufacture of prior art has a dielectric layer 103, the corresponding metal layers 107-1, 107-2, the surface dielectric layer 104 and the corresponding metal layers 108-1, 108-2, 108-3 which are connected with bond pad layers 102-1, 102-2, 102-3 thereabove.
The Flip-Chip package shown in FIG. 2 is a common technique in the package technology today, such that Flip-Chip package is a skill to make the chip device face down to connect contacts 112-1, 112-2, 112-3 on the chip device surface with the bond pad layers 102-1, 102-2, 102-3 by metal bumps 120-1, 120-2, 120-3. The bond pad layers 102-1, 102-2, 102-3 have to connect and match with the contacts (electrodes) 112-1, 112-2, 112-3 precisely one to one. Therefore, in the Flip-Chip package, the multi-layer substrate is fixed in advance on a package tool for aligning the metal bumps 120-1, 120-2, 120-3 of the chip device with the bond pad layers 102-1, 102-2, 102-3 of the multi-layer substrate in precise respective positions. Thereafter, the Flip-Chip package is processed by hot pressing the contacts 112-1, 112-2, 112-3, and the bond pad layers 102-1, 102-2, 102-3, whose respective contacts will precisely connect thereto by respective metal bumps to complete the packaging.
However, because the design of the electric circuit of the multi-layer substrate, there may be metal layers 107-1, 107-2 under the metal layers 108-1, 108-3 but no corresponding metal layer under the metal layer 108-2. Therefore, the height of the bond pad layer 102-2 is lower than the height of the bond pad layers 102-1, 102-3. As the Flip-Chip package is processed, the metal bump 120-2 may fail to bond the bond pad layer 102-2 and the contact 112-2 of the chip device together.
Not only in the Flip-Chip package, but also in other high integration multi-contact package, such as, BGA package, LGA package, or CSP package, even one single metal bump fails to bond the bond pad, the whole package will fail. Therefore, the demand for the flatness and the coplanarity of the multi-layer substrate or the metal bump top is more than ever.
Generally, the tolerance of the metal bump can be about ±10 micrometers at 100 micrometers bond height and as aforementioned, with the greater increase of the integration of integrated circuits, the bump pitch also decreases. Furthermore, the bond height decreases accordingly at the same time, and aforesaid tolerance certainly becomes more critical. Consequently, the flatness of the multi-layer substrate surface (or the coplanarity of the bond pad layer and the surface dielectric layer) has to be more accurate. General thickness of the metal layer is about dozens of micrometers, even a few micrometers, and if the surface of the multi-layer substrate can not be flat enough, the yield and the reliability of the Flip-Chip package can be affected critically.
Therefore, a Flip-Chip package or other high integration multi-contact package can be benefited by a flat surface multi-layer substrate. A better package reliability can be obtained and bump height can be decreased further to increase the integration of the entire package.

Multi-layer substrate and manufacture method thereof


A fiber optic aimable spotlight luminaire includes a generally cylindrical tubular housing having a proximal end, a distal end and an optical axis therethrough. A fiber optics light guide light has a first end receiving light from a remote source of illumination and a second, light-emitting end on the optical axis in the proximal end of the housing. An optical element on the optical axis of the housing has a focus generally at the second end of the fiber optics light guide, whereby light emitted by the light guide forms a generally collimated beam of light from the optical element. The position of the light guide within the housing is axially adjustable to de-collimate and zoom the beam. A rotatable and bendable bracket supports a mirror at the distal end of the housing with the mirror oriented at an angle whereby the collimated beam of light is reflected off aids as a transverse beam of light at an angle to the optical axis of the lens. In a preferred embodiment the housing is externally threaded and is retained in a planar panel by nuts engaging the threaded exterior of the housing and compressively engaging with the panel.

This invention applies to the field of fiber optics, and more particularly to spotlight luminaires for ceiling mounting with the capability of being aimed in any desired direction. This function has previously been performed by track light fixtures that are attached to a ceiling and are gimballed for aiming the light beam, such as is shown in the inventor's U.S. Pat. No. 4,906,743.
Prior art aimable fiber optic light spotlights are known, but are in the form known as "eyeball" fixtures that are mountable in a ceiling panel, but are limited to aiming at no more than a 30.degree. angle from nadir. Other prior art fiber optic luminaires are aimable by bending a deformable sheath, such as is shown in the Churchill U.S. Pat. No. 5,000,535 for a fiber optic light bar.
The primary purpose of the present invention is to provide a fiber optic luminaire having a beam on an optical axis and mountable at any location on a planar panel, such as a ceiling, in which the light beam may be reflectively aimed off axis from nadir up to 90.degree. in elevation; and the off-axis beam may be rotated about optical axis of the luminaire over 360.degree. in azimuth.


In normal operation, a primary signaling controller in a first RAN manages bearer connectivity and tracking area updates for a UE and further interfaces with a second RAN over a primary signaling interface to facilitate inter-RAN signaling related to transition of the UE from being served by the first RAN to being served by the second RAN, such as circuit-switched fallback signaling. Upon detecting failure of the primary signaling interface, the first RAN is dynamically reconfigured to have such inter-RAN signaling for the UE pass over a secondary signaling interface between the second RAN and a secondary signaling controller of the first RAN, while the primary signaling controller continues to manage bearer connectivity and tracking area updates for the UE.

Unless otherwise indicated herein, the materials described in this section are not prior art to the claims and are not admitted to be prior art by inclusion in this section.
A radio access network (RAN) may include a number of base stations that radiate to define wireless coverage areas, such as cells and cell sectors, in which user equipment devices (UEs) such as cell phones, tablet computers, tracking devices, embedded wireless modules, and other wirelessly equipped communication devices, can operate. Further, each base station may include or be coupled with network infrastructure that provides connectivity with one or more transport networks, such as the Internet and/or the public switched telephone network (PSTN) for instance. With this arrangement, a UE within coverage of the RAN may engage in air interface communication with a base station and may thereby communicate via the base station with various entities on a transport network and/or with other UEs served by the RAN.
In general, the network infrastructure in such a RAN may include a switch or gateway system that physically connects with one or more transport networks. Further, the network infrastructure may include a controller, integrated with or separate from the switch or gateway system, that manages various RAN functions such as registration and tracking of UEs in the RAN and setup and control of bearer connections for UEs.
For instance, when a UE begins operating in coverage of the RAN, the controller may receive from the UE a registration or "attach" request, and the controller may responsively trigger authentication of the UE and obtain and store a service profile record for the UE. In turn, as the UE moves throughout the RAN, the controller may receive tracking area updates from the UE and may process those updates to record where in the RAN the UE is located, so as to facilitate paging the UE or the like.
Further, when a UE is served by a particular base station, the controller may engage in signaling with the base station and with the switch or gateway system to set up one or more bearer connections for carrying communication traffic between the UE and the switch or gateway system, and thus between the UE and one or more transport networks. And the controller may manage each such bearer connection, including maintaining context data for the bearer connection, engaging in signaling to suspend, resume, release, or transfer the connection between base stations, and so forth.
In addition, such a controller in one RAN may have a signaling interface with another RAN, through which to engage in signaling to facilitate transition of a UE to be served with communications by the other RAN. For instance, a first RAN may primarily serve UEs with packet-data communication service, a second RAN may primarily serve UEs with PSTN voice call communication service, and the first RAN may include a controller that has a signaling interface for engaging in signaling with the second RAN. In a "circuit-switched fallback" (CSFB) arrangement, when a UE is being served by the first RAN and the UE seeks to place a PSTN voice call, or the second RAN seeks to connect a PSTN voice call to the UE, the second RAN may engage in call setup signaling with the UE through the controller of the first RAN.
For instance, the UE may transmit via its serving base station to the controller a PSTN voice call origination request, and the controller may send that request to an interworking server (IWS) of the second RAN, which may pass the request to a controller of the second RAN. The controller of the second RAN may then work to set up the requested PSTN voice call, and may engage in further signaling with the UE via the controller of the first RAN. Alternatively, a controller of the second RAN may transmit to the UE via the controller of the first RAN a page message to alert the UE of an incoming PSTN voice call. In either case, as a result of the inter-RAN signaling, the UE may then ultimately transition from being served by the first RAN to being served by the second RAN so as to engage in the PSTN voice call served by the second RAN.
When a UE engages in such a transition, the controller of the first RAN, as manager of bearer connections for the UE in the first RAN, may suspend one or more bearer connections that were in place for the UE in the first RAN, pending return of the UE to be served by the first RAN. Upon completion of the PSTN voice call, the UE may then return to be served by the first RAN, and the controller of the first RAN may resume the suspended bearer connection(s), to enable the UE to engage in further packet-data communication served by the first RAN.

Dual controller functionality in a wireless communication system