The invention relates to compounds of formula:

This application is a 371 of PCT/FR01/00509 filed Feb. 22, 2001.
A subject-matter of the present invention is novel 1,3-dihydro-2H-indol-2-one derivatives, a process for their preparation and the pharmaceutical compositions comprising them.
The compounds according to the present invention exhibit an affinity and a selectivity for arginine-vasopressin (AVP) V1b receptors or for both V1b and V1a receptors.
AVP is a hormone known for its antidiuretic effect and its effect in regulating arterial pressure. It stimulates several types of receptors: V1 (V1a, V1b) or V2. These receptors are located in particular in the liver, vessels (coronary, renal, cerebral), platelets, kidney, uterus, adrenal glands, pancreas, central nervous system or pituitary gland. AVP thus exerts cardiovascular, heptatic, pancreatic, antidiuretic and platelet-aggregating effects and effects on the central and peripheral nervous system and on the uterine sphere.
The localization of various receptors is described in: S. Jard et al., Vasopressin and oxytocin receptors: an overview, in Progress in Endocrinology, H. Imura and K. Shizurne ed., Experta Medica, Amsterdam, 1988, 1183-1188, and in the following articles: J. Lab. Clin. Med., 1989, 114 (6), 617-632 and Pharmacol. Rev., 1991, 43 (1), 73-108.
More particularly, AVP V1a receptors are located in numerous peripheral organs and in the brain. they have been cloned in the rat and man and they regulate the majority of known effects of AVP: platelet aggregation; uterine contractions; vessel contraction; the secretion of aldosterone, of cortisol, of CRF (corticotropin-releasing factor) and of adrenocorticotrophic hormone (ACTH); heptatic glycogenolysis, cell proliferation and the main central effects of AVP (hypothermia, memory, and the like).
The V1b receptors were initially identified in the adenohypophysis of various animal species (rat, pig, cow, sheep, and the like), including in man (S. Jard et al., Mol. Pharmacol., 1986, 30, 171-177; Y. Arsenijevic et al., J. Endocrinol., 1994, 141, 383-391; J. Schwartz et al., Endocrinology, 1991, 129 (2), 1107-1109; Y. de Keyser et al., FEBS Letters, 1994, 356, 215-220), where they stimulate the release of adrenocorticotrophic hormone by AVP and potentiate the effects of CRF on the release of ACTH (G. E. Gillies et al., Nature, 1982, 299, 355). In the hypothalamus, the V1b receptors also induce a direct release of CRF (Neuroendocrinology, 1994, 60, 503-508) and are, in these various respects, implicated in stress situations.
These V1b receptors have been cloned in the rat, man and mouse (Y. de Keyser, FEBS Letters, 1994, 356, 215-220; T. Sugimoto et al., J. Biol. Chem., 1994, 269 (43), 27088-27092; M. Saito et al., Biochem. Biophys. Res. Commun., 1995, 212 (3), 751-757; S.J. Lolait et al., Neurobiology, 1996, 92, 6783-6787; M. A. Ventura et al., Journal of Molecular Endocrinology, 1999, 22, 251-260) and various studies (in situ hybridization, PCR (Polymerase Chain Reaction), and the like) reveal ubiquitous localization of these receptors in various central tissues (brain, hypothalamus and adenohypophysis, in particular) and peripheral tissues (kidney, pancreas, adrenal glands, heart, lungs, intestine, stomach, liver, mesentery, bladder, thymus, spleen, uterus, retina, thyroid, and the like) and in some tumours (hypophyseal or pulmonary tumours, and the like), suggesting a broad biological and/or pathological role of these receptors and potential involvement in various diseases.
By way of examples, in the rat, studies have shown that AVP, via the V1b receptors, regulates the endocrine pancreas, stimulating the secretion of insulin and of glucagon (B. Lee et al., Am. J. Physiol., 269 (Endocrinol. Metab. 32), E1095-E1100, 1995) or the production of catecholamines in the medulloadrenal, which is the site of a local synthesis of AVP (E. Grazzini et al., Endocrinology, 1996, 137 (a), 3906-3914). Thus, in the last tissue, AVP, via these receptors, would have a crucial role in some types of suprarenal pheochromocytomas which secrete AVP and which, for this reason, bring about a sustained production of catecholamines which are the cause of hypertensions which are resistant to angiotensin-II receptor antagonists and to converting enzyme inhibitors. The adrenal cortex is also rich in V1a receptors involved in the production of gluco- and mineralocorticoids (aldosterone and cortisol). Via these receptors, AVP (circulating or synthesized locally) can bring about production of aldosterone with an effectiveness comparable to that of angiotensin II (G. Guillon et al., Endocrinology, 1995, 136 (3), 1285-1295). Cortisol is a powerful regulator of the production of ACTH, the stress hormone.
Recent studies have also shown that the adrenal glands are capable of directly releasing CRF and/or ACTH via the activation of the V1b and/or V1a receptors carried by the cells of the medulla (G.
Mazzocchi et al., Peptides, 1997, 18(2), 191-195; E. Grazzini et al., J. Clin. Endocrinol. Metab., 1999, 84 (6), 2195-2203).
The V1b receptors are also regarded as a label for ACTH-secreting tumours, which are some pituitary tumours and some bronchial (small cell lung cancers or SCLC), pancreatic, adrenal and thyroid carcinomas, resulting in some cases in Cushing""s syndrome (J. Bertherat et al., Eur. J. Endocrinol., 1996, 135, 173; G. A. Wittert et al., Lancet, 1990, 335, 991-994; G. Dickstein et al., J. Clin. Endocrinol. Metab., 1996, 81 (8), 2934-2941). The V1a receptors are, for their part, a more specific label for small cell lung cancers (SCLC) (P. J. Woll et al., Biochem. Biophys. Res. Commun., 1989, 164 (1), 66-73). Thus, the compounds according to the present invention are obvious diagnostic tools and offer a novel therapeutic approach in the proliferation and detection of these tumours, at an early stage too (radiolabelling; SPECT (Single Photon Emission Computed Tomography); PET Scan (Positron Emission Tomography Scanner)).
The lavish presence of the messenger of the V1b receptors in the stomach and intestine suggests involvement of AVP via this receptor in the release of gastrointestinal hormones, such as cholecystokinin, gastrin or secretin (T. Sugimoto et al., Molecular cloning and functional expression of V1b receptor gene, in Neurohypophysis: Recent Progress of Vasopressin and Oxytocin Research; T. Saito, K. Kurokawa and S. Yoshida ed., Elvesier Science, 1995, 409-413).
1,3-Dihydro-2H-indol-2-one derivatives have been disclosed in some patent applications as ligands of the arginine-vasopressin and/or oxytocin receptors: mention may be made of Patent Applications WO 93/15051, EP 636 608, EP 636 609, WO 95/18105, WO 97/15556 and WO 98/25901.
To date, no nonpeptide compound having an affinity and a selectivity for arginine-vasopressin V1b receptors or for both V1b and V1a receptors is known.
Novel 1,3-dihydro-2H-indol-2-one derivatives have now been found which exhibit an affinity and a selectivity for arginine-vasopressin V1b receptors or for both V1b and V1a receptors.
These compounds can be used for the preparation of medicaments of use in the treatment or prevention of any pathology where arginine-vasopressin and/or the V1b receptors or both the V1b receptors and the V1a receptors are implicated, in particular in the treatment or prevention of conditions of the cardiovascular system, for example hypertension, of the central nervous system, for example stress, anxiety, depression, obsessive-compulsive disorder or panic attacks, of the renal system or of the gastric system and in the treatment of small cell lung cancers, of obesity, of type-II diabetes, of insulin resistance, of hypertriglyceridaemia, of atherosclerosis, of Cushing""s syndrome or of any pathology resulting from stress and chronic stress conditions.
Thus, according to one of its aspects, the subject-matter of the present invention is compounds of formula:
in which:
n is 0, 1 or 2 and p is 0, 1 or 2; the sum n+p being equal to 1 or 2;
R1 represents a halogen atom; a (C1-C4) alkyl; a (C1-C4)alkoxy; a trifluoromethyl radical; or a trifluoromethoxy-radical;
R2 represents a hydrogen atom; a halogen atom; a (C1-C4)alkyl; a (C1-C4)alkoxy; or a trifluoromethyl radical;
or else R2 is in the 6-position of the indol-2-one ring and R1 and R2 together-represent the bivalent trimethylene radical;
R3 represents a halogen atom; a hydroxyl; a (C1-C2)alkyl; a (C1-C2)alkoxy; or a trifluoromethoxy radical;
R4 represents a hydrogen atom; a halogen atom; a (C1-C2)alkyl; or a (C1-C2)alkoxy;
or else R4 is in the 3-position of the phenyl and R3 and R4 together represent the methylenedioxy radical;
R5 represents an ethylamino group; a dimethylamino group; an azetidin-1-yl radical; or a (C1-C2) alkoxy;
R6 represents a (C1-C4)alkoxy;
R7 represents a (C1-C4)alkoxy;
R8 represents a hydrogen atom; a halogen atom; a (C1-C4)alkyl; or a (C1-C4)alkoxy;
R9 represents a hydrogen atom; a halogen atom; a (C1-C4)alkyl; or a (C1-C4)alkoxy;
and their solvates and/or hydrates.
The compounds of formula (I) comprise at least 2 asymmetric carbon atoms. The optically pure isomers of the compounds of formula (I) and their mixtures in any proportion form part of the invention.
The term xe2x80x9chalogen atomxe2x80x9d is understood to mean a chlorine, bromine, fluorine or iodine atom.
The term xe2x80x9calkylxe2x80x9d or the term xe2x80x9calkoxyxe2x80x9d are respectively understood to mean a linear or branched alkyl or alkoxy radical respectively.
In the compounds of formula (I), the radical:
represents one of the following radicals:
According to the present invention, preference is given to the compounds of formula (I) in which:
n is 0, 1 or 2 and p is 0, 1 or 2; the sum n+p being equal to 1 or 2;
R1 represents a halogen atom; a (C1-C4) alkyl; a trifluoromethyl radical; or a trifluoromethoxy radical;
R2 represents a hydrogen atom; a halogen atom; a (C1-C4)alkyl; a (C1-C4)alkoxy; or a trifluoromethyl radical;
or else R2 is in the 6-position of the indol-2-one ring and R1 and R2 together represent the bivalent trimethylene radical;
R3 represents a halogen atom; a hydroxyl; or a (C1-C2)alkoxy;
R4 represents a hydrogen atom; a halogen atom; a (C1-C2)alkyl; or a (C1-C2)alkoxy;
or else R4 is in the 3-position of the phenyl and R3 and R4 together represent the methylenedioxy radical;
R5 represents an ethylamino group; a dimethylamino group; an azetidin-1-yl radical; or a (C1-C2) alkoxy;
R6 represents a (C1-C4)alkoxy;
R7 represents a (C1-C4)alkoxy;
R8 represents a hydrogen atom;
R8 represents a hydrogen atom;
and their solvates and/or hydrates.
According to the present invention, the compounds of formula (I) having an (A), (D) or (E) radical are preferred.
According to the present invention, preference is given to the compounds of formula (I) in which R1 represents a chlorine atom, a methyl radical or a trifluoromethoxy radical.
According to the present invention, preference is given to the compounds of formula (I) in which R2 represents a hydrogen atom or is in the 4- or 6-position of the indol-2-one and represents a chlorine atom, a methyl radical, a methoxy radical or a trifluoromethyl radical.
According to the present invention, preference is given to the compounds of formula (I) in which R3 represents a chlorine atom or a methoxy radical.
According to the present invention, preference is given to the compounds of formula (I) in which R4 represents a hydrogen atom or is in the 3- or 4-position of the phenyl and represents a methoxy radical; or else R4 is in the 3-position of the phenyl and together with R3 represent a methylenedioxy radical.
According to the present invention, preference is given to the compounds of formula (I) in which R5 represents a dimethylamino group, an azetidin-1-yl radical or a methoxy radical.
According to the present invention, preference is given to the compounds of formula (I) in which R6 is in the 2-position of the phenyl and represents a methoxy radical.
According to the present invention, preference is given to the compounds of formula (I) in which R7 represents a methoxy radical.
According to the present invention, preference is given to the compounds of formula (I) in which R8 and R8 each represent a hydrogen atom.
Preference is more particularly given to the compounds of formula (I) in which:
the
xe2x80x83radical represents an (A), (D) or (E) radical;
R1 represents a chlorine atom or a methyl radical;
R2 represents a hydrogen atom or is in the 4- or 6-position of the indol-2-one and represents a chlorine atom, a methyl radical or a methoxy radical;
R3 represents a methoxy radical or a chlorine atom;
R4 represents a hydrogen atom or is in the 3- or 4-position of the phenyl and represents a methoxy radical;
or else R4 is in the 3-position of the phenyl and together with R3 represent a methylenedioxy radical;
R8 represents a dimethylamino group or a methoxy radical;
R6 is in the 2-position of the phenyl and represents a methoxy radical;
R8 represents a methoxy radical;
R8 and R8 represent a hydrogen atom;
and their solvates and/or hydrates.
According to the present invention, preference is given to the compounds of formula (I) in the form of optically pure isomers.
More particularly, preference is given to the optically pure isomers of the compounds of formula:
in which n, p, R1, R2, R3, R4, R5, R6, R7, R8 and R8 are as defined for a compound of formula (I), the carbon atom carrying the COR5 substituent has the (S) configuration and the carbon atom in the 3-position of the indol-2-one has either the (R) configuration or the (S) configuration.
Preference is very particularly given to the levorotatory isomer of the compounds of formula (Ia).
The following compounds:
(3S)-2-[5-Chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide, levorotatory isomer;
(1S)-2-[5-Chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-1-carboxamide, levorotatory isomer;
(2S)-1-[5-Chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-N,N-dimethyl-2,3-dihydro-1H-indole-2-carboxamide, levorotatory isomer;
Methyl ester of (3S)-2-[5-chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, levorotatory isomer;
(3S)-2-[5,6-Dichloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide, levorotatory isomer;
(3S)-2-[5-Chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-methoxyphenyl)-6-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl]-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide, levorotatory isomer;
(3S)-2-[5-Chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-6,7-dimethoxy-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide, levorotatory isomer;
(3S)-2-[5-Chloro-3-(2-chlorophenyl)-1-[(2,4-dimethoxyphenyl)sulphonyl]-2-oxo-2,3-dihydro-1H-indol-3-yl]-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide, levorotatory isomer;
(3S)-2-[5-Chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2,3-dimethoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide, levorotatory isomer;
(3S)-2-[5-Chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2,4-dimethoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide, levorotatory isomer;
(3S)-2-[5-Chloro-3-(1,3-benzodioxol-4-yl)-1-[(2,4-dimethoxyphenyl)sulphonyl]-2-oxo-2,3-dihydro-1H-indol-3-yl]-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide, levorotatory isomer;
(3S)-2-[5,6-Dichloro-3-(2-chlorophenyl)-1-[(2,4-dimethoxyphenyl)sulphonyl]-2-oxo-2,3-dihydro-1H-indol-3-yl]-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide, levorotatory isomer;
(3S)-2-[5-Chloro-3-(2-chlorophenyl)-1-[(2,4-dimethoxyphenyl)sulphonyl]-6-methoxy-2-oxo-2,3-dihydro-1H-indol-3-yl]-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide, levorotatory isomer;
(3S)-2-[4-Chloro-1-[(2,4-dimethoxyphenyl)sulphonyl]-3-(2-methoxyphenyl)-5-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl]-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide, levorotatory isomer;
and their solvates and/or hydrates are more particularly preferred.
According to another of its aspects, a subject-matter of the present invention is a process for the preparation of the compounds of formula (I), their solvates and/or their hydrates, characterized in that:
a compound of formula:
xe2x80x83in which n, p, R1, R2, R3, R4, R5, R8 and R8 are as defined for a compound of formula (I), is reacted, in the presence of a base, with a halide of formula:
xe2x80x83in which R6 and R7 are as defined for a compound of formula (I) and Hal represents a halogen atom.
The reaction is carried out in the presence of a strong base, such as a metal hydride, for example sodium hydride, or an alkali metal alkoxide, for example potassium tert-butoxide, in an anhydrous solvent, such as N,N-dimethylformamide or tetrahydrofuran, and at a temperature of between xe2x88x9270xc2x0 C. and +60xc2x0 C. The reaction is preferably carried out by using a compound of formula (III) in which Hal=Cl.
The compounds of formula (I) thus obtained can subsequently be separated from the reaction mixture and purified according to conventional methods, for example by crystallization or chromatography.
The compounds of formula (II) are prepared by the reaction of a 3-halo-1,3-dihydro-2H-indol-2-one compound of formula:
in which R1, R2, R3 and R4 are as defined for a compound of formula (I) and Hal represents a halogen atom, preferably chlorine or bromine, with a compound of formula:
in which n, p and R5, R8 and R9 are as defined for a compound of formula (I). The reaction is carried out in the presence of a base, such as diisopropylethylamine or triethylamine, in an inert solvent, such as dichloromethane, chloroform or tetrahydrofuran or a mixture of these solvents, and at a temperature of between ambient temperature and the reflux temperature of the solvent.
The compounds of formula (III) are known or prepared by known methods, such as those disclosed in EP-0 469 984 B and WO 95/18105. For example, the compounds of formula (III) can be prepared by halogenation of the corresponding benzenesulphonic acids or of their salts, for example of their sodium or potassium salts. The reaction is carried out in the presence of a halogenating agent, such as phosphorus oxychloride, thionyl chloride, phosphorus trichloride, phosphorus tribromide or phosphorus pentachloride, without a solvent or in an inert solvent, such as a halogenated hydrocarbon or N,N-dimethylformamide, and at a temperature of between xe2x88x9210xc2x0 C. and 200xc2x0 C.
2,4-Dimethoxybenzenesulphonyl chloride is prepared according to J. Am. Chem. Soc., 1952, 74, 2008. 3,4-Dimethoxybenzenesulphonyl chloride is commercially available or prepared according to J. Med. Chem., 1977, 20 (10), 1235-1239.
The compounds of formula (IV) are known and are prepared according to known methods, such as those disclosed in WO 95/18105.
For example, a compound of formula:
in which R1, R2, R3 and R4 are as defined for a compound of formula (I), is converted into a compound of formula (IV) in which Hal=Cl by the action of thionyl chloride in the presence of a base, such as pyridine, in an inert solvent, such as dichloromethane, and at a temperature between 0xc2x0 C. and ambient temperature.
According to another example of the preparation of the compounds of formula (IV), a compound of formula:
in which R1, R2, R3 and R4 are as defined for a compound of formula (I), is converted into a compound of formula (IV) by means of a halogenating agent, such as bromine, according to the process described in Farm. Zh. (Kiev), 1976, 5, 30-33.
The compounds of formula (VI) are known and are prepared according to known methods, such as those disclosed in WO 95/18105.
For example, a compound of formula (VI) is prepared by reaction of a 1H-indole-2,3-dione derivative of formula:
in which R1 and R2 are as defined for a compound of formula (I), with an organomagnesium derivative of formula:
in which R3 and R4 are as defined for a compound of formula (I) and Hal represents a halogen atom, preferably bromine or iodine, in an inert solvent, such as tetrahydrofuran or diethyl ether, and at a temperature of between 0xc2x0 C. and the reflux temperature of the solvent.
A compound of formula (VI) in which R3 is as defined for a compound of formula (I) and R4, which is other than hydrogen, is in the 3- or 6-position of the phenyl can also be prepared by the reaction of a compound of formula:
in which R3 is as defined for a compound of formula (I) and R4 is in the 2- or 5-position of the phenyl, with a lithium derivative, such as n-butyllithium, and then the lithiated intermediate thus obtained is reacted with a compound of formula (VIII). The reaction is carried out in a solvent, such as diethyl ether, tetrahydrofuran, hexane or a mixture of these solvents, at a temperature of between xe2x88x9270xc2x0 C. and ambient temperature.
The 1H-indole-2,3-dione derivatives (VIII) are commercially available or prepared according to the methods described in Tetrahedron Letters, 199,8, 39, 7679-7682; Tetrahedron Letters, 1994, 35, 7303-7306; J. Org. Chem., 1977, 42 (8), 1344-1348; J. Org. Chem., 1952, 17, 149-156; J. Am. Chem. Soc., 1946, 68, 2697-2703, Organic Syntheses, 1925, V, 71-74 and Advances in Heterocyclic Chemistry, A. R. Katritzky and A. J. Boulton, Academic Press, New York, 1975, 18, 2-58.
The organomagnesium derivatives (IX) are prepared according to conventional methods well known to a person skilled in the art.
A compound of formula (VI) can also be prepared by air oxidation of a compound of formula (VII) in the presence of a base, such as sodium hydride, and in the presence of dimethyl disulphide.
Specifically, the compounds of formula (VI) in which R3=(C1-C2)alkoxy and R4=H or else R3xe2x95x90R4=(C1-C2)alkoxy with R4 in the 3- or 6-position of the phenyl, R2 is other than a halogen atom and R1 is as defined for a compound of formula (I) can be prepared by following the process described in SCHEME 1.
In stage a1 of SCHEME 1, a compound of formula (X) is first of all reacted with a lithium derivative, such as n-butyllithium, in the absence or in the presence of a base, such as N,N,Nxe2x80x2,Nxe2x80x2-tetramethylenediamine, and then the lithiated intermediate thus obtained is reacted with diethyl oxalate to give the compound of formula (XI). The reaction is carried out in an inert solvent, such as diethyl ether or tetrahydrofuran, and at a temperature of between xe2x88x9270xc2x0 C. and ambient temperature.
In stage b1, a compound of formula (XII) is first of all reacted with two equivalents of a lithium derivative, such as tert-butyllithium, and then the lithiated intermediate obtained is reacted with the compound of formula (XI) to give the expected compound of formula (VI). The reaction is carried out in an inert solvent, such as diethyl ether or tetrahydrofuran, and at a temperature of between xe2x88x9270xc2x0 C. and ambient temperature.
The compounds of formula (X) are commercially available or are synthesized in a conventional way.
The compounds of formula (XII) are prepared by reaction of the corresponding aniline derivatives with di-tert-butyl dicarbonate according to conventional methods.
The compounds of formula (VII) are known and are prepared according to known methods, such as those disclosed in WO 95/18105 or in J. Org. Chem., 1968, 33, 1640-1643.
The compounds of formula (V) are known or are prepared according to known methods. Thus, for example, the compounds of formula (V) in which R5 represents an ethylamino or dimethylamino group or an azetidin-1-yl radical are prepared according to SCHEME 2 below, in which Pr represents an N-protecting group, in particular tert-butoxycarbonyl or 9-fluorenylmethoxycarbonyl, and n, p, R8 and R9 are as defined for a compound of formula (I).
In stage a2 of SCHEME 2, the nitrogen atom of the compound of formula (XIII) is protected according to conventional methods to obtain a compound of formula (XIV). Some of the compounds of formula (XIV) are commercially available.
The acid (XIV) is reacted in stage b2 with ethylamine, dimethylamine or azetidine according to conventional peptide coupling methods to give the compound of formula (XV), which is deprotected in stage c2 according to known methods to give the expected compound of formula (V). In particular, when Pr represents a 9-fluorenylmethoxycarbonyl group, deprotection is carried out using the method described in Synthetic Communications, 1994, 24 (2), 187-195.
The compounds of formula (V) in which R5 represents a (C1-C2)alkoxy are known or are prepared according to known methods, such as, for example, by an esterification reaction starting with the acids of formula (XIII), or according to the methods described in Tetrahedron Letters, 1986, 27, 2409-2410; J. Am. Chem. Soc., 1970, 92, 2476-2488; Tetrahedron Asymmetry, 1998, 9, 4295-4299; J. Med. Chem., 1994, 37, 3956-3968; J. Chem. Soc. Perkin Trans 1, 1977, 596-600; Gazz. Chim. Ital., 1976, 106, 65; Chem. Pharm. Bull., 1983, 31, 312-314; J. Med. Chem., 1983, 26, 1267-1277; J. Org. Chem., 1997, 62, 7679-7689; J. Med. Chem., 1992, 35, 1942-1953; Justus Liebigs Ann. Chem., 1976, 367-382; J. Org. Chem., 1978, 43, 2115-2119; Tetrahedron Letters, 1997, 38, 6977-6980; Helv. Chim. Acta, 1959, 42, 2431-2436.
The acids of formula (XIII) are commercially available or are prepared according to known methods. Thus, for example:
2,3-Dihydro-1H-indole-2-carboxylic acids are prepared according to J. Med. Chem., 1983, 26, 394-403; Agric. Biol. Chem., 1987, 51, 1833-1838; J. Med. Chem., 1983, 26, 1267-1277; Helv. Chim. Acta, 1962, 45, 638; Helv. Chim. Acta, 1968, 51, 1476.
1,2,3,4-Tetrahydroquinoline-2-carboxylic acids are prepared according to J. Org. Chem., 1990, 55, 738-741; J. Med. Chem., 1992, 35, 1942-1953;
Isoindoline-1-carboxylic acids are prepared according to J. Heterocyclic. Chem., 1984, 21, 1355-1360;
1,2,3,4-Tetrahydroisoquinoline-3-carboxylic acids are prepared according to Synthesis, 1992, 11, 1157-1160; Int. J. Peptide Protein Res., 1994, 43, 62-68; Liebigs Ann./Recueil, 1997, 3, 533-540; J. Med. Chem., 1988, 31, 2092-2097; J. Chem. Soc., 1938, 172-175; J. Chem. Soc., 1950, 1534-1537; Synthesis, 1990, 550-556; Heterocycles, 1992, 34, 757-764; J. Med. Chem., 1983, 26, 1267-1277;
1,2,3,4-Tetrahydroisoquinoline-1-carboxylic acids are prepared according to J. Med. Chem., 1993, 36, 314-319 or according to WO 93/12091.
When it is desired to prepare an optically pure compound of formula (I), an optically pure compound of formula (II) is preferably reacted with a compound of formula (III) according to the process of the invention.
The optically pure compounds of formula (II) are prepared by reaction of the racemic compound of formula. (IV) with an optically pure compound of formula (V), followed by separation of the mixture of diastereoisomers according to conventional methods, for example by crystallization or chromatography.
Alternatively, the mixture of diastereoisomers of the compound of formula (II) can be reacted with the compound of formula (III) and the mixture of diastereoisomers of the compound of formula (I) thus obtained can be separated.
During any one of the stages for the preparation of the compounds of formula (I) or of the intermediate compounds of formula (II), (IV), (V) or (VI), it may be necessary and/or desirable to protect the reactive or sensitive functional groups, such as amine, hydroxyl or carboxyl groups, present on any one of the molecules concerned. This protection can be achieved by using conventional protecting groups, such as those described in Protective Groups in Organic Chemistry, J. F. W. McOmie, published by Plenum Press, 1973, in Protective Groups in Organic Synthesis, T. W. Greene and P. G. M. Wutts, published by John Wiley and Sons, 1991 or in Protecting Groups, Kocienski P. J., 1994, Georg Thieme Verlag. The protecting groups can be removed at an appropriate subsequent stage using methods known to a person skilled in the art which do not affect the remainder of the molecule concerned.
The N-protecting groups optionally used are conventional N-protecting groups well known to a person skilled in the art, such as, for example, the tert-butoxycarbonyl, fluorenylmethoxycarbonyl, benzyl, benzhydrylidene or benzyloxycarbonyl group.
The compounds of formula (II) are novel and form part of the invention.
Thus, according to another of its aspects, a subject-matter of the invention is compounds of formula:
in which:
n is 0, 1 or 2 and p is 0, 1 or 2; the sum n+p being equal to 1 or 2;
R1 represents a halogen atom; a (C1-C4) alkyl; a (C1-C4)alkoxy; a trifluoromethyl radical; or a trifluoromethoxy radical;
R2 represents a hydrogen atom; a halogen atom; a (C1-C4)alkyl; a (C1-C4)alkoxy; or a trifluoromethyl radical;
or else R2 is in the 6-position of the indol-2-one ring and R1 and R2 together represent the bivalent trimethylene radical;
R3 represents a halogen atom; a hydroxyl; a (C1-C2)alkyl; a (C1-C2)alkoxy; or a trifluoromethoxy radical;
R4 represents a hydrogen atom; a halogen atom; a (C1-C2) alkyl; or a (C1-C2) alkoxy;
or else R4 is in the 3-position of the phenyl and R3 and R4 together represent the methylenedioxy radical;
R5 represents an ethylamino group; a dimethylamino group; an azetidin-1-yl radical; or a (C1-C2) alkoxy;
R8 represents a hydrogen atom; a halogen atom; a (C1-C4) alkyl; or a (C1-C4) alkoxy;
R8 represents a a hydrogen atom; a halogen atom; a (C1-C4) alkyl; or a (C1-C4) alkoxy;
and their salts with inorganic or organic acids, in the form of optically pure isomers or in the form of a mixture of diastereoisomers or in the form of a racemic mixture.
The salts of the compounds of formula.(II) comprise those with inorganic or organic acids which make possible suitable separation or crystallization of the compounds of formula (II), such as the hydrochloride, hydrobromide, oxalate, maleate, succinate, fumarate, citrate or acetate.
The compounds of above formula (I) also comprise those in which one or more hydrogen or carbon atoms have been replaced by their radioactive isotope, for example tritium or carbon-14. Such labelled compounds are of use in research, metabolism or pharmacokinetic studies or in biochemical assays as receptor ligand.
The compounds according to the invention have formed the subject of biochemical studies.
The affinity of the compounds of formula (I) according to the invention for arginine-vasopressin V1b receptors was determined in vitro by using the method described by Y. De Keyser et al., FEBS Letters, 1994, 356, 215-220. This-method consists in studying in vitro the displacement of tritiated arginine-vasopressin ([3H]-AVP) at the V1b receptors present on adenohypophysal membrane or cell preparations carrying rat or human V1b receptors. The 50% inhibitory concentrations (IC50) for the attachment of tritiated arginine-vasopressin of the compounds according to the invention are low and vary from 10xe2x88x926 to 10xe2x88x929M, more particularly from 10xe2x88x927 to 10xe2x88x929M.
The affinity of the compounds of formula (I) according to the invention for arginine-vasopressin V1a receptors was determined in vitro using the method described by M. Thibonnier et al., J. Biol. Chem., 1994, 269, 3304-3310. This method consists in studying in vitro the displacement of tritiated arginine-vasopressin ([3H]-AVP) at the V1a receptors present on membrane or cell preparations carrying rat or human V1a receptors. Some of the compound of formula (I) also exhibit an affinity for arginine-vasopressin V1a receptors, with IC50 values which vary from 10xe2x88x926 to 10xe2x88x929M, more particularly from 10xe2x88x927 to 10xe2x88x928M.
The affinity of the compounds of formula (I) according to the invention for vasopressin V2 receptors has also been studied (method described by M. Birnbaumer et al., Nature (Lond.), 1992, 357, 333-335). The compounds studied have little or no affinity for the V2 receptors.
The compounds of the present invention are in particular active principles of pharmaceutical compositions, the toxicity of which is compatible with their use as medicaments.
According to another of its aspects, the present invention relates to the use of the compounds of formula (I), of their solvates and/or of their hydrates which are pharmaceutically acceptable for the preparation of medicaments intended for the treatment of any pathology where arginine-vasopressin and/or its V1b receptors or both its V1b receptors and its V1a receptors are implicated.
According to another of its aspects, the present invention relates to the use of the compounds of formula (I), of their solvates and/or of their hydrates which are pharmaceutically acceptable in the preparation of medicaments intended for the treatment of pathologies of the cardiovascular system, of the central nervous system, of the renal system or of the gastric system and of small cell lung cancers, obesity, type-II diabetes, insulin resistance, hypertriglyceridaemia, atherosclerosis, Cushing""s syndrome or any pathology resulting from stress and chronic stress conditions.
Thus, the compounds according to the invention may be used, in man or in animals, in the treatment or prevention of various vasopressin-dependent conditions, such as cardiovascular conditions, for example hypertension, pulmonary hypertension, cardiac insufficiency, myocardial infarction or coronary vasospasm, in particular in smokers, Raynaud""s syndrome, unstable angina and PTCA (percutaneous transluminal coronary angioplasty), cardiac ischaemia or haemostasis disturbances; conditions of the central nervous system, such as migraine, cerebral vasospasm, cerebral haemorrhage, cerebral oedema, depression, anxiety, stress, obsessive-compulsive disorder, panic attacks, psychotic states or memory disorders, for example; conditions of the renal system, such as renal vasospasm, necrosis of the renal cortex or nephrogenic diabetes insipidus; conditions of the gastric system, such as gastric vasospasm, cirrhosis of the liver, ulcers or the pathology of vomiting, for example nausea, including nausea due to chemotherapy or travel sickness; or diabetic nephropathy. The compounds according to the invention can also be used in the treatment of disorders of sexual behaviour; in women, the compounds according to the invention can be used to treat dysmenorrhoea or premature labour. The compounds according to the invention can also be used in the treatment of small cell lung cancers; hyponatremic encephalopathy; pulmonary syndrome; Mxc3xa9nixc3xa8re""s disease; glaucoma; cataracts; obesity; type-II diabetes; atherosclerosis; Cushing""s syndrome; insulin resistance; or hypertriglyceridaemia; or in post-operative treatments, in particular after abdominal surgery.
The compounds according to the invention can also be used in the treatment or prevention of any pathology resulting from stress, such as fatigue and its syndromes, ACTH-dependent disorders, cardiac disorders, pain, modifications in gastric emptying, in faecal excretion (colitis, irritable bowel syndrome or Crohn""s disease) or in acid secretion, hyperglycaemia, immunosuppression, inflammatory processes (rheumatoid arthritis and osteoarthritis), multiple infections, cancers, asthma, psoriasis, allergies and various neuropsychiatric disorders, such as anorexia nervosa, bulimia, mood disorders, depression, anxiety, sleep disorders, panic states, phobias, obsession, disorders of pain perception (fibromyalgia), neurodegenerative diseases (Alzheimer""s disease, Parkinson""s disease or Huntington""s disease), substance dependence, haemorrhagic stress, muscle spasms or hypoglycaemia. The compounds according to the invention can also be used in the treatment or prevention of chronic stress conditions, such as immunodepression, fertility disorders or dysfunctionings of the hypothalamopituitaryadrenal axis.
The compounds according to the invention can also be used as psychostimulants, resulting in an increase in alertness or emotional reactivity to the surroundings and making adaptation easier.
The compounds of above formula (I), their solvates and/or their hydrates which are pharmaceutically acceptable can be used at daily doses of 0.01 to 100 mg per kilo of body weight of the mammal to be treated, preferably at daily doses of 0.1 to 50 mg/kg. In man, the dose can preferably vary from 0.1 to 4000 mg per day, more particularly from 0.5 to 1000 mg, depending upon the age of the subject to be treated or the type of treatment; prophylactic or curative.
For their use as medicaments, the compounds of formula (I) are generally administered in dosage units. The said dosage units are preferably formulated in pharmaceutical compositions in which the active principle is mixed with one or more pharmaceutical excipients.
Thus, according to another of its aspects, the present invention relates to pharmaceutical compositions including, as active principle, a compound of formula (I), one of its solvates and/or one of its hydrates which are pharmaceutically acceptable.
In the pharmaceutical compositions of the present invention for administration by the oral, sublingual, inhaled, subcutaneous, intramuscular, intravenous, transdermal, local or rectal route, the active principles can be administered in single-dose administration forms, as a mixture with conventional pharmaceutical vehicles, to animals and human beings. The appropriate single-dose administration forms comprise forms by the oral route, such as tablets, gelatin capsules, powders, granules and oral solutions or suspensions, sublingual and buccal administration forms, aerosols, topical administration forms, implants, subcutaneous, intramuscular, intravenous, intranasal or intraocular administration forms and rectal administration forms.
When a solid composition is prepared in the form of tablets or gelatin capsules, a mixture of pharmaceutical excipients is added to the micronized or nonmicronized active principle, which mixture can be composed of diluents, such as, for example, lactose, microcrystalline cellulose, starch or dicalcium phosphate, of binders, such as, for example, polyvinylpyrrolidone or hydroxypropylmethylcellulose, of disintegrating agent, such as crosslinked polyvinylpyrrolidone or crosslinked carboxymethylcellulose, of flow agents, such as silica or talc, or of lubricants, such as magnesium stearate, stearic acid, glyceryl tribehenate or sodium stearylfumarate.
Wetting agents or surfactants, such as sodium lauryl sulphate, polysorbate 80 or poloxamer 188, can be added to the formulation.
The tablets can be prepared by various techniques: direct tableting, dry granulation, wet granulation or hot-melt.
The tablets can be bare or sugar-coated (with sucrose, for example) or coated with various polymers or other appropriate materials.
The tablets can have a flash, delayed or sustained release by preparing polymeric matrices or by using specific polymers when forming the thin film.
The gelatin capsules may be soft or hard and may or may not be coated with a thin film, so as to have a flash, sustained or delayed activity (for example via an enteric form).
They can comprise not only a solid formulation formulated as above for tablets but also liquids or semi-solids.
A preparation in the form of a syrup or elixir can comprise the active principle in conjunction with a sweetener, preferably a calorie-free sweetener, methylparaben and propylparaben, as antiseptic, a flavouring agent and an appropriate colorant.
The water-dispersible powders or granules can comprise the active principle as a mixture with dispersing agents, wetting agents or suspending agents, such as polyvinylpyrrolidone, as well as with sweeteners or flavour enhancers.
For rectal administration, recourse is had to suppositories which are prepared with binders which melt at the rectal temperature, for example cocoa butter or polyethylene glycols.
For parenteral, intranasal or intraocular administration, use is made of aqueous suspensions, isotonic saline solutions or sterile and injectable solutions which comprise pharmacologically compatible dispersing agents and/or solubilizing agents, for example propylene glycol.
Thus, to prepare an aqueous solution which can be injected by the intravenous route, use may be made of a cosolvent, such as, for example, an alcohol, such as ethanol, or a glycol, such as polyethylene glycol or propylene glycol, and of a hydrophilic surfactant, such as polysorbate 80 or poloxamer 188. To prepare an oily solution which can be injected by the intramuscular route, the active principle can be dissolved with a triglyceride or a glyceryl ester.
For local administration, use may be made of creams, ointments, gels, eyewashes or sprays.
For transdermal administration, use may be made of patches in multilaminar or reservoir form, in which the active principle can be in alcoholic solution, or sprays.
For administration by inhalation, use is made of an aerosol comprising, for example, sorbitan trioleate or oleic acid and trichlorofluoromethane, dichlorofluoromethane, dichlorotetrafluoroethane, freon substitutes or any other biologically compatible propellant gas; use may also be made of a system comprising the active principle, alone or in combination with an excipient, in powder form.
The active principle can also be presented in the form of a complex with a cyclodextrin, for example xcex1, xcex2- or xcex3-cyclodextrin or 2-hydroxypropyl-xcex2-cyclodextrin.
The active principle can also be formulated in the form of microcapsules or microspheres, optionally with one or more vehicles or additives.
Use may be made of implants among the sustained-release forms of use in the case of chronic treatments. These implants can be prepared in the form of an oily suspension or in the form of a suspension of microspheres in an isotonic medium.
The active principle of formula (I) is present in each dosage unit in the amounts suited to the daily doses envisaged. In general, each dosage unit is suitably adjusted according to the dosage and the type of administration provided, for example tablets, gelatin capsules and the like, sachets, blisters, syrups and the like, or drops, so that such a dosage unit comprises from 0.1 to 1000 mg of active principle, preferably from 0.5 to 250 mg, which has to be administered one to four times daily.
Although these dosages are examples of average situations, there may be specific cases where higher or lower dosages are appropriate; such dosages also form part of the invention. According to the usual practice, the dosage appropriate to each patient is determined by the physician according to the method of administration and the age, the weight and the response of the said patient.
The compositions of the present invention can comprise, in addition to the compounds of formula (I), their solvates and/or their hydrates which are pharmaceutically acceptable, other active principles which can be of use in the treatment of the disorders or diseases indicated above.
Thus, another subject-matter of the present invention is pharmaceutical compositions comprising several active principles in combination, one of which is a compound according to the invention.
Thus, according to the present invention, pharmaceutical compositions can be prepared which comprise a compound according to the invention in combination with a compound which has an effect on the CRF receptors.
The compounds according to the invention can also be used for the preparation of compounds for veterinary use.

1,3-dihydro-2h-indol-2-one, preparation method and pharmaceutical compositions containing same

Abstract: and their solvates and/or hydrates exhibiting an affinity and a selectivity for arginine-vasopressin V1b receptors or for both V1b and V1a receptors.


A fluid jet drilling nozzle and associated drilling method. The nozzle is adapted to be connected to a source of high pressure fluid and to be rotated about a rotation axis, and comprises a body formed so that it partially encloses a cavity, which cavity is in fluid communication with the source of high pressure fluid when the nozzle is connected to such source. The nozzle further comprises means for allowing high pressure fluid in the cavity to exit the nozzle in the form of a high velocity fluid jet which intersects the axis of rotation of the nozzle. Such a nozzle may be mounted in any drilling apparatus capable of supplying high pressure fluid to the cavity and of rotating or oscillating the nozzle about its rotation axis.

This invention relates to fluid jet drilling nozzles and methods for fluid jet drilling.
Although high velocity fluid jets have found a considerable number of applications in the cutting or scoring of various materials, the use of fluid jets for drilling in rock or other substances have received relatively little attention. One of the problems inherent in fluid jet drilling is that the fluid jets lose much of their cutting ability if the jet forming nozzle is too great a distance from the surface being cut. It is therefore necessary for a fluid jet drilling technique to be capable of drilling a hole of large enough diameter for the drilling nozzle to enter, so that the nozzle may be advanced into the hole as it is cut. Fluid jets, however, are of quite small diameter, typically 0.01 inches, and therefore at any one instant the jet can only cut against a very small area of the rock. A practical technique is therefore needed by which a small diameter fluid jet can cut a hole having a diameter much larger than the jet.


A part-circle sprinkler having a sprinkler head incorporating a nozzle continually oscillates between two positions. The sprinkler head is connected to a transmission driven by an impeller The impeller is driven by a reversible stator which can direct a plurality of channelized streams of water against either side of the blades of the impeller and thereby cause the impeller, sprinkler head and nozzle to rotate in a clockwise or a counterclockwise direction. The reversing stator is controlled by a resilient switching arm operated by adjustable fingers on the exterior of the sprinkler head, which set its limits of rotation. As each limit of rotation is reached, one finger exerts a torque on the switching arm. The torque causes the arm to twist until it exerts sufficient force on the reversing stator to overcome the force of the water on the stator vanes and thus reverse the direction of the stator. The sprinkler head then rotates in the opposite direction, which brings the other finger toward the switching arm. The flow of water through the sprinkler is axial from inlet to nozzle.

Automatic part-circle sprinklers are known in the art. Many are designed to attach to underground water pipes and incorporate pop-up heads which rise above the ground when water is supplied to the sprinkler and which lie flush with the ground when not in use.
The limitations of the part-circle sprinklers found in the prior art are numerous. First, most utilize complicated control mechanisms which are susceptible to being jammed by the various debris flowing through the water pipes of most sprinkler systems. As a result, expensive screens are required to protect the control mechanisms.
Second, in many of the part-circle sprinklers found in the prior art, the limits of coverage of the sprinkler are set internally within the sprinkler and thus partial disassembly of the sprinkler is usually required when these limits are to be changed.
Third, in those sprinklers which provide a precise adjustment of the area of coverage, the sprinkler rotates only to the preset limit of rotation. As a result, the presence of any wind or a slight misadjustment of the area of coverage often results in the outer limits of the area not being sprayed with water.
Finally, most of the devices found in the prior art have no means for maintaining a constant speed of rotation when sudden changes occur in the volume of water supplied to the device. As a result, these volume changes cause erratic operation of these part-circle sprinklers.
Accordingly, it is a principal object of this invention to reduce the complexity of the control mechanism required in a part-circle sprinkler.
It is another object of this invention to simplify the adjustment of the limits of rotation of a part-circle sprinkler.
It is still another object of this invention to insure that the outer limits of the predetermined area of coverage of a part-circle sprinkler receive adequate water.
It is a final object of this invention to prevent volumetric changes in the water supplied to a part-circle sprinkler from disturbing its speed of rotation.

Part-circle sprinkler with reversible stator


A method and control system are disclosed for adjusting orientations of knockdown rollers for sugarcane harvesters. An upper knockdown roller may be moved along a first adjustment path using a first actuator. A lower knockdown roller may be moved along a second adjustment path using a second actuator. A substantially tangential alignment may be maintained for an outer diameter of the upper knockdown roller and an outer diameter of the lower knockdown roller with respect to a reference point along a cutting path of the base cutter assembly, during or after movement of the upper and lower knockdown rollers.

In order to harvest sugarcane from a field, a sugarcane harvester may move along a sugarcane field in order to gather sugarcane plants for further processing. One or more knockdown rollers may be mounted at or near the front of the harvester in order to assist in aligning the plants for intake into the harvester. In certain harvesters, a front or upper knockdown roller may be oriented at a relatively forward and upward position, and a rear or lower knockdown roller may be oriented at a relatively rearward and downward position. Accordingly, as these harvesters move along a sugarcane field, sugarcane plants may be aligned for further processing by one or both of the upper knockdown roller and lower knockdown roller.

Adjustable knockdown rollers for sugarcane harvester


An air flow guide device for mounting on a heat dispensing fan includes a U-shaped frame and each of the three sides of the frame has a curve outer surface. A plate is connected between two distal ends of the frame and extends inclinedly from a top edge of the two distal ends of the frame, and a slot is defined between the two distal ends of the frame and the plate. Air flow smoothly flows over the curve smooth surfaces and is sucked by the fan. The plate prevents the exhausted air from being sucked by the fan.

The present invention relates to an air flow guide device mounted to a computer heat dispensing fan and includes three smooth surfaces to guide the air flows and a plate to prevent the exhausted air from being re-sucked in the fan.
A conventional heat dispensing fan for use in notebook computer is shown in FIGS. 1 and 2 and generally includes a casing 10 having a fan device 110 received therein and a top hole is defined in a top of the casing 10 so as to suck air therethrough. A side hole 120 is defined in one of four sides of the casing 10 so that the heat air is exhausted from the side hole 120. However, because the casing 10 has vertical four sides so that when the heat dispensing fan is installed in an air path 200 in the computer, the vertical walls are located at an right angle to the surface in the air path 200 and air flow could be stopped by the walls and there reducing the efficiency of the heat dispensing fan. In addition, the exhausted air released from the side hole 120 could be re-sucked again by the fan 110 and the air flow sucked into the casing will bounce back at the inside of the three closed walls so that the sucking force of the is reduced.
In accordance with one aspect of the present invention, there is provided an air flow guide device for mounting on a heat dispensing fan which includes a casing with a fan received therein and having a top hole and a side hole. The air flow guide device includes a U-shaped frame and each of the three sides of the frame had a curve outer surface. A plate is connected between two distal ends of the frame and extends inclinedly from a top edge of the two distal ends of the frame. A slot is defined between the two distal ends of the frame and the plate.
The primary object of the present invention is to provide a air flow guide device for mounting on the heat dispensing fan in computers wherein a plate extending from the guide device effectively prevents the exhausted air from being sucked by the fan again.
The present invention will become more obvious from the following description when taken in connection with the accompanying drawings which show, for purposes of illustration only, a preferred embodiment in accordance with the present invention.

Air flow guide device on heat dispensing fan

No. 6, East Section, Industrial Sixth Road


An adaptive backlight module and a method and system for producing an adaptive backlight module are described herein. In one example, an adaptive backlight module includes a light source, a polarizer, at least one enhancement film disposed between the light source and the polarizer, and a diffuser disposed between the light source and the enhancement film. The diffuser includes a first electrode coupled to a first substrate and a second electrode coupled to a second substrate. A liquid crystal layer is disposed between the first electrode and the second electrode of the diffuser.

Backlight units for display devices are often one of the largest draws on power consumption, causing battery endurance to be limited in mobile electronics. Often a large portion of the light exiting a display screen is not needed for a single user, and is vulnerable to being viewed by non-users in the line of sight. Many current privacy filters and films for laptops, monitors, and some mobile devices absorb light, thereby reducing energy efficiency of the device. Additionally, these current privacy filters and films are expensive, and are cumbersome in that they interfere with touch screen functionality and must be physically removed to enable wide-angle viewing of the display.
Thus, a need exists for techniques to reduce power consumption from the emission of excess light, and to provide privacy for a user.
To facilitate understanding, identical reference numerals have been used, where possible, to designate identical elements that are common to the figures. It is contemplated that elements and features of one embodiment may be beneficially incorporated in other embodiments without further recitation.

Energy efficient communication and display device


An upright display stand for mounting a hanging display tray erected from a corrugated paperboard blank. The display stand includes rectangular front panel having a locking slot for engagement of a transverse brace with the upper edge of the front panel including spaced apart notches for the engagement of hooks on the back of the hanging display tray. The display stand also includes a first integral side panel and a second integral side panel of generally triangular configuration and a rear panel. The upper end of the rear panel includes an integral brace section which folds downwardly and inwardly to engage the locking slot formed in the front panel to create the transverse brace. The display stand, when fully assembled, is generally rigid and stable and well suited to support a hanging display tray.

This invention relates generally to paperboard display apparatus and, more specifically, to a paperboard display having an upright base to support a paperboard tray, particularly a hanging display tray.
Generally speaking, paperboard display trays are known to the art. They can be used to display for viewing and/or sale a multitude of items or products from good stuffs to eyeglasses to toys or apparel. Hanging display trays have been employed which include a corrugated paperboard tray having plastic or metal hooks on the back. The hooks are used to hang the tray in a metal store fixture. Hence, the use of such hanging trays are limited to stores, for example, which have appropriate metal fixtures. These metal fixtures can be expensive and lack diversity.
In the past, attempts have been made to provide corrugated paperboard display bases to support the trays, thus eliminating the need for the metal fixtures. These prior paperboard bases generally are limited to the conventional A-frame design with a tuck top. However, this conventional design has several drawbacks. For example, such designs do not provide sufficient rigidity. Furthermore, they can be difficult and time consuming to fold into shape and set up.
Therefore, it would be advantageous to have a corrugated paperboard stand to support a display tray, the stand having improved rigidity while still being easy to erect.


Multilayer printed wiring boards are conventionally laminated using epoxy adhesives. When the boards are drilled, a residual smear often remains within the drilled holes. This smear prevents proper through plating of the holes and the layers are left without some of the intended interconnections. In the past, the residual smear was removed by wet etching. A technique is described using plasma etching with the conductive surface layers of the drilled boards as the electrodes to generate the plasma. The plasma forms directly within the holes and effectively removes the smear. A dielectric material in contact or close proximity to the perimeter of each board provides uniformity of treatment over the panels.

Multilayer printed wiring boards have added valuable new dimensions to printed circuit design. The design freedom resulting from the added crossover capability creates more compact and efficient packaging of complex circuits than is possible with the conventional two-sided board. Interconnection between levels, however, has also become a more complex problem than the simple plated-through interconnections on a single two-sided printed circuit board. A persistent difficulty is the smearing of the adhesive and dielectric that occurs when the multilayer board (MLB) is drilled. Smeared adhesive and dielectric materials that coat the sidewalls of the drilled holes prevent proper electrical contact between inner conducting layers when the holes are through-plated.
This problem is addressed by U.S. Pat. No. 4,012,307. The solution proposed there is to clean the holes, before plating, using a gas plasma cleaning technique. The plasma technique is represented to be superior in several respects to the chemical etching technique used earlier to attack the same problem.
We have verified that the use of plasma etching to remove adhesive and dielectric smear from the sidewalls of the holes in multilayer printed wiring boards does indeed have merit. We have found, however, that the process taught by the patent just mentioned can be improved upon significantly. That improvement is the subject of this patent.
According to the prior art, multilayer boards having holes with sidewalls coated with unwanted dielectric material are treated in a plasma chamber. The plasma formed within the chamber etches away the dielectric material and other contaminants. However, we have found that the use of the plasma chamber, according to the teachings of the prior art, leads in many cases to incomplete or ineffective removal of the dielectric material. We have determined that the major problem with the prior art etching system is the unreliable nonuniform and inefficient penetration of the plasma to the walls within the holes.
This realization led us to investigate a more efficient plasma configuration in which the plasma is shaped to the configuration of the boards through the use of a parallel plate electrode geometry. The advantages of this approach over the plasma chamber of the prior art (using ring electrodes mounted outside the cylindrical chamber) are the relatively short diffusion path from the electrodes to the MLB, the uniformity of the concentration of the etching gas over the surface of the MLB, and the greater control over the gas flow rate over that surface.
Experiments with the parallel plate configuration were promising and indicated that development along these lines would likely produce results superior to those obtained with the unshaped plasma of the plasma chamber. However, we were unsatisfied with our results using the parallel plate configuration. In several etching attempts, residual dielectric material still remained within the holes of the MLB after the plasma treatment.

Treating multilayer printed wiring boards

Bell Telephone Laboratories, Incorporated


A back-up ring for use in a liner top test tool for testing casing integrity in a wellbore is disclosed. The back-up ring is comprised of first and second ring elements that are biased apart by a compression springs. The first ring element has a plurality of radially extending flanges that cover a plurality of channels in the second ring element when the back-up ring is compressed against a seal element on the liner top test tool to seal the wellbore casing.

Oil and gas wells typically require boreholes that are drilled into the earth where zones of oil or gas will be encountered. A borehole is usually lined or cased with a heavy-weight steel pipe called casing that is secured in place in the well borehole by cement that is injected between the outer surface of the casing and the borehole. Depending upon the depth of the well, additional segments of smaller diameter casing, called liner pipe, are suspended in sequence from the pipe casing and each other to extend the casing of the well borehole. When liner pipe is so suspended, a gap is created between inner and outer surfaces of the succeeding adjoining liner pipe segments.
Once the liner pipe is suspended and set in place, heavy drilling mud in the well bore is used to contain any leak occurring between casing and liner. A liner seal is then installed between the top and bottom of adjoining segments of different diameter casing or liner pipe to pressure seal any annular joint spaces created between the upper and lower liner pipe segments. When such liner seals are placed in a wellbore casing or liner, it is important to pressure test the integrity of these seals before the heavy drilling mud is removed.
A liner top test tool is used to test the integrity of the liner seal. A typical liner top test tool will have a plurality of resilient annular seal plugs that are positioned on a back-up ring or rings and a mill-head restrained by shear pins that creates fluid passages or flow paths between the seal plug back-up rings and the mill-head.
For use the liner top test tool is positioned on a work-string and slowly lowered into the wellbore through the heavy drilling mud. The drill bit on the work-string serves as a guide until the liner top test tool comes in contact with the top of the lower liner. The mill-head is then rotated to loosen any extraneous cement or debris from the liner top and heavy mud is circulated into the work-string and out of the casing to carry and remove any loosened debris from the casing.
The work-string weight on the mill-head is then increased to shear the mill-head restraining pins. When the mill-head restraining pins are sheared, the mill-head is pushed against the seal back-up rings to squeeze the resilient seals against the top of the lower liner, block the flow paths between the seal plug back-up ring and the mill-head, and form a pressure seal between the liner top test tool and the casing. In most test procedures pressure on the seal will be from the top down.
When the liner top test tool is positioned at the top of the lower liner, the fluid force in the work-string and the casing are still in balance. The work-string and test tool are then raised a few feet above the liner top and a light fluid such as seawater is pumped into the work-string until the heavy mud is pushed to a few feet above the test tool. The pressure of the light fluid now balances the force of the heavy mud. The light fluid is then slowly bled down from work-string to a point where it is determined that the light fluid can contain well pressure and that there is no leak at the pressure seal between the liner top test tool and the casing. When such condition exists, the heavy mud is no longer needed to contain the well pressure. The liner top test tool may then be pulled up, the seals released, and the heavy mud may then be pumped out of the well.
A problem with previous liner top test tool seal back-up ring designs is the restricted fluid flow passages that are created between the test tool, with the seals and back-up rings, and the casing wall as the test tool, with the seals and back-up rings, is moved through heavy mud into or out of the casing. A restriction on the diameter of a tool is its "drift diameter". Drift diameter is a casing term determined by formula which gives the largest diameter tool that can be passed or run through a casing of a certain size/weight. It is common for tools to have drift diameters only 0.125 inches less than the interior diameter ("ID") of the of casing. In such a situation, only 0.062 inch gap would exist between the casing ID and back-up ring OD. This leaves a limited fluid flow passage.
The limited fluid flow passages or paths also limit the cross-sectional area provided to deliver high pressure on the seal as well as impede the mud flow needed to carry the debris out of the well. In performing such a seal test, it would be an advantage have a liner top test tool with back-up seal rings that would provide an increase in the fluid passage area between the back-up rings and the mill-head in order to produce a resulting increase in mud fluid flow rates and an increase in the seal test pressure rating.
Traditional seal back-up rings are one piece solid rings. These rings, when sized to maximum drift diameter, limit fluid flow over the back-up ring when the seal is not set. If the back-up ring is much smaller than the drift diameter the fluid flow over the ring increases but the chance of seal extrusion over the ring increases. At higher test pressures a seal can extrude over the edges of a back-up ring like oozing bubble gum.


Various embodiments provide an enhanced mobile computing experience by providing an input device in a mobile electronic device that is configured to accurately and quickly re-center a button or other user interface while providing a sensation of enhanced tactile feedback to a user. The biasing force of a magnetic re-centering mechanism is employed to overcome frictional forces acting on the button during its travel forwards and backwards and tilting to insure that the button is returned quickly and accurately to a resting position. The magnetic re-centering mechanism has a low profile, and permits the input device and the mobile electronic device within which the input device is disposed to have small form factors.

The optical mouse has been popular for controlling functions of computers and other electronic devices. The conventional optical mouse is too big and unsuitable for use in many portable electronic devices, however, such as personal digital assistants, telephones, and the like. Accordingly, other types of conventional input devices such as TOUCHPAD™ and THINPAD™ devices, and LOGITECH™ REVOLUTION™ mice, have been developed for use in portable electronic devices such as laptop computers, phones and the like. These input devices have become more important as portable electronic devices continue to incorporate additional functionality, such as electronic mail, wireless computing, photography and so on.
Conventional puck-based input devices are attractive for handheld electronic devices because of their low profile. In some conventional puck-based input devices, a resilient mechanism, such as a spring, is deployed in association with the puck to maintain a desired position of the puck. The resilient mechanism is arranged to bias the puck to return to a center position after the puck has been moved to an off-center position, in which the user captures a user input. Unfortunately, such mechanisms are subject to mechanical wear and tear over time, and susceptible to the ingress of debris and moisture potentially resulting in device failure. In rate control devices such as the IBM™ TRACKPOINT™ the position of the stick maps to the velocity of the cursor. For rate control devices, accurate re-centering is important because if the puck is not returned precisely to center, the cursor may drift when the user is not touching it. To work around this problem, these conventional input devices typically employ a sufficiently large central "dead zone," or use a very stiff restoring spring, both of which are detrimental to a good user experience. The NEUROPOINTER™ by NEC™ is an example of a conventional portable puck-based navigation device which uses a rubber membrane to re-center the puck. Because the membrane is essentially a linear spring, the re-centering accuracy is relatively poor.
Other conventional input devices attempt to address the accuracy of re-centering a puck with re-centering mechanisms having alternative force restoring force profiles. Unfortunately, these conventional input devices are too thick to fit in many portable electronic devices.
Users continue to demand more precision and accuracy in user input devices of portable electronic devices, while designers face continual pressure toward increasing miniaturization and increased functionality. Faced with these challenges, conventional input devices often fall short of market expectations by exhibiting inaccurate puck centering and positioning.
Further details concerning various aspects of prior art devices and methods are set forth in: (1) U.S. patent application Ser. No. 11/606,556 entitled "Linear Positioning Input Device" to Harley filed Nov. 30, 2006; (2) U.S. Provisional Patent Application Ser. No. 60/794,723 entitled "Linear Positioning Device" to Harley filed Apr. 25, 2006; (3) U.S. patent application Ser. No. 10/723,957 entitled "Compact Pointing Device" to Harley filed Nov. 24, 2003; (4) U.S. patent application Ser. No. 11/407,274 entitled Re-Centering Mechanism for an Input Device" to Orsley filed Apr. 19, 2006; (5) U.S. patent application Ser. No. 11/923,653 entitled "Control and Data Entry Apparatus" to Orsley filed Oct. 25, 2007, each of which is hereby incorporated by reference herein, each in its respective entirety.
What is need is a capacitive sensing input device that is capable of re-centering itself accurately and quickly, may be re-centered from both slide and tilt positions, has a small form factor, is more mechanically robust and less susceptible to the effects of wear and tear, may be fabricated as a sealed package that prevents the ingress of dirt and moisture, may be employed as a replacement mechanism for conventional 5-way navigation devices as well as mouse tilt-wheel mechanisms, and may be manufactured without undue cost or complexity.

Magnetic re-centering mechanism for a capacitive input device

Avago Technologies ECBU IP (Singapore) Pte. Ltd.


A control system for use in missiles and other projectiles which provides pitch, yaw and roll control. The control system includes two opposing pairs of flaps configured in the aft end of the missile case. Each flap is attached for rotation about its leading edge. Prior to actuation, the flaps conform to the exterior surface of the missile. Upon actuation, the flaps extend into the airstream to induce aerodynamic forces. The axis of rotation of each flap is positioned at an oblique angle to the radial plane of the missile.

1. The Field of the Invention
The present invention is related to a control system for providing pitch, yaw and roll control in a guided projectile. More particularly, the present invention is related to a finless missile control system which utilizes two pairs of opposing flaps to provide control.
2. Technical Background
Increased performance capabilities of tactical aircraft, sea-skimming missiles and other tactical weapons require the development of enhanced missile guidance and control systems to provide a defense to such armaments. Current technology in missile guidance and control systems includes the use of pulse motors and thrust vector control systems.
Pulse motors provide an efficient means of managing the energy of the missile while significantly enhancing missile performance and flexibility. Missiles utilizing pulse motors may be made to be highly maneuverable, particularly under high-g requirements, by incorporating a thrust vector control system in the missile. The terminal homing of a missile is one example of an application requiring a highly maneuverable missile.
Thrust vector control systems have been developed using a variety of means, including movable nozzles, jet tabs, jet vanes and injection of fluid into the nozzle. Of these systems, optimal performance is generally obtained through the use of a movable nozzle. Until recently, however, movable nozzles were not incorporated into small, tactical missiles because they could not be made sufficiently small and light. Recent developments in this area, including the development of advanced elastomeric materials and improved flexible bearing and trapped-ball designs, have yielded viable tactical missiles having vectorable nozzles.
Notwithstanding the availability of vectorable nozzles and pulse motors for use in tactical missiles, such missiles do continue to suffer from some performance limitations. One of the principal disadvantages accompanying the use of thrust vector control systems is that they are ineffective during coast periods. To address this problem, thrust vector control systems have been integrated with aerofins to achieve conventional four-axis aerofin control during coast periods.
The use of fins, however, can significantly reduce the number of missiles which can be packaged into a given cross section, such as the payload bay of an airplane or ship. Consequently, designs have been proposed which utilize flaps or panels which lie flush with the skin of the missile when not in use but which can be actuated to extend into the airstream to control the missile. Such flap systems are generally designed to provide pitch, yaw and roll control.
A significant disadvantage to the use of prior art flap designs is the difficulty in incorporating a design which effectively achieves roll control in addition to yaw and pitch control. In order to induce the aerodynamic forces necessary to provide roll control, the flaps must be capable of actuation at an angle, with one side of the flap extending into the airstream a greater distance than the other. Some designs address this problem by utilizing a triangular shaped flap mounted to the case with a pin joint. An actuator mounted on each side of the flap then provides the capability of actuating one side to a greater degree than the other side, thereby providing roll control. As will be appreciated by one of skill in the art, however, such designs require the use of complex and bulky actuation devices. In many cases, these actuation devices cannot be successfully implemented into a tactical missile while retaining the size and weight of the missile within a desirable range.
From the foregoing, it will be appreciated that it would be an advancement in the art to provide an effective control system which will provide pitch, roll and yaw control in a guided projectile. It would be a further advancement if such a control system would provide control even during coast periods.
It would be an additional advancement in the art if such a control system could be provided which did not utilize fins and which also avoided the use of complicated actuator systems generally necessitated by control systems utilizing flaps.
Such a control system is disclosed and claimed herein.


A thermally developable color photosensitive material comprises a support, having thereon a photosensitive silver halide, a binder, an electron transfer agent, an electron donor, and a reducible dye donating compound which is capable of being reduced and releasing a diffusible dye, wherein the reducible dye donating compound and a compound represented by the following formula (1) are present together in the form of an emulsified dispersion in the binder.

Thermally developable photosensitive materials are known, and thermally developable photosensitive materials and the processes involved have been described, for example, on pages 242-255 of Fundamentals of Photographic Engineering, Non-silver Salt Photography Section (published by Corona, 1982) and in U.S. Pat. No. 4,500,626.
In addition, methods for the formation of dye images by means of a coupling reaction between the oxidized form of a developing agent and couplers have been described, for example, in U.S. Pat. Nos. 3,761,270 and 4,021,240. Furthermore, methods for the formation of positive color images using a photosensitive silver dye-bleach system have been described, for example, in U.S. Pat. No. 4,235,957.
Methods in which diffusible dyes are released or formed in the form of an image by thermal development and in which the diffusible dyes are transferred to a dye fixing element have been proposed more recently. With these methods, it is possible to obtain both negative dye images and positive dye images by changing the type of dye donating compounds which are used or by changing the type of silver halide which is used. More details have been disclosed, for example, in U.S. Pat. Nos. 4,500,626, 4,483,914, 4,503,137 and 4,559,290, JP-A-58-149046, JP-A-60-133449, JP-A-59-218443, JP-A-61-238056, European Patent laid open 220746A2, Kokai Giho 87-6199 and European Patent laid open 210660A2. (The term "JP-A" as used herein signifies an "unexamined published Japanese patent application".)
Many methods have also been suggested for obtaining positive color images by thermal development. For example, a method has been proposed in U.S. Pat. No. 4,559,290, in which compounds for which so-called DDR compounds have been formed into a oxide form which has no dye releasing capacity and a reducing agent or precursor thereof are included, the reducing agent is oxidized in accordance with the exposure of the silver halide by thermal development, reduction is achieved with the remaining un-oxidized reducing agent and a diffusible dye is released. Furthermore, thermally developable photosensitive materials in which compounds which release diffusible dyes by a reductive cleavage of an N--X bond (where X represents an oxygen atom, a nitrogen atom or a sulfur atom) are used as compounds which release a diffusible dye via the same mechanism, have been disclosed in European Patent laid open 220746A and in Kokai Giho 87-6199 (Vol. 12 No. 22)
When photographically useful additives, such as dye donating compounds, which are insoluble in water are added to a photosensitive material such as those mentioned above, the addition is generally made by the method of emulsification and dispersion which is well known to those in this field. In the emulsification and dispersion method, the photographically useful additive is dissolved together with a high boiling point organic solvent in a low boiling point organic solvent, and the solution is added to an aqueous gelatin solution in the presence of an appropriate surfactant and emulsified and dispersed as an O/W type emulsion using an emulsifying machine such as a homogenizer for example, and such methods have been disclosed, for example, on pages 213-255 of Fundamentals of Photographic Engineering, Silver Salt Photography Section (published by Corona, 1978) and U.S. Pat. No. 2,322,027. Coating liquids which contain emulsions which have been prepared using the abovementioned method of emulsification and dispersion are not used immediately after preparation. Rather they are used after being kept warm and ageing after preparation. But when a coating liquid which has been kept warm and aged in this way is used, there are cases where large lumpy particles are formed by cohesion of the emulsion particles and by precipitation of the photographically useful additives which are insoluble in water such as the dye donating compounds for example, and spot-like defects are produced in the image and discrimination becomes poor.

Thermally developable color photosensitive materials with U.V. absorbers


A generator for fire retardant foam utilizes a foamable liquid in a fire hose terminating in a nozzle. The generator includes a housing having an inner chamber with a first entrance opening and a second exit opening. A moveable screen is disposed within the housing to aid in the generation of the foam. A connector is also employed for fastening the housing to the fire hose nozzle utilizing a plurality of hingable elements connected to the housing and a clamp for fixing the plurality of elements to the exterior of the fire hose.

The present invention relates to a novel fire retardant foam generator usable with a conventional fire hose nozzle.
Fire extinguishing materials include the use of water, and foam producing chemicals. Fire hoses normally deliver water under pressure received from a particular utility agency, or pressure provided by a pumping mechanism, such as a pumper truck.
Certain fires classified as class B and class C require extinguishing based on principles other than the cooling effect provided by water. For example, foam type extinguishing materials spread a layer of foam over burning material and extinguishes the fire by excluding oxygen. Similarly, fire extinguishing systems employ carbon dioxide, halogen, and the like to remove oxygen.
Foam materials have been applied to wildland types of fires by utilizing fire hoses and fire hose nozzles, generally employed with simple water delivery in conjunction with foam generating equipment. In this regard, U.S. Pat. Nos. 2,774,583 and 3,667,687 describe apparatuses for producing foams to fight fires which may be used with or in substitution for nozzles employed with large fire hoses.. Attention is also drawn to a foam making attachment for fire hose nozzles known as MX-Foamjet manufactured by Task Force Tips of Valparaiso, Ind. Prior art devices, however, are difficult to adapt to fire hose nozzles of different sizes. Such lack of universal fittings and connectors is often fatal during fire emergencies.
A fire retardant foam generator which is simple to manufacture, use, and adapt to existing fire hose nozzles would be a notable advance in the fire fighting field.


A Drywall tub device including a tub having sidewalls, endwalls, a bottom and a snap-down top, also including a belt attachment and three essential accessory attachments needed to perform the drywall task. The tub which includes the sidewalls, endwalls, bottom and a male snap-down locking tabs on each endwall is molded out of a thermoplastic compound or suitable substance. The hollow tub is used to hold a cleaning solution. The snap-down top is also molded from a thermoplastic compound or suitable substance having two female snap-locks molded into each endwall. The snap-down top's underside has a flexible rubber seal circumferencing the inside outer corner, for when locked into position this will prevent cleaning solution leakage. The snap-down top's underside middle has an attached square rubber piece open and slotted in its middle for holding and cleaning drywall taping knives. The holders used for all accessories; belt loop, screwdriver, tape and sheetrock knife is molded out a thermoplastic compound or suitable substance and attached to the tub device.

The invention relates to a new, original and practical cleaning and holding Drywall device that is attached to a Drywall Craftsman belt. Drywall Craftsman provide the skills needed to apply the compound cement and drywall tape over sheetrock seams, screw holes and corners. They prepare sheetrock walls to a finished state for painting, wallpapering, paneling, etc. Common problems Drywall Craftsman have during the procedure of drywalling is having all accessories on their person that are needed which include: various size drywall taping knives, water to keep the taping knives clean and moist for proper tool performance, a screwdriver that is needed for setting screws left above the surface, drywall tape used over sheetrock seams and corners, a sheetrock knife used for cutting excess sheetrock. Previously, a Drywall Craftsman would lose costly time locating the many accessories needed to perform the drywall task, such as, walking to and from a bucket of water to clean and moisten trowels, locating the many different sized drywall taping knives needed during the procedure and locating a screwdriver, drywall tape and sheetrock knives.
The instant invention provides the Drywall Craftsman with a device that is attached to his/her belt which enables the craftsman to carry on his/her person a tub with a snap-down lid to clean drywall taping knives through a rubber squeegee, and have attachments to hold all the accessories needed to perform the drywall task.


The present invention discloses a wrench rack comprising a main frame, two recess bases, a linkage member and a cover plate. Two recess bases are set on the main frame, and each recess base has a plurality of recesses defined on its front for handle portions of wrenches to be engaged. The linkage member links with the main frame and the cover plate respectively. When the cover plate covers up the front of the main frame, the wrenches are limited. When the cover plate is flipped to the rear of the main frame, the cover plate is able to sustain the main frame along with the stand of the main frame. Therefore, the stability of the holder to place wrenches can be improved and so can the flexibility for users.

According to the prior art of a wrench holder disclosed in U.S. Pat. No. 5,346,063, it comprises a flat main frame which has two pieces of plates protruded from its both sides on the front. There is a plurality of recesses symmetrically defined on the two plates for wrenches to be placed. Each opening of the recess has a hook, and the wrenches are prevented falling from the recesses by the hooks. There are certain disadvantages from the prior art:
1. Wrenches are not able to be firmly held in the recesses with only two plates and simple-designed recesses on the main frame.
2. The holder can only be laid down due to the flat design of the main frame. Because the wrench holder is not standable, it causes inconvenient for users to choose proper wrenches.
The present invention will become more obvious from the following description when taken in connection with the accompanying drawings which show, for purposes of illustration only, a preferred embodiment in accordance with the present invention.


A method for improving a purge conversion efficiency of a Lean NOx Trap coupled downstream of a lean-burn internal combustion engine is presented. This method proposes adjusting the purge air-fuel ratio of the device based on its temperature. According to the proposed method, a less rich air-fuel ratio is provided at lower operating temperatures to reduce hydrocarbon emissions since within this temperature range air-fuel ratio does not have a significant affect on NOx emissions. At mid-range operating temperatures, the air-fuel ratio is gradually decreased (made more rich) to reduce NOx emissions. And, finally, at high operating temperatures, HC and NOx emissions are reduced, and therefore, the purge air-fuel is kept at a constant more rich value. This method improves emission control and fuel economy during purge.

The present invention relates to a system and a method for controlling the air-fuel ratio in an internal combustion engine, and more particularly, to controlling the air-fuel ratio such that NOx and hydrocarbon emissions are reduced.
Internal combustion engines are typically coupled to an emission control device known as a three-way catalytic converter (TWC) designed to reduce combustion by-products such as carbon monoxide (CO), hydrocarbon (HC) and oxides of nitrogen (NOx). Engines can operate at air-fuel mixture ratios lean of stoichiometry, thus improving fuel economy. For lean engine operation, an additional three-way catalyst commonly referred to as a Lean NOx Trap (LNT), is usually coupled downstream of an upstream three-way catalyst. The LNT, like the upstream TWC, stores exhaust gas constituents such as, for example, nitrogen oxides, NOx, when the engine is operating at a lean air-fuel ratio, and reduces (purges) them when the engine is operating at a rich or stoichiometric air-fuel ratio.
Because continued lean operation will ultimately saturate the LNT with NOx, the prior art teaches periodically varying the air-fuel ratio from a nominally lean setting to a rich setting, during which stored NOx are released from the LNT and reduced by the available hydrocarbons and carbon monoxide in the enriched operating condition. However, during the purge, some of the exhaust gas constituents, such as NOx and HC are not reduced, and are emitted into the atmosphere.
The inventors herein have recognized that the amount of NOx and HC released during a purge is a function of the temperature of the LNT and the air-fuel ratio of the purge mixture. In other words, the inventors have recognized that when the LNT operating at lower temperatures, the purge air-fuel ratio has little effect on NOx emissions, however, HC emissions increase with richer purge air-fuel ratios. Further, the inventors herein have recognized that at higher LNT operating temperatures, NOx emissions reduce with richer purge air-fuel ratios, while HC emissions increase.
In solving the above problem, a system and a method are provided for decreasing emissions of exhaust gas constituents by selecting an optimum purge air-fuel ratio based on the operating temperature of the exhaust gas aftertreatment device.
In carrying out the above solution, features and advantages of the present invention, a system and a method for improving a conversion efficiency of an exhaust gas aftertreatment device coupled downstream of a lean-burn internal combustion engine during a NOx purge, include: providing a base rich air-fuel ratio of an exhaust gas mixture entering the device; adjusting said base air-fuel ratio so as to increase a first exhaust gas mixture component conversion efficiency when the device is in a first operating temperature range; and adjusting said base air-fuel ratio so as to increase a second exhaust gas mixture component conversion efficiency when the device is in a second operating temperature range.
An advantage of the present invention is improved emission control, due to the fact that selecting the most appropriate air-fuel ratio based on the temperature of the LNT reduces NOx and HC emissions during purge.


A mechanism for loading compact discs or similar rotary discs, in which two guide arms are rotatably mounted on a base plate symmetrically with respect to its center line and a disc detect arm is rotatably mounted on each guide arm. Each guide arm has a large-diametered disc holding portion for holding a large-diametered disc and a small-diametered disc holding portion for holding a small-diametered disc. Each guide arm is being applied a moment which reverses its direction when the guide arm passes a predetermined rotational angular position of the guide arm. The disc detect arm is being applied a moment in a direction in which a projection provided at its one end enters into the large-diametered disc holding portion and the other end of the disc detect arm slides in an L-shaped guide slot made in the base plate, thereby limiting the rotational movement of the disc detect arm and the rotational movement of the guide arm. In consequence, each guide arm is normally held in its locked state at a rotational angular position for receiving the small-diametered disc. When the large-diametered disc is loaded, it collides with the projections of the disc detect arms to turn them, by which the guide arms are each unlocked and permitted to turn to a rotational angular position for receiving the large-diametered disc.

The present invention relates to a novel rotary disc loading mechanism by which compact discs (hereinafter referred to as CDs), video discs, records, or similar rotary discs of different outer diameters can each be loaded substantially vertically with its center set at a predetermined position.
The spread and growth of CDs in recent years are amazing and their sales volume has already exceeded that of LP records. Besides standard 12 cm diameter CDs (playing for 60 minutes each side), 8 cm diameter single CDs (playing for about 20 minutes each side) have recently been placed on the market.
FIG. 1 shows in section the principal part of a conventional CD loading mechanism adapted to load a CD for driving in an upright position. A lid 2 is pivotally secured to a disc housing of a CD player. In this example the lid 2 has its lower portion bent inwardly just about 90 degrees and extended to form a bottom 2a, the end portion of which has at either side a through hole 2b extending therethrough in parallel to the major surface of the lid 2. The lid 2 is hingedly fixed to a case 1 or the like of the CD player by means of bolts (not shown) inserted into the through holes 2b. The lid 2 has a circular cavity 2c centrally thereof, the bottom of which has a centrally-disposed circular hole 2d made therein coaxially with the cavity 2c and a circumferential marginal portion 2e surrounding the hole 2d.
A hollow cylindrical magnet 3 is disposed in the circular hole 2d. A CD holding disc 4 and a presser disc S are mounted on the inside and outside of the magnet 3, respectively, and they are coaxially assembled together by means of a screw 6. The CD holding disc 4 has an outer diameter a little larger than that of the circumferential marginal portion 2e. The central portion of the disc 4 is truncated-cone-shaped and juts out into the hollow cylindrical magnet 3. The outer diameter of the presser disc 5 is smaller than the inner diameter of the circular cavity 2c but larger than the diameter of the circular hole 2d. The magnet 3 and the discs 4 and 5 attached to the both sides thereof constitute a bobbin-shaped CD holding unit 7, which has an engaging recess 8 corresponding to a winding space, for engagement with the circumferential marginal portion 2e.
A square base plate 9, which has a circular hole 9a centrally thereof, is screwed onto the inside of the lid 2 with spacers held therebetween. The circular hole 9a has an inner diameter a little larger than the outer diameter of the circumferential marginal portion 2e and is held coaxially therewith. The base plate 9 has, centrally of its lower marginal edge, an inwardly projecting arc-shaped disc support 9b formed integrally therewith and coaxially with the circular hole 9a. The distance between the center of the circular hole 9a and the inner peripheral surface of the disc support 9b is equal to the 6 cm radius of the standard CD.
With this conventional CD loading mechanism, the standard type 12 cm diameter CD indicated by 11 is loaded in the following manner. After opening the lid 2 outwardly, the CD 11 needs only to be inserted into the opening so that it slides down along the inner surface of the CD holding disc 4. The CD 11 is automatically guided onto the disc support 9b and set at a pre-determined position.
Then, upon closing the lid 2, the disc holding unit 7 partly pops out toward a turntable 12 by virtue of the magnetic force acting between the magnet 3 and the turntable 12; so that a circular recess 4a of the CD holding disc 4 receives a trapezoidal portion 12a of the turntable 12 through a center hole 11a of the CD 11. At the same time, the CD 11 thus put on the turntable 12 rises just about 1.5 mm along its trapezoidal portion 12a, and consequently, the lower marginal edge of the CD 11 slightly moves up from the disc support 9b. In this way, the CD 11 is gripped between the CD holding disc 4 and the turntable 12.
On the other hand, an 8 cm diameter small sized CD must be set on a 12 cm diameter adapter 12 such as shown in FIGS. 2A and 2B, for loading into the above-mentioned CD loading mechanism. As shown in FIGS. 2A and 2B, the adapter 12 is an about 2 mm thick doughnut-shaped disc which is made of synthetic resin and has an 8 cm diameter hole 14a centrally thereof. The adapter 14 has notches 14b cut therein at equiangular intervals with respect to the center of the hole 14a and extending therefrom in its circumferential direction so that CD gripping portions 14c are defined between the notches 14b and the hole 14a. On the inner peripheral surface of the central hole 14a adjacent each CD gripping portion 14c there are protrusively provided a pair of parallel, opposed lugs 14d and 14e, which define therebetween a groove 14f for receiving the marginal edge of the CD. The lug 14d is less protrusive than the lug 14 e.
The small-sized CD is set on the adapter 14 in the following manner. The first step is to press the marginal portion of the CD into the grooves of two of the three gripping portions 14c from the side of the lugs 14d, followed by urging the CD toward the inner peripheral surface of the hole 14a intermediate between the two gripping portions 14c, by which the base portions of the two gripping portions 14c are elastically deformed and, at the same time, the notches 14b are narrowed. Then, by removing the force to the CD while holding the marginal portion of the CD opposite the remaining groove 14f of the remaining gripping portion 14c, the first two gripping portions 14c are restored to their initial state, pressing the marginal edge of the CD into the groove 14f of the remaining gripping portion 14c. Thus the small-sized CD is elastically gripped at its marginal edge by the three gripping portions 14c of the adapter 14.
As described above, according to the conventional CD loading mechanism, the small-sized CD cannot be set directly thereon and must be present on an adapter for loading in a CD player, which is very troublesome. Furthermore, the adapter utilizes the elasticity of its material (synthetic resin) for mounting, dismounting and holding of the small-sized CD, but a play is liable to occur between the adapter and the small-sized CD due to a decrease in the elasticity of the material by aging, a warp of the adapter surface and wear of the grooves 14f of the gripping portions, and consequently, the adapter is short-lived.