Having -c(=x)-, Wherein X Is Chalcogen, Bonded Directly To Ring Carbon Of The Additional Six-membered Hetero Ring (e.g., Nicotinic Acid, Etc.) Patents (Class 544/365)
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Patent number: 6156752Abstract: This invention provides a compound of the formula (I): ##STR1## and its pharmaceutically acceptable salts, wherein A.sup.1 and A.sup.2 are each halo; R.sup.1 and R.sup.2 are independently C.sub.1-4 alkyl; R.sup.3 is substituted or unsubstituted, phenyl or naphthyl; Y is heterocyclic group selected from C.sub.5-10 azacycloalkyl, C.sub.6-10 diazacycloalkyl, C.sub.7-10 azabicycloalkyl and the like; and R.sup.4 is selected from (a) substituted or unsubstituted C.sub.1-8 alkyll; (b) substituted or unsubstituted amino; (c) substituted or unsubstituted C.sub.2-6 alkanoyl; (d) substituted or unsubstituted C.sub.3-8 cycloalkyl or C.sub.7-14 bicycloalkyl; (e) substituted or unsubstituted C.sub.5-10 azacycloalkyl or C.sub.6-10 diazacycloalkyl, and (f) substituted or unsubstituted C.sub.7-14 mono- or di-azabicycloalkyl. These compounds are useful for the treatment of medical conditions caused by bradykinin such as inflammation, cardiovascular disease, pain, etc.Type: GrantFiled: August 13, 1998Date of Patent: December 5, 2000Assignee: Pfizer IncInventors: Takafumi Ikeda, Mitsuhiro Kawamura, Yu-Ting Ge
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Patent number: 6150527Abstract: New compounds are disclosed for multimerizing immunophilins and proteins containing immunophilin or immunophilin-related domains.Type: GrantFiled: February 28, 1997Date of Patent: November 21, 2000Assignee: Ariad Pharmaceuticals, Inc.Inventors: Dennis A. Holt, Terence P. Keenan, Tao Guo, Edgardo Laborde, Wu Yang
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Patent number: 6136808Abstract: This invention relates to a taxane derivative represented by the following formula (1): ##STR1## (wherein A represents a substituted piperazino or piperidino group, X represents an alkyl, pyridyl, thienyl, furyl, cycloalkyloxy or the like and Y represents H or trialkylsilyl) and also to a drug containing the same.This compound has high solubility in water and also has excellent antitumor activities.Type: GrantFiled: March 16, 2000Date of Patent: October 24, 2000Assignee: Kabushiki Kaisha Yakult HonshaInventors: Atsuhiro Abe, Hideaki Shimizu, Seigo Sawada, Takanori Ogawa, Hiroshi Nagata
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Patent number: 6131226Abstract: A compound of formula (I) and its pharmaceutically acceptable salts, wherein A.sup.1 and A.sup.2 are each halo; X is direct bond, CH.sub.2, CO, O, S, S(O) or S(O).sub.2 ; R.sup.1 is selected from a variety of groups such as hydrogen; substituted or unsubstituted C.sub.1-4 alkyl; substituted or unsubstituted piperidinyl; substituted or unsubstituted C.sub.5-14 cycloalkyl, bicycloalkyl or tricycloalkyl; substituted or unsubstituted C.sub.7-14 azacyclo-, azabicyclo- or azatricyclo-alkyl; bicyclo C.sub.7-10 alkenyl; benzocyclo C.sub.5-7 alkyl; and heterocyclic; R.sup.2 is hydrogen, C.sub.1-4 alkyl, substituted or unsubstituted phenyl or heterocyclic; and R.sup.3 and R.sup.4 are each C.sub.1-5 alkyl.Type: GrantFiled: February 1, 1999Date of Patent: October 17, 2000Assignee: Pfizer Inc.Inventor: Takafumi Ikeda
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Patent number: 6133456Abstract: New compounds are disclosed for multimerizing immunophilins and proteins containing immunophilin or immunophilin-related domains. The compounds are of the formulaM.sup.1 --L--M.sup.2where M.sup.1 and M.sup.2 are independently moieties of the formula: ##STR1## in which B.sup.1, B.sup.2, B.sup.3, R.sup.1, R.sup.2, n, W, X and Y are as defined.Type: GrantFiled: February 28, 1997Date of Patent: October 17, 2000Assignee: ARIAD Gene Therapeutics, Inc.Inventors: Dennis A. Holt, Terence P. Keenan, Tao Guo, Edgardo Laborde, Wu Yang
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Patent number: 6133265Abstract: Amido, amino and sulfonamide substituted benzylamine derivatives useful in treating eating disorders have the formula ##STR1## where X.sub.1, X.sub.2, and X.sub.3, independently represent substituents of formula ##STR2## D=H, lower straight or branched chain alkyl having 1-6 carbon atoms, a methylene unit incorporated into a ring connected with G as in the cases of pyrrolidine, pyrrolidone, piperidine, and piperidone;E=O or H.sub.2 ;O=0 or 1;G=straight or branched chain lower alkyl having 1-6 carbon atoms, aryl, aryl substituted with halogen, straight or branched chain lower alkyl having 1-6 carbon atoms, heteroaryl--selected from the group consisting of 2-, 3-, or 4-pyridyl, 2-pyrazyl, 2-, or 3-thienyl, 2-pyrazinyl, 2-, 3-, or 4-quinolyl, 1-, 3-, or 4-isoquinolyl, 2-quinoxalyl, 3-, or 4-cinnolyl, said heteroaryl substituted with halogen, hydroxy, straight or branched chain lower alkyl having 1-6 carbon atoms, straight or branched chain lower alkoxy having 1-6 carbon atoms;and A, T and R.sub.1 -R.sub.Type: GrantFiled: July 18, 1997Date of Patent: October 17, 2000Assignee: Neurogen CorporationInventors: Charles A. Blum, Robert DeSimone, Alan Hutchison, John M. Peterson
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Aryl- and hetaryl-sulfonamide derivatives, their preparation and their use as endothelin antagonists
Patent number: 6133442Abstract: Compounds of formula I ##STR1## wherein R.sup.1 signifies phenyl, substituted phenyl or heterocyclyl;R.sup.2 signifies phenyl or substituted phenyl;R.sup.3 signifies hydrogen, lower-alkyl, cyano, carboxy, esterified carboxy, phenyl, substituted phenyl, heterocyclyl or a residue --CONR.sup.5 R.sup.6 or --NR.sup.5 COR.sup.7 ;R.sup.4 signifies hydrogen or lower-alkyl;R.sup.5 signifies hydrogen or a residue R.sup.7, andR.sup.6 signifies --(CH.sub.2).sub.m R.sup.7 ; orR.sup.5 and R.sup.6 together with the N atom associated with them signify a heterocyclic residue;R.sup.7 signifies phenyl, substituted phenyl, cycloalkyl, heterocyclyl, lower-alkyl, cyano-lower-alkyl, hydroxy-lower-alkyl, di-lower-alkylamino-lower-alkyl, carboxy-lower-alkyl, lower-alkoxycarbonyl-lower-alkyl, lower-alkoxycarbonylamino-lower-alkyl or phenyl-lower-alkoxycarbonyl;R.sup.a signifies hydrogen, lower-alkyl or hydroxy;R.sup.b signifies hydrogen or lower-alkyl;Z signifies hydroxy, amino or a residue --OR.sup.8, --OC(O)NHR.sup.8, --OC(O)OR.sup.Type: GrantFiled: March 5, 1999Date of Patent: October 17, 2000Assignee: Hoffmann-La Roche Inc.Inventors: Volker Breu, Kaspar Burri, Jean-Marie Cassal, Martine Clozel, Georges Hirth, Bernd-Michael Loffler, Marcel Muller, Werner Neidhart, Henri Ramuz -
Patent number: 6124283Abstract: New piperidinyl- or piperazinyl-substituted-1,2,3,4-tetrahydronaphthalene derivatives having the formula ##STR1## wherein X is N or CH;Y is NR.sub.2 CH.sub.2, CH.sub.2 --NR.sub.2, NR.sub.2 --CO, CO--NR.sub.2 or NR.sub.2 SO.sub.2 ;R.sub.1 is H, C.sub.1 -C.sub.6 alkyl or C.sub.3 -C.sub.6 cycloalkyl;R.sub.3 is C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl or (CH.sub.2).sub.n -aryl,where aryl is phenyl or a heteroaromatic ring containing one or two heteroatoms selected from N, O and S and which may be mono- or di-substituted;n is 0-4;as (R)-enantiomer, (S)-enantiomer or a racemate in the form of the free base or a pharmaceutically acceptable salt or hydrate thereof; a pharmaceutical formulation containing the compounds, use of the compounds in the treatment of 5-hydroxytryptamine mediated disorders, processes for the preparation of the compounds and intermediates for the preparation of the compounds.Type: GrantFiled: April 25, 1997Date of Patent: September 26, 2000Assignee: Astra AktiebolagInventors: Stefan Berg, Lennart Florvall, Svante Ross, Seth-Olov Thorberg
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Patent number: 6114335Abstract: The present invention relates to novel benzoylguanidine derivatives, processes for preparing them and their use in the preparation of pharmaceutical compositions.The novel benzoylguanidine derivatives correspond to general formula (I) ##STR1## which benzoylguanidine derivatives are useful in the treatment of ischemia.Type: GrantFiled: September 25, 1998Date of Patent: September 5, 2000Assignee: Boehringer Ingelheim KGInventors: Erich Buerger, Christian Eickmeier, Otto Roos
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Patent number: 6080767Abstract: The compounds according to the invention are substituted N-[(aminoiminomethyl or aminomethyl)phenyl]propyl amides of formula I herein which exhibit useful pharmacological activity and accordingly are incorporated into pharmaceutical compositions and used in the treatment of patients suffering from certain medical disorders. More especially, they are Factor Xa inhibitors. The present invention is directed to compounds of formula I, compositions containing compounds of formula I, methods for their preparation and their use, which are for treating a patient suffering from, or subject to, conditions which can be ameliorated by the administration of an inhibitor of Factor Xa.Type: GrantFiled: June 27, 1997Date of Patent: June 27, 2000Assignee: Aventis Pharmaceuticals Products Inc.Inventors: Scott I. Klein, Kevin R. Guertin, Alfred P. Spada
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Patent number: 6071915Abstract: This invention relates to a series of arylsubstituted piperazines, of Formula I ##STR1## pharmaceutical compositions containing them and intermediates used in their manufacture. The compounds of the invention selectively inhibit binding to the .alpha.-1a adrenergic receptor, a receptor which has been implicated in benign prostatic hyperplasia. As such the compounds are potentially useful in the treatment of this and other disease.Type: GrantFiled: May 8, 1998Date of Patent: June 6, 2000Assignee: Ortho-McNeil Pharmaceutical, Inc.Inventors: Linda Jolliffe, William Murray, Virginia Pulito, Allen Reitz, Xiaobing Li, Linda Mulcahy, Cynthia Maryanoff, Frank Villani
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Patent number: 6066651Abstract: Orally-active nipecotamide glycolamide ester derivatives of formula (I): ##STR1## are disclosed as useful in treating platelet-mediated thrombotic disorders.Type: GrantFiled: October 20, 1998Date of Patent: May 23, 2000Assignee: Ortho-McNeil Pharmaceutical, Inc.Inventor: William J. Hoekstra
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Patent number: 6046201Abstract: N-(12-Nitroxydodecyl)-6-(4-ethyl or isopropyl-1-piperazinyl)pyridine-3-carboxamide or physiologically acceptable salts thereof. The said compounds have excellent inhibiting activity of cerebral edema, especially ischemic cerebral edema, and inhibiting activity of delayed neuronal death (an inhibiting activity of Ca-influx in neuronal cells). Cerebral edema is a pathologic condition accompanying cerebrovascular disorders, especially the acute stage cerebrovascular disorders and then the compounds are useful as an inhibiting agent for cerebral edema or a therapeutic agent for cerebrovascular disorders. Moreover, because the compounds do hardly show a behavior suppressing action, which is considered to be side effect in treating cerebrovascular disorders at the acute stage, they are an excellent therapeutic agent for, in particular, the acute stage cerebrovascular disorders.Type: GrantFiled: July 15, 1998Date of Patent: April 4, 2000Assignee: Nisshin Flour Milling Co., Ltd.Inventors: Norio Oshida, Yoji Mimaki, Hiroaki Satoh, Shinji Yokoyama, Yukiko Muraki, Kazumi Nishimura, Tamiko Hamada, Einosuke Sakurai, Hiroshi Sakai, Toshiji Sugai, Tomomi Tonoike, Koichi Itoh
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Patent number: 6001836Abstract: A series of non-peptidergic antagonists of NPY have been synthesized and are comprised of cyanoguanidine derivatives of 4-phenyl-1,4-dihydropyridines of Formula (I). ##STR1## As antagonists of NPY-induced feeding behavior, these compounds are expected to act as effective anorexiant agents in promoting weight loss and treating eating disorders.Type: GrantFiled: May 26, 1998Date of Patent: December 14, 1999Assignee: Bristol-Myers Squibb CompanyInventors: Graham S. Poindexter, R. Thomas Swann, Marc A. Bruce, Mendi A. Morton, Yazhong Huang, Sing-Yuen Sit, James Guy Breitenbucher
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Patent number: 5972947Abstract: The present invention concerns new oxazolidinone derivatives, processes for their production as well as pharmaceutical agents containing these substances. The present invention concerns compounds of the general formula I ##STR1## in which the symbols have the meanings as listed in the claims.Type: GrantFiled: December 31, 1998Date of Patent: October 26, 1999Assignee: Roche Diagnostics GmbHInventors: Christos Tsaklakidis, Wolfgang Schafer, Liesel Dorge, Walter-Gunar Friebe, Angelika Esswein
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Patent number: 5972943Abstract: Pyridinecarboxamide derivatives of the formula ##STR1## (wherein n represents an integer of 14-18, and R represents a hydrogen atom or a straight or branched C.sub.1 -C.sub.4 alkyl group) or physiologically acceptable salts thereof. The compounds have excellent inhibiting activity of cerebral edema, especially ischemic cerebral edema, and inhibiting activity of delayed death of neuronal cells (an inhibiting activity of Ca-influx in neuronal cells). Cerebral edema is a pathologic condition accompanying cerebrovascular disorders, especially the acute stage of cerebrovascular disorders and then the compounds are useful as an agent for inhibiting cerebral edema or a therapeutic agent for cerebrovascular disorders. Moreover, the compounds have no hypotensive action which is considered to be side-effect in treating the acute stage cerebrovascular disorders and hardly show a behavior suppressing action so that they are an excellent therapeutic agent for, in particular, the acute stage cerebrovascular disorders.Type: GrantFiled: July 20, 1998Date of Patent: October 26, 1999Assignee: Nisshin Flour Milling Co., Ltd.Inventors: Norio Oshida, Yoji Mimaki, Hiroaki Satoh, Shinji Yokoyama, Yukiko Muraki, Kazumi Nishimura, Tamiko Hamada, Einosuke Sakurai, Hiroshi Sakai, Toshiji Sugai, Tomomi Tonoike, Koichi Itoh
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Patent number: 5968929Abstract: The invention relates to compounds of the formula ##STR1## wherein Z, R.sub.c, y, m, u, Ar.sub.2, n, X, R.sub.c', l and Ar.sub.2 are as described herein. These compounds are neurokinin antagonists. These compounds are useful in the treatment of chronic airway diseases such as asthma.Type: GrantFiled: October 28, 1997Date of Patent: October 19, 1999Assignee: Schering CorporationInventors: David J. Blythin, Xiao Chen, Richard J. Friary, Kevin D. McCormick, John J. Piwinski, Neng-Yang Shih, Ho-Jane Shue
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Aryl- and hetaryl-sulfonamide derivatives, their preparation and their use as endothelin antagonists
Patent number: 5962682Abstract: Compounds of formula (I) ##STR1## wherein R.sup.1 signifies phenyl, substituted phenyl or heterocyclyl; R.sup.2 signifies phenyl or substituted phenyl; R.sup.3 signifies hydrogen, lower-alkyl, cyano, carboxy, esterified carboxy, phenyl, substituted phenyl, heterocyclyl or a residue --CONR.sup.5 R.sup.6 or --NR.sup.5 COR.sup.7 ; R.sup.4 signifies hydrogen or lower-alkyl; R.sup.5 signifies hydrogen or a residue R.sup.7, and R.sup.6 signifies --(CH.sub.2).sub.m R.sup.7 ; or R.sup.5 and R.sup.6 together with the N atom associated with them signify a heterocyclic residue; R.sup.7 signifies phenyl, substituted phenyl, cycloalkyl, heterocyclyl, lower-alkyl, cyano-lower-alkyl, hydroxy-lower-alkyl, di-lower-alkylamino-lower-alkyl, carboxy-lower-alkyl, lower-alkoxycarbonyl-lower-alkyl, lower-alkoxycarbonylamino-lower-alkyl or phenyl-lower-alkoxycarbonyl; R.sup.a signifies hydrogen, lower-alkyl or hydroxy; R.sup.b signifies hydrogen or lower-alkyl; Z signifies hydroxy, amino or a residue --OR.sup.8, --OC(O)NHR.sup.Type: GrantFiled: August 18, 1997Date of Patent: October 5, 1999Assignee: Hoffmann-La Roche Inc.Inventors: Volker Breu, Kaspar Burri, Jean-Marie Cassal, Martine Clozel, Georges Hirth, Bernd-Michael Loffler, Marcel Muller, Werner Neidhart, Henri Ramuz -
Patent number: 5962456Abstract: An N-acylpiperazine derivative or a salt thereof expressed by the following formula 1: ##STR1## wherein R.sub.1 represents a pyridylcarbonyloxy lower alkyl group, a benzoylamino lower alkyl group, benzyl group, carbamoyl group, pyridyl group, or diphenylmethyl group;R.sub.2 represents a lower alkyl group or a lower alkoxy group;n represents an integer of 0 to 2;R.sub.3 represents a hydrogen atom, an alkenyl group, or benzyl group; andm represents an integer of 1 to 3.The N-acylpiperazine derivative or a salt thereof has an anti-ulcer effect, an antibacterial activity against Helicobacter pyroli, and high safety to be available for prevention or cure of various ulcers.Type: GrantFiled: September 29, 1997Date of Patent: October 5, 1999Assignee: Shiseido Co., Ltd.Inventors: Chikao Nishino, Fumitaka Sato, Hirotada Fukunishi
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Patent number: 5935958Abstract: Di-N-substituted piperazine or 1,4-di-substituted piperidine compounds in accordance with formula I (including all isomers, salts, esters, and solvates) ##STR1## wherein Q, n, R, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.21, R.sup.27, R.sup.28, X, and Z are as defined herein are muscarinic antagonists useful for treating cognitive disorders such as Alzheimer's disease. Pharmaceutical compositions and methods of preparation are also disclosed. Also disclosed are synergistic combinations with acetyl-cholinesterase inhibitors of compounds capable of enhancing acetylcholine release and having the above formula.Type: GrantFiled: June 26, 1997Date of Patent: August 10, 1999Assignee: Schering CorporationInventors: Joseph A. Kozlowski, Derek B. Lowe, Wei K. Chang, Sundeep Dugar
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Patent number: 5929077Abstract: Inhibition of farnesyl transferase, which is an enzyme involved in ras oncogene expression, is effected b ##STR1## its enantiomers, diastereomers, and pharmaceutically acceptable salts and solvates thereof.Type: GrantFiled: October 17, 1997Date of Patent: July 27, 1999Inventor: Katerina Leftheris
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Patent number: 5919777Abstract: The present invention relates to novel compounds of the general formula I ##STR1## which can be used for treating medical disorders resulting from a deficiency in growth hormone.Type: GrantFiled: April 23, 1997Date of Patent: July 6, 1999Assignee: Novo Nordisk A/SInventors: Thomas Kruse Hansen, Bernd Pesche, Knud Erik Andersen
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Patent number: 5900486Abstract: N-Benzylazolium derivatives of the general formula (I), ##STR1## wherein Q is the remainder of an azole compound of the formula II ##STR2## possessing antifungal activity; Z is nitrogen or methine;R.sup.1 and R.sup.2 are each independently a hydrogen atom or a group --OY ?in which Y is a group easily hydrolyzable under physiological condition!;R.sup.3 and R.sup.4 are each independently a hydrogen or halogen atom, lower alkyl, lower alkoxy, lower alkylthio, (lower alkylcarbonyl)thiomethyl, carboxy or methoxycarbonyl; andX.sup.- is a pharmaceutically acceptable anion,as well as salts, hydrates or solvates of the compounds of the general formula (I) have antifungal properties.Type: GrantFiled: September 9, 1997Date of Patent: May 4, 1999Assignee: Hoffmann-La Roche Inc.Inventors: Shigeyasu Ichihara, Chikako Murasaki, Noriko Ohga, Jun Ohwada, Daisuke Sawada, Nobuo Shimma, Michio Shirai, Isao Umeda
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Patent number: 5891877Abstract: Diketopiperazines of the formula ##STR1## where one or both of R.sub.1 and R.sub.2, which are different, are chosen from X and a phenyl group substituted by X, C(O)X, OC(O)CH.sub.2 X, OCH.sub.2 CH.sub.2 X, CH.sub.2 X, CONH(CH.sub.2).sub.n X, O(CH.sub.2).sub.n CH(OH)(CH.sub.2).sub.n X ##STR2## and, where appropriate, the other of R.sub.1 and R.sub.2 is a phenyl group optionally substituted by one or more groups selected from halogen, nitro, methoxy, NHC(O)R.sub.12, CO.sub.2 H, O(CH.sub.2).sub.n N(R.sub.12 R.sub.13), C.sub.1 -C.sub.4 alkyl and (CH.sub.2).sub.n C(O)OR.sub.12 ; X is a five- or six-membered heterocyclic ring selected from the group consisting of pyridyl, imidazolyl, furyl, pyrrolyl, pyrrolidinyl, thienyl, piperazinyl, piperidinyl, morpholinyl, quinolyl, isoquinotyl and indolyl, the heteroatom(s) of the said heterocyclic ring, when nitrogen, being optionally substituted by hydrogen, methyl, oxygen, tertiary-butyloxycarbonyl, or SO.sub.Type: GrantFiled: September 25, 1996Date of Patent: April 6, 1999Assignee: Xenova LimitedInventors: Stephen James Brocchini, Justin Stephen Bryans, Adrian John Folkes, Christopher John Latham, Julie Elizabeth Brumwell
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Patent number: 5892037Abstract: The invention relates to compounds obtainable by polymerization of esters or phenol ethers of the formula V ##STR1## and/or of the formula VI ##STR2## in which m and n are each 0 or 1, and A, E, R.sup.1 to R.sup.6 and X are as defined in claim 1, and up to 50 mol % of other, ethylenically unsaturated compounds. The homopolymers and copolymers according to the invention can advantageously be employed for the stabilization of organic polymers against the harmful effect of light, oxygen and/or heat.Type: GrantFiled: March 12, 1996Date of Patent: April 6, 1999Assignee: Ciba Specialty Chemicals CorporationInventor: Alfred Steinmann
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Patent number: 5869488Abstract: The invention relates to compounds of the formula ##STR1## wherein Z, R.sub.c, y, m, u, Ar.sub.2, n, X, R.sub.c', I and Ar.sub.2 are as described herein. These compounds are neurokinin antagonists. These compounds are useful in the treatment of chronic airway diseases such as asthma.Type: GrantFiled: August 29, 1996Date of Patent: February 9, 1999Assignee: Schering CorporationInventors: Ho-Jane Shue, Neng-Yang Shih, David J. Blythin, Xiao Chen, John J. Piwinski, Kevin D. McCormick
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Patent number: 5863913Abstract: An aromatic compound of the formula (I): ##STR1## specifically, for example, 3-??(4-carboxyphenyl)methyl!valeramido!-4-dimethylaminobenzoic acid 4'-methylpiperazide, or a salt thereof, and a pharmaceutical composition comprising said aromatic compound or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent which provides sufficiently effective alleviation of renal dysfunction without affecting blood pressure at a low blood concentration.Type: GrantFiled: May 15, 1997Date of Patent: January 26, 1999Assignee: Kureha Chemical Industry Co., Ltd.Inventors: Mikiro Yanaka, Hiroyuki Enari, Toru Yamazaki, Hiroshi Maruoka, Toshikazu Dewa, Fuyuhiko Nishijima, Hiroshi Takahashi, Michihito Ise
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Patent number: 5861402Abstract: A compound of the formula: ##STR1## and its pharmaceutically acceptable salts, wherein A.sup.1 and A.sup.2 are each halo or H; X.sup.1 is CH.sub.2, CO, SO or SO.sub.2 ; X.sup.2 is CH.sub.2 or CO; Y is piperazinyl-(CH.sub.2).sub.n --, 2,3,4,5,6,7-hexahydro-1H-1,4-diazepinyl-(CH.sub.2).sub.n --or --N(R.sup.5)--(CH.sub.2).sub.n -- wherein R.sup.5 is H or C.sub.1-4 alkyl, and n is 0, 1, 2, 3, or 4; R.sup.1 is selected from the following: (a) N-morpholino-C.sub.1-4 alkylphenyl, C.sub.1-4 alkoxycarbonyl, C.sub.2-5 acyl, dihydroimidazolyl, formamidino, guanidino or dihydroimidazolylamino, etc.; (b) hydrogen, C.sub.1-4 alkyl, etc.; (c) piperidinyl; (d) C.sub.5-14 cycloalkyl, bicycloalkyl or tricycloalkyl; (e) C.sub.7-14 azacyclo-, azabicyclo- or azatricyclo-alkyl; and (f) C.sub.7-10 bicycloalkenyl, benzo C.sub.5-7 cycloalkyl or heterocyclic, etc., with proviso that when Y is piperazinyl, at least one of A.sup.1 and A.sup.2 is H; X.sup.2 is CH.sub.2 ; and/or R.sup.1 is a group selected from group (a); R.sup.Type: GrantFiled: January 31, 1997Date of Patent: January 19, 1999Assignee: Pfizer Pharmaceuticals, Inc.Inventor: Takafumi Ikeda
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Patent number: 5859011Abstract: Compound of formula (1) and their pharmaceutically acceptable salts wherein A1,A2,R1, R2,R3,R4,X are as defined in the specification have excellent bradykinin antagonistic activity.Type: GrantFiled: July 1, 1997Date of Patent: January 12, 1999Assignee: Pfizer Inc.Inventors: Fumitaka Ito, Hiroshi Kondo, David L. Hageman, John A. Lowe, III, Susumu Nakanishi, Fredric J. Vinick
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Patent number: 5856328Abstract: A circulatory disorder improving agent comprising, as an active ingredient, a dihydropyridine derivative of the formula (I) ##STR1## or an acid addition salt thereof. Said circulatory disorder improving agent is particularly useful as an organ circulation disorder improving agent or peripheral circulation improving agent.Type: GrantFiled: August 20, 1997Date of Patent: January 5, 1999Assignee: The Green Cross CorporationInventors: Hiroshi Shinyama, Toru Kawamura, Minori Okita, Takeshi Uchida, Masahiro Watanabe
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Patent number: 5849912Abstract: A biphenyl derivative represented by the following formula (I) or a pharmacologically acceptable salt thereof: ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are defined in the specification, is clinically useful for treating and ameliorating mental disorders such as cerebrovascular disorder, aggressive behavior due to senile dementia, mental excitation, poriomania, delirium, hallucination, hyperkinesia, schizophrenia, emotional disturbance, depression, neurosis, psychophysiologic disorder and anxiety neurosis. The compounds exhibit dopamine 2 receptor antagonism and/or serotonin 2 receptor antagonism.Type: GrantFiled: May 12, 1997Date of Patent: December 15, 1998Assignee: Eisai Co., Ltd.Inventors: Kozo Akasaka, Masahiro Yonaga, Akiharu Kajiwara, Kunizo Higurashi, Kohshi Ueno, Satoshi Nagato, Makoto Komatsu, Noritaka Kitazawa, Masataka Ueno, Yoshiharu Yamanishi, Yoshimasa Machida, Yuki Komatsu, Naoyuki Shimomura, Norio Minami, Toshikazu Shimizu, Atsushi Nagaoka
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Patent number: 5849745Abstract: A compound of formula (I): ##STR1## In which: R.sub.1 represents linear or branched (C.sub.1 -C.sub.6) alkyl,X represents oxygen or sulfur,R.sub.2 represents optionally substituted alkyl, alkoxy, optionally substituted phenyl, optionally substituted cycloalkyl, 4-(2,3-dithiacyclopent-1-yl)butyl, pyridyl or optionally substituted amino or any one of the groups as defined in the description,R.sub.3 represents hydrogen or cycloalkyl, formyl, optionally substituted phenyl, pyridyl or optionally substituted alkyl,the isomers thereof, the addition salts thereof with a pharmaceutically acceptable acid or base, and medicinal compounds containing them are useful for the treatment of chronic or cellular ischemia.Type: GrantFiled: December 15, 1997Date of Patent: December 15, 1998Assignee: ADIR et CompagnieInventors: Michel Wierzbicki, Marie-Fran.cedilla.oise Boussard, Serge Labidalle, Daniel Guyot, Yves Rolland, Jean-Paul Tillement, Bernard Testa, Aime Crevat
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Patent number: 5834471Abstract: Novel amide derivatives, processes for their preparation, and pharmaceutical compositions containing them are disclosed.Type: GrantFiled: February 2, 1996Date of Patent: November 10, 1998Assignee: SmithKline Beecham p.l.c.Inventors: David Malcolm Duckworth, Sarah Margaret Jenkins, Andrew John Jennings
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Patent number: 5817677Abstract: 5-Membered heterocyclic compounds, of which the following compounds are exemplary:(a) 4-??trans-4-(2-carboxyethyl)cyclohexyl!aminocarbonyl!-1-(4-piperidyl)imida zole,(b) 5-??trans-4-(2-carboxyethyl)cyclohexyl!aminocarbonyl!-4-methyl-2-(4-piperi dyl)-1,3-thiazole,(c) 5-??4-(carboxymethoxy)phenyl!aminocarbonyl!-4-methyl-2-(4-piperidyl)-1,3-t hiazole,(d) 5-??trans-4-(2-carboxyethyl)cyclohexyl!aminocarbonyl!-2-(4-piperidyl)-1,3, 4-thiadiazole,(e) 5-??4-(carboxymethoxy)phenyl!aminocarbonyl!-2-(4-piperidyl)-1,3,4-thiadiaz ole,(f) 5-??trans-4-(carboxymethoxy)cyclohexyl!aminocarbonyl!-2-(4-piperidyl)-1,3- thiazole,(g) 5-??4-(carboxymethoxy)phenyl!aminocarbonyl!-2-(4-piperidyl)-1,3-thiazole,(h) 5-??trans-4-(2-carboxyethyl)cyclohexyl!aminocarbonyl!-2-(4-piperidyl)-1,3- thiazole, and(i) 4-??trans-4-carboxycyclohexyl!aminocarbonyl!-1-?2-(4-piperidyl)ethyl!imida zole.Type: GrantFiled: October 18, 1996Date of Patent: October 6, 1998Assignee: Dr. Karl Thomae GmbHInventors: Gunter Linz, Frank Himmelsbach, Helmut Pieper, Volkhard Austel, Brian Guth, Johannes Weisenberger
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Patent number: 5807853Abstract: A method of inhibiting Ras function and therefore inhibiting the abnormal growth of cells is disclosed. The method comprises the administration of a compound of Formula 1.0: ##STR1## to a biological system. In particular, the method inhibits the abnormal growth of cells in a mammal such as a human being. Novel compounds of formulas 5.0, 5.1 and 5.2, wherein R is --C(R.sup.20)(R.sup.21)(R.sup.46), and 5.3, 5.3A and 5.3B, wherein R is --N(R.sup.25)(R.sup.48), are disclosed. Also disclosed are processes for making 3-substituted compounds of Formulas 5.0, 5.1, 5.2 and 5.3. Further disclosed are novel compounds which are intermediates in the process for making 3-substituted compounds of Formulas 5.0, 5.1, 5.2 and 5.3.Type: GrantFiled: May 25, 1995Date of Patent: September 15, 1998Assignee: Schering CorporationInventors: W. Robert Bishop, Ronald J. Doll, Alan K. Mallams, F. George Njoroge, Joanne M. Petrin, John J. Piwinski, Ronald L. Wolin, Arthur G. Taveras, Stacy W. Remiszewski
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Patent number: 5773442Abstract: Disclosed are benzamidine derivatives of the following general formula (I), salts thereof, hydrates thereof or solvates thereof, and pharmaceutical compositions comprising the derivatives, salts thereof, hydrates thereof or solvates thereof along with pharmaceutically-acceptable carriers. ##STR1## The derivatives and their compositions have GPIIb/IIIa receptor antagonistic activity and are useful for the treatment and prophylaxis of vascular system disorders as medicines for ameliorating ischemic cardiac disorders, adminicula in cardiosurgery operations or in vascular surgery operations, medicines for ameliorating cerebrovascular disorders, and medicines for ameliorating peripheral artery disorders.Type: GrantFiled: August 4, 1997Date of Patent: June 30, 1998Assignee: Yamanouchi Pharmaceutical Co., Ltd.Inventors: Seijiro Akamatsu, Yuzo Matsumoto, Masato Ichihara, Tomihisa Kawasaki, Seiji Kaku, Isao Yanagisawa
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Patent number: 5750702Abstract: The present invention encompasses structures of the formula: ##STR1## or the pharmaceutically acceptable non-toxic salts thereof wherein: ##STR2## wherein: W represents substituted or unsubstituted phenyl;X is hydrogen, hydroxy or lower alkyl;T is hydrogen, halogen, hydroxy, nitro, amino or alkyl;R.sub.3 is hydrogen or an organic group;R.sub.4 is hydrogen or substituted or unsubstituted organic substituent;R.sub.5 and R.sub.6 represent organic, and inorganic substituents; andn is 1, 2, 3, or 4,which compounds are highly selective agonists, antagonists or inverse agonists for GABAa brain receptors or prodrugs of agonists, antagonists or inverse agonists for GABAa brain receptors. These compounds are useful in the diagnosis and treatment of anxiety, sleep and seizure disorders, overdose with benzodiazepine drugs and for enhancement of memory.Type: GrantFiled: July 16, 1996Date of Patent: May 12, 1998Assignee: Neurogen CorporationInventors: Pamela Albaugh, Alan Hutchison
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Patent number: 5700801Abstract: Piperazine derivatives useful in the treatment or prevention of inflammation, bone degradation, thrombosis and tumor metastasis. Exemplary species are:(a) ?4-trans-?3-?4-(4-Pyridyl)-piperazin-1-yl!propionyl!amino!-cyclohexanecarb oxylic acid,(b) 3-?4-trans-?4-(4-Pyridyl)-piperazin-1-yl!carbonylamino!-cyclohexylpropioni c acid,(c) 3-?4-trans-?4-(4-Pyridyl)-piperazin-1-yl!malonylamino!cyclohexylcarboxylic acid,(d) Methyl ?4-trans-?3-?4-(4-pyridyl)-piperazin-1-yl!-propionyl!-amino!cyclohexane carboxylate,(e) Methyl 3-?4-trans-?4-(4-pyridyl)-piperazin-1-yl!-carbonylamino!cyclohexyl propionate,(f) Methyl ?4-trans-?4-(4-pyridyl)-piperazin-1-yl!-malonylamino!-cyclohexyl carboxylate,(g) Cyclohexyl ?4-trans-??4-(4-pyridyl)-piperazin-1-yl!-acetyl!-amino!-cyclohexane carboxylate, and(h) Isobutyl ?4-trans-??4-(4-pyridyl)-piperazin-1-yl!-acetyl!-amino!-cyclohexane carboxylate.Type: GrantFiled: December 13, 1995Date of Patent: December 23, 1997Assignee: Karl Thomae, GmbHInventors: Helmut Pieper, Volkhard Austel, Frank Himmelsbach, Gunter Linz, Brian Guth, Johannes Weisenberger
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Patent number: 5691339Abstract: A circulatory disorder improving agent comprising, as an active ingredient, a dihydropyridine derivative of the formula (I) ##STR1## or an acid addition salt thereof. Said circulatory disorder improving agent is particularly useful as an organ circulation disorder improving agent or peripheral circulation improving agent.Type: GrantFiled: April 21, 1995Date of Patent: November 25, 1997Assignee: The Green Cross CorporationInventors: Hiroshi Shinyama, Toru Kawamura, Minori Okita, Takeshi Uchida, Masahiro Watanabe
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Patent number: 5688795Abstract: The present invention relates to novel .alpha..sub.1 -adrenoceptor antagonists of Formula I: ##STR1## in which: p is 0 or 1;t is 0, 1 or 2;X is O, S or NR.sup.6 (in which R.sup.6 is hydro or (C.sub.1-6)alkyl);Y and Z are independently CH or N;R.sup.1 is hydro, hydroxy, halo, nitro, amino, cyano, (C.sub.1-4)alkylthio, acetylamino, trifluoroacetylamino, methylsulfonylamino, (C.sub.1-6)alkyl, (C.sub.3-6)cycloalkyl, (C.sub.3-6)cycloalkyl (C.sub.1-4)alkyl, oxazol-2-yl, aryl, heteroaryl, aryl (C.sub.1-4)alkyl, heteroaryl (C.sub.1-4)alkyl, (C.sub.1-6)alkyloxy, (C.sub.3-6)cycloalkyloxy, (C.sub.3-6)cycloalkyl (C.sub.1-4)alkyloxy, 2-propynyloxy, aryloxy, heteroaryloxy, aryl (C.sub.1-4)alkyloxy or heteroaryl (C.sub.1-4)alkyloxy (wherein alkyl is optionally substituted with one to three halo atoms and aryl or heteroaryl is optionally substituted with one to two substituents independently selected from halo and cyano);R.sup.2 is hydro, hydroxy, halo, cyano, (C.sub.1-6)alkyl or (C.sub.Type: GrantFiled: November 8, 1994Date of Patent: November 18, 1997Assignee: Syntex (U.S.A.) Inc.Inventors: Jurg Roland Pfister, David Ernest Clarke, Todd Richard Elworthy, David John Morgans, Jr., David Bruce Repke, Eric Brian Sjorgren, Helen Yen-hui Wu
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Patent number: 5686609Abstract: The invention relates to compounds of the formula ##STR1## in which: m is 2 or 3;Ar and Ar' independently are a thienyl group; a substituted or unsubstituted phenyl group; or an imidazolyl group; it also being possible for Ar' to be a benzothienyl group which is unsubstituted or substituted by a halogen; a naphthyl group which is unsubstituted or substituted by a halogen; a biphenyl group; or a substituted or unsubstituted indolyl;X is hydrogen;X' is hydrogen or a hydroxyl group or is joined to X" below to form a carbon-carbon bond, or X and X' together form an oxo group or a dialkylaminoalkoxyimino group of the formula .dbd.N--O--(CH.sub.2).sub.p --Am, in which p is 2 or 3 and Am is a dialkylamino group;Y is a nitrogen atom or a group C(X"), in which X" is hydrogen or forms a carbon-carbon bond with X';Q is hydrogen, a C.sub.1 -C.sub.4 alkyl group or an aminoalkyl group of the formula --(CH.sub.2).sub.Type: GrantFiled: March 11, 1994Date of Patent: November 11, 1997Assignee: SanofiInventors: Xavier Emonds-Alt, Pierre Goulaouic, Vincenzo Proietto, Didier Van Broeck
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Patent number: 5686454Abstract: The invention is directed to a series of novel compounds of the formula ##STR1## where Y is carbonyl or sulfonyl; R.sup.7 and R.sup.8 are alkyl, or R.sup.7 and R.sup.8, together with the carbon to which they are attached, form a C.sub.3-6 carbocyclic ring; R.sup.9 and R.sup.10 are each independently selected from hydrogen, hydroxyl, oximido, methyl, carboxyl, carboxyalkyl, unsubstituted or substituted alkoxycarbonyl, alkylcarbonyloxyalkyl, cyanoalkyl, hydroxyalkyl or unsubstituted amino; R.sup.11 is hydrogen, oxo, --N(R.sup.12)--CO--R.sup.13 or --CO--N(R.sup.14)--R.sup.15 ; R.sup.12 is hydrogen or unsubstituted or substituted alkyl; R.sup.13 is alkoxyl, unsubstituted or substituted heterocyclic rings selected from ##STR2## or unsubstituted or substituted alkyl; and R.sup.14 and R.sup.15 are each independently selected from hydrogen or unsubstituted or substituted alkyl. The Y moiety cannot be bonded to the camphor ring at the 3 or 6 positions.Type: GrantFiled: January 16, 1996Date of Patent: November 11, 1997Assignee: Merck & Co., Inc.Inventors: Mark G. Bock, Doug W. Hobbs
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Patent number: 5658910Abstract: Novel compounds of the formula: ##STR1## wherein R is selected from saturated or unsaturated alkyls, saturated or unsaturated cycloalkyls, heterocyclic compounds, or from (a) or (b) wherein G is carbon wherein G is carbon or nitrogen; m is 0-10, wherein R.sub.1, R.sub.2, and R.sub.3 are the same or different and selected from hydrogen, halogen, alkyl having 1 to 5 carbon atoms, electron donor groups such as alkoxy having 1-5 carbons or hydroxy, electron acceptor groups selected from cyano, nitro, trifluoroalkyl and the pharmacologically acceptable salts thereof; being useful for treating disorder in the central nervous system.Type: GrantFiled: May 3, 1995Date of Patent: August 19, 1997Assignee: Pharmacia ABInventors: Anders Bjork, Gunnar Andersson, Catarina Ludwig, Elisabeth Seifert, Arne Nilsson, Torbjorn Lundstedt, Lisbeth Abramo, Goran Pettersson, Curt Nordvi, Jin Chang Wu
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Patent number: 5658908Abstract: Diarylmethylpiperazine compounds having utility as receptor-binding species, e.g., for mediating analgesia, and for combatting drug addiction, alcohol addiction, and drug overdose. The compounds may be administered orally, rectally, topically, nasally, ophthalmically, or parenterally (subcutaneously, intramuscularly, and intravenously), for veterinary and human use, and include delta receptor and mu receptor binding species.Type: GrantFiled: August 3, 1994Date of Patent: August 19, 1997Assignee: Delta Pharmaceuticals, Inc.Inventors: Kwen-Jen Chang, Grady Evan Boswell, Dulce Garrido Bubacz, Mark Allan Collins, Ann Otstot Davis, Robert Walton McNutt, Jr.
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Patent number: 5656758Abstract: A process for preparing a compound of the formula (I): ##STR1## in which, R.sup.1 and R.sup.2 each represents hydrogen or C.sub.1 -C.sub.6 alkyl, or R.sup.1 and R.sup.2 together with the nitrogen atom to which they are attached form a heterocycle; E represents methylene, sulfur, oxygen or imino group optionally substituted with C.sub.1 -C.sub.6 alkyl or aralkyl; ring A is aryl or heteroaryl ring, optionally substituted; R.sup.3 is hydrogen or C.sub.1 -C.sub.6 alkyl and R.sup.4 is hydrogen or R.sup.3 and R.sup.4 together represent a group of formula (IV):--(CR.sup.a R.sup.a).sub.m --C(.dbd.Y)-- (IV)(wherein R.sup.a and R.sup.a is C.sub.1 -C.sub.6 alkyl or hydrogen, up to a maximum of 3 alkyl groups, m is 1, 2, or 3, and Y is two hydrogens or oxygen); provided that when E represents a methylene group, then R.sup.3 is a C.sub.1 -C.sub.6 alkyl group or R.sup.3 and R.sup.Type: GrantFiled: March 24, 1995Date of Patent: August 12, 1997Assignee: Sankyo Company, LimitedInventors: Atsusuke Terada, Yoshio Iizuka, Kazuyuki Wachi, Kenji Fujibayashi
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Patent number: 5652240Abstract: The present invention concerns compounds of the formula (I) ##STR1## wherein Ar are the same or different and are a phenyl group, optionally substituted with fluorine, or a pyrid-4-yl group, R.sub.1 and R.sub.2 are the same or different and are selected from hydrogen or lower alkyl, n is 2 or 3, X is nitrogen or methine and A is pyrimid-2-yl or a substituted or unsubstituted pyridyl group. The compounds are useful for treating mental disorders.Type: GrantFiled: January 31, 1995Date of Patent: July 29, 1997Assignee: Pharmacia AktiebolagInventors: Lisbeth Abramo, Torbjorn Lundstedt, Curt Nordvi, Knut Gunnar Olsson, Martin Brodszki
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Patent number: 5648352Abstract: The invention is directed to a series of novel piperazinylcamphorsulfonyl compounds where the camphor ring is substituted by amides, amines, alkanes, alkenes, alkylamines, halogens, hydroxy, carboxy, alkoxycarbonyl and heterocyclic tings. Such compounds are oxytocin antagonists useful in the treatment of preterm labor, dysmenorrhea and for the stoppage of labor preparatory to cesarean delivery.Type: GrantFiled: May 26, 1995Date of Patent: July 15, 1997Assignee: Merck & Co., Inc.Inventors: Mark G. Bock, Jill M. Erb, Doug W. Hobbs, James B. Hoffman, Joseph M. Pawluczyk, Debra S. Perlow, Daniel F. Veber, Peter D. Williams
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Patent number: 5635503Abstract: A series of non-peptidergic antagonists of NPY have been synthesized and are comprised of piperazine and homopiperazine derivatives of 4-phenyl-1,4-dihydropyridines of Formula (I). ##STR1## As antagonists of NPY-induced feeding behavior, these compounds are expected to act as effective anorexiant agents in promoting weight loss and treating eating disorders.Type: GrantFiled: June 7, 1995Date of Patent: June 3, 1997Assignee: Bristol-Myers Squibb CompanyInventors: Graham S. Poindexter, Marc Bruce, Graham Johnson, Michael Kozlowski, Karen LeBoulluec, Ivo Monkovic, Ramakrishna Seethala, Charles P. Sloan
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Patent number: 5633248Abstract: A compound of the formula: ##STR1## wherein Ar.sup.1 and Ar.sup.2 independently represent an optionally substituted aromatic group; P and Q independently represent a divalent aliphatic hydrocarbon group having at least 2 carbon atoms and optionally having either oxygen or sulfur in the carbon chain; R.sup.1 and R.sup.3 independently represent --CO--R, --CONH--R (R represents a hydrocarbon group or a heterocyclic group) or a hydrocarbon group; R.sup.2 and R.sup.4 independently represent hydrogen or an alkyl group; R.sup.2 and R.sup.4 independently represent hydrogen or an alkyl group; R.sup.1 and R.sup.2 or R.sup.3 and R.sup.4, taken together with the adjacent nitrogen atom, may form a nitrogen-containing heterocyclic group; and j represents 0 or 1, or a salt thereof, has excellent GnRH-receptor antagonizing activity and is useful as a prophylactic and therapeutic agent for hormone-dependent and other diseases.Type: GrantFiled: November 21, 1995Date of Patent: May 27, 1997Assignee: Takeda Chemical Industries, Ltd.Inventors: Kaneyoshi Kato, Yoshihiro Sugiura, Koichi Kato
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Patent number: 5625060Abstract: The invention relates to polycyclic amine compounds of formula (I) ##STR1## and their enantiomers, useful as neurokinin receptor antagonists.Type: GrantFiled: June 5, 1995Date of Patent: April 29, 1997Assignee: Elf SanofiInventors: Xavier Emonds-Alt, Patrick Gueule, Vincenzo Proietto, Pierre Goulaouic, deceased, Marie Bousquet, legal representative, Catherine M. L. Goulaouic, legal representative