Carbocyclic Ring Containing Patents (Class 546/213)
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Patent number: 6174900Abstract: Disclosed herein is a substituted piperidine derivative represented by the following general formula (1): wherein R1 means an aryl or heteroaryl group which may have at least one substituent, R2 denotes an alkyl, alkenyl or aralkyl group, R3 stands for a hydrogen atom or an alkyl group, and R4 is a hydrogen atom, an alkyl group, or an aryl, heteroaryl, aralkyl, aralkenyl or heteroaralkyl group which may have at least one substituent, or a salt thereof. A medicine including this compound is also disclosed. The compound has excellent anticholinergic effect and calcium antagonism and inhibits reflex bladder contraction and is hence useful for prophylaxis of and treatment for a urinary disturbance such as pollakiuria.Type: GrantFiled: June 14, 1999Date of Patent: January 16, 2001Assignee: SS Pharmaceutical Co., Ltd.Inventors: Tomomi Okada, Fujiko Konno, Terumitsu Kaihoh, Masago Ishikawa, Yoshinori Takahashi, Hiroyuki Mizuno, Haruyoshi Honda, Susumu Sato, Hideaki Matsuda
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Patent number: 6172057Abstract: Matrix metalloproteinases (MMPs) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. TNF-&agr; converting enzyme (TACE), a pro-inflammatory cytokine, catalyzes the formation of TNF-&agr; from membrane bound TNF-&agr; precursor protein. It is expected that small molecule inhibitors of MMPs and TACE therefore have the potential for treating a variety of disease states. The present invention provides low molecular weight, non-peptide inhibitors of matrix metalloproteinases (MMPs) and TNF-&agr; converting enzyme (TACE) for the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection.Type: GrantFiled: February 19, 1998Date of Patent: January 9, 2001Assignee: American Cyanamid CompanyInventors: Aranapakam Mudumbai Venkatesan, George Theodore Grosu, Jamie Marie Davis, Baihua Hu, Derek Cecil Cole, Jannie Lea Baker, Marcy Pamela Jacobson, Matthew Robin O'Dell
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Patent number: 6140349Abstract: The present invention is directed to cyclic amines of the formula I: ##STR1## (wherein R.sup.1, R.sup.2, R.sup.3, m and n are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-1, CCR-2, CCR-2A, CCR-2B, CCR-3, CCR-4, CCR-5, CXCR-3, and/or CXCR-4.Type: GrantFiled: February 1, 1999Date of Patent: October 31, 2000Assignee: Merck & Co., Inc.Inventors: Charles G. Caldwell, Malcolm Maccoss, Paul E. Finke, Sander G. Mills, Bryan Oates, Shankaran Kothandaraman, Dooseop Kim, Liping Wang
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Patent number: 6083943Abstract: A compound of the chemical formula (I) and its pharmaceutically acceptable salt: ##STR1## wherein Y is C.sub.2 -C.sub.4 alkylene; Z is a valence bond or C.sub.1 -C.sub.6 alkylene; R.sup.1 is substituted or unsubstituted aryl (e.g., phenyl and naphthyl) or heteroaryl (e.g., thienyl and furyl); R.sup.2 is hydrogen or C.sub.1 -C.sub.6 alkyl; R.sup.3 is hydrogen, hydroxy or the like; R.sup.4 is substituted or unsubstituted benzyl or the like. Typical examples are (2S*,3S*,4R*,5R*)-4-Carboxy-3-[N-(5-Isopropyl-2-methoxy-benzyl)amino]-5-me thyl-2-phenylpyrrolidine and (2S*,3S*,5S*)-5-Carboxy-3-[N-(2-methoxy-5-trifluoromethoxybenzyl)amino]-2- phenylpiperidine. The novel substituted azaheterocyclecarboxylic acids in this invention have excellent substance P antagonistic activity and are thus useful for the treatment of gastrointestinal disorders, central nervous system disorders, allergy, inflammatory diseases, asthma, pain, emesis or migraine in mammals, especially humans.Type: GrantFiled: March 19, 1999Date of Patent: July 4, 2000Assignee: Pfizer IncInventors: Masaya Ikunaka, Yuji Shishido, Masami Nakane
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Patent number: 6066636Abstract: Heterocyclic derivatives of di-N-substituted piperazine or 1,4 di-substituted piperidine compounds in accordance with formula I (including all isomers, salts and solvates) ##STR1## wherein wherein one of Y and Z is --N-- and the other is --N-- or --CH--;X is --O--, --S--, --SO--, --SO.sub.2 -- or --CH.sub.2 --;Q is ##STR2## R is alkyl, cycloalkyl, optionally substituted aryl or heteroaryl; R.sup.1, R.sup.2 and R.sup.3 are H or alkyl;R.sup.4 is alkyl, cycloalkyl or ##STR3## R.sup.5 is H, alkyl, --C(O)alkyl, arylcarbonyl, --SO.sub.2 alkyl, aryl-sulfonyl --C(O)Oalkyl, aryloxycarbonyl, --C(O)NH-alkyl or aryl-aminocarbonyl, wherein the aryl portion is optionally substituted;R.sup.6 is H or alkyl; andR.sup.7 is H, alkyl, hydroxyalkyl or alkoxyalkyl; are muscarinic antagonists useful for treating cognitive disorders such as Alzheimer's disease.Type: GrantFiled: June 28, 1999Date of Patent: May 23, 2000Assignee: Schering CorporationInventors: Joseph A. Kozlowski, Stuart W. McCombie, Jayaram R. Tagat, Susan F. Vice
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Patent number: 6066650Abstract: Compounds are provided which inhibit microsomal triglyceride transfer protein and thus are useful for lowering serum lipids and treating atherosclerosis and related diseases. The compounds have the structure ##STR1## wherein R.sup.1 to R.sup.7, Q, X and Y are as defined herein.Type: GrantFiled: July 21, 1997Date of Patent: May 23, 2000Assignee: Bristol-Myers Squibb CompanyInventors: Scott A. Biller, John K. Dickson, R. Michael Lawrence, David R. Magnin, Michael A. Poss, Richard B. Sulsky, Joseph A. Tino, John E. Lawson, Henry M. Holava, Richard A. Partyka
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Patent number: 6013656Abstract: New 2-(arylalkenyl)azacycloalkane derivatives which are ligands for sigma receptors, of the formula (I) ##STR1## in which: Ar is aryl or heteroaryl, optionally mono- to trisubstituted,m has the value 1 or 2,n has the value 1 to 3,R is phenyl, or cycloalkyl containing 3 to 7 carbon atoms,their isomers and their addition salts.Medicinal drugs which are antipsychotic agents and are useful in gastroenterology.Type: GrantFiled: September 2, 1998Date of Patent: January 11, 2000Assignee: Warner-Lambert CompanyInventors: Alain Pierre Calvet, Henry Jacobelli, Jean-Louis Junien, Pierre Riviere, Fran.cedilla.ois-Joseph Roman
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Patent number: 6008223Abstract: Compounds of formula I ##STR1## wherein Q.sup.1, Q.sup.2, Q.sup.3, and Q.sup.4 have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists of SP and NKA are useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.Type: GrantFiled: January 20, 1998Date of Patent: December 28, 1999Assignee: Zeneca LimitedInventors: Peter R. Bernstein, Scott C. Miller
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Patent number: 5968956Abstract: Disclosed herein is a substituted piperidine derivative represented by the following general formula (1): ##STR1## wherein R.sup.1 means an aryl or heteroaryl group which may have at least one substituent, R.sup.2 denotes an alkyl, alkenyl or aralkyl group, R.sup.3 stands for a hydrogen atom or an alkyl group, and R.sup.4 is a hydrogen atom, an alkyl group, or an aryl, heteroaryl, aralkyl, aralkenyl or heteroaralkyl group which may have at least one substituent, or a salt thereof. A medicine including this compound is also disclosed. The compound has excellent anticholinergic effect and calcium antagonism and inhibits reflex bladder contraction and is hence useful for prophylaxis of and treatment for a urinary disturbance such as pollakiuria.Type: GrantFiled: June 26, 1996Date of Patent: October 19, 1999Assignee: SS Pharmaceutical Co., Ltd.Inventors: Tomomi Okada, Fujiko Konno, Terumitsu Kaihoh, Masago Ishikawa, Yoshinori Takahashi, Hiroyuki Mizuno, Haruyoshi Honda, Susumu Sato, Hideaki Matsuda
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Patent number: 5948792Abstract: Novel fluorine-containing 1,4-disubstituted piperidine derivatives, represented by general formula ?I! ##STR1## such as, for example, (2R)-N-?1-(6-aminopyridin-2-ylmethyl)piperidin-4-yl!-2-?(1R)-3,3-difluoroc yclopentyl!-2-hydroxy-2-phenylacetamide or pharmaceutically acceptable salt thereof, are potent and selective antagonists for muscarinic M.sub.3 receptors with little side effects. The compounds of formula ?I! exhibit excellent oral activity, duration of activity and pharmacolkinetics. They are useful for treatment and prophylaxis of respiratory diseases, such as chronic obstructive pulmonary diseases; urinary diseases, such as urinary incontinence; and digestive diseases, such as irritable bowel syndrome, and motion sickness.Type: GrantFiled: July 31, 1997Date of Patent: September 7, 1999Assignee: Banyu Pharmaceutical Co., Ltd.Inventors: Yoshimi Tsuchiya, Takashi Nomoto, Hirokazu Ohsawa, Kumiko Kawakami, Kenji Ohwaki, Masaru Nishikibe
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Patent number: 5939332Abstract: Novel analogs of phencyclidine (PCP) are disclosed. The analogs are capable of reacting with anti-PCT antibodies and are useful in immunoassays.The following analogs are described: ##STR1## wherein wherein X is --OH or a reporter molecule selected from the group consisting of aminofluorescein and aminomethylfluorescein and n is an integer between 1 and 10, inclusive.Type: GrantFiled: February 27, 1998Date of Patent: August 17, 1999Assignee: Roche Diagnostics Corp.Inventors: James C. Lee, Luis Fernando Del Corral, Richard A. Clark, Pedro A. Bonilla
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Patent number: 5935951Abstract: The invention relates to novel 1-acyl-4-aliphatylaminopiperidine compounds of ##STR1## formula (I), in which R.sub.1 is a benzoyl, naphthoyl or cycloalkanoyl radical which is unsubstituted or substituted by lower alkyl, lower alkoxy, halogen and/or trifluoromethyl; R.sub.2 is cycloalkyl or a phenyl or naphthyl radical which is unsubstituted or substituted by lower alkyl, lower alkoxy, halogen, nitro, cyano and/or trifluoromethyl; R.sub.3 and R.sub.4 together are lower alkylene or aza-, oxa- or thia-lower alkylene; or R.sub.3 is lower alkyl, lower alkoxy-lower alky, di-lower alkylamino-lower alkyl or a radical of the formula --(CH.sub.2).sub.n --C(.dbd.O)--R.sub.5 (Ia); and R.sub.4 is hydrogen, lower alkyl or a radical of the formula --(CH.sub.2).sub.n --C(.dbd.O)--R.sub.5 (Ia); R.sub.Type: GrantFiled: March 5, 1997Date of Patent: August 10, 1999Assignee: Novartis Finance CorporationInventors: Silvio Ofner, Siem Jacob Veenstra
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Patent number: 5932594Abstract: A compound of the formula: or a pharmaceutically acceptable salt thereof,wherein Y is a direct link, --(CH.sub.2 --, --(CH.sub.2).sub.2 --, --CH.sub.2 O-- or CH.sub.2 S--; R is --CN or --CONH.sub.2 ;and R.sup.1 is a group of the formula: ##STR1## where R.sup.2 and R.sup.3 are each independently H, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, --(CH.sub.2).sub.n OH, halo, trifluoromethyl, cyano, --(CH.sub.2).sub.n NR.sup.4 R.sup.5, --CO(C.sub.1 -C.sub.4 alkyl), --OCO(C.sub.1 -C.sub.4 alkyl), --CH(OH) (C.sub.1 -C.sub.4 alkyl), --C(OH) (C.sub.1 -C.sub.4 alkyl).sub.2, --SO.sub.2 NH.sub.2, --(CH.sub.2).sub.n CONR.sup.4 R.sup.5 or --(CH.sub.2).sub.n COO(C.sub.1 -C.sub.4 alkyl; R.sub.4 and R.sup.5 are each independently H or C.sub.1 -C.sub.4 alkyl; n is 0, 1 or 2;and "Het" is pyridyl, pyrazinyl or thienyl.The compounds are muscarinic receptor antagonists usedful in the treatment of diseases associated with the altered motility and/or tone of smooth muscle, especially irritable bowel syndrome.Type: GrantFiled: April 24, 1995Date of Patent: August 3, 1999Assignee: Pfizer, Inc.Inventors: Peter Edward Cross, Alexander Roderick MacKenzie
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Patent number: 5925654Abstract: The present invention provides compounds having the structure: ##STR1## and pharmaceutically acceptable salts and stereoisomers thereof that are useful in the treatment of inflammatory diseases which are mediated by LTB.sub.4 production, such as psoriasis, ulcerative colitis, IBD, and asthma.Type: GrantFiled: March 12, 1997Date of Patent: July 20, 1999Assignee: G.D. Searle & Co.Inventors: Barbara Baosheng Chen, Helen Chen, Mark Andrew Russell, Julie Marion Miyashiro, James Malecha, Thomas Dale Penning
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Patent number: 5914406Abstract: The compounds of formula I: wherein R.sup.1 --R.sup.9, R.sup.15, A, X, Y, and Z have the meaning given in the specification are active as protein kinase inhibitors and can be used as medicaments, particularly for the treatment of inflammatory skin disorders and alopecia.Type: GrantFiled: February 6, 1998Date of Patent: June 22, 1999Assignee: Hoffman-LA Roche Inc.Inventors: Pierre Barbier, Isabelle Huber, Fernand Schneider, Josef Stadlwieser, Sven Taylor
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Patent number: 5908934Abstract: A process for the preparation of compounds of formula I ##STR1## where R.sup.1, R.sup.2, R.sup.3, m, n and q are as defined herein; which comprises the steps of (a)reacting a compound of formula III ##STR2## with a chiral acid in an organic solvent to form a salt of a compound of formula I and (b) treating the salt of a compound of formula I with an aqueous base to obtain the compounds of formula I. Compounds of formula I are intermediates useful in the preparation of protein kinase inhibitors.Type: GrantFiled: September 12, 1997Date of Patent: June 1, 1999Assignee: Bristol-Myers Squibb CompanyInventor: Kyoung Soon Kim
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Patent number: 5856492Abstract: An efficient method for the quantitative preparation and isolation of a compound of formula I ##STR1## or its enantiomer, a chiral mediator used in enantioselective synthesis.Type: GrantFiled: January 5, 1998Date of Patent: January 5, 1999Assignee: Merck & Co., Inc.Inventors: Cheng Yi Chen, Feng Xu, Richard D. Tillyer, Dalian Zhao
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Patent number: 5849760Abstract: New 2-(arylalkenyl)azacycloalkane derivatives which are ligands for sigma receptors, of the formula (I) ##STR1## in which: Ar is aryl or heteroaryl, optionally mono- to trisubstituted,m has the value 1 or 2,n has the value 1 to 3,R is phenyl, or cycloalkyl containing 3 to 7 carbon atoms,their isomers and their addition salts. Medicinal drugs which are antipsychotic agents and are useful in gastroenterology.Type: GrantFiled: June 7, 1996Date of Patent: December 15, 1998Assignee: Institut de Recherche JouveinalInventors: Alain Pierre Calvet, Henry Jacobelli, Jean-Louis Junien, Pierre Riviere, Fran.cedilla.ois-Joseph Roman
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Patent number: 5834460Abstract: A serine derivative represented by the general formula (I) ##STR1## (symbols in the formula represent the following meanings; X: a sulfur atom or an oxygen atom,Y: a nitrogen atom or CH,R.sup.1 and R.sup.2 : the same or different from each other and each represents a hydrogen atom, a lower alkyl group or a protecting group for the amino group, or R.sup.1 and R.sup.2 may be combined together to form a four- to nine-membered nitrogen-containing cycloalkyl group,R.sup.3 : a hydrogen atom, a carboxyl group, a protected carboxyl group, an aralkyl group, or a lower alkyl group unsubstituted or substituted with a hydroxyl group,R.sup.4 : a hydrogen atom or a hydroxyl group,R.sup.Type: GrantFiled: October 12, 1995Date of Patent: November 10, 1998Assignee: Yamanouchi Pharmaceutical Co., Ltd.Inventors: Ichio Noda, Masahiro Iwata, Shuichi Sakamoto, Kazuo Koshiya, Takuma Morita, Atsuyuki Kohara
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Patent number: 5834447Abstract: A method of controlling Take-all disease of plants by applying, preferably to the seed prior to planting, a fungicide of the formula ##STR1## wherein Z.sub.1 and Z.sub.2 are C or N and are part of an aromatic ring selected from benzene, pyridine, thiophene, furan, pyrrole, pyrazole, thiazole, and isothiazole;A is selected from --C(X)--amine, --C(O)--SR.sub.3, --NH--C(X)R.sub.4, and --C(.dbd.NR.sub.3)--XR.sub.7 ;B is --W.sub.m --Q(R.sub.2).sub.3 or selected from o-tolyl, 1-naphthyl, 2-naphthyl, and 9-phenanthryl, each optionally substituted with halogen or R.sub.4 ;Q is C, Si, Ge, or Sn;W is --C(R.sub.3).sub.p H.sub.(2-p) --; or when Q is C, W is selected from --C(R.sub.3).sub.p H.sub.(2-p) --, --N(R.sub.3).sub.m H.sub.(1-m) --, --S(O).sub.Type: GrantFiled: December 8, 1995Date of Patent: November 10, 1998Assignee: Monsanto CompanyInventors: Dennis Paul Phillion, Diane Susan Braccolino, Matthew James Graneto, Wendell Gary Phillips, Karey Alan Van Sant, Daniel Mark Walker, Sai Chi Wong
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Patent number: 5824722Abstract: The present invention provides a stabilizer comprising a substituted cyclohexene compound of a hindered piperidine type wherein the 1- and 2-positions on a cyclohexene ring are doubly bonded, a carbon atom situated at the 4-position and/or the 5-position of the cyclohexene ring contains a substituent having a C.dbd.O group at its alpha-position, at least one carbon atom of the cyclohexene ring located adjacent to said carbon atom having the C.dbd.O group has a hydrogen atom as a substituent, and at least one group containing a 2,2,6,6-tetramethyl-4-piperidyl group attached to the 3-, 4-, 5- or 6-position of the cyclohexene ring; and/or other substituted cyclohexene compound of a hindered piperidine and/or a compound of a hindered piperidine. The stabilizers of the present invention can exhibit improved properties in light stability and in bleed out resistance even without a phenol type antioxidant.Type: GrantFiled: February 27, 1997Date of Patent: October 20, 1998Assignees: Mitsubishi Chemical Corporation, Harima Chemicals, Inc.Inventors: Akiyoshi Ohnishi, Machiko Mekada, Noriaki Hata, Hiroyuki Suzuki, Hiroyuki Morikawa
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Patent number: 5795893Abstract: This invention relates to novel compounds which inhibit platelet aggregation, pharmaceutical compositions containing the compounds, and methods of using the compounds.Type: GrantFiled: June 20, 1997Date of Patent: August 18, 1998Assignee: SmithKline Beecham CorporationInventors: William E. Bondinell, Thomas Wen-Fu Ku
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Patent number: 5786373Abstract: Novel fibrinogen receptor antagonists of the formula: X--Y--Z-Aryl-A--B and the pharmaceutically acceptable salts thereof, wherein Aryl is a 5-membered aromatic ring system containing 1 or 2 heteroatoms chosen from N, O or S wherein ring atoms may be unsubstituted or substituted with R.sup.5 and wherein S may be substituted with 0, 1 or 2 oxygen atoms; and X comprises various Nitrogen substituents including aromatic or nonaromatic systems; Y comprises, for example, alkyl or alkylaminocarbonylalkyl groups and Z and A are substituents which when present are independently chosen from alkyl or alkyloxyalkyl or other groups as defined herein; B is (a) or (b). The claimed compounds exhibit fibrinogen receptor antagonist activity, inhibit platelet aggregation and are therefore useful in modulating or preventing thrombus formation.Type: GrantFiled: May 31, 1995Date of Patent: July 28, 1998Assignee: Merck & Co., Inc.Inventors: George D. Hartman, John D. Prugh, Melissa S. Egbertson, Mark E. Duggan, William Hoffman
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Patent number: 5767118Abstract: The present invention is directed to certain novel compounds identified as 4-heterocycle substituted piperidines of the general structural formula: ##STR1## wherein R.sup.1, R.sup.4, R.sup.5, A, R.sup.3 and the dashed line are as defined herein. These compounds promote the release of growth hormone in humans and animals. This property can be utilized to promote the growth of food animals to render the production of edible meat products more efficient, and in humans, to treat physiological or medical conditions characterized by a deficiency in growth hormone secretion, such as short stature in growth hormone deficient children, and to treat medical conditions which are improved by the anabolic effects of growth hormone. Growth hormone releasing compositions containing such compounds as the active ingredient thereof are also disclosed.Type: GrantFiled: October 26, 1994Date of Patent: June 16, 1998Assignee: Merck & Co., Inc.Inventors: Ravi Nargund, Arthur A. Patchett, Lihu Yang
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Patent number: 5756732Abstract: The present invention discloses novel substituted aryl- and heteroarylphenyloxazolidinones which are useful as anti-bacterial agents. More specifically, the substituted aryl- and heteroarylphenyloxazolidinones of the invention are characterized by oxazolidinones having an aryl or heteroaryl group at the p-position of the 3-phenyl ring and additional substitutions at the m-position(s) of the 3-phenyl ring. A compound representative of this new class of oxazolidinones is (.+-.)-5-(acetamidomethyl)-3-?4-(3-pyridyl)-3,5-difluorophenyl!-2-oxazolid inone.Type: GrantFiled: June 6, 1995Date of Patent: May 26, 1998Assignee: Pharmacia & Upjohn CompanyInventors: Michael R. Barbachyn, Steven J. Brickner
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Patent number: 5753661Abstract: Fused benzo compounds of formula I are provided, wherein A is a 2 to 6 membered hydrocarbon spacer group, B is a polar divalent group selected from a group (a); U is C, N or CH; X is a divalent 3-4 membered chain optionally comprising one or more heteroatoms; R.sup.1 is an aliphatic hydrocarbon group, arylalkyl or diphenylalkyl; R.sup.2 and R.sup.3 are hydrogen or alkyl or together form an ethylene or propylene bridge; R.sup.4, R.sup.5 and R.sup.6 are hydrogen or substituents; R.sup.7 and R.sup.8 are hydrogen or substituents including --COOR.sup.9 and --CONR.sup.10 R.sup.11 ; are 5-HT.sub.1A receptor ligands useful in the treatment of CNS disorders. Pharmaceutical compositions comprising the compounds and their use for the manufacture of a pharmaceutical preparation are also provided.Type: GrantFiled: June 6, 1995Date of Patent: May 19, 1998Assignee: H. Lundbeck A/SInventors: Ejner K. Moltzen, Jens Perregaard, Henrik Pedersen
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Process for preparing benzoic acid derivative intermediates and benzothiophene pharmaceutical agents
Patent number: 5750688Abstract: Novel processes are provided for producing compounds of formula II ##STR1## wherein R.sup.1 and R.sup.2 each are independently C.sub.1 -C.sub.4 alkyl, or combine to form piperidinyl, pyrrolidinyl, methylpyrrolidinyl, dimethylpyrrolidinyl, morpholino, dimethylamino, diethylamino, or 1-hexamethyleneimino;R.sup.3 and R.sup.4 each are H or a hydroxy protecting group; andn is 2 or 3;or a pharmaceutically acceptable salt thereof by reacting a haloalkylamine with a phenolic ester in the presence of an alkylacetate solvent and a base.Type: GrantFiled: April 9, 1996Date of Patent: May 12, 1998Assignee: Eli Lilly and CompanyInventors: Douglas P. Kjell, Fred M. Perry -
Patent number: 5750540Abstract: This invention provides novel 1,4-di-substituted piperidine derivatives of the general formula ?I! ##STR1## and the pharmaceutically acceptable salts thereof, wherein: Ar represents a phenyl group or a five- or six-membered heteroaromatic group having one or two hetero atoms selected from the group consisting of an oxygen atom, a sulfur atom and a nitrogen atom in which one or two optional hydrogen atoms on the ring may be replaced by substituent groups selected from the group consisting of a halogen atom and a lower alkyl group;R.sup.1 represents a cycloalkyl group of 3 to 6 carbon atoms or a cycloalkenyl group of 3 to 6 carbon atoms;R.sup.2 represents a saturated or unsaturated aliphatic hydrocarbon radical of 5 to 15 carbon atoms; andX represents O or NH.These compounds have selective antagonistic activity against the muscarinic M.sub.3 receptors and can hence be used safely with a minimum of side effects.Type: GrantFiled: July 31, 1996Date of Patent: May 12, 1998Assignee: Banyu Pharmaceutical Co., Ltd.Inventors: Yoshimi Tsuchiya, Takashi Nomoto, Hirokazu Ohsawa, Kumiko Kawakami, Kenji Ohwaki, Masaru Nishikibe
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Patent number: 5739135Abstract: Compounds are provided which inhibit microsomal triglyceride transfer protein and thus are useful for lowering serum lipids and treating atherosclerosis and related diseases. The compounds have the structure ##STR1## wherein R.sup.1 to R.sup.7, Q, X and Y are as defined herein.Type: GrantFiled: June 6, 1995Date of Patent: April 14, 1998Assignee: Bristol-Myers Squibb CompanyInventors: Scott A. Biller, John K. Dickson, R. Michael Lawrence, David R. Magnin, Michael A. Poss, Richard B. Sulsky, Joseph A. Tino
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Patent number: 5721243Abstract: Novel anticholinergics which are related to vesamicol are particularly useful when radiolabeled for evaluating cholinergic innervation in the living human brain. The cholinergic deficit in the Alzheimer's brain should be identifiable with these radioligands.Type: GrantFiled: June 13, 1994Date of Patent: February 24, 1998Assignee: Regents of the University of MinnesotaInventors: Simon Mbua Ngale Efange, Stanley M. Parsons
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Patent number: 5717092Abstract: The present invention relates to compounds that can maintain, increase, or restore sensitivity of cells to therapeutic or prophylactic agents. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well-suited for treatment of multi-drug resistant cells, for prevention of the development of multi-drug resistance, and for use in multi-drug resistant cancer therapy.Type: GrantFiled: March 29, 1996Date of Patent: February 10, 1998Assignee: Vertex Pharmaceuticals Inc.Inventors: David M. Armistead, Jeffrey O. Saunders
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Patent number: 5714500Abstract: Compounds of formula (I) ##STR1## in which R.sub.1 is hydrogen, R.sub.2 is hydrogen or C.sub.1-6 alkyl, R.sub.3 and R.sub.4 independently represent one or more radicals selected from hydrogen, NH.sub.2, NO.sub.2, halogen, hydroxy, C.sub.1-6 alkoxy or C.sub.1-6 alkyl, X represents S or --CH.dbd.CH-- group and pharmaceutically acceptable salts are NMDA receptor antagonists.Type: GrantFiled: March 4, 1994Date of Patent: February 3, 1998Assignee: Astra ABInventors: Ronald Conrad Griffith, Richard Jon Schmiesing, Robert John Murray
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Patent number: 5712279Abstract: Compounds are provided which inhibit microsomal triglyceride transfer protein and thus are useful for lowering serum lipids and treating atherosclerosis and related diseases. The compounds have the structure ##STR1## wherein Z, X.sup.1, X.sup.2, x and R.sup.5 are as defined herein.Type: GrantFiled: January 11, 1996Date of Patent: January 27, 1998Assignee: Bristol-Myers Squibb CompanyInventors: Scott A. Biller, John K. Dickson, R. Michael Lawrence, David R. Magnin, Michael A. Poss, Jeffrey A. Robl, Richard B. Sulsky, Joseph A. Tino
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Patent number: 5710169Abstract: Compounds of formula I ##STR1## wherein Q.sup.1, Q.sup.2, Q.sup.3, Q.sup.4, and Q.sup.5 have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists of SP and NKA are useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.Type: GrantFiled: October 24, 1995Date of Patent: January 20, 1998Assignee: Zeneca LimitedInventor: Keith Russell
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Patent number: 5703065Abstract: The invention relates to compounds of the formula ##STR1## and to pharmaceutically acceptable salts thereof, wherein A, W, P, R.sup.3, Q and R.sup.1 are as defined herein. The compounds of formula I, and pharmaceutically acceptable salts thereof, are substance P antagonists and as such are useful in the treament of various inflammatory and central nervous system disorders.Type: GrantFiled: May 7, 1996Date of Patent: December 30, 1997Assignee: Pfizer Inc.Inventor: Harry R. Howard, Jr.
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Patent number: 5698581Abstract: The invention relates to heteroaroylguanidines of the formula I ##STR1## in which the substituents HA and R(1) to R(5) have the meanings given in the specification. These compounds exhibit very good antiarrhythmic properties and are outstandingly suitable for use as antiarrhythmic pharmaceuticals possessing a cardioprotective component for the prophylaxis and treatment of infarction and for the treatment of angina pectoris, in connection with which they also inhibit or strongly reduce, in a preventative manner, the pathophysiological processes associated with the genesis of ischemically induced damage, in particular associated with the elicitation of ischemically induced cardiac arrhythmias.Type: GrantFiled: April 7, 1995Date of Patent: December 16, 1997Assignee: Hoechst AktiengesellschaftInventors: Heinz-Werner Kleemann, Hans-Jochen Lang, Jan-Robert Schwark, Andreas Weichert, Wolfgang Scholz, Udo Albus
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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: 5674890Abstract: A compound of formula I ##STR1## in which Ar.sub.1 is naphthyl and phenyl, quinolyl or isoquinolyl optionally substituted; Ar.sub.2 is phenyl or thienyl optionally substituted; R.sub.1, R.sub.2 and R'.sub.2 are independently of each other H or (C.sub.1 -C.sub.4)alkyl or R.sub.1 represents a bond and N is covalently bonded to Ar.sub.2, and optionally R.sub.2 and R'.sub.2 form a double bond, or R.sub.1 or R.sub.2 is covalently bonded to Ar.sub.2 and represents a (C.sub.1 -C.sub.3 )alkylene; R.sub.3 and R.sub.4 are independently of each other H or (C.sub.1 -C.sub.4)alkyl or form, with the nitrogen atom to which they are attached pyrrolidine, ppiperidine, or hexahydroazepine; Z.sub.1 represents (C.sub.1 -C.sub.12)alkylene, optionally interrupted by a radical selected from the group consisting of (C.sub.5 -C.sub.7)cycloalkyl and phenyl or substituted with a radical selected from the group consisting of (C.sub.5 -C.sub.7)cycloalkyl and phenyl; Q.sub.1 is selected from the group consisting of methyl, amino, (C.sub.Type: GrantFiled: January 4, 1996Date of Patent: October 7, 1997Assignee: SanofiInventors: Bernard Christophe, Loic Foulon, Alain Pellet, Claudine Serradeil-Le Gal, Gerard Valette
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Patent number: 5674881Abstract: The present invention relates to quaternary ammonium salts of the formula ##STR1## in which: J is either a group Ar--CXX'--CX" or a group Ar--(CH.sub.2).sub.x CH.sub.1, in which:Ar is a substituted or unsubstituted phenyl, a cycloalkyl, a pyridyl or a thienyl;X is hydrogen;X' is hydrogen or is combined with X" below to form a carbon-carbon bond, or else X and X' together form an oxo group;X" is hydrogen or forms a carbon-carbon bond with X';X is zero or one; andX.sub.1 is hydrogen (n=0), a hydroxyl, an alkoxy, an acyloxy, a carboxyl, a carbalkoxy, a cyano or an alkoxyamino group;Q is an alkyl group or a benzyl group;A.crclbar. is an anion;m is 2 or 3;Ar', R, T and Z are as defined in the specification, are neurokinin receptor antagonists.Type: GrantFiled: November 21, 1994Date of Patent: October 7, 1997Assignee: Elf SanofiInventors: Xavier Emonds-Alt, Vincenzo Proietto, Didier Van Broeck, Jean-Claude Breliere
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Patent number: 5663375Abstract: Pharmaceutical compounds of the formula ##STR1## in which n is 0, 1 or 2 and R.sup.1 is attached at any of the positions 7, 8, 9 or 10, and each R.sup.1 is halo, carboxy, trifluoromethyl, hydroxy, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, hydroxy-C.sub.1-4 alkyl, hydroxy-C.sub.1-4 alkoxy, nitrogen-containing heterocyclyl, nitro, trifluoromethoxy, --COOR.sup.5 where R.sup.5 is an ester group, --COR.sup.6, --CONR.sup.6 R.sup.7 or --NR.sup.6 R.sup.7 where R.sup.6 and R.sup.7 are each hydrogen or C.sub.1-4 alkyl;R.sup.2 is phenyl, naphthyl or heteroaryl selected from thienyl, pyridyl, benzothienyl, quinolinyl, benzofuranyl or benzimidazolyl, said phenyl, naphthyl and heteroaryl groups being optionally substituted, or R.sup.2 is furanyl optionally substituted with C.sub.1-4 alkyl;R.sup.3 is nitrile, carboxy, --COOR.sup.8 where R.sup.8 is an ester group, or --CONR.sup.9 R.sup.10 where R.sup.9 and R.sup.10 are each hydrogen or C.sub.1-4 alkyl; andR.sup.4 is --NR.sup.11 R.sup.12, --NR.sup.11 COR.sup.Type: GrantFiled: August 22, 1994Date of Patent: September 2, 1997Assignees: Eli Lilly and Company, Lilly Industries LimitedInventors: Michael Brunavs, Colin Peter Dell, Peter Thaddeus Gallagher, William Martin Owton, Colin William Smith
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Patent number: 5654299Abstract: The present invention concerns the novel use of aryl substituted heterocycles of formula I, set out below, which antagonize the pharmacological actions of one of ent endogenous neuropeptide tachykinins an the neurokinin 2 (NK2) receptor making them useful whenever such antagonism is desired, such as in the treatment of asthma and related conditions. The invention also provides pharmaceutical compositions containing the aryl substituted heterocycles for use in such treatment. Certain novel aryl substituted heterocycles of formula I and novel intermediates for their manufacture are also provided.Type: GrantFiled: April 18, 1994Date of Patent: August 5, 1997Assignee: Zeneca LimitedInventors: Ashokkumar Bhikkappa Shenvi, Robert Toms Jacobs
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Patent number: 5651923Abstract: Described are novel reversible photochromic 2H-naphtho[1,2-b]pyran compounds, examples of which are compounds fused on the naphtho-portion of the naphthopyran ring with an indeno group or certain heterocyclic substituents. Certain substituents are also present at the 2 and 5 positions and sometimes at the 6 position of the naphthopyran ring. Also described are organic host materials that contain or that are coated with such compounds. Articles such as ophthalmic lenses or other plastic transparencies that incorporate the novel naphthopyran compounds or combinations thereof with complementary photochromic compounds, e.g., spiro(indoline) type compounds, are also described.Type: GrantFiled: December 12, 1995Date of Patent: July 29, 1997Assignee: Transitions Optical, Inc.Inventors: Anil Kumar, David B. Knowles, Barry Van Gemert
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Patent number: 5646144Abstract: 1-Acylpiperidine compound of the formula I ##STR1## in which R.sub.1 is an optionally substituted aralkyl, aryloxyalkyl, heteroaralkyl, aroyl, heteroaroyl, cycloalkylcarbonyl, aralkanoyl, heteroarylalkanoyl, aralkoxycarbonyl or arylcarbamoyl radical or the acyl radical of an .alpha.-amino acid which is optionally N-substituted by lower alkanoyl or carbamoyl-lower-alkanoyl, R.sub.2 is cycloalkyl or an optionally substituted aryl or heteroaryl radical, R.sub.3 is hydrogen, alkyl, carbamoyl or an alkanoyl or alkenoyl radical which is optionally substituted by carboxyl or esterified or amidated carboxyl, R.sub.4 is an optionally substituted aryl or optionally partially hydrogenated heteroaryl radical, X.sub.1 is methylene, ethylene, a direct linkage, an optionally ketalized carbonyl group or an optionally etherified hydroxymethylene group, X.sub.2 is alkylene, carbonyl or a direct linkage, and X.sub.Type: GrantFiled: June 7, 1995Date of Patent: July 8, 1997Assignee: Ciba-Geigy CorporationInventors: Walter Schilling, Silvio Ofner, Siem J. Veenstra
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Patent number: 5635537Abstract: A compound of the formula ##STR1## Z is hydrogen or halogen, Q is COR.sup.1 or 5-or 6-membered aryl which may contain 1 or 2 heteroatoms selected from N, 0 or S and may be substituted or fused wherein R is hydrogen or C.sub.1 -methyl (cis-configuration), R.sup.1 is C.sub.1 -C.sub.6 alkyl or an aromatic ring which may contain heteroatoms selected from O and S and may be substituted or fused to an optionally substituted benzene ring, R.sup.2 is hydrogen or C.sub.1 -C.sub.6 alkyl and R.sup.3 may be different groups defined in claim 1, and enantiomers/salts thereof, processes for preparation of said compounds, pharmaceutical preparations containing said compounds, use of and method of treatment of disorders in CNS by using said compounds.Type: GrantFiled: March 18, 1993Date of Patent: June 3, 1997Assignee: Astra AktiebolagInventors: Nils-Erik Anden, Berit C. E. Backlund Hook, Anna L. Bjork, Uli A. Hacksell, Sven-Erik Hillver, Ye Liu, Eva C. Mellin, Eva M. Persson, Karl J. Vallg.ang.rda, Hong Yu
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Patent number: 5629329Abstract: Methods are disclosed utilizing the optically pure (+) isomer of cisapride. This compound is a potent drug for the treatment of gastro-esophageal reflux disease while substantially reducing the concomitant liability of adverse effects associated with the racemic mixture of cisapride. This compound is also useful in treating or preventing emesis while substantially reducing adverse effects associated with racemic cisapride. The optically pure (+) isomer of cisapride is also useful for the treatment of dyspepsia and such other conditions as may be related to the activity of (+) cisapride as a prokinetic agent, such as gastroparesis, constipation, post-operative ileus, and intestinal pseudo-obstruction, without the concomitant liability of adverse effects associated with the racemic mixture of cisapride. The (+) isomer of cisapride also exhibits longer duration of action than does racemic cisapride and is useful for treatment of disorders of the central nervous system.Type: GrantFiled: July 19, 1996Date of Patent: May 13, 1997Assignee: Sepracor Inc.Inventors: Nancy M. Gray, James W. Young
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Patent number: 5620993Abstract: This invention relates to certain novel compounds and derivatives thereof, their synthesis, and their use as selective alpha-1a adrenergic receptor antagonists. One application of these compounds is in the treatment of benign prostatic hyperplasia. These compounds are selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing orthostatic hypotension. One such tissue is found surrounding the urethral fining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia are achieved.Type: GrantFiled: June 7, 1995Date of Patent: April 15, 1997Assignee: Merck & Co., Inc.Inventors: Michael A. Patane, Mark G. Bock, Roger M. Friedinger
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Patent number: 5620971Abstract: The present invention relates to novel compounds which possess a broad range of useful biological activities. These compounds can maintain, increase, or restore sensitivity of cells to therapeutic or prophylactic agents. They can also suppress, modify, or significantly reduce an immune response, including an autoimmune response in a mammal. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well-suited for treatment of multi-drug resistant cells, for prevention of the development of multi-drug resistance, for use in multi-drug resistant cancer therapy, and for prevention or treatment of graft rejection and various autoimmune diseases.Type: GrantFiled: March 25, 1994Date of Patent: April 15, 1997Assignee: Vertex Pharmaceuticals IncorporatedInventors: David M. Armistead, Jeffrey O. Saunders, Joshua S. Boger
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Patent number: 5618938Abstract: Compounds of the formula ##STR1## and their salts with mineral or organic acids are useful as neurokinin receptor antagonists. Methods of preparing the compounds, especially pure STEREO ISOMERS thereof, are provided.Type: GrantFiled: June 7, 1995Date of Patent: April 8, 1997Assignee: SanofiInventors: Xavier Emonds-Alt, Pierre Goulaouic, Vincenzo Proietto, Didier Van Broeck
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Patent number: 5607950Abstract: The invetion is a method of treating irritable bowel syndrome with a compound selected from the formula ##STR1## wherein R, R.sup.1, m, n p are as defined in the specification, or a pharmaceutically acceptable salt thereof.Type: GrantFiled: February 10, 1994Date of Patent: March 4, 1997Assignee: Pfizer Inc.Inventors: David Alker, Peter E. Cross, Alexander R. Mackenzie
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Patent number: 5594151Abstract: The present invention relates to a novel class of phenylboronic acid complexing reagents useful for the preparation of bioconjugates, and the method of making and using such reagents. In the present invention, in the place of prior art Avidin-Biotin and Digoxigenin-anti-Digoxigenin systems, phenylboronic acid complexing reagents are utilized in conjunction with phenylboronic acid reagents (many of which are known in the prior art) to facilitate chemical conjugation without the use of intermediary biological macromolecules. Reagents suitable for the modification of a bioactive species for the purpose of incorporating a phenylboronic acid complexing moiety for subsequent conjugation to a different bioactive species having pendant phenylboronic acid moleties are of General Formula I or General Formula II. ##STR1## wherein group X is selected from either H, OH, NH.sub.2, NHCH.sub.3, NHOH and NHOCH.sub.Type: GrantFiled: January 28, 1994Date of Patent: January 14, 1997Assignee: Prolinx, Inc.Inventor: Mark L. Stolowitz