Quinuclidines (including Unsaturated) Patents (Class 546/133)
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Patent number: 6008357Abstract: A process for resolving 1-azabicyclo[2.2.2]octan-3-amine, (2-diphenylmethyl)-N-[[2-methoxy-5-(1-methylethyl)phenyl]methyl] in which 1-azabicyclo[2.2.2]octan-3-amine, (2-diphenylmethyl)-N-[[2-methoxy-5-(1-methylethyl)phenyl]methyl] is reacted with 1R-(-)-10-camphorsulfonic acid in a solvent capable of dissolving both the foregoing reactants and selectively dissolving the camphorsulfonic acid salt of the corresponding (2R, 3R) enantiomer relative to the (2S, 3S) enantiomer.Type: GrantFiled: December 16, 1997Date of Patent: December 28, 1999Assignee: Pfizer IncInventors: Derek L. Tickner, Morgan Meltz
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Patent number: 5998404Abstract: The present invention relates to therapeutically active azacyclic or azabicyclic compounds of formula I ##STR1## and to pharmaceutical formulations comprising these compounds and methods of treatment comprising administering these compounds to a subject in need of treatment. The novel oxadiazole compounds, such as (.+-.)-3-butyloxy-4-(1-azabicyclo[2.2.2]octyl-3-oxy)-1,2,5-oxadiazole, are useful in treating central nervous system disorders caused by malfunctioning of the muscarinic cholinergic system.Type: GrantFiled: June 1, 1995Date of Patent: December 7, 1999Assignee: Eli Lilly and CompanyInventors: Leander Merritt, John S. Ward
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Patent number: 5990124Abstract: Alkoxy and/or acyloxy disubstituted and polysubstituted aralkyl and aralkenyl bis-quaternary ammonium derivatives of cyclic alkanol diesters have neuromuscular relaxant properties.Type: GrantFiled: October 24, 1997Date of Patent: November 23, 1999Inventors: Laszlo Gyermek, Chingmuh Lee, Young-Moon Cho
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Patent number: 5981525Abstract: A compound of formula (I) or a salt thereof, or a solvate thereof, wherein either (i) Ra represents a group R.sub.5 which is hydrogen, alkyl or optionally substituted aryl and R.sub.5 represents a moiety of formula (a); wherein X represents a hydroxy or an alkoxy group wherein the alkyl group may be substituted or unsubstituted or X represents a group NR.sub.s R.sub.t wherein R.sub.s and R.sub.t each independently represent hydrogen, alkyl, substituted alkyl, optionally substituted alkenyl, optionally substituted aryl, optionally substituted arylalkyl, an optionally substituted heterocyclic group or an optionally substituted heterocyclylalkyl group, or R.sub.s and R.sub.t together may form a heterocyclic group; R.sub.1 represents an alkyl or a substituted or unsubstituted aryl group; and R.sub.2, R.sub.3 and R.sub.4 each independently represent hydrogen, alkyl, aryl or substituted aryl or (ii) R.sub.a represents a moiety of the above defined formula (a) and R.sub.b represents the above defined R.sub.5 ; R.Type: GrantFiled: October 9, 1997Date of Patent: November 9, 1999Assignee: SmithKline Beecham CorporationInventors: Carlo Farina, Stefania Gagliardi, Carlo Parini, Mario Pinza, Guy Marguerite Marie Gerard Nadler, Marcel Jean-Marie Morvan
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Patent number: 5981545Abstract: A compound of formula (I) or a pharmaceutically acceptable salt thereof: ##STR1## in which one of X and Y represents hydrogen and the other represents Z, where Z is a group ##STR2## in which Q represents a 3-membered divalent residue completing a 5-membered aromatic ring and comprises zero, one or two nitrogen atoms, Q being optionally C-substituted by a group R.sub.1 selected from halogen, CN, OR.sub.2, SR.sub.2, N(R.sub.2).sub.2, NHCOR.sub.2, NHCOOCH.sub.3, NHCOOC.sub.2 H.sub.5, NHOR.sub.2, N.sub.3, NHNH.sub.2, NO.sub.2, COR.sub.2, COR.sub.3, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, cyclopropyl or C.sub.1-2 alkyl optionally substituted with OR.sub.2, N(R.sub.2).sub.2, SR.sub.2, CO.sub.2 R.sub.2, CON(R.sub.2).sub.2 or one, two or three halogen atoms, in which each R.sub.2 is independently hydrogen or C.sub.1-2 alkyl and R.sub.3 is OR.sub.2, NH.sub.2 or NHR.sub.2 ; r represents an integer of 2 or 3, s represents an integer of 1 or 2 and t represents 0 or 1; R.sub.a and R.sub.Type: GrantFiled: October 4, 1990Date of Patent: November 9, 1999Assignee: Beecham Group p.l.c.Inventors: Sarah Margaret Jenkins, Harry John Wadsworth, Barry Sidney Orlek, Steven Mark Bromidge
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Patent number: 5977129Abstract: The present invention relates to compounds of formula I: whereinone or both G is an azacyclic ring of formula II: ##STR1## and Z is oxygen or sulfur and the remaining variables are as defined in the specification. The compounds are useful as stimulants of the cognitive function of the forebrain and hippocampus of mammals and especially in the treatment of Alzheimer's disease, severe painful conditions and glaucoma.Type: GrantFiled: May 3, 1995Date of Patent: November 2, 1999Assignee: Novo Nordisk A/SInventors: Preben H. Olesen, Per Sauerberg
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Patent number: 5977380Abstract: A process for synthesizing N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanine derivatives of the following formula (I): ##STR1## in which the definition of R has the same meaning as given in the description by using a sulfite derivative to activate the C-terminus of the three dimensional structure of an amino acid of N-[1-(S)-ethoxycarbonyl-3- phenylpropyl]-L-alanine, which can effectively couple with another amino acid to form a dipeptide of formula (I). The compound of fomula (I) is an inhibitor of ACE.Type: GrantFiled: February 17, 1999Date of Patent: November 2, 1999Assignee: Everlight USA, Inc.Inventors: Suh-Wan Yang, Yu-An Chang, Yu-Liang Liu
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Patent number: 5939434Abstract: This invention provides a compound of the formula: ##STR1## and its pharmaceutically acceptable salts, wherein R.sup.1 is halo, C.sub.1 -C.sub.6 alkyl, halo C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy or halo C.sub.1 -C.sub.6 alkoxy; R.sup.2 is hydrogen, C.sub.1 -C.sub.6 alkyl, halo C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkyl-S-, C.sub.1 -C.sub.6 alkyl-SO--, C.sub.1 -C.sub.6 alkyl-SO.sub.2 --, cyclopropyl, phenyl, --NH.sub.2, --NH(CH.sub.3), --NHC(.dbd.O)CH.sub.3, --N(CH.sub.3).sub.2, --N(C.sub.2 H.sub.5).sub.2 or --CH.sub.2 C(.dbd.O)CF.sub.3 ; Ar.sup.1 and Ar.sup.2 are independently phenyl, halophenyl or thienyl; X is NH, O or S; and Y is hydrogen, --COOR.sup.3 or --CONR.sup.4 R.sup.5, wherein R.sup.3, R.sup.4 and R.sup.5 are independently hydrogen or C.sub.1 -C.sub.6 alkyl.Type: GrantFiled: September 5, 1997Date of Patent: August 17, 1999Inventor: Kunio Satake
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Patent number: 5939433Abstract: Compounds of the formula ##STR1## wherein R.sup.1 is methoxy and R.sup.2 is selected from the group consisting of methyl, ethyl, isopropyl, sec-butyl and tert-butyl; and the pharmaceutically acceptable salts of such compounds.These compounds are substance P antagonists and useful in the treatment of gastrointestinal disorders, inflammatory disorders, central nervous system disorders and pain.Type: GrantFiled: April 30, 1997Date of Patent: August 17, 1999Assignee: Pfizer IncInventors: Fumitaka Ito, Hiroshi Kondo, Masami Nakane, Kaoru Shimada, John Adams Lowe, III, Terry Jay Rosen
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Patent number: 5936088Abstract: The present invention relates to therapeutically active azacyclic and azabicyclic compounds, to methods for their preparation and to pharmaceutical compositions comprising the compounds. These compounds are useful in treating diseases in the central nervous system related to malfunctioning of the nicotinic cholinergic system.Type: GrantFiled: March 20, 1998Date of Patent: August 10, 1999Assignee: Novo Nordisk A/SInventor: Preben Houlberg Olesen
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Patent number: 5925661Abstract: The invention relates to compounds of the formula: ##STR1## Compounds of the above formula have a great affinity for the neurotensin receptors.Type: GrantFiled: November 24, 1997Date of Patent: July 20, 1999Assignee: SANOFIInventors: Bernard Labeeuw, Danielle Gully, Francis Jeanjean, Jean-Charles Molimard, Robert Boigegrain
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Patent number: 5919793Abstract: Compounds of formula (I) wherein R.sup.1 is hydrogen or hydroxy; R.sup.2 is hydrogen; or R.sup.1 and R.sup.2 are joined together so that CR.sup.1 14 CR.sup.2 is a double bond; X is selected from --Ch.sub.2 CH.sub.2 --, --C.dbd.CH--, --C.tbd.C--, --CH.sub.2 O--, --OCH.sub.2, CH.sub.2 NH--, --NHCH.sub.2 --, --CH.sub.2 CO--, --COCH.sub.2 --, --CH.sub.2 S(O).sub.n -- and --S(O).sub.n CH.sub.Type: GrantFiled: October 26, 1995Date of Patent: July 6, 1999Assignee: Zeneca LimitedInventors: George Robert Brown, Paul Robert Owen Whittamore, David Robert Brittain
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Patent number: 5912343Abstract: A compound comprising at least one cyclic amine, having an organolithium side-chain, defined according to formula (I) ##STR1## wherein Z is a lithium atom (Li); R.sub.1 is selected from the group consisting of organic groups containing from 1 to about 12 carbon atoms and a bridging bond; each R.sub.2 is independently selected from the group consisting of hydrogen, organic groups containing from 1 to about 12 carbon atoms, and a bridging bond; each R.sub.3 is independently selected from the group consisting of hydrogen and organic groups containing from 1 to about 12 carbon atoms; a is an integer from 4 to about 16; and b is an integer from 0 to about 12; and optionally including a bridge, formed by the selection of two of said bridging bonds, the bridge having 0 to about 6 carbon atoms between the bridging ring members.Type: GrantFiled: December 31, 1996Date of Patent: June 15, 1999Assignee: Bridgestone CorporationInventors: David F. Lawson, William L. Hergenrother, Michael L. Kerns
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Patent number: 5892047Abstract: Compounds of structure (I) in which R is C.sub.1-8 alkyl(phenyl)p, C.sub.2-8 alkenyl(phenyl)p, C.sub.2-8 alkenyl(phenyl)p, C.sub.3-8 cycloalkyl or C.sub.1-8 alkylC.sub.3-8 cycloalkyl; p is 0 to 2; n is 0 to 6; A is a bond, oxygen, sulphur or NR.sup.1 ; R.sup.1 is hydrogen, C.sub.1-8 alkylphenylC.sub.1-4 alkyl; m is 0 to 3; and Ar is aryl or heteroaryl, each of which may be optionally substituted, and salts thereof processes for preparing said compounds, pharmaceutical compositions containing them and their use in therapy, in particular as calcium blocking agents.Type: GrantFiled: August 4, 1997Date of Patent: April 6, 1999Assignee: NeuroSearch A/SInventors: Dan Peters, Oskar Axelsson
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Patent number: 5889019Abstract: The present invention relates to therapeutically active heterocyclic compounds and to pharmaceutical compositions comprising the compounds. The novel compounds are useful in treating diseases in the central nervous system caused by malfunctioning of the muscarinic cholinergic system.Type: GrantFiled: October 31, 1996Date of Patent: March 30, 1999Assignee: Eli Lilly and CompanyInventor: Charles Howard Mitch
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Patent number: 5886009Abstract: This invention relates to the quinuclidine derivative (2S, 3S)-N-(5-n-propyl-2-methoxyphenyl)methyl-2-diphenylmethyl-1-azabicyclo?2.2 .2!octan-3-amine and its pharmaceutically acceptable salts. These compounds are substance P antagonists and are useful in the treatment of gastrointestinal disorders, inflammatory disorders, central nervous system disorders and pain.Type: GrantFiled: June 19, 1995Date of Patent: March 23, 1999Assignee: Pfizer Inc.Inventors: Fumitaka Ito, Hiroshi Kondo, Masami Nakane, Kaoru Shimada
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Patent number: 5883107Abstract: The present invention provides peptide aldehydes having an azetidinyl, prolyl or pipecolyl group as part of the peptide backbone and an arginine mimic group such as an amidinopiperidine or amidinophenyl tail. These compounds are potent and specific inhibitors of thrombin. Their pharmaceutically acceptable salts, pharmaceutically acceptable compositions thereof, and methods of using them as therapeutic agents for disease states in mammals characterized by abnormal thrombosis are also described.Type: GrantFiled: June 7, 1995Date of Patent: March 16, 1999Assignee: Corvas International, Inc.Inventors: Odile Esther Levy, Susan Yoshiko Tamura, Ruth Foelsche Nutt, William Charles Ripka
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Patent number: 5880284Abstract: The invention relates to cyclic urea derivatives of general formula I ##STR1## wherein R.sub.a, R.sub.b, X and Y are defined as in claim 1, the tautomers, stereoisomers and salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, which have valuable pharmacological properties, preferably aggregation inhibiting effects, and to drugs containing the compounds and processes for preparing them.Type: GrantFiled: May 28, 1997Date of Patent: March 9, 1999Assignee: Dr. Karl Thomae GmbHInventors: Frank Himmelsbach, Volkhard Austel, Gunter Linz, Helmut Pieper, Brian Guth, Thomas Muller, Johannes Weisenberger
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Patent number: 5872117Abstract: This invention relates to a 1,2-ethanediol derivative and a salt thereof, a process for producing the same, and a cerebral function-improving agent comprising the same. The cerebral function-improving agent of this invention is useful for treating cerebrovascular dementia, senile dementia, Alzheimer's dementia, sequelae of ischemic encephalopathy and cerebral apoplexy.Type: GrantFiled: November 4, 1997Date of Patent: February 16, 1999Assignee: Toyama Chemical Co., Ltd.Inventors: Satoshi Ono, Tetsuo Yamafuji, Hisaaki Chaki, Mutsuko Maekawa, Yozo Todo, Hirokazu Narita
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Patent number: 5852038Type: GrantFiled: November 18, 1996Date of Patent: December 22, 1998Assignee: Pfizer IncInventors: Fumitaka Ito, Toshihide Kokura, Masami Nakane, Kunio Satake, Hiroaki Wakabayashi
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Patent number: 5840903Abstract: This invention relates to compounds of the formula: ##STR1## or a pharmaceutically acceptable salt thereof wherein Z is selected from the group consisting of ##STR2## R.sub.1 is alkoxy of one to six carbon atoms; R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are the same or different and are selected from the group consisting of hydrogen, halogen, CF.sub.3, hydroxy, alkoxy of one to six carbon atoms, acyl of two to seven carbon atoms, amino, amino substituted by one or two alkyl groups of one to six carbon atoms, C.sub.2 -C.sub.7 acylamino, aminocarbonyl, aminosulfone optionally substituted by one or two alkyl groups of one to six carbon atoms, C.sub.1 -C.sub.6 alkylsulfone and nitro;m is 1 or 2;X is O or NR.sub.7 ; andR.sub.7 is hydrogen or alkyl of 1 to 6 carbon atoms.Type: GrantFiled: July 27, 1992Date of Patent: November 24, 1998Assignee: G. D. Searle & Co.Inventors: Daniel Lee Flynn, Robert L. Shone
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Patent number: 5837711Abstract: Certain novel substituted quinuclidine compounds having the ability to antagonize substance P and having the following formula: ##STR1## wherein Ar.sup.1 and Ar.sup.2 are each, independently, thienyl, phenyl, fluorophenyl, chlorophenyl or bromophenyl;X is --CONR.sup.3 R.sup.4, --CO.sub.2 R.sup.3, --CH.sub.2 OR.sup.3, --CH.sub.2 NR.sup.3 R.sup.4 or --CONR.sup.3 OR.sup.4 ;R.sup.1, R.sup.3 and R.sup.4 are each, independently, hydrogen or alkyl having 1 to 4 carbon atoms;R.sup.Type: GrantFiled: April 28, 1995Date of Patent: November 17, 1998Assignee: Pfizer Inc.Inventors: Fumitaka Ito, Toshihide Kokura, Masami Nakane, Kunio Satake, Hiroaki Wakabayashi
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Patent number: 5834499Abstract: A 5-HT.sub.3 receptor against containing a thiazole derivative as the effective ingredient is provided and is represented by the Formula (I): ##STR1## wherein the A ring is substituted or unsubstituted and represents a benzene or a heterocyclic ring with one or two heteroatoms;one of L.sub.1 or L.sub.Type: GrantFiled: August 26, 1996Date of Patent: November 10, 1998Assignee: Yamanouchi Pharmaceutical Co., Ltd.Inventors: Kiyoshi Iwaoka, Hideki Anan, Naoki Imanishi, Kenichi Kazuta, Hiroyuki Koshio, Takeshi Suzuki, Hirotsune Itahana, Hiroyuki Ito, Keiji Miyata, Mitsuaki Ohta
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Patent number: 5830902Abstract: A quinuclidine derivative represented by the following general formula (I), a pharmaceutically acceptable salt thereof, a hydrate thereof or a solvate thereof, which has strong squalene synthase inhibiting activity and is useful as a cholesterol lowering agent without causing side effects. ##STR1## (Symbols in the formula represent the following meanings; R.sub.1 : a hydrogen atom, a halogen atom or a lower alkyl group,R.sub.2 : a hydrogen atom, a hydroxyl group or a lower alkoxy group,. . : a single bond or a double bond, with the proviso thatR.sub.2 does not exist when . . . is a double bond,X and Y: the same or different from each other and each represents a bond, an oxygen atom (--O--), a carbonyl group (--CO--), a group represented by the formula --S(O).sub.p -- or a group represented by the formula --NR.sub.3 --,p: 0, 1 or 2,R.sub.3 : a hydrogen atom or a lower alkyl group which may have a substituent,A: a saturated or unsaturated lower alkylene group, a group of the formula --(CH.sub.2).sub.m Z(CH.sub.Type: GrantFiled: August 21, 1997Date of Patent: November 3, 1998Assignee: Yamanouchi Pharmaceutical Co., Ltd.Inventors: Masahiko Isaka, Tsukasa Ishihara, Koyo Matsuda, Hirotoshi Kakuta, Hiroshi Moritani
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Patent number: 5807867Abstract: Compounds of the formula ##STR1## wherein R.sup.1 is methoxy and R.sup.2 is selected from the group consisting of methyl, ethyl, isopropyl, sec-butyl and tert-butyl; and the pharmaceutically acceptable salts of such compounds.These compounds are substance P antagonists and useful in the treatment of gastrointestinal disorders, inflammatory disorders, central nervous system disorders and pain.Type: GrantFiled: May 23, 1994Date of Patent: September 15, 1998Assignee: Pfizer Inc.Inventors: Fumitaka Ito, Hiroshi Kondo, Masami Nakane, Kaoru Shimada, John Adams Lowe, III, Terry Jay Rosen
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Patent number: 5808075Abstract: A process for the preparation of a compound of formula (I) or a pharmaceutically acceptable salt thereof wherein R.sub.1 represents (a) in which r represents an integer of 2 to 4, s represents 1 or 2 and t represents 0 or 1; R.sub.2 is a group OR.sub.4, where R.sub.4 is C.sub.1-4 alkyl, C.sub.2-4 alkenyl or C.sub.2-4 alkynyl or a group OCOR.sub.5 where R.sub.5 is hydrogen or R.sub.4 ; and R.sub.3 is CN; said process comprising reacting a compound of formula (II) wherein R.sub.1 ' is R.sub.1 or a group convertible thereto, and R.sub.3 ' is an electron withdrawing group, with a source of nitrous acid, and thereafter converting the resulting .dbd.NOH group to .dbd.NR.sub.2 wherein R.sub.2 is as defined in formula (I), converting R.sub.1 ' and R.sub.3 ' when other than R.sub.1 and R.sub.3 to R.sub.1 and R.sub.3, and thereafter optionally forming a pharmaceutically acceptable salt.Type: GrantFiled: November 12, 1996Date of Patent: September 15, 1998Inventors: Steven Mark Bromidge, Martyn Voyle, Erol Ali Faruk, Mark Jason Hughes, John Kitteringham, Gary Thomas Borrett
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Patent number: 5795890Abstract: A sulfonamide derivatives of formula (I) ##STR1## a non-toxic salts, an acid addition salts or a solvates thereof which has an inhibitory effect on elastase.Type: GrantFiled: September 24, 1996Date of Patent: August 18, 1998Assignee: ONO Pharmaceutical Co., Ltd.Inventors: Takahiko Nakae, Masashi Kato, Takehito Fujita, Kazuhito Kawabata, Hiroyuki Ohno
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Patent number: 5792777Abstract: Biphenylylquinuclidine compounds of the formula I: ##STR1## and pharmaceutically-acceptable salts thereof; wherein R.sup.1 is hydrogen or hydroxy; R.sup.2 is hydrogen; or R.sup.1 and R.sup.2 are joined together so that CR.sup.1 -CR.sup.2 is a double bond; and one or both ring A and ring B may be optionally unsubstituted or independently substituted by one or more substituents selected from halogeno, hydroxy, amino, nitro, cyano, carboxy, carbamoyl, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylamino, di-?(1-6C)alkyl!amino, N-?(1-6C)alkyl!carbamoyl, N,N-di-?(1-6C)alkyl!carbamoyl, (1-6C)alkoxycarbonyl, (1-6C)alkylthio, (1-6C)alkylsulphinyl, (1-6C)alkylsulphonyl and halogeno-(1-6C)alkyl; are inhibitors of squalene synthase and are hence useful in treating diseases or medical conditions such as hypercholesterolemia, atherosclerosis and fungal diseases.Type: GrantFiled: June 30, 1993Date of Patent: August 11, 1998Assignee: Zeneca LimitedInventors: George Robert Brown, Peter John Harrison, deceased, Keith Blakeney Mallion
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Patent number: 5780466Abstract: The invention relates to compounds of the formula ##STR1## in which: A is a divalent radical selected from:A.sub.1) --O--CO--A.sub.2) --CH.sub.2 --O--CO--A.sub.3) --O--CH.sub.2 --CO--A.sub.4) --O--CH.sub.2 --CH.sub.2 --A.sub.5) --N(R.sub.1)--CO--A.sub.6) --N(R.sub.1)--CO--CO--A.sub.7) --N(R.sub.1)--CH.sub.2 --CH.sub.2 --A.sub.8) --O--CH.sub.2 --in which:R.sub.1 is a hydrogen or a (C.sub.1 -C.sub.4)-alkyl; andAm is a nitrogen-containing heterocycle.Type: GrantFiled: August 27, 1996Date of Patent: July 14, 1998Assignee: SanofiInventors: Xavier Emonds-Alt, Isabelle Grossriether, Patrick Gueule, Vincenzo Proietto, Didier Van Broeck, Joelle Taillades
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Patent number: 5777122Abstract: A process for cleaving cinchona alkaloids to a quinoline derivative and an enantiomerically pure, functionalized 1-azabicyclo(2.2.2)octane, includes treating a cinchona alkaloid with a complex metal hydride while simultaneously oxidizing by exposure to air in an ether or tetrahydrofuran. Enantiomerically pure 1-azabicyclo(2.2.2)octanes of the formula ##STR1## in which R is hydrogen, a straight-chain or branched alkoxycarbonyl group with 1 to 12 carbon atoms, a straight-chain or branched alkyl group with 1 to 12 carbon atoms, alkylated silyl groups, or a substituted phenyl or benzyl substituent, are also provided.Type: GrantFiled: February 5, 1997Date of Patent: July 7, 1998Assignee: Buchler GmbHInventor: H. Martin R. Hoffmann
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Patent number: 5773458Abstract: The compound of the formula: ##STR1## where R is H, alkyl, haloalkyl, cycloalkyl, alkenyl or alkynyl; Y is oxygen, sulfur or NR.sub.2 where R.sub.2 is H or alkyl; or a pharmaceutically acceptable salt thereof, are centrally active muscarinic agents.Type: GrantFiled: October 17, 1997Date of Patent: June 30, 1998Assignee: American Home Products CorporationInventors: Annmarie L. Sabb, Reinhardt P. Stein
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Patent number: 5773619Abstract: A process for the preparation of a compound of formula (I) or a pharmaceutically acceptable salt thereof: ##STR1## wherein R.sub.1 represents ##STR2## in which r represents an integer of 2 to 4, s represents 1 or 2 and t represents 0 or 1;R.sub.2 is a group OR.sub.4, where R.sub.4 is C.sub.1-4 alkyl, C.sub.2-4 alkenyl or C.sub.2-4 alkynyl or a group OCOR.sub.5 where R.sub.5 is hydrogen or R.sub.4 ; andR.sub.3 is CN;said process comprising reacting a compound of formula (II): ##STR3## wherein R.sub.1 ' is R.sub.1 or a group convertible thereto, and R.sub.3 ' is an electron withdrawing group, with a source of nitrous acid, and thereafter converting the resulting .dbd.NOH group to .dbd.NR.sub.2 wherein R.sub.2 is as defined in formula (I), converting R.sub.1 ' and R.sub.3 ' when other than R.sub.1 and R.sub.3 to R.sub.1 and R.sub.3, and thereafter optionally forming a pharmaceutically acceptable salt.Type: GrantFiled: May 12, 1995Date of Patent: June 30, 1998Assignee: SmithKline Beecham p.l.c.Inventors: Steven Mark Bromidge, Martyn Voyle, Erol Ali Faruk, Mark Jason Hughes, John Kitteringham, Gary Thomas Borrett
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Patent number: 5770608Abstract: Quinuclidine compounds of the formula I: ##STR1## R.sup.1 is hydrogen or hydroxy; R.sup.2 is hydrogen;or R.sup.1 and R.sup.2 are joined together so that CR.sup.1 --CR.sup.2 is a double bond;X is selected from --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --C.tbd.C--, --CH.sub.2 O--, --OCH.sub.2 --, --CH.sub.2 NH--, --NHCH.sub.2 --, --CH.sub.2 CO--, --COCH.sub.2 --, --CH.dbd.N--, --N.dbd.CH--, --CH.sub.2 S--, --SCH.sub.Type: GrantFiled: February 24, 1997Date of Patent: June 23, 1998Assignee: Imperial Chemical Industries PLCInventors: George Robert Brown, Keith Blakeney Mallion, Peter John Harrison, deceased
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Patent number: 5744606Abstract: Optically active 3-quinuclidinol is obtained by the asymmetric hydrogenation of 3-quinuclidinone, its Lewis acid adducts or its tertiary or quaternary salts, for example, 1-(diphenylmethyl)-3-oxoquinuclidinium bromide. Rhodium/chiral diphosphine complexes with a metallocene structure are preferably used as catalysts. Optically active 3-quinuclidinol is a synthetic building block for pharmaceutical active substances (M.sub.1 receptor agonists).Type: GrantFiled: January 16, 1997Date of Patent: April 28, 1998Assignee: Lonza AGInventor: Walter Brieden
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Patent number: 5744480Abstract: The present invention relates to novel fluoroalkoxybenzylamino derivatives of nitrogen containing heterocyclic compounds, and specifically, to compounds of the formula ##STR1## wherein Q, X.sup.1, X.sup.2 and X.sup.3 are as defined below. These novel compounds are useful in the treatment of inflammatory and central nervous system disorders, as well as other disorders.Type: GrantFiled: May 22, 1995Date of Patent: April 28, 1998Assignee: Pfizer Inc.Inventors: John Adams Lowe, III, Terry Jay Rosen
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Patent number: 5741819Abstract: The present invention is directed to non-peptidic factor Xa inhibitors which are useful for the treatment of arterial and venous thrombotic occlusive disorders, inflammation, cancer, and neurodegenerative diseases. The factor Xa inhibitors provide compounds of structure: ##STR1## or pharmaceutically acceptable salts thereof; whereinR.sup.1 is alkyl, substituted alkyl, cycloalkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl; R.sup.2 is one of hydrogen, alkyl, cycloalkyl or aryl; R.sup.3 is one of hydrogen, hydroxy or alkoxy; R.sup.4 is one of --NH.sub.2, phenyl or pyridyl, wherein said phenyl and said pyridyl are optionally substituted with one or two of halogen, hydroxy, hydroxyalkyl, alkoxy, amino, monoalkylamino, dialkylamino, aminoalkyl, monoalkylaminoalkyl and/or dialkylaminoalkyl; X is one of --CH.sub.2 -- or --C(O)--; and n is from zero to eleven; provided that when R.sup.4 is --NH.sub.2, then R.sup.3 is hydrogen and n is other than zero; and also provided that when R.sup.Type: GrantFiled: June 7, 1995Date of Patent: April 21, 1998Assignee: 3-Dimensional Pharmaceuticals, Inc.Inventors: Carl R. Illig, Richard M. Soll, Joseph M. Salvino, Bruce E. Tomczuk, Tianbao Lu, Nalin L. Subasinghe
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Patent number: 5741797Abstract: Compounds useful in the treatment of inflammatory disorders, central nervous system disorders and other disorders of the formula I and the pharmaceutically-acceptable salts thereof; ##STR1## wherein R is C.sub.1 -C.sub.6 alkyl; X is C.sub.1 -C.sub.6 alkyl having one or more substituents which include at least one heteroatom; Ar.sup.1 and Ar.sup.2 are each, independently, aryl optionally substituted by one C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkylthio, halogen, cyano, nitro, phenoxy, mono C.sub.1 -C.sub.6 alkylamino, di C.sub.1 -C.sub.6 alkylamino, halosubstituted C.sub.1 -C.sub.6 alkyl, or halosubstituted C.sub.1 -C.sub.6 alkoxy; Y is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.3 -C.sub.8 cycloalkyl, Z--(CH.sub.2).sub.p --, or W--(CH.sub.2).sub.m --CHR.sup.2 --(CH.sub.2).sub.n --NR.sup.1 CO-- wherein Y is at the 4-, 5- or 6-position on the quinuclidine ring; R.sup.1 is hydrogen, C.sub.1 -C.sub.6 alkyl, benzyl or --(CH.sub.2).sub.r --W; R.sup.Type: GrantFiled: November 20, 1995Date of Patent: April 21, 1998Assignee: PFizer Inc.Inventor: Kunio Satake
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Patent number: 5731323Abstract: Compounds of formula (I) and their pharmaceutically acceptable salts in which R.sup.1 is hydrogen or hydroxy; R.sup.2 is hydrogen; or R.sup.1 and R.sup.2 are joined together so that CR.sup.1 --CR.sup.2 is a double bond; X is selected from --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --C.ident.C--, --CH.sub.2 O--, --OCH.sub.2 --, --CH.sub.2 NH--, --NHCH.sub.2 --, --CH.sub.2 CO--, --COCH.sub.2 --, --N.dbd.CH--, --CH.dbd.N--, --CH.sub.2 S-- and --SCH.sub.Type: GrantFiled: June 5, 1995Date of Patent: March 24, 1998Assignee: Zeneca LimitedInventor: Paul Robert Owen Whittamore
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Patent number: 5726313Abstract: Compound of Formula (I), wherein W.sub.1 is an oxygen atom; an --NR-- group wherein R is hydrogen, C.sub.1 -C.sub.7 alkyl or benzyl; and B is for example a substituted piperidine or quinuclidine. The disclosed compounds are useful as neurokinin receptor antagonists.Type: GrantFiled: November 29, 1995Date of Patent: March 10, 1998Assignee: SanofiInventors: Jean-Philippe Ducoux, Patrick Gueule, Xavier Emonds-Alt
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Patent number: 5723103Abstract: This invention provides compounds of the formula I ##STR1## wherein, R.sup.1, R.sup.2, and R.sup.3 are independently ?a first halogen atom,! fluorine, chlorine, bromine, iodine, alkyl, alkenyl, alkynyl, alkoxy, alkenoxy, or alkynoxy, wherein R.sup.2 and R.sup.3 can also independently be H, wherein at least one of R.sup.1, R.sup.2, and R.sup.3 is ?a second halogen atom! fluorine, bromine, iodine or is substituted with ?a second halogen atom,! fluorine, bromine or iodine and R.sup.4 is H or lower alkyl. The invention also provides precursors of formula I, radioactive analogs of formula I, and methods of using the compounds for the identification of 5-HT-3 receptors and the detection and treatment of abnormal conditions associated therewith.Type: GrantFiled: December 9, 1994Date of Patent: March 3, 1998Assignee: Vanderbilt UniversityInventors: Tomas de Paulis, Dennis E. Schmidt, William Hewlett, Michael H. Ebert
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Patent number: 5716965Abstract: Compounds of the formula ##STR1## wherein W, Ar.sup.1, Ar.sup.2 and Ar.sup.3 are defined as below; and the pharmaceutically acceptable salts of such compounds.These compounds are substance P antagonists and useful in the treatment of gastrointestinal disorders, inflammatory disorders, central nervous system disorders and pain.Type: GrantFiled: December 20, 1993Date of Patent: February 10, 1998Assignee: Pfizer Inc.Inventors: Fumitaka Ito, Toshihide Kokura, Masami Nakane, Kunio Satake, Hiroaki Wakabayashi
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Patent number: 5714496Abstract: Compounds of formula (I) and their pharmaceutically acceptable salts in which R.sup.1 is hydrogen or hydroxy; R.sup.2 is hydrogen; or R.sup.1 and R.sup.2 are joined together so that CR.sup.1 -CR.sup.2 is a double bond; X is selected from --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --C.tbd.C--, --CH.sub.2 O--, --CH.sub.2 NH--, --NHCH.sub.2 --, --CH.sub.2 CO--, --COCH.sub.2 --, --CH.sub.2 S-- and --SCH.sub.2 --; Ar.sup.1 is a phenylene moiety; Ar.sup.2 is a heteroaryl moiety; and wherein one or both of Ar.sup.1 and Ar.sup.2 may optionally bear one or more substituents independently selected from halogeno, hydroxy, amino, nitro, cyano, carboxy, carbamoyl, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, di-alkylamino, N-alkylcarbamoyl, di-N,N-alkylcarbamoyl, alkoxycarbonyl, alkylthio, alkylsulphinyl, alkylsulphonyl, halogeno-alkyl, carboxyalkyl and alkanoylamino; provided that when R.sup.1 is hydroxy, X is not selected from --NHCH.sub.2 -- and --SCH.sub.Type: GrantFiled: February 28, 1995Date of Patent: February 3, 1998Assignee: Zeneca LimitedInventors: George Robert Brown, Keith Blakeney Mallion, Paul Robert Owen Whittamore, David Robert Brittain
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Patent number: 5712288Abstract: The invention relates to quaternary basic amides of the formula ##STR1## in which Ar is an optionally substituted mono-, di- or tri-cyclic aromatic or heteroaromatic group;T is a direct bond, a hydroxymethylene group, an alkoxymethylene group in which the alkoxy group is C.sub.1 -C.sub.4, or a C.sub.1 -C.sub.5 -alkylene group;Ar' is an unsubstituted or mono- or poly-substituted phenyl, a thienyl, a benzothienyl, a naphthyl or an indolyl;R is hydrogen or a C.sub.1 -C.sub.4 -alkyl, or a C.sub.1 -C.sub.4 -.omega.-alkoxy(C.sub.2 -C.sub.4)alkyl, or a C.sub.2 -C.sub.4 -.omega.-alkanoyloxy (C.sub.1 -C.sub.4)alkyl;Q is hydrogen;or else Q and R together form a 1,2-ethylene, 1,3-propylene or 1,4-butylene group;Am.sup..sym. is the radical ##STR2## in which X.sub.1, X.sub.2 and X.sub.3, together with the nitrogen atom to which they are bonded, form a 1-azoniabicyclo?2.2.2!octane optionally substituted by a phenyl or benzyl group; andA.sup..crclbar. is a pharmaceutically acceptable anion.Type: GrantFiled: October 18, 1996Date of Patent: January 27, 1998Assignee: SanofiInventors: Xavier Emonds-Alt, Patrick Gueule, Vincenzo Proietto, Didier Van Broeck
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Patent number: 5712270Abstract: This invention relates to methods of treating neurological illnesses related to acetylcholine deficiency in the CNS including memory loss attending senility, Parkinson's disease, Down's syndrome or senile pugilistica by administering a therapeutically effective compound of the formula: ##STR1## where R.sub.1, R.sub.2 and R.sub.3 are, independently, H, alkyl, halo, perhaloalkyl, hydroxy, alkoxy, aryl or arylalkyl; n is an integer from 0-5; R is azabicyclo?2.2.2!octyl or azabicyclo?2.2.1!heptyl when n.sub.1 is zero, or R is NR.sub.4 R.sub.5 when n.sub.1 is 1, 2, 3, 4, or 5, in which R.sub.4 and R.sub.5 are alkyl or R.sub.4 and R.sub.5, taken with the nitrogen atom to which they are attached, are N-(substituted aryl)piperazinyl in which said substituent is alkoxy, halo or perhaloalkyl; N-(pyridyl)piperazinyl; N-(pyrimidinyl)piperazinyl; or 3-azabicyclo-?3.2.2!non-3-yl; X is oxygen or NH; n and n.sub.1 are, independently, one of the integers 0, 1, 2, 3, 4 or 5; or a pharmaceutically acceptable salt thereof.Type: GrantFiled: October 30, 1996Date of Patent: January 27, 1998Assignee: American Home Products CorporationInventor: Annmarie L. Sabb
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Patent number: 5710191Abstract: A method for preparing a polyurethane foam which comprises reacting an organic polyisocyanate and a polyol in the presence of a blowing agent, a cell stabilizer and a catalyst composition comprising at least one compound of either of the following formulas IA and IB: ##STR1## where R is hydrogen, methyl or hydroxymethyl. The preferred catalysts comprise 3-hydroxymethyl quinuclidine, 3-methyl-3-hydroxymethyl quinuclidine and 4-hydroxymethyl quinuclidine.Type: GrantFiled: May 21, 1996Date of Patent: January 20, 1998Assignee: Air Products and Chemicals, Inc.Inventors: Mark Leo Listemann, Kristen Elaine Minnich, Brian Eugene Farrell, Lisa Ann Mercando, Michael John Kimock, James Dudley Nichols
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Patent number: 5691349Abstract: Quinuclidine derivatives of formula, and their pharmaceutically acceptable salts, in which: R.sup.1 is hydrogen or hydroxy; R.sup.2 is hydrogen; pr R.sup.1 and R.sup.2 are joined together so that CR.sup.1 -CR.sup.2 is a double bond; X is selected from --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --C.dbd.C--, --CH.sub.2 O--, --OCH.sub.2 --, --CH.sub.2 NH--, NHCH.sub.2 --, --CH.sub.2 CO--, --COCH.sub.2 --, --CH.sub.2 S(O).sub.n -- and --S(O).sub.n CH.sub.2 -- wherein n is 0, 1 or 2; and AR is phenyl which may be optionally unsubstituted or substituted by one or more substituents such as halogeno, hydroxy, amino, nitro, cyano, carboxy, carbamoyl, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, dialkylamino, N-alkylcarbamoyl, N,N-di-alkylcarbamoyl, alkoxycarbonyl, alkythio, alkylsulphinyl, alkylsulphonyl, halogeno alkyl, alkanoylamino, alkylenedioxy, alkanoyl and oxime derivatives thereof and O-alkyl ethers of said oximes; provided that when X is selected from --OCH.sub.2 --, --NHCH.sub.2 --, and SCH.sub.2 --, R.sup.Type: GrantFiled: June 23, 1995Date of Patent: November 25, 1997Assignee: Zeneca LimitedInventors: Keith Blakeney Mallion, George Robert Brown, Paul Robert Owen
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Patent number: 5686463Abstract: A class of novel oxadiazoles, substituted on one of the ring carbon atoms with a non-aromatic azacyclic or azabicyclic ring, and substituted on the other ring carbon atom with a substituent of low lipophilicity; are potent muscarinic agonists, and have good CNS penetrability. The compounds are therefore useful in the treatment of neurological and mental illnesses.Type: GrantFiled: March 19, 1987Date of Patent: November 11, 1997Assignee: Merck, Sharp & Dohme, Ltd.Inventors: Raymond Baker, Kevin John Merchant, Angus Murray MacLeod, John Saunders
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Patent number: 5686461Abstract: The invention relates to compounds of formula (I). ##STR1## or a salt, or metabolically labile ester thereof wherein R.sub.1 represents a group selected from halogen, alkyl, alkoxy, amino, alkylamino, dialkylamino, hydroxy, trifluoromethyl, trifluoromethoxy, nitro, cyano, SO.sub.2 R.sub.3 or COR.sub.3 wherein R.sub.3 represents hydroxy, methoxy, or amino; m is zero or an integer 1 or 2;A represents an ethynyl group or an optionally substituted ethenyl group;X represents a bond or a C.sub.1-4 alkylene chain;R.sub.2 represents a bridged cycloalkyl or bridged heterocyclic group; which are antagonists of excitatory amino acids, to processes for their preparation and to their use in medicine.Type: GrantFiled: September 18, 1995Date of Patent: November 11, 1997Assignee: Glaxo Wellcome S.p.A.Inventors: Alfredo Cugola, Giovanni Gaviraghi, Fabrizio Micheli
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Patent number: 5675007Abstract: A compound of formula (I) or a pharmaceutically acceptable salt thereof (I) wherein R.sub.1 represents (a), R.sub.2 is a group OCH.sub.3, and R.sub.3 is cyano, for use in the treatment and/or prophylaxis of dementia in mammals.Type: GrantFiled: November 12, 1996Date of Patent: October 7, 1997Assignee: SmithKline Beecham p.l.c.Inventors: John Keogh, Gary Thomas Borrett, Steven Mark Bromidge, Erol Ali Faruk, Mark Jason Hughes, John Kitteringham, Martyn Voyle
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Patent number: 5662828Abstract: A compound having an unsaturated side chain represented by the formula: ##STR1## in which A and B are the same and different and represent an aromatic or heterocyclic group or either one of A and B represents a single bond; X.sub.1, X.sub.2 and X.sub.3 are the same or different and represent a hydrogen atom or a lower alkyl group; R.sub.1 represents a saturated or unsaturated alkyl group which may be substituted with a halogen atom or an alkoxyalkyl group which may be substituted with a halogen atom; X represents --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --C.tbd.C-- or a single bond; n is an integer of 0 to 6; q is an integer of 1 to 15; p and s are each 0 or 1; and the asterisk * indicates an asymmetric carbon atom, which is useful as an intermediate of a liquid crystal or a monomer of a liquid crystalline polymer.Type: GrantFiled: June 6, 1995Date of Patent: September 2, 1997Assignee: Sumitomo Chemical Company, LimitedInventors: Yoshiaki Tsubata, Kayoko Ueda, Koichi Fujisawa, Takayuki Higashii, Masayoshi Minai, Naoyuki Takano, Yukari Fujimoto