The Chalcogen Is Bonded Directly To A Ring Carbon Of The Five-membered Hetero Ring Which Is Adjacent To The Ring Nitrogen (e.g., 2-indolinones, Etc.) Patents (Class 548/486)
-
Patent number: 5336781Abstract: There is disclosed a process for the preparation of a compound of structure (I) ##STR1## in which n is 1 to 3 and each group R is hydrogen or C.sub.1-4 alkyl, which comprises, reaction of compound of structure (II) ##STR2## (prepared by esterifying the hydroxyl compound) in which R.sup.1 is C.sub.1-4 alkyl, phenyl or substituted phenyl and n is 1 to 3, with an amine HNR.sub.2 in which R is as described for structure (I), and optionally thereafter forming a salt. Intermediates are also disclosed.Type: GrantFiled: October 14, 1992Date of Patent: August 9, 1994Assignee: SmithKline & French Laboratories LimitedInventors: Robert Giles, Timothy C. Walsgrove
-
Patent number: 5330981Abstract: This application describes 3-arylalkyl esters of 4,5-dihydro-9,10-dioxo-2-anthracenecarboxylic acid and a process for making them. Also described is a method of using the compounds in the treatment of arthritis.Type: GrantFiled: December 30, 1992Date of Patent: July 19, 1994Assignee: Istituto Gentili S.p.A.Inventors: Sergio Rosini, Maurizio Mian
-
Patent number: 5310935Abstract: The synthesis of optically active 5-oxygenated (3S)-1,3-dimethyloxindole-3-acetic acids ##STR1## and their use in the synthesis of optically active (3aS-cis)-eseroline and (3aS-cis)-N.sup.1 -benzylnoreseroline, which are important intermediates in the synthesis of compounds related to (3aS-cis)-physostigmine and carbamate analogs, and of (3aS-cis)-N.sup.1 -benzylnor- and N.sup.1 -norphysostigmine and their carbamate analogs.Type: GrantFiled: June 30, 1992Date of Patent: May 10, 1994Assignee: Pharmagroup InternationalInventors: Arnold Brossi, Danilo C. Massari, Qian-Sheng Yu
-
Patent number: 5302724Abstract: This invention provides certain sulfonamide compounds, formulations and method of use of certain sulfonamide compounds in treating susceptible neoplasms.Type: GrantFiled: April 29, 1992Date of Patent: April 12, 1994Assignee: Eli Lilly and CompanyInventors: J. Jeffry Howbert, Fariborz Mohamadi, Michael M. Spees
-
Patent number: 5288749Abstract: The present invention provides tertiary and secondary amine compounds of the formula ##STR1## and the pharmaceutically acceptable salts thereof which are antagonists for alpha-2 adrenoreceptors and which inhibit serotonin (5-hydroxytryptamine, 5-HT) uptake.Type: GrantFiled: December 20, 1991Date of Patent: February 22, 1994Assignee: Abbott LaboratoriesInventors: Michael D. Meyer, John F. DeBernardis, Rajnandan Prasad, Kevin B. Sippy, Karin R. Tietje
-
Patent number: 5284960Abstract: A process for the production of 5-chloroxindole starting from chloronitrobenzene.Type: GrantFiled: May 7, 1993Date of Patent: February 8, 1994Assignee: Lonza Ltd.Inventors: Rene Imwinkelried, Felix Previdoli
-
Process for the enantioselective synthesis of intermediates used in the preparation of physostigmine
Patent number: 5274117Abstract: A process for the stereoselective synthesis of [R]- and [S]-2,3-dihydro-1,3-dimethyl-2-oxo-1H-indole-3-acetonitriles comprises reacting racemic and 5-alkoxy-substituted (.+-.)-1,3-dimethyloxindoles with a halogenated acetonitrile in the presence of a substituted N-benzyl cinchoninium, quinidinium, cinchonidinium, or quininium catalyst. The resulting alkylated oxindoles can be converted to primary amines by catalytic reduction in the presence of hydrogen gas. One of the primary amines, such as enantiomers of 3-(2-aminoethyl)-1,3-dihydro-1,3-dimethyl-5-methoxy-2H-indol-2-one, can be enriched by contact with a chiral tartaric acid in an amount sufficient to preferentially precipitate a salt of the chiral acid and one of the enantiomers. The product can be used in the synthesis of stereospecific forms of physostigmine and related compounds having pharmaceutical activity.Type: GrantFiled: February 12, 1992Date of Patent: December 28, 1993Assignee: Hoechst-Roussel Pharmaceuticals, Inc.Inventors: Thomas B. K. Lee, George S. K. Wong -
Patent number: 5260452Abstract: This invention relates to 4- and 6-carbamates related to physostigmine of the formula ##STR1## where R.sub.1 is alkyl, cycloalkyl, bicycloalkyl, aryl or arylloweralkyl; R.sub.2 is hydrogen or alkyl or the group --NR.sub.1 R.sub.2 taken together forms a monocyclic or bicyclic ring of 5 to 12 carbons; m is 0,1, or 2; each X is independently hydrogen, halogen, loweralkyl, nitro or amino; and the pharmaceutically acceptable acid addition salts thereof, and where applicable, the geometric and optical isomers and racemic mixtures thereof. This invention also relates to novel intermediates useful in the preparation of the 4- and 6-carbamates. The compounds of this invention display utility for alleviating various memory dysfunctions characterized by a decreased cholinergic function, such as Alzheimer's disease.Type: GrantFiled: September 3, 1991Date of Patent: November 9, 1993Assignee: Hoechst-Roussel Pharmaceuticals Inc.Inventors: Edward J. Glamkowski, Barbara E. Kurys
-
Patent number: 5252317Abstract: Disclosed are amplifier molecules: various organic compounds having branched structures terminating with amine groups to which pharmacologically active groups can be chemically attached. A number of MRI contrast-enhancing agents were synthesized, each comprising plural active groups, such as stable nitroxides and complexes of trivalent metal cations. Such syntheses were successfully performed using a number of amplifiers having different branched structures, demonstrating the general utility of the pertinent chemistry in the synthesis of amplifiers having any of a wide variety of pharmacologically active groups. Amplifiers were also synthesized having linkers terminating with chemically reactive groups such as isothiocyanates, which render the amplifier bifunctional: attachable to polymers, biomacromolecules, or other biocompatible entity possessing multiple reactive sites such as terminal amines.Type: GrantFiled: May 22, 1992Date of Patent: October 12, 1993Assignee: The State of Oregon Acting by and through the State Board of Higher Education on Behalf of the University of OregonInventor: John F. W. Keana
-
Patent number: 5250565Abstract: Pro-drugs of potent 5-lipoxygenase inhibiting compounds comprise compounds of the formula ##STR1## in which A is an alkylene or alkenylene group, X is oxygen, sulfur, sulfoxyl, or substituted nitrogen, and Y is a group which includes substituted or unsubstituted carbocyclic or substituted or unsubstituted heterocyclic aryl. R.sup.1 is an alkyl, alkenyl, amino, alkylamino, dialkylamino, or hydroxyamino group or an amine group bearing a metabolically cleavable leaving group. M is hydrogen, a pharmaceutically acceptable cation or a metabolically cleavable leaving group, with the proviso that either M or R.sup.1 must bear a metabolically cleavable leaving group.Type: GrantFiled: January 21, 1992Date of Patent: October 5, 1993Assignee: Abbott LaboratoriesInventors: Dee W. Brooks, James B. Summers
-
Patent number: 5232936Abstract: The present invention relates to novel hydantoin derivatives, processes for producing said hydantoin derivatives, pharmaceutical compositions containing at least one of said hydantoin derivatives as aldose reductase inhibitors and novel intermediate compounds in the synthesis of said hydantoin derivatives.The present invention is based on the selection of a hydantoin which is bonded by a sulfonyl group to various substituents at the 1-position of the hydantoin skeleton.The compounds of the present invention have a strong inhibitory activity against aldose reductase. These compounds are extremely useful for the treatment and/or prevention of various forms of diabetic complications based on the accumulation of polyol metabolites.Type: GrantFiled: January 23, 1991Date of Patent: August 3, 1993Assignee: Mochida Pharmaceutical Co., Ltd.Inventors: Ei Mochida, Kimihiro Murakami, Kazuo Kato, Katsuaki Kato, Jun Okuda, Ichitomo Miwa
-
Patent number: 5216148Abstract: Described herein are compounds of the formula ##STR1## wherein R.sup.1 signifies hydrogen, lower-alkyl or a cation;R.sup.2 signifies hydrogen, lower-alkyl, lower-alkoxy or halogen;M signifies --CONH-- or --NHCO--;X and Y are each independently selected from the group consisting of >CR.sup.3 R.sup.4 and --CONR.sup.5 --;Z signifies >CR.sup.6 R.sup.7 ;R.sup.3, R.sup.4, R.sup.6 and R.sup.7 are each independently selected from the group consisting of hydrogen and lower-alkyl;R.sup.5 signifies alkyl; andn signifies 0, 1 or 2;provided that at least one of X or Y is --CONR.sup.5 -- which is bonded to the phenyl ring via the N atom.These compounds are useful in the treatment and prophylaxis of neoplasms, dermatoses and aging of the skin.Type: GrantFiled: February 27, 1992Date of Patent: June 1, 1993Assignee: Hoffmann-La Roche Inc.Inventors: Michael Klaus, Peter Mohr
-
Patent number: 5210212Abstract: Process for the production of 5-fluoro-6-chloro- oxindole, (III), which is useful in the synthesis of certain analgesic and antiinflammatory agents, via two different synthetic pathways.Compounds of formula (I) and (II) shown below ##STR1## which are intermediates in the process of this invention.Type: GrantFiled: August 14, 1992Date of Patent: May 11, 1993Assignee: Pfizer IncInventor: Robert W. Dugger
-
Patent number: 5206235Abstract: There are disclosed certain novel compounds identified as benzo-fused lactams which 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 increase the stature of those afflicted with a lack of a normal secretion of natural growth hormone. Growth promoting compositions containing such benzo-fused lactams as the active ingredient thereof are also disclosed.Type: GrantFiled: February 28, 1992Date of Patent: April 27, 1993Assignee: Merck & Co., Inc.Inventors: Michael H. Fisher, William R. Schoen, Matthew J. Wyvratt, Robert J. DeVita
-
Patent number: 5206261Abstract: The present invention provides an oxindole derivative which has the following formula and is useful as medicaments for treating senile dementia, i.e., as cerebral function improving agents and cerebral metabolism activators or anoxic brain damage protectives ##STR1## wherein R.sup.1 is hydrogen atom, halogen atom, lower alkyl group or lower alkoxyl group, R.sup.2 is hydrogen atom or lower alkyl group, R.sup.3 is --CH.sub.2 --R.sup.5 group (R.sup.5 being alkyl group which may form a ring; benzodioxanyl group; or phenyl group which may have plural substituents selected from among halogen atom, lower alkyl group, lower alkoxyl group, hydroxyl group, diethylamino group, trifluoromethyl group, nitrile group, nitro group and benzyloxy group), R.sup.2 and R.sup.3 may form together .dbd.CH--R.sup.5 (R.sup.5 being same as above), R.sup.Type: GrantFiled: March 20, 1991Date of Patent: April 27, 1993Assignee: Taiho Pharmaceutical Company, LimitedInventors: Akihiro Kawaguchi, Atsushi Sato, Makoto Kajitani, Mitsugi Yasumoto, Junji Yamamoto
-
Patent number: 5196541Abstract: There is described a new process for the preparation of substituted 3-aminoacrylic esters of the general formula (I) ##STR1## in which R.sup.1, R.sup.2, R.sup.3, R.sup.4, X and n have the meaning given in the description.The 3-aminoacrylic esters of the formula (I) are obtained by reacting acetic esters of the formula (II)R.sup.1 --(X).sub.n --CH.sub.2 --COOR.sup.Type: GrantFiled: August 2, 1991Date of Patent: March 23, 1993Assignee: Bayer AktiengesellschaftInventors: Herbert Gayer, Alexander Klausener, Peter C. Knuppel, Fritz Maurer
-
Patent number: 5169860Abstract: This invention provides the use of certain benzofuransulfonamide, benzothiophenesulfonamide, and indolesulfonamide derivatives in the treatment of susceptible neoplasms in mammals. Also provided are certain novel benzofuransulfonamide and benzothiophenesulfonamide derivatives and their pharmaceutical formulations.Type: GrantFiled: March 13, 1992Date of Patent: December 8, 1992Assignee: Eli Lilly and CompanyInventors: Fariborz Mohamadi, Michael M. Spees
-
Patent number: 5166401Abstract: Process for the production of 5-fluoro-6-chlorooxindole, (III), which is useful in the synthesis of certain analgesic and antiinflammatory agents, via two different synthetic pathways.Compounds of formula (I) and (II) shown below ##STR1## which are intermediates in the process of this invention.Type: GrantFiled: June 25, 1991Date of Patent: November 24, 1992Assignee: Pfizer IncInventor: Robert W. Dugger
-
Patent number: 5151518Abstract: A process for the N-arylation of isatins with organo bismuth reagents is disclosed.Type: GrantFiled: November 30, 1989Date of Patent: September 29, 1992Assignee: Abbott LaboratoriesInventors: James E. Dombrowski, Phillip G. Mattingly
-
Patent number: 5137909Abstract: An indole derivative represented by the general formula (I) ##STR1## wherein R is hydrogen, lower alkyl having 1 to 6 carbons, carboxymethyl, or substituted or unsubstituted aralkyl; R.sup.1, R.sup.2, R.sup.3, and R.sup.4 may be the same with or different from each other and are hydrogen, halogen, lower alkyl having 1 to 6 carbons, lower alkoxy having 1 to 6 carbons, acyl, substituted or unsubstituted amino, nitro, hydroxy, acyloxy, substituted or unsubstituted aralkyl, substituted or unsubstituted aryloxy, or substituted or unsubstituted aralkyloxy, or a combination of R.sup.2 and R.sup.3 may be methylenedioxy;R.sup.5 is hydrogen, lower alkyl having 1 to 6 carbons, or substituted or unsubstituted aralkyl; R and R.sup.4, or R.sup.1 and R.sup.5 may form together a six-membered ring constituted of methylene chains which may contain a heteroatom;R.sup.6 and R.sup.Type: GrantFiled: May 14, 1990Date of Patent: August 11, 1992Assignee: Kyorin Seiyaku Kabushiki KaishaInventors: Hidehiko Miura, Naoki Harano, Yasuo Takano, Toshiro Mochizuki, Yoshinori Takahashi, deceased, Takashi Nagayama
-
Patent number: 5135737Abstract: Disclosed are amplifier molecules: various organic compounds having branched structures terminating with amine groups to which pharmacologically active groups can be chemically attached. A number of MRI contrast-enhancing agents were synthesized, each comprising plural active groups, such as stable nitroxides and complexes of trivalent metal cations. Such syntheses were successfully performed using a number of amplifiers having different branched structures, demonstrating the general utility of the pertinent chemistry in the synthesis of amplifiers having any of a wide variety of pharmacologically active groups. Amplifiers were also synthesized having linkers terminating with chemically reactive groups such as isothiocyanates, which render the amplifier bifunctional: attachable to polymers, biomacromolecules, or other biocompatible entity possessing multiple reactive sites such as terminal amines.Type: GrantFiled: September 5, 1989Date of Patent: August 4, 1992Assignee: The State of Oregon Acting by and through the State Board of Higher Education on behalf of the University of OregonInventor: John F. W. Keana
-
Patent number: 5132319Abstract: Compounds having the formula I: ##STR1## are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis and allograft rejection and in preventing the formation of atherosclerotic plaques.Type: GrantFiled: March 28, 1991Date of Patent: July 21, 1992Assignee: Merck Frosst Canada, Inc.Inventors: Yves Girard, Pierre Hamel, Daniel Delorme, Rejean Fortin
-
Patent number: 5124347Abstract: The present invention is for selected novel compounds which are indoles substituted at the 3-position with [3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methylene as well as pharmaceutical compositions and methods of use thereof. These compounds have activity useful in treating allergies, arthritis, and inflammation.Type: GrantFiled: July 31, 1991Date of Patent: June 23, 1992Assignee: Warner-Lambert Co.Inventors: David T. Connor, Ila Sircar, Jagadish C. Sircar
-
Patent number: 5122537Abstract: The invention relates to new arylvinylamide derivatives of formula ##STR1## wherein Y is a bicyclic ring system chosen from (A), (B), (C), (D), and (E); ##STR2## in which m is zero, 1 or 2; R is hydrogen, a C.sub.1 -C.sub.6 alkyl or C.sub.1 -C.sub.6 alkanoyl group;R.sub.1 is hydrogen or C.sub.1 -C.sub.6 alkyl;R.sub.2 is hydrogen, halogen, cyano or C.sub.1 -C.sub.6 alkyl; andn is an integer of 1 to 3; and wherein each of the substituents --CH.dbd.CHNHCOR.sub.1, OR and R.sub.2 may be independently on either of the aryl and heteroaryl moieties of the bicyclic ring system (A), (C), (D) and (E); whereas only the benzene ring may be substituted in the bicyclic ring system (B),which are useful as tyrosine kinase inhibitors.Type: GrantFiled: November 2, 1990Date of Patent: June 16, 1992Assignee: Farmitalia Carlo Erba S.r.l.Inventors: Franco Buzzetti, Angelo Crugnola
-
Patent number: 5120856Abstract: A compound of the general formula ##STR1## or a salt or complex thereof, in which X, Y and Z are all optionally substituted carbon atoms and R is hydrogen, optionally substituted hydrocarbyl or acyl or --COOR.sup.7 and R.sup.7 is hydrocarbyl has anti-microbial properties. Particular examples are compounds in which X is --CH.sub.2 -- or --C(CH.sub.3).sub.2 -- and Y and Z are both --CH.sub.2 -- or X is is --CH.sub.2 -- and Y and Z are carbon atoms of a benzene ring. The zinc complexes have useful properties.Type: GrantFiled: July 19, 1990Date of Patent: June 9, 1992Assignee: Imperial Chemical Industries PLCInventors: Mark R. James, Gordon A. Thomson
-
Patent number: 5118703Abstract: Certain enol ethers and esters of the formula ##STR1## where X and Y are each hydrogen, fluoro or chloro; R.sup.1 is 2-thienyl or benzyl and R is alkanoyl, cycloalkylcarbonyl, phenylalkanoyl, chlorobenzoyl, methoxybenzyl, phenyl, thenoyl, omega-alkoxycarbonylalkanoyl, alkoxycarbonyl, phenoxycarbonyl, 1-alkoxyalkyl, 1-alkoxycarbonyloxyalkyl, alkyl, alkylsulfonyl, methylphenylsulfonyl or dialkylphosphonate are useful as prodrug forms the known 3-acyl-2-oxindole-1-carboxamide antiinflammatory and analgesic agents.Type: GrantFiled: April 8, 1991Date of Patent: June 2, 1992Assignee: Pfizer Inc.Inventors: Lawrence A. Reiter, Thomas C. Crawford
-
Patent number: 5103007Abstract: Lipid derivatives represented by the formula: ##STR1## wherein R.sup.1 stands for an optionally substituted higher alkyl group, R.sup.2 stands for an optionally substituted lower alkyl group or an optionally substituted nitrogen-containing heterocyclic group, R.sup.3 stands for a tertiary amino group or a quaternary ammonium group, J stands for oxygen atom or S(O)t (where t deontes 0, 1 or 2), m and n respectively denotes 1 or 2, p denotes 0, 1 or 2, q and r respectively denote an integer of 2 to 5.and salts thereof have antitumor activities including differentiation-inducing activity and are useful as antitumor agents.Type: GrantFiled: October 27, 1989Date of Patent: April 7, 1992Assignee: Takeda Chemical Industries, Ltd.Inventors: Hiroaki Nomura, Hiroshi Akimoto, Keizo Inoue
-
Patent number: 5091533Abstract: Compounds of the formula: ##STR1## where R.sup.2 contains certain aryls or heteroaryls are effective leukotriene inhibitors.Type: GrantFiled: March 12, 1990Date of Patent: February 25, 1992Assignee: Merck Frosst Canada, Inc.Inventors: Patrice C. Belanger, Claude Dufresne, Brian Fitzsimmons, deceased, Maryann Fitzsimmons, Heir, Yvan Guindon, Cheuk K. Lau, Joshua Rokach, John Schiegetz, Michel Therien, Robert N. Young
-
Patent number: 5084455Abstract: Novel indole-carboxamides of the formula ##STR1## wherein R and R.sub.1 are individually selected from the group consisting of hydrogen, alkyl of 1 to 5 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, cycloalkylalkyl of 4 to 7 carbon atoms and aralkyl of 7 to 12 carbon atoms optionally substituted with 1 to 3 members of the group consisting of halogen, methyl, ethyl, methoxy, ethoxy, --CF.sub.3, CH.sub.3 S--, --NH.sub.2 and --NO.sub.2 or R.sub.1 and R taken together with the nitrogen atom form an optionally unsaturated heterocycle optionally containing a member of the group consisting of --O--, --S-- and ##STR2## R' is selected from the group consisting of hydrogen, alkyl of 1 to 5 carbon atoms, phenyl, naphthyl, aralkyl of 7 to 12 carbon atoms and substituted phenyl, R.sub.3 is selected from the group consisting of hydrogen, alkyl of 1 to 5 carbon atoms, alkoxy of 1 to 3 carbon atoms, chlorine, bromine, iodine --NO.sub.2, --NH.sub.Type: GrantFiled: November 17, 1989Date of Patent: January 28, 1992Assignee: Roussel UclafInventors: Francois Clemence, Jacques Guillaume, Gilles Hamon
-
Patent number: 5081245Abstract: A compound represented by the formula: ##STR1## wherein R represents a hydrogen atom or a lower alkyl group;R.sup.1 represents a higher alkyl group which may be substituted;R.sup.2 represents a hydrogen atom or a lower alkyl group, a lower alkanoyl group or a nitrogen-containing 5- to 7-membered heterocyclic group each of which may be substituted; X represents a divalent group represented by the formula:--(OCH.sub.2 CH.sub.2).sub.p --wherein p represents an integer of 1 to 5, a divalent group represented by the formula:--O(CH.sub.2).sub.q --wherein q represents an integer of 3 to 8, or a divalent group represented by the formula:--(OCH.sub.2 CH.sub.2).sub.p --J--(CH.sub.2).sub.q --wherein J represents an oxygen atom or a group represented by the formula: --S(O).sub.Type: GrantFiled: August 18, 1989Date of Patent: January 14, 1992Assignee: Takeda Chemical Industries, Ltd.Inventors: Hiroaki Nomura, Hiroshi Akimoto, Eiko Imamiya, Keizo Inoue
-
Patent number: 5047554Abstract: This invention relates to novel 3-substituted-2-oxindole derivatives which are inhibitors of prostaglandin H.sub.2 synthase, 5-lipoxygenase and interleukin-1 biosynthesis. The compounds of the invention are useful as inhibitors of prostaglandin H.sub.2 synthase and interleukin-1 biosynthesis, per se, and as analgesic, antiinflammatory and antiarthritic agents in the treatment of chronic inflammatory diseases. This invention also relates to pharmaceutical compositions comprising said 3-substituted-2-oxindole derivatives; to methods of inhibiting prostaglandin H.sub.2 synthase and biosynthesis of interleukin-1; and to treating chronic inflammatory diseases in a mammal with said compounds. Further, this invention relates to certain novel carboxylic acids useful as intermediates in the preparation of the 3-substituted-2-oxindole derivatives of this invention and to a process for the preparation of the 3-substituted-2-oxindole derivatives.Type: GrantFiled: January 31, 1990Date of Patent: September 10, 1991Assignee: Pfizer Inc.Inventors: Frederick J. Ehrgott, Carl J. Goddard, Gary R. Schulte
-
Patent number: 5030654Abstract: A series of novel spiro-substituted glutaramide derivatives have been prepared, including the pharmaceutically acceptable salts thereof and bioprecursors therefor, wherein the spiro-substituent completes a 5- or 6-membered carbocycyclic ring and is located at the carbon atom adjacent to the carbamoyl group. These particular compounds are inhibitors of the neutral endopeptidase E.C.3.4.24.11 enzyme and are therefore useful in therapy as diuretic agents for the treatment of hypertension, heart failure, renal insufficiency and other disorders. Methods for preparing these compounds from known starting materials are provided.Type: GrantFiled: May 19, 1989Date of Patent: July 9, 1991Assignee: Pfizer Inc.Inventors: Ian T. Barnish, John C. Danilewicz, Keith James, Gillian M. R. Samuels, Nicholas K. Terrett, Michael T. Williams, Martin J. Wythes
-
Patent number: 5019587Abstract: The present invention provides compounds of the general formula (I) which inhibit the aggregation of erythrocytes or thrombocytes ##STR1## wherein A is hydrogen or C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl, C.sub.2 -C.sub.6 -alkynyl, benzyl or C.sub.3 -C.sub.7 -cycloalkyl radical, B is hydrogen, R.sub.1 is a C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl or C.sub.3 -C.sub.7 -cycloalkyl radical, R.sub.2 is a C.sub.1 -C.sub.6 -alkyl, C.sub.2 -C.sub.6 -alkenyl, C.sub.3 -C.sub.7 -cycloalkyl, C.sub.1 -C.sub.6 -alkylcarbonyl, C.sub.1 -C.sub.6 -alkoxycarbonyl, aminocarbonyl or hydrazinocarbonyl radical, or R.sub.1 and R.sub.2, together with the carbon atom to which they are attached, form a C.sub.3 -C.sub.7 -cycloalkyl ring, n is 0, X is a valency bond or a C.sub.1 -C.sub.6 -alkylene radical, R.sub.3 is a carbocyclic aromatic ring, which may be substituted; and the tautomers, optically-active forms and physiologically acceptable salts thereof with organic and inorganic acids.Type: GrantFiled: June 5, 1989Date of Patent: May 28, 1991Assignee: Boehringer Mannheim GmbHInventors: Wolfgang V. Von Der Saal, Alfred Mertens, Erwin Boehm
-
Patent number: 5010079Abstract: An indolone derivative is useful for the treatment of anxiety, depression and schizophrenia and is a 5HT.sub.1A agonist and 5HT.sub.2 antagonist, which is a compound of formula (I): ##STR1## in which R.sub.1 is a hydrogen or halogen atom or a (C.sub.1-4)alkyl radical,R.sub.2 is a hydrogen atom or a (C.sub.1-4)alkyl radical,R.sub.3 is a hydrogen atom, a (C.sub.1-4)alkyl radical or an S-(C.sub.1-4) alkyl radical; andR.sub.4 is a phenyl, chlorophenyl, naphthyl, 7-methoxy-1-naphthyl, 6-methoxy-1-indanyl, 2-methoxy-6-pyridyl, 3-methoxy-2-pyridyl, isoquinolyl, 7-methoxy-1-isoquinolyl, 7-methoxy-1,2,3,4-tetrahydro-1-naphthyl or 7-fluoro-1-naphthyl radical;or a pharmaceutically acceptable acid addition salt thereof.Type: GrantFiled: August 2, 1989Date of Patent: April 23, 1991Assignee: SynthelaboInventors: Philippe Manoury, Jean Binet, Daniel Obitz, Gerard Defosse, Elisabeth Dewitte, Corinne Veronique
-
Patent number: 5003079Abstract: Process for the preparation of benzimidazolones of the formula (1) ##STR1## in which R.sub.1 and R.sub.2 are identical or different and denote hydrogen or halogen atoms, or alkyl(C.sub.1 -C.sub.4), alkoxy(c.sub.1 -C.sub.4), trifluoromethyl, phenyl, phenoxy or nitro groups, by reacting o-phenylenediamines of the formula (2) ##STR2## in which R.sub.1 and R.sub.2 have the meaning given, with phosgene in water in the presence of an alkali metal base or alkaline earth metal base or a salt of an alkali metal hydroxide or alkaline earth metal hydroxide and a weakly inorganic or organic acid or a mixture of such salts or a suitable buffer system, at a pH of about 6 to about 12, and at a temperature of about 20.degree. to 100.degree. C.Type: GrantFiled: November 24, 1989Date of Patent: March 26, 1991Assignee: Hoechst AktiengesellschaftInventors: Michael Meier, Gunther Semler
-
Patent number: 4999429Abstract: Aryl difluoromethyl sulfone adds to aldehydes under phase transfer conditions to give novel substituted alcohols of the general formulaRCH(OH)CF.sub.2 SO.sub.2 Ar (I)wherein R is an aryl, cycloaliphatic, sec- or tert-aliphatic, or heterocyclic group and Ar is an aryl group. The substituted alcohols of formula I are of particular utility as intermediates in the synthesis of a variety of useful end products. For example, the products of formula I may be utilized in desulfonylation reactions, oxidation reactions and fluorination reactions.Type: GrantFiled: November 13, 1989Date of Patent: March 12, 1991Assignee: Ethyl CorporationInventor: G. Patrick Stahly
-
Patent number: 4997954Abstract: This invention relates to an improved process for the preparation of substituted indolinone derivatives using reductive cyclization conditions.Type: GrantFiled: June 15, 1988Date of Patent: March 5, 1991Assignee: Smith Kline & French Laboratories LimitedInventor: Joseph M. Fortunak
-
Patent number: 4994474Abstract: The present invention relates to aminoalkoxyphenyl derivatives of formula: ##STR1## and its N-oxide and pharmaceutically acceptable salts, in which: B represents a--S--, --SO-- or --SO.sub.2 -- group,R.sub.1 and R.sub.2, which are identical or different, each denote hydrogen, a methyl or ethyl radial or a halogen atom,A denotes a straight-or branched-alkylene radical having from 2 to 5 carbon atoms or a 2-hydroxypropylene radial in which the hydroxy is optionally substituted by a lower alkyl radical,R.sub.3 denotes an alkkyl radical or a radical of formula:--Alk--Arin which Alk denotes a single bond or a linear- or branched-alkylene radical having from 1 to 5 carbon atoms and Ar denotes a pyridyl, phenyl, 2,3-methylenedioxyphenyl or 3,4-methylenedioxyphenyl radical or a phenyl group substituted with one or more substituents, which may be identical or different, selected from halogen atoms, lower alkyl group or lower alkoxy groups,R.sub.Type: GrantFiled: February 6, 1989Date of Patent: February 19, 1991Assignee: SanofiInventors: Jean Gubin, Pierre Chatelain, Henri Inion
-
Patent number: 4985448Abstract: Lactam compounds of the formula ##STR1## in which: R is hydrogen, alkyl or cycloalkyl;R.sup.1 is hydrogen, alkyl, alkenyl or cycloalkyl;R.sup.2 is alkyl, alkenyl, cyano or a carbonyl substituted hydroxyl, alkyl, alkoxy, amino, alkylamino or hydrazino; orR.sup.1 and R.sup.2 together represent alkylidene cycloalkylidene; orR.sup.1, R.sup.2 and the adjacent carbon atom form a spirocyclic ring;n is 0 or 1;A is a --Co--NH--, --NH--CO--NH-- or --O--CO--NH--;X is a valency bond, alkylene or alkenylene; andR.sup.3 is optionally substituted phenyl, pyridyl, methylenedioxyphenyl or a five-membered heterocycle; or when X is a valency bond, R.sup.3 can also be an optionally substituted alkyl or alkino group, or cycloalkyl. The compounds are useful for the inhibition of erythrocyte and thrombocyte aggregation.Type: GrantFiled: February 6, 1989Date of Patent: January 15, 1991Assignee: Boehringer Mannheim GmbHInventors: Harald Zilch, Alfred Mertens, Wolfgang Von Der Saal, Erwin Boehm, Klaus Strein
-
Patent number: 4978773Abstract: A new process for the preparation of 2,6-dichlorodiphenylamine derivatives is described, which process provides the desired active compound in a high yield and with a very high degree of purity by a technically simple and realizable procedure.Type: GrantFiled: June 21, 1989Date of Patent: December 18, 1990Assignee: Heumann Pharma GmbH & Co.Inventors: Ingomar Grafe, Helmut Schickaneder, Kurt H. Ahrens
-
Patent number: 4977178Abstract: Certain substituted 1-phenyl-3-(aminoalkylidene)-2(1H,3H)-indolones are highly potent gabaergic agents, valuable in the treatment of individuals suffering from schizophrenia or reversing the side effects of a previously or concurrently administered neuroleptic agent; or in the treatment of epilepsy. A wider class of substituted 1-phenyl-3-(aminoalkylidene)-2(1H,3H)-indolones, together with 1-phenyl-3-(2-pyrrolidinylidene)-2(1H,3H)-indolones, and homologs thereof, are valuable in the treatment of anxiety.Type: GrantFiled: July 19, 1989Date of Patent: December 11, 1990Assignee: Pfizer Inc.Inventors: Harry R. Howard, Jr., Reinhard Sarges
-
Patent number: 4977274Abstract: The invention relates to new 4-hydroxyindole derivatives of general formula: ##STR1## in which R represents a labile protective group and R.sub.1 can represent hydrogen, a C.sub.1 -C.sub.6 alkyl radical, a C.sub.3 -C.sub.6 cycloalkyl radical, a lower alkoxy radical, a lower hydroxyalkyl radical, a lower (lower alkoxy) alkyl radical, a phenyl radical optionally substituted with a halogen atom or a lower alkyl or lower alkoxy radical, a cyano radical, a radical of formula ##STR2## in which R.sub.2 and R.sub.3, which may be identical or different, each represent hydrogen or a lower alkyl radical, R.sub.4 represents a hydroxy group, a lower alkyl or lower alkoxy radical or a radical ##STR3## in which R.sub.2 and R.sub.3 have the same meaning as above, R.sub.5 represents a lower alkyl radical and Alk represents a single bond or a straight- or branched-chain alkylene radical having from 1 to 4 carbon atoms.Type: GrantFiled: August 28, 1989Date of Patent: December 11, 1990Assignee: SanofiInventors: Marcel Descamps, Walter Verstraeten
-
Patent number: 4973772Abstract: A process is disclosed for preparing fluoroaromatic compounds (such as fluoronitrobenzene compounds) by reaction of corresponding chloroacromatic compounds (such as chloronitrobenzene compounds) with alkali metal fluoride salts in the presence of alkyldiorganoaminopyridinium salts as phase transfer catalysts. A tertiary carbon atom is directly attached to the alkyl carbon atom which is directly attached to the ring nitrogen atom. A preferred catalyst is N-neopentyl-4-(4'-methylpiperidinyl)pyridinium chloride.Type: GrantFiled: February 7, 1987Date of Patent: November 27, 1990Assignee: Mallinckrodt, Inc.Inventor: Gary L. Cantrell
-
Patent number: 4960785Abstract: A series of novel 3-mono(substituted methyl)- and 3,3-di(substituted methyl)-2-oxo-indoline-1-alkanoic acid compounds have been prepared, including their lower alkyl esters and unsubstituted amide derivatives, as well as the base salts of said acids with pharmacologically acceptable cations. These compounds are useful in therapy as aldose reductase inhibitors for the control of certain chronic diabetic complications. Said oxindole-1-alkanoic acid compounds are of the formulae: ##STR1## wherein X is hydrogen and X.sup.1 is hydrogen, hydroxy, fluorine, chlorine, bromine, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy; or X and X.sup.1, when taken separately, are each chlorine, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy, and when taken together are --OCH.sub.2 (CH.sub.2).sub.n O-- at the 4,5-, 5,6- or 6,7-positions of the molecule wherein n is zero or one; R.sub.1 is hydrogen or methyl; R.sub.2 is hydrogen, C.sub.1 -C.sub.Type: GrantFiled: December 16, 1988Date of Patent: October 2, 1990Assignee: Pfizer Inc.Inventors: Harry R. Howard, Jr., Reinhard Sarges
-
Patent number: 4952598Abstract: Calcium antagonists of the formula ##STR1## with R(1), R(2), R(3) and R(4) being, inter alia, H, alkyl, alkoxy, halogen, in some cases phenyl; m being 1-4; n being 0-3; X being CH.sub.2, O, S, CO, CHOH or CR.sub.2, and R(5) being various groups containing nitrogen atoms, are described.They are obtained by reaction of compounds II which are likewise new and which contain in place of R(5) a leaving group Y (Cl, Br, I) with the appropriate (cyclic) amino compound.Another synthesis comprises reaction of the appropriate indollinone derivative IV which has a non-etherified hydroxyl group with a side chain which contains a terminal leaving group Z (Cl, Br, I) in the presence of a base.Furthermore, indolinone derivatives VI with an ether side chain with a terminal epoxide group can be reacted with (cyclic) amines to give compounds I.Type: GrantFiled: November 1, 1989Date of Patent: August 28, 1990Assignee: Hoechst AktiengesellschaftInventors: Ulrich Lerch, Henning Rainer, Joachim Kaiser
-
Patent number: 4952703Abstract: Preparation of 2-oxindole-1-carboxamides by reaction of 2-oxindoles with trichloracetyl isocyanate to produce novel N-trichloroacetyl-2-oxindole-1-carboxamides which are then hydrolyzed to 2-oxindole-1-carboxamides useful as analgesic and anti-inflammatory agents and/or intermediates for such agents.Type: GrantFiled: May 25, 1989Date of Patent: August 28, 1990Assignee: Pfizer Inc.Inventor: Sarah E. Kelly
-
Patent number: 4950765Abstract: This invention relates to a catalytic transfer hydrogenation process using water as a solvent in the preparation of substituted indolinone derivatives.Type: GrantFiled: August 24, 1987Date of Patent: August 21, 1990Assignee: Smith Kline & French Laboratories LimitedInventors: Timothy C. Walsgrove, Paul Oxley
-
Patent number: 4933336Abstract: A compound of formula (I), or a pharmaceutically acceptable salt thereof, ##STR1## in which, R.sub.1 is hydrogen, lower alkyl or CH.sub.2 OR.sub.6 ;R.sub.2 is hydrogen or lower alkyl;R.sub.3 is hydrogen or lower alkyl;each of W and Z, which are different, represents --CR.sub.4 R.sub.5 -- or --(CR.sub.x R.sub.y).sub.n --, in which,R.sub.4 is hydrogen, C.sub.1-3 alkyl, C.sub.1-3 alkylthio or C.sub.1-3 alkoxy;R.sub.5 is C.sub.1-3 alkyl, C.sub.1-3 alkylthio or C.sub.1-3 alkoxy; or together R.sub.4 and R.sub.5 form a 3 to 6 membered carbocyclic ring, or a heterocyclic ring containing one or two ring oxygen, nitrogen or sulphur atoms;or R.sub.4 and R.sub.5 together form an oxo or methylene group;each of R.sub.x and R.sub.y is hydrogen or C.sub.1-3 alkyl; n is zero or 1;R.sub.6 is hydrogen, lower alkyl, lower alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, heteroarylcarbonyl, optionally substituted aminocarbonyl, lower alkoxycarbonyl and aryloxycarbonyl;R.sub.Type: GrantFiled: August 9, 1988Date of Patent: June 12, 1990Assignee: Laboratoires Sobio S.A.Inventors: Michel Martin, Guy Nadler, Richard Zimmermann
-
Patent number: 4933361Abstract: Disclosed are cis, exo- and trans-compounds of the formula I ##STR1## in which n denotes 0, 1 or 2, R.sub.1 denotes hydrogen, (C.sub.1 -C.sub.6)-alkyl which can optionally be substituted by amino, (C.sub.1 -C.sub.4)-acyl- or bezoylamino, (C.sub.2 -C.sub.6)-alkenyl, (C.sub.5 -C.sub.9)-cycloalkyl, (C.sub.5 -C.sub.9)-cycloalkenyl, (C.sub.5 -C.sub.7)-cycloalkyl-(C.sub.1 -C.sub.4)-alkyl, aryl or partially hydrogenated aryl, which can, in each case, be substituted by (C.sub.1 -C.sub.2)-alkyl, (C.sub.1 -C.sub.2)-alkoxy or halogen, aryl-(C.sub.1 -C.sub.4)-alkyl, /which can be substituted as defined previously in the aryl radical/, a monocyclic or bicyclic sulfur or nitrogen and/or nitrogen heterocyclic radical, or a side chain of naturally occurring aminoacid, R.sub.2 denotes hydrogen, (C.sub.1 -C.sub.6)-alkyl, (C.sub.2 -C.sub.6)-alkenyl or aryl-(C.sub.1 -C.sub.4)-alkyl, Y denotes hydrogen or hydroxyl, Z denotes hydrogen or Y and Z together denote oxygen, X denotes (C.sub.1 -C.sub.6)-alkyl, (C.sub.2 -C.sub.Type: GrantFiled: April 28, 1989Date of Patent: June 12, 1990Assignee: Hoechst AktiengesellschaftInventors: Hansjorg Urbach, Rainer Henning, Volker Teetz, Rolf Geiger, Reinhard Becker, Holger Gaul
-
Patent number: 4927980Abstract: A process is disclosed for preparing fluoroaromatic compounds (such as fluoronitrobenzene compounds) by reaction of corresponding chloroaromatic compounds (such as chloronitrobenzene compounds) with alkali metal fluoride salts in the presence of alkyldiorganoaminopyridinium salts as phase transfer catalysts. A secondary carbon atom is directly attached to the alkyl carbon atom which is directly attached to the ring nitrogen atom. A preferred catalyst is N-(2-ethylhexyl)-4-(N',N'- dimethylamino)pyridinium chloride.Type: GrantFiled: February 9, 1987Date of Patent: May 22, 1990Assignee: Mallinckrodt Inc.Inventor: Gary L. Cantrell