Nitrogen Attached Indirectly To Ring Carbon Of The Five-membered Hetero Ring By Acyclic Nonionic Bonding (e.g., Tryptamine, Etc.) Patents (Class 548/504)
-
Patent number: 5401854Abstract: A process for the production of indole derivatives, which is characterized in that in the presence of phosphoric acid a substitution with an imine is performed, and intermediate products of this process and the production of these intermediate products are described.Type: GrantFiled: March 8, 1993Date of Patent: March 28, 1995Assignee: Schering AktiengesellschaftInventors: Gregor Haffer, Helmut Borner, Wolfgang Kubler, Klaus Nickisch
-
Patent number: 5399574Type: GrantFiled: March 3, 1992Date of Patent: March 21, 1995Assignee: Burroughs Wellcome Co.Inventors: Alan D. Robertson, Alan P. Hill, Robert C. Glen, Graeme R. Martin
-
Patent number: 5382592Abstract: A series of serotonergic 5-cyclobutenedionylamino-substituted tryptamine derivatives of Formula I is disclosed for use in the alleviation of vascular headaches. ##STR1## The formula I substituents, as further defined in the specification, are: R.sup.1 is hydrogen, halogen, and alkyl; R.sup.2 and R.sup.3 can be hydrogen or alkyl; R.sup.4 is hydrogen, alkyl, acyl or alkylsulfonyl; m is 0 to 3 and n is 1 to 5; and X is amino, alkoxy, hydrogen, alkyl, aryl or alkylaryl.Type: GrantFiled: September 16, 1993Date of Patent: January 17, 1995Assignee: Bristol-Myers Squibb CompanyInventors: Jonas A. Gylys, Edward H. Ruediger, David W. Smith, Carola Solomon, Joseph P. Yevich
-
Patent number: 5348976Abstract: The present invention provides a condensed heterocyclic derivative represented by a formula: ##STR1## wherein R.sup.1 represents a lower alkyl group, an alkenyl group, or the like, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 independently represent a hydrogen atom, a lower alkyl, or the like, W is represented by --OC(O)--, --SC(O)--, or the like, and Z represents a 2-indolyl group or the like. The present invention also provides an agricultural or horticultural fungicide which comprises an amount of the condensed derivative known to be effective as a fungicide. The agricultural or horticultural fungicide according to the present invention exhibits a superior control effect for downy mildew and late blight, without harm to nonfungal, photosynthesizing plants.Type: GrantFiled: September 7, 1993Date of Patent: September 20, 1994Assignees: Kumai Chemical Industry Co., Ltd., Ihara Chemical Industry Co., Ltd.Inventors: Masaru Shibata, Shigekazu Ito, Jun-etsu Sakai, Shigeru Hayashi
-
Patent number: 5334606Abstract: Compounds of formula (I): ##STR1## wherein Q.sup.1 represents a phenyl group substituted by one or more halo; naphthyl; indolyl; benzthiophenyl; benzofuranyl; benzyl; or fluorenyl;R.sup.1 is H, C.sub.1-6 alkyl or C.sub.2-6 alkenyl;R.sup.2 is phenyl(C.sub.1-4 alkyl) optionally substituted in the phenyl ring by one or more groups selected from C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halo, cyano, nitro, trifluoromethyl, SR.sup.b, SOR.sup.b, SO.sub.2 R.sup.b, OR.sup.b, NR.sup.b R.sup.c, NR.sup.b COR.sup.c, NR.sup.b COOR.sup.c, COOR.sup.b or CONR.sup.b R.sup.c, where R.sup.b and R.sup.c independently represent H, C.sub.1-6 alkyl, phenyl or trifluoromethyl; andZ is O, S, NR.sup.8 or CR.sup.9 R.sup.10, where R.sup.8 represents H C.sub.1-6 alkyl, phenyl, phenyl(C.sub.1-4 alkyl), COR.sup.11, COOR.sup.11, CONR.sup.9 R.sup.10 where R.sup.11 is phenyl, phenyl(C.sub.1-4 alkyl) or C.sub.1-6 alkyl, and R.sup.9 and R.sup.10 are each H, C.sub.1-6 alkyl, phenyl or phenyl(C.sub.Type: GrantFiled: November 30, 1992Date of Patent: August 2, 1994Assignee: Merck Sharpe & Dohme Ltd.Inventor: Angus M. MacLeod
-
Patent number: 5328927Abstract: Compounds of formula (I), and salts and prodrugs thereof ##STR1## wherein Q.sup.1 is halo substituted phenyl; naphthyl; indolyl; benzthiophenyl; benzofuranyl; benzyl; or fluorenyl;. . is an optional covalent bond;one of X and Y is H and the other is hydroxy or C.sub.1-6 alkoxy, or X and Y are together .dbd.0 or .dbd.NOR.sup.5 ;R.sup.1 and R.sup.2 are H; C.sub.1-6 alkyl optionally substituted by hydroxy, cyano, COR.sup.c, CO.sub.2 R.sup.c, CONR.sup.c R.sup.d, or NR.sup.c R.sup.d (where R.sup.c and R.sup.d are H, C.sub.1-6 alkyl or phenyl(C.sub.0-4 alkyl) optionally substituted by C.sub.1-6 alkyl, C.sub.1-6 alkoxy, halo and trifluoromethyl); phenyl(C.sub.1-4 alkyl) (optionally substituted by C.sub.1-6 alkyl, C.sub.1-6 alkoxy, halo or trifluoromethyl); COR.sup.c ; CO.sub.2 R.sup.c ; CONR.sup.c R.sup.d ; COC.sub.1-6 alkylNR.sup.c R.sup.d ; CONR.sup.c COOR.sup.d ; or SO.sub.2 R.sup.c ;R.sup.3 is H, C.sub.1-6 alkyl or C.sub.2-6 alkenyl; andR.sup.4 is phenyl optionally substituted by C.sub.1-6 alkyl, C.sub.Type: GrantFiled: February 24, 1993Date of Patent: July 12, 1994Assignee: Merck Sharpe & Dohme, Ltd.Inventors: Richard T. Lewis, Kevin J. Merchant, Angus M. MacLeod
-
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: 5298491Abstract: Derivatives of biologically active molecules containing a primary amine group and a hydroxylated nucleus, and their addition salts with mineral or organic acids, having general formula I:R'R"N--A--B--O--CH.sub.2 --CO--NH--R (I)A=linear or branched C.sub.1 -C.sub.5 alkylene;B=C.sub.4 -C.sub.10 aromatic nucleus with optional heteroatom, or=group --B.sub.1 --X--B.sub.2 --, wherein X=O or C.sub.1 -C.sub.4 alkylene;--NH--R=amine residue or alcohol residue; andR', R"=C.sub.1 -C.sub.5 alkyl, H or hydrophobic radical, and their addition salts with mineral or organic acids, method of preparation, applications, especially to visualization, purification, the preparation of antibodies and the assay of the total hormone, and as drugs, compositions in which they are present and analytical kits.Type: GrantFiled: May 13, 1991Date of Patent: March 29, 1994Assignee: ImmunotechInventors: Jacques Chauveau, Michel Delaage, Anne Morel, Louis Segu
-
Patent number: 5270333Abstract: Compounds are disclosed of general formula: ##STR1## wherein R.sup.1 is H, C.sub.1-6 alkyl or C.sub.3-6 alkenyl; R.sup.2 is H, C.sub.1-3 alkyl, C.sub.3-6 alkenyl, aryl, ar(C.sub.1-4)-alkylene, or C.sub.5-7 cycloalkyl;R.sup.3 is H or C.sub.1-3 alkyl;R.sup.4 and R.sup.5 each represents H, C.sub.1-3 alkyl or 2-propenyl, or R.sup.4 and R.sup.5 together form an aralkylidene group;R.sup.6 represents --CO.sub.2 R.sup.7, COR.sup.7, --COCO.sub.2 R.sup.7, or --CONHR.sup.7, whereR.sup.7 represents H, C.sub.1-4 alkyl, C.sub.3-7 cycloalkyl, C.sub.2-4 alkenyl, aryl or ar(C.sub.1-4)alkylene (with the provisos that (a) R.sup.7 does not represent H or benzyl when R.sup.6 is --CO.sub.2 R.sup.7 and (b) R.sup.7 does not represent alkenyl when R.sup.6 is --CONHR.sup.7); and Alk represents an alkylene chain containing two or three carbon atoms which may be unsubstituted or substituted by not more than two C.sub.1-3 alkyl group, and physiologically acceptable salts and solvates (e.g. hydrates) thereof.Type: GrantFiled: August 16, 1991Date of Patent: December 14, 1993Assignee: Glaxo Group LimitedInventors: David E. Bays, Alexander W. Oxford
-
Patent number: 5256661Abstract: Certain novel compounds having the structural formula ##STR1## where R.sub.2, R.sub.3 and R.sub.4 are each selected from the group consisting of H and OA; A is H or is selected from the group consisting of hydrocarbyl radicals, e.g. lower alkyl radicals, i.e. methyl, ethyl, propyl, etc., or ##STR2## wherein R.sub.5 is selected from the group consisting of hydrocarbyl radicals, e.g. alkyl and aromatic residues; n is 2 or 3; and R.sub.1 is selected from the group consisting of organic radicals having fused aromatic rings, that is, radicals comprising at least two rings that share a pair of carbon atoms or share a carbon and nitrogen atom are useful for inducing a dopaminergic response and reducing the intraocular pressure in a mammal.Type: GrantFiled: September 28, 1992Date of Patent: October 26, 1993Assignee: Whitby Research, Inc.Inventor: Alan S. Horn
-
Patent number: 5245046Abstract: Provided are novel .alpha.-aminoindole-3-acetic acid derivatives having the formula ##STR1## wherein R through R9 are as defined in the specification, and pharmacologically acceptable salts of compounds wherein R.sub.9 is not OM, which are useful as anti-diabetic, anti-obesity and anti-atherosclerotic agents.Type: GrantFiled: May 8, 1991Date of Patent: September 14, 1993Assignee: The Upjohn CompanyInventors: Gilbert A. Youngdale, John C. Sih, Steven P. Tanis, Chiu-Hong Lin
-
Patent number: 5233050Abstract: An alkyl indole of the formula: ##STR1## is a useful antimigraine agent.Type: GrantFiled: February 7, 1992Date of Patent: August 3, 1993Assignee: Merck & Co., Inc.Inventors: Robert P. Borris, Yiu-Kuen T. Lam, Lawrence Koupal
-
Patent number: 5229413Abstract: Compositions containing certain indole-2-carboxylate compounds and derivatives are described as being therapeutically effective in treatment of CNS disorders resulting from neurotoxic damage or neurodegenerative diseases, particularly those CNS disorders resulting from ischemic events. Preferred compounds are of the formula ##STR1## wherein each of R.sup.5 and R.sup.6 is independently selected from hydrido, bromo, chloro and fluoro, and wherein each of R.sup.10 and R.sup.12 is independently selected from hydrido and lower alkyl, and pharmaceutically-acceptable salts thereof.Type: GrantFiled: February 3, 1992Date of Patent: July 20, 1993Assignee: G. D. Searle & Co.Inventors: Nancy M. Gray, Brian K. Cheng, William F. Hood, Michael S. Dappen, Alex A. Cordi
-
Patent number: 5219859Abstract: The invention relates to indole derivatives of formula 1, ##STR1## in which: R.sub.1 and R.sub.2 represent H, alkyl, alkenyl, cycloalkyl, N-alkylamino- or N,N-dialkylaminoalkyl, benzyl, pyridylmethyl or phenyl, optionally substituted,R.sub.3 and R.sub.4 represent H, halogen, alkyl, alkoxy, alkylthio, CF.sub.3, NO.sub.2, N-alkylamino or N,N-dialkylamino, benzyl or phenyl, optionally substituted,R.sub.5 represents H, alkyl, cycloalkyl or optionally substituted benzyl,R.sub.6 denotes an alkyl, phenyl or heterocyclic radical, optionally substituted,Z denotes the bivalent radicals --(CH.sub.2).sub.n --C(R.sub.7 R.sub.8)--(CH.sub.2).sub.p --, --CH=CH--C(R.sub.7 R.sub.8)-- in which n=0--2, p=0--2 and n+p.ltoreq.2, R.sub.7 and R.sub.Type: GrantFiled: March 20, 1992Date of Patent: June 15, 1993Assignee: Lipha, Lyonnaise Industrielle PharmaceutiqueInventors: Didier Festal, Denis Descours, Robert Bellemin, Jacques Decerprit
-
Patent number: 5198553Abstract: A process for the production of gramine derivatives is described, which is characterized in that an indole is reacted with an imine under acid catalysis in the presence of primary amines.Type: GrantFiled: December 26, 1991Date of Patent: March 30, 1993Assignee: Schering AktiengesellschaftInventors: Wolfgang Kubler, Gregor Haffer, Reiner Wierzchowski, Klaus Nickisch
-
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: 5142052Abstract: Aryl- and heterocyclic-methanamines are prepared by reacting a hydroxy-aryl carbinol or a heterocyclic carbinol with a primary or a secondary amine in the presence of a cationic effect reagent.Type: GrantFiled: October 21, 1988Date of Patent: August 25, 1992Assignee: Laboratoires SyntexInventors: Serge Beranger, Bruno Francois
-
Patent number: 5130327Abstract: Compounds of structure (1); ##STR1## and pharmaceutically acceptable salts are described, whereR is hydrogen or C.sub.1-4 alkyl,R' is hydrogen, C.sub.1-4 alkyl, or a C.sub.1-4 alkyl group substituted by an alkyne or allene group provided that R' is not methyl when R and R" are both hydrogen, andR" is hydrogen or a C.sub.1-4 alkyl group substituted by an alkyne or allene group.These compounds have anti-depressant activity. Processes for the preparation of the compounds, pharmaceutical compositions and methods of use, are described.Type: GrantFiled: October 2, 1990Date of Patent: July 14, 1992Assignee: Consejo Superior de Investigaciones CientificasInventors: Eldiberto F. Alvarez, Carlos E. Recalde, Maria Angeles C. Villalobos, Antonio Diaz Diaz, Carlos B. Barrios, Maria del Carmen O. Estomba
-
Patent number: 5122535Abstract: A method of synthesizing an indole derivative of the tryptamine type particularly melatonine, comprising the steps of 1) reacting potassium phthalimide and 1,3-di-bromopropane to obtain 3-bromopropylphthalimide; 2) reacting 3-bromopropylphthalimide with sodium acetoacetic ester in ethanol to obtain ethyl-2-acetyl-5-phthalimidopentanoate; 3) reacting the product from step 2) with diazo-p-anisidine to obtain 2-carboxyethyl-3-(2-phthalimidoethyl)-5-methoxy-indole; 4) reacting the 2-carboxyethyl-3-(2-phthalimidoethyl)-5-methoxy-indole with 2N/NaOH and then 20% H.sub.2 SO.sub.4 to obtain impure 5-methoxytriptamine, which is purified by means of hexamethyldisilazane. The mono and disubstituted derivatives are obtained and the monosubstituted derivative is hydrolyzed with aqueous methanol and then recrystallized from ethanol. The N-acetyl derivative is prepared by reaction with acetic anhydride. Melatonine of high purity is obtained for prophylaxy and also against AIDS (Acquired Immuno Deficiency Syndrome).Type: GrantFiled: February 17, 1989Date of Patent: June 16, 1992Inventors: Franco Fraschini, Luigi Di Bella, Ermanno Duranti
-
Patent number: 5103020Abstract: A method for the preparation of 3-(2-aminoethyl)-N-methyl-1H-indole-5-methanesulphonamide by reaction of 4-hydrazino-N-methylbenzenemethanesulphonamide and 4-chloro-1-hydroxybutanesulphonic acid, sodium salt in the presence of an acid.Type: GrantFiled: June 20, 1991Date of Patent: April 7, 1992Assignee: Glaxo Group LimitedInventors: Frederick D. Albinson, John W. M. MacKinnon, Derek L. Crookes
-
Patent number: 5095031Abstract: Substituted indolyl compounds of the formula ##STR1## are potent inhibitors of the lipoxygenase enzymes and are useful as agents for the treatment of allergies and inflammatory disease states.Type: GrantFiled: August 20, 1990Date of Patent: March 10, 1992Assignee: Abbott LaboratoriesInventors: Dee W. Brooks, George W. Carter, Joseph F. Dellaria, Robert G. Maki, Karen E. Rodriques
-
Patent number: 5037845Abstract: A compound of formula (I) ##STR1## and its physiologically acceptable salts and solvates are described as useful in treating and/or preventing pain resulting from dilatation of the cranial vasculature in particular migraine.Type: GrantFiled: March 1, 1989Date of Patent: August 6, 1991Assignee: Glaxo Group LimitedInventor: Alexander W. Oxford
-
Patent number: 5026909Abstract: A method according to the invention comprises mixing the starting biologically active organic compound, an inorganic vehicle and a catalyst in the form of a platinum-group metal, followed by reacting the resulting mixture with an isotope of hydrogen at a temperature of 373-523 K. and cooling the reaction mixture to a temperature of 288-303 K. and isolation of the desired product therefrom. The invention can be useful, for example, in medical and biological studies.Type: GrantFiled: March 22, 1989Date of Patent: June 25, 1991Inventors: Jury A. Zolotarev, Dmitry A. Zaitsev, Vadim J. Tatur, Nikolai F. Myasoedov
-
Patent number: 5021458Abstract: Amine derivatives having the general formula (I): ##STR1## wherein X is selected from the group consisting of ##STR2## wherein Q is oxygen, sulfur or nitrogen atom, and ##STR3## wherein Q is as above; Y is selected from the group consisting of ##STR4## R.sup.1 is hydrogen atom or an alkyl group; R.sup.2 is hydrogen atom or an alkyl group; R.sup.3 is hydrogen atom, a halogen atom or an alkyl group; R.sup.4 is hydrogen atom, an alkyl group, a cycloalkyl group, a halogenated alkyl group or a halogen atom; R.sup.5 is hydrogen atom, an alkyl group, an alkoxy group, a halogen atom, nitro group or hydroxy group; R.sup.5 is attached to an arbitrary position of X, and R.sup.3 or R.sup.4 is attached to an arbitrary position of Y.The amine derivatives (I) are useful as fungicides.Type: GrantFiled: December 7, 1988Date of Patent: June 4, 1991Assignee: Kaken Pharmaceutical Co., Ltd.Inventors: Tetsuya Maeda, Toshiyuki Yamamoto, Mituo Takase, Kazuya Sasaki, Tadashi Arika, Mamoru Yokoo, Rieko Hashimoto, Kouji Amemiya, Sakae Koshikawa
-
Patent number: 5021430Abstract: Disclosed are compound of the formula ##STR1## wherein X and Y independently represent hydroxymethyl; cyano; carboxy; functionally modified carboxy selected from esterified carboxy, carbamoyl, and N-substituted carbamoyl; 5-tetrazolyl; 2-oxazolyl, 4,5-dihydro-2-oxazolyl, or each said grouping substituted by lower alkyl; R and R.sub.o independently represent lower alkyl, (C.sub.3 -C.sub.7)-cycloalkyl-lower alkyl, or aryl-lower alkyl; A represents methylene; or A represents methylene substituted by lower alkyl, by lower alkylthio-lower alkyl, by aryl-lower alkylthio-lower alkyl, by arylthio-lower alkyl, by hydroxy-lower alkyl, by acyloxy-lower alkyl, by lower alkoxy-lower alkyl, by aryl-lower alkyloxy-lower alkyl, by aryloxy-lower alkyl, by amino-lower alkyl, by acylamino-lower alkyl, by guanidino-lower alkyl, by (C.sub.3 -C.sub.7)-cycloalkyl, by (C.sub.3 -C.sub.Type: GrantFiled: June 29, 1987Date of Patent: June 4, 1991Assignee: Ciba-Geigy CorporationInventor: Gary M. Ksander
-
Patent number: 4994483Abstract: Indole derivatives are disclosed of the general formula (I): ##STR1## wherein R.sub.1 is hydrogen, C.sub.1-6 alkyl or C.sub.3-6 alkenyl; R.sub.2 is a hydrogen, C.sub.1-3 alkyl, C.sub.3-6 alkenyl, phenyl, phen(C.sub.1-4)alkyl or C.sub.5-7 cycloalkyl; R.sub.3 and R.sub.4 are hydrogen, C.sub.1-3 alkyl or propenyl groups or together form an aralkylidene group; Alk is C.sub.2 -C.sub.3 alkylene chain and A is C.sub.2 -C.sub.5 alkylene chainand its physiologically acceptable salts and solvates.The compounds may be prepared, for example, by cyclization of a compound of general formula (II): ##STR2## where Q is the group NR.sub.3 R.sub.4 or a protected derivative thereof or a leaving group and R.sub.1 l, R.sub.2, R.sub.3, R.sub.4, A and Alk are as defined for formula (I).The compounds have a selective vosoconstrictor action and are useful in treating pain such as migraine. The compounds may be formulated as pharmaceutical compositions in conventional manner, preferably for oral administration.Type: GrantFiled: November 30, 1989Date of Patent: February 19, 1991Assignee: Glaxo Group LimitedInventors: Alexander W. Oxford, Brian Evans, Michael D. Dowle, Ian H. Coates
-
Patent number: 4980368Abstract: A compound of formula (I) or a pharmaceutically acceptable salt thereof: ##STR1## wherein: R.sub.1 is hydrogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy or halogen;R.sub.2 and R.sub.3 are both hydrogen or together represent a bond;R.sub.4 is selected from C.sub.1-6 alkyl, phenyl, phenyl C.sub.1-4 alkyl, COR.sub.8 where R.sub.8 is hydroxy, C.sub.1-6 alkoxy or NR.sub.9 R.sub.10 where R.sub.9 and R.sub.10 are independently hydrogen or C.sub.1-4 alkyl and CH.sub.2 OR.sub.11 and R.sub.11 is hydrogen, C.sub.1-4 alkyl or C.sub.1-4 alkanoyl;R.sub.5 is hydrogen, C.sub.1-6 alkyl or phenyl C.sub.1-4 alkyl;R.sub.6 is phenyl C.sub.1-7 alkyl in which the phenyl moiety is optionally substituted by one or two of halogen, ortho-nitro, meta- or para-methoxy, methyl or NR.sub.12 R.sub.13 wherein R.sub.12 and R.sub.13 are independently hydrogen or C.sub.1-6 alkyl or R.sub.12 and R.sub.13 together are C.sub.2-6 polymethylene or the phenyl moiety is 3,4-disubstituted by methylenedioxy or ethylenedioxy; andR.sub.7 is hydrogen or C.sub.Type: GrantFiled: December 23, 1986Date of Patent: December 25, 1990Assignee: Beecham-Wuelfing GmbH & Co. KGInventors: Dietrich Thielke, Dagmar Hoeltje
-
Patent number: 4963689Abstract: Heterocyclicguanidines as 5HT.sub.3 antagonists useful in the treatment of nausea, anxiety, pain, schizophrenia and gastrointestinal disorders.Type: GrantFiled: May 19, 1989Date of Patent: October 16, 1990Assignee: Pfizer Inc.Inventors: Arthur A. Nagel, James P. Rizzi, Terry J. Rosen
-
Patent number: 4939174Abstract: The invention involves the formation of a prodrug from a fatty acid carrier and a neuroactive drug. The prodrug is stable in the environment of both the stomach and the bloodstream and may be delivered by ingestion. The prodrug passes readily through the blood brain barrier. Once in the central nervous system, the prodrug is hydrolyzed into the fatty acid carrier and the drug to release the drug.In a preferred embodiment, the carrier is 4,7,10,13,16,19 docosahexa-enoic acid and the drug is dopamine. Both are normal components of the central nervous system. The covalent bond between the drug and the carrier preferably is an amide bond, which bond may survive the conditions in the stomach. Thus, the prodrug may be ingested and will not be hydrolyzed completely into the carrier molecule and drug molecule in the stomach.Type: GrantFiled: February 26, 1988Date of Patent: July 3, 1990Inventor: Victor E. Shashoua
-
Patent number: 4933324Abstract: The invention involves the formation of a prodrug from a fatty acid carrier and a neuroactive drug. The prodrug is stable in the environment of both the stomach and the bloodstream and may be delivered by ingestion. The prodrug passes readily through the blood brain barrier. Once in the central nervous system, the prodrug is hydrolyzed into the fatty acid carrier and the drug to release the drug.In a preferred embodiment, the carrier is 4, 7, 10, 13, 16, 19 docosahexa-enoic acid and the drug is dopamine. Both are normal components of the central nervous system. The covalent bond between the drug and the carrier preferably is an amide bond, which bond may survive the conditions in the stomach. Thus, the prodrug may be digested and will not be hydrolyzed completely into the carrier molecule and drug molecule in the stomach.Type: GrantFiled: February 24, 1989Date of Patent: June 12, 1990Inventor: Victor E. Shashoua
-
Patent number: 4894387Abstract: Compounds are disclosed of the general formula (I) ##STR1## wherein R.sub.1 represents halogen, alkyl, alkoxy or hydroxyl, or a group NR.sub.a R.sub.b or CON.sub.a R.sub.b, where R.sub.a and R.sub.b are hydrogen, alkyl or alkenyl or with the nitrogen atom form a saturated monocyclic 5 to 7-membered ring;R.sub.2 represents hydrogen or alkyl;R.sub.3 and R.sub.4 represent hydrogen, C.sub.1-3 alkyl or propenyl or R.sub.3 and R.sub.4 together form an aralkylidene group; Alk represents a C.sub.2-3 alkylene chain;n and m, are integers of 1 to 4 or n is zero, and their physiologically acceptable salts and solvates.The compounds are described as useful in treating pain originating from dilatation of the cranial vasculature in particular migraine and cluster headache and can be formulated in conventional manner as pharmaceutical compositions with carriers or excipients for administration by any convenient route.Type: GrantFiled: March 26, 1987Date of Patent: January 16, 1990Assignee: Glaxo Group LimitedInventors: Darko Butina, Michael D. Dowle, Ian H. Coates
-
Patent number: 4879305Abstract: This invention relates to pharmacologically-active novel compounds comprising .beta.-fluoromethylene-5-hydroxytryptophan and derivatives, to methods of inhibiting monoamine oxidase and to treating depression, and to pharmaceutical compositions containing the compounds.Type: GrantFiled: December 2, 1988Date of Patent: November 7, 1989Assignee: Merrell Dow PharmaceuticalsInventors: Ian A. McDonald, Michael G. Palfreyman, Jean-Noel Collard
-
Patent number: 4876267Abstract: Indole derivatives are disclosed of the formula (I): ##STR1## wherein R.sub.1 represents H, or C.sub.1-6 alkyl or C.sub.3-6 Alkenyl;R.sub.2 represents a H, C.sub.1-3 alkyl, C.sub.3-6 alkenyl or C.sub.5-7 cycloalkyl, or a phenyl or phen(C.sub.1-4)alkyl group in which the phenyl ring is optionally substituted by halogen or C.sub.1-3 alkyl, C.sub.1-3 alkoxy or hydroxyl, or by a group NR.sup.a R.sup.b, or CONR.sup.a R.sup.b, wherein R.sup.a and R.sup.b each independently represents H or C.sub.1-3 alkyl;R.sub.3 and R.sub.4, each independently represents H or C.sub.1-3 alkyl or 2-propenyl;and physiologically acceptable salts and solvates (e.g. hydrates) thereof.The compounds have potent and selective vasoconstrictor activity and are indicated as useful for the treatment of migraine. The compounds may be formulated as pharmaceutical compositions with pharmaceutically acceptable carriers or excipients for administration by any suitable means. Various methods for the preparation of the compounds are disclosed.Type: GrantFiled: June 26, 1987Date of Patent: October 24, 1989Assignee: Glaxo Group LimitedInventors: Darko Butina, Michael D. Dowle, David E. Bays, Colin F. Webb
-
Patent number: 4870096Abstract: Indoles are disclosed of formula (I): ##STR1## wherein R.sub.1 represents R.sub.5 R.sub.6 NCOCH.sub.2 --, R.sub.5 CONH(CH.sub.2).sub.p --,R.sub.5 R.sub.6 NSO.sub.2 (CH.sub.2).sub.p -- or R.sub.7 SO.sub.2 NH(CH.sub.2).sub.p --, (where R.sub.5 and R.sub.6 each represents a hydrogen atom or a C.sub.1-3 alkyl group, R.sub.7 represents C.sub.1-3 alkyl and p is zero or one),R.sub.2 is hydrogen or C.sub.1-3 alkyl;R.sub.3 and R.sub.4 each represents hydrogen atom, C.sub.1-3 alkyl, or 2-propenyl;m is zero or an integer from 1 to 4; andn is an integer from 2 to 5; and physiologically acceptable salts and solvates (e.g. hydrates) thereof.The compounds have potent and selective vasoconstrictor activity and are indicated as useful for the treatment of migraine. They may be formulated as pharmaceutical compositions with pharmaceutically acceptable carriers of excipients for administration by any convenient route.Various methods for the preparation of the compounds (I) are disclosed.Type: GrantFiled: December 11, 1986Date of Patent: September 26, 1989Assignee: Glaxo Group LimitedInventors: Alexander W. Oxford, Ian H. Coates, David E. Bays, Colin F. Webb
-
Patent number: 4855314Abstract: Compounds are disclosed of formula (I): ##STR1## wherein R.sub.1 is halogen, a C.sub.1-3 alkoxy, R.sub.6 R.sub.7 NCO(CH.sub.2).sub.p --, R.sub.6 CONH(CH.sub.2).sub.p --, R.sub.6 R.sub.7 NSO.sub.2 (CH.sub.2).sub.p --, or R.sub.8 SO.sub.2 NH(CH.sub.2).sub.p -- (where R.sub.6 and R.sub.7 each represents hydrogen or C.sub.1-3 alkyl, R.sub.8 represents C.sub.1-3 alkyl and p is zero or 1);R.sub.2 represents hydrogen or C.sub.1-3 alkyl; R.sub.3 represents hydrogen or C.sub.1-3 alkyl;R.sub.4 and R.sub.5 each represents hydrogen, C.sub.1-3 alkyl or 2-propenyl;A represents --CO-- or --SO.sub.2 --;n represents an integer from 2 to 5; and m represents zero or an integer from 1 to 4; and physiologically acceptable salts and solvates (e.g. hydrates) thereof.The compounds have potent and selective vasoconstrictor activity and are indicated as useful for the treatment of migraine.Type: GrantFiled: January 8, 1987Date of Patent: August 8, 1989Assignee: Glaxo Group LimitedInventors: Alexander W. Oxford, Ian H. Coates, David E. Bays, Colin F. Webb, Michael D. Dowle, Keith Mills, Colin D. Eldred
-
Patent number: 4855448Abstract: 2-Amino-3-aroyl-.gamma.-oxobenzenebutanoic acids and derivatives having the formula: ##STR1## wherein X is hydrogen, halogen, or loweralkyl; Y is hydrogen, halogen, loweralkyl, loweralkoxy, nitro, or trifluoromethyl; n is 1 or 2; and R is hydrogen, loweralkyl, or a pharmaceutically acceptable cation, are disclosed having anti-inflammatory activity.Type: GrantFiled: August 8, 1988Date of Patent: August 8, 1989Assignee: A. H. Robins Company, IncorporatedInventor: David A. Walsh
-
Patent number: 4839377Abstract: Compounds are disclosed of general formula (I) ##STR1## wherein R.sub.1 represents a group CHO, COR.sub.8, CO.sub.2 R.sub.8, CONR.sub.9 R.sub.10, CSNR.sub.9 R.sub.10 or SO.sub.2 NR.sub.9 R.sub.10,where R.sub.8 represents an alkyl, cycloalkyl, aryl or aralkyl group,R.sub.9 represents a hydrogen atom or an alkyl group, andR.sub.10 represents a hydrogen atom or an alkyl, cyclo-alkyl, aryl or aralkyl group;R.sub.2, R.sub.3, R.sub.4, R.sub.6 and R.sub.7, which may be the same or different, each represents a hydrogen atom or a C.sub.1-3 alkyl group;R.sub.5 represents a hydrogen atom or an alkyl, cycloalkyl, alkenyl or an aralkyl group orR.sub.4 and R.sub.5 together form an aralkylidene group orR.sub.4 and R.sub.5 together with the nitrogen atom to which they are attached form a saturated monocyclic 5- to 7-membered ring; andAlk represents an alkylene chain containing two or three carbon atoms which may be unsubstituted or substituted by not more than two C.sub.1-3 alkyl groups;with the provisos that when R.sub.Type: GrantFiled: August 6, 1987Date of Patent: June 13, 1989Assignee: Glaxo Group LimitedInventors: David E. Bays, Colin F. Webb, Michael D. Dowle
-
Patent number: 4833153Abstract: Compounds are disclosed of formula (I): ##STR1## wherein one of R.sup.1, R.sup.2 and R.sup.3 represents hydrogen, C.sub.1-6 alkyl C.sub.3-6 alkenyl, hydroxy, C.sub.1-4 alkoxy or a C.sub.2-5 alkoxycarbonyl group, a phenyl or substituted phenyl group or a phen(C.sub.1-4)alkyl or substituted phen(C.sub.1-4)alkyl group; and the other two each independently represents hydrogen, C.sub.1-6 alkyl, or R.sup.2 and R.sup.3 together form an alkylene chain --(CH.sub.2).sub.n --where n is 2 or 3, bridging the nitrogen atoms to which they are attached; R.sup.4 and R.sup.5, each independently represents hydrogen, C.sub.1-3 alkyl or propenyl; R.sup.6 represents hydrogen, C.sub.1-3 alkyl, and the physiologically acceptable salts and solvates thereof.The compounds (I) have potent and selective vasoconstrictor activity and are potentially useful for the treatment of migraine. The compounds (I) may be formulated in conventional manner as pharmaceutical compositions for administration by any convenient route.Type: GrantFiled: November 7, 1986Date of Patent: May 23, 1989Assignee: Glaxo Group LimitedInventors: Michael D. Dowle, Brian Evans, Peter Clark
-
Patent number: 4816470Abstract: Indole derivatives of the general formula (I) are disclosed: ##STR1## where R.sub.1 is H or an alkyl or alkenyl group, R.sub.2 is H, or an alkyl, alkenyl, aryl, aralkyl or cycloalkyl group;R.sub.3 is H or an alkyl group;R.sub.4 and R.sub.5 are independently H or an alkyl or propenyl group or together form an aralkylidene group; andAlk is an optionally substituted alkylene chain; and their physiologically acceptable salts and solutes.These compounds are potentially useful for the treatment of migraine and may be formulated as pharmaceutical compositions in conventional manner.Various methods for the production of the compounds are disclosed including a Fischer-indole cyclization process.Type: GrantFiled: November 15, 1985Date of Patent: March 28, 1989Assignee: Glaxo Group LimitedInventors: Michael D. Dowle, Ian H. Coates
-
Patent number: 4803218Abstract: Compounds useful as antihypertensive agents which are 3-aminoalkyl-1H-indole-5-urea or amide derivatives having the following formula: ##STR1## or a pharmaceutically acceptable acid addition salts thereof, wherein: R is C.sub.1-4 loweralkyl, C.sub.1-4 loweralkoxy, phenyl, ##STR2## pyrrolyl, pyridyl or is a substituted nitrogen represented by: ##STR3## wherein R.sub.1 is H or a C.sub.1-4 loweralkyl or phenyl or cycloalkyl; R.sub.2 is H or a C.sub.1-4 loweralkyl; Y is H or halo; R.sub.3 is H or a C.sub.1-4 loweralkyl; R.sub.4 is H or a C.sub.1-4 loweralkyl; R.sub.5 is H or a C.sub.1-4 loweralkyl or carboxymethyl or carboxytrifluoromethyl; R.sub.6 is H or a C.sub.1-4 loweralkyl, and R.sub.5 and R.sub.6 may also be taken together as an N-loweralkyl-pyrrolidinylidene group.Type: GrantFiled: September 29, 1982Date of Patent: February 7, 1989Assignee: McNeilab, Inc.Inventors: Kerry G. Stanley, Winston Ho
-
Patent number: 4795756Abstract: Compounds are disclosed of formula (I) ##STR1## wherein R.sub.1 is H, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, phenyl optionally substituted by C.sub.1-3 alkoxy or phen(C.sub.1-4) alkyl in which the phenyl ring is optionally substituted by C.sub.1-3 alkoxy;R.sub.2 is H or C.sub.1-6 alkyl;R.sub.3 is H or C.sub.1-3 alkyl;R.sub.4 and R.sub.5 independently represents H, C.sub.1-3 alkyl or 2-propenyl; andn represents zero or 1;and physiologically acceptable salts and solvates (e.g. hydrates) thereof.The compounds have potent selective vasoconstrictor activity and are indicated as useful for the treatment of migraine. The compounds may be formulated as pharmaceutical compositions with physiologically acceptable carrier or excipients for administration by any convenient route. Various methods for the preparation of the compounds (I) are disclosed.Type: GrantFiled: March 27, 1987Date of Patent: January 3, 1989Assignee: Glaxo Group LimitedInventors: Alexander W. Oxford, Michael D. Dowle
-
Patent number: 4785016Abstract: Indole derivatives are disclosed of formula (I): ##STR1## wherein R.sub.1 represents H, alkyl or alkenyl;R.sub.2 represents H, alkyl, alkenyl, cycloalkyl or phenyl or phenyl alkyl the phenyl ring being optionally substituted by halogen, alkyl, alkoxy, hydroxyl or by a group --NR.sub.a R.sub.b, or --CONR.sub.a R.sub.b, wherein R.sub.a and R.sub.b are H, alkyl, alkenyl, or with the nitrogen atom form a saturated monocyclic ring;R.sub.3 and R.sub.4 are H, alkyl or propenyl or together form an aralkylidene group;Alk represents a Cf.sub.2-3 alkyl chain optionally substituted by one or two alkyl groups; andA.sup.1 represents a C.sub.2-5 alkenyl chain and salts and solvates thereof.The compounds have selective vasoconstrictor activity and are useful in treating and/or preventing pain resulting from dilatation of the cranial vasculature, particularly migraine. The compounds may be formulated in conventional manner with pharmaceutically acceptable carriers or excipients.Type: GrantFiled: December 3, 1985Date of Patent: November 15, 1988Assignee: Glaxo Group LimitedInventors: Brian Evans, Alexander W. Oxford, Darko Butain
-
Patent number: 4772726Abstract: Melatonine is obtained by methylating N-acetyl serotonine in the 5-position. Mexamine is obtained by de-acetylating melatonine in a hot alkaline solution containing a water-insoluble alcohol and acidifying the alcohol phase with hydrochloric acid.Type: GrantFiled: October 31, 1986Date of Patent: September 20, 1988Assignee: Nestec S. A.Inventors: Raymond Bertholet, Pierre Hirsbrunner
-
Patent number: 4772599Abstract: New benzodiazepine derivatives of the general formula ##STR1## wherein X.sup.1 and X.sup.2 independently are ##STR2## wherein R.sup.1 is C.sub.1-3 -alkyl, C.sub.3-5 -cycloalkyl, C.sub.1-3 -alkoxymethyl, C.sub.1-3 -hydroxyalkyl, or aryl,R.sup.4 is hydrogen, andR.sup.5 is C.sub.1-6 -alkyl, or wherein R.sup.4 and R.sup.5 together form a 2-4 membered alkylene chain.The compounds are useful in psychopharmaceutical preparations as anticonvulsants, anxiolytics, hypnotics, and nootropics.Type: GrantFiled: March 13, 1987Date of Patent: September 20, 1988Assignee: A/S FerrosanInventor: Frank Watjen
-
Patent number: 4720585Abstract: Aminopeptidase inhibitory activity is exhibited by compounds having the formula ##STR1## wherein R.sub.1 is hydrogen, alkyl, carboxyalkyl, halo-substituted alkyl, hydroxyalkyl, aminoalkyl, mercaptoalkyl, alkylthioalkyl, (cycloalkyl)alkyl, (heteroaryl)alkyl, arylalkyl, carbamoylalkyl, guanidinylalkyl or heteroaryl; andR.sub.2 and R.sub.3 are each independently hydrogen, alkyl, cycloalkyl, hydroxyalkyl, aminoalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl.Type: GrantFiled: September 18, 1985Date of Patent: January 19, 1988Assignee: E. R. Squibb & Sons, Inc.Inventors: Jollie D. Godfrey Jr., Eric M. Gordon
-
Patent number: 4675405Abstract: There are disclosed compounds of the formula ##STR1## wherein X is ##STR2## W is --O--, --S--, ##STR3## when n=0, or W is ##STR4## when n=1, and the dotted line represents an optional double bond; Y is --CH.sub.2 O--, --OCH.sub.2 --, --CH.sub.2 S--, --SCH.sub.2 --, ##STR5## n is 0-1; R.sup.1 is hydrogen, loweralkyl, loweralkoxy, lower alkanoyl, halo, trifluoromethyl, cyano or nitro;R.sup.2 is hydrogen or loweralkyl;R.sup.3 is loweralkyl, perfluoroloweralkyl or perfluorophenyl, with the proviso that when X=N, W=O or S and n=0, R.sup.3 is other than loweralkyl;and the pharmaceutically acceptable salts thereof, and their use in the treatment of leukotriene-mediated naso-bronchial obstructive airpassageway conditions, such as allergic rhinitis, allergic bronchial asthma and the like, and in antithrombotic therapy.Type: GrantFiled: January 27, 1986Date of Patent: June 23, 1987Assignee: American Home Products CorporationInventors: John H. Musser, Dennis M. Kubrak, Anthony F. Kreft, III
-
Patent number: 4672067Abstract: Compounds are disclosed of formula (I) ##STR1## wherein R.sub.1 represents CHO, COR.sub.8, CO.sub.2 R.sub.8, CONR.sub.9 R.sub.10, CSNR.sub.9 R.sub.10 or SO.sub.2 NR.sub.9 R.sub.10, whereR.sub.8 represents alkyl, cycloalkyl, aryl or aralkyl,R.sub.9 represents hydrogen or alkyl, andR.sub.10 represents hydrogen or alkyl, cycloalkyl, aryl or aralkyl;R.sub.2, R.sub.3, R.sub.4, R.sub.6 and R.sub.7 each independently represents hydrogen or C.sub.1-3 alkyl;R.sub.5 represents hydrogen, or alkyl, cycloalkyl, alkenyl or aralkyl, orR.sub.4 and R.sub.5 together form an aralkylidene group or R.sub.4 and R.sub.5 together with the attached nitrogen atom form a saturated monocyclic 5- to 7-membered ring; andAlk represents C.sub.2-3 alkylene chain optionally substituted by not more than two C.sub.1-3 alkyl groups;and physiologically acceptable salts and solvates thereof.Type: GrantFiled: June 28, 1984Date of Patent: June 9, 1987Assignee: Glaxo Group LimitedInventors: Ian H. Coates, Keith Mills, Colin F. Webb, Michael D. Dowle, David E. Bays
-
Patent number: 4650810Abstract: Compounds are disclosed of general formula (I): ##STR1## wherein R.sub.1, R.sub.3, R.sub.4, R.sub.6 and R.sub.7, which may be the same or different, each represents a hydrogen atom or an alkyl group;R.sub.2 represents a hydrogen atom or an alkyl, aryl, aralkyl, cycloalkyl or alkenyl group;or R.sub.1 and R.sub.2, together with the nitrogen atom to which they are attached, form a saturated monocyclic 5 to 7-membered ring which may optionally contain a further hetero function;R.sub.5 represents a hydrogen atom or an alkyl or alkenyl group;or R.sub.4 and R.sub.5 together form an aralkylidene group;Alk represents an alkylene chain containing two or three carbon atoms which may be unsubstituted or substituted by not more than two C.sub.1-3 alkyl groups; andX represents an oxygen or sulphur atom; and physiologically acceptable salts, solvates and bioprecursors thereof.Type: GrantFiled: January 26, 1983Date of Patent: March 17, 1987Assignee: Glaxo Group LimitedInventors: David E. Bays, Colin F. Webb, Michael D. Dowle
-
Patent number: 4636521Abstract: Compounds are disclosed of general formula (I) ##STR1## wherein R.sub.1 represents an alkyl, cycloalkyl, aryl or aralkyl group;R.sub.2, R.sub.3, R.sub.4, R.sub.6 and R.sub.7, which may be the same or different, each represents a hydrogen atom or a C.sub.1-3 alkyl group;R.sub.5 represents a hydrogen atom or an alkyl, cycloalkyl, alkenyl or an aralkyl group; or R.sub.4 and R.sub.5 together form an aralkylidene group or R.sub.4 and R.sub.5 together with the nitrogen atom to which they are attached form a saturated monocyclic 5- to 7-membered ring; Alk represents an alkylene chain containing two or three carbon atoms which may be unsubstituted or substituted by not more than two C.sub.1-3 alkyl groups; and physiologically acceptable salts, solvates and bioprecursors thereof. The compounds are described as potentially useful for the treatment of migraine and may be formulated as pharmaceutical compositions in conventional manner using one or more pharmaceutically acceptable carriers or excipients.Type: GrantFiled: June 29, 1984Date of Patent: January 13, 1987Assignee: Glaxo Group LimitedInventors: Ian H. Coates, Keith Mills, Colin F. Webb, Michael D. Dowle, David E. Bays
-
Patent number: 4581457Abstract: There are disclosed compounds of the formula ##STR1## wherein X is ##STR2## W is ##STR3## Y is ##STR4## n is 0-8; R.sup.1 is hydrogen, loweralkyl, loweralkoxy, lower alkanoyl, halo, trifluoromethyl, cyano or nitro;R.sup.2 is hydrogen or loweralkyl;and the pharmaceutically acceptable salts thereof, and their use in the treatment of leukotriene-mediated naso-bronchial obstructive airpassageway conditions, such as allergic rhinitis, allergic bronchial asthma and the like, and in antithrombotic therapy.Type: GrantFiled: September 21, 1984Date of Patent: April 8, 1986Assignee: American Home Products CorporationInventors: John H. Musser, Dennis M. Kubrak