Chalcogen Or Additional Nitrogen Attached Indirectly To Ring Carbon Of The Five-membered Hetero Ring By Acyclic Nonionic Bonding Patents (Class 548/507)
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Patent number: 5674889Abstract: The present invention relates to compounds of formula (I) and salts and prodrugs thereof, wherein Q.sup.1 represents a phenyl group substituted by one or more halo optionally substituted naphthyl, optionally substituted indolyl, optionally substituted benzthiophenyl, optionally substituted benzofuranyl, optionally substituted benzyl or optionally substituted fluorenyl; R.sup.1 represents H or C.sub.1-6 alkyl; R.sup.2 represents H, C.sub.1-6 alkyl or C.sub.2-6 alkenyl; Z.sup.1 represents a group selected from (a) or (b). The compounds are tachykinin antagonists useful for treating pain or inflammation, migraine or emesis.Type: GrantFiled: August 21, 1995Date of Patent: October 7, 1997Assignee: Merck, Sharp & Dohme, Ltd.Inventors: Fintan Kelleher, Richard Thomas Lewis, Angus Murray Macleod
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Patent number: 5668180Abstract: A compound selected from those of formula (I): ##STR1## in which A, R, Y, R.sup.1, R.sup.2 and R.sup.3 are as defined in the description,and a medicinal product containing the same useful for treating a disorder of the melatoninergic system.Type: GrantFiled: May 30, 1996Date of Patent: September 16, 1997Assignee: Adir Et CompagnieInventors: Daniel Lesieur, Patrick Depreux, Veronique Leclerc, Philippe Delagrange, Pierre Renard
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Patent number: 5635528Abstract: 3-Ethanamine and 3-ethanamine related compounds are provided that are useful intermediates and have beneficial central nervous system activity.Type: GrantFiled: June 7, 1995Date of Patent: June 3, 1997Assignee: Eli Lilly and CompanyInventors: James E. Audia, James J. Droste, Deborah A. Evrard, Pawel Fludzinski, Gwyn L. Murdoch, David L. Nelson
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Patent number: 5614631Abstract: Novel 1-alkyl-, 1-alkenyl-, and 1-alkynylaryl-2-amino-1,3-propanediols, intermediates and processes for the preparation thereof, and methods of reducing inflammation and cell proliferation, and relieving memory dysfunction, and inhibiting bacterial and fungal growth are disclosed.Type: GrantFiled: April 21, 1995Date of Patent: March 25, 1997Assignee: Hoechst Marion Roussel, Inc.Inventors: John J. Tegeler, Barbara S. Rauckman, Russell R. L. Harner, Brian S. Freed, Gregory H. Merriman
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Patent number: 5569668Abstract: The invention is drawn to an antibiotic, NEMATOPHIN, 3-indoleethyl 3'-methyl-2-oxo-pentanamide (+stereoisomer, -stereoisomer and racemic mixture) and its derivatives, 3-indoleethyl 2-oxo-alkanamides, 3-indoleethyl 2-oxo-alkanoates with or without substitute(s) on the indole ring, produced by bacterial symbiont Xenorhabdus nematophilus and/or other Xenorhabdus species or synthesized by reaction of tryptamine or substituted tryptamine and 2-oxo-alkanoic acid or its derivative, the additional salts thereof, the pharmaceutical compositions thereof and their use as medicaments, particularly in the treatment of infectious diseases involving microorganisms susceptible to them, including antibiotic-resistant Staphylococcus.Type: GrantFiled: March 29, 1995Date of Patent: October 29, 1996Inventors: John M. Webster, Jianxiong Li, Genhui Chen
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Patent number: 5559150Abstract: The present invention is directed to novel compounds that are non-peptidic thrombin inhibitors. The compounds have the structure: ##STR1## and pharmaceutically acceptable salts thereof; wherein R.sup.1 is one of alkyl, substituted alkyl, cycloalkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl; and n is from zero to five. The compounds of the invention are useful for the treatment of arterial and venous thrombotic occlusive disorders, inflammation, cancer, and neurodegenerative diseases.Type: GrantFiled: June 6, 1995Date of Patent: September 24, 1996Assignee: 3-Dimensional Pharmaceuticals, Inc.Inventor: Richard M. Soll
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Patent number: 5552428Abstract: The novel compounds of formula: ##STR1## in which R is isopropyl, cyclohexyl, phenyl, CH.sub.3, Br or I; or H R.sub.1 is CH.sub.3 or cyclopropyl and R.sub.2 is H or Br, and when R.sub.1 is cyclopropyl and R.sub.2 is H, R is other than H, and when R.sub.1 is CH.sub.3 and R.sub.2 is H, R is other than H, and when R.sub.1 is CH.sub.3 and R.sub.2 is H, R is other than I, and when R is CH.sub.3 and R.sub.2 is H, R.sub.1 is other than CH.sub.3, and when R is phenyl and R.sub.2 is H, R.sub.1 is other than CH.sub.3, exhibit superior activity in the treatment of pathologies which interfere with the circadian rhythm. A novel method of preparation is described according to which the pharmaceutical compositions containing the novel compounds, as well as compounds already known, are administered transdermally. The novel method of administration results in sustained peripheral blood level. Novel pharmaceutical compositions are described suitable for transdermal administration.Type: GrantFiled: February 15, 1994Date of Patent: September 3, 1996Assignee: Instituto Farmacologico Lombardo-IFLO, S.a.S.Inventors: Franco Fraschini, Bojidar Stankov, Margherita Borgonovo, Carlo Introini, Aldo Laguzzi, Ermanno Duranti, deceased, Maria T. Moni, heir
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Patent number: 5545838Abstract: Compounds of the formula ##STR1## wherein Z is SO or SO.sub.2 possess renin inhibition activity and are useful in treating hypertension and other diseases where the reduction of the levels of circulating angiotensin II are beneficial.Type: GrantFiled: January 27, 1992Date of Patent: August 13, 1996Assignee: E. R. Squibb & Sons, Inc.Inventor: Michael A. Poss
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Patent number: 5516789Abstract: Compounds having the structure ##STR1## or a pharmaceutically acceptable salt thereof have activity as inhibitors of cylooxygenase and 5-lipoxygenase, reduce the biosynthesis of leukotrienes B.sub.4, C.sub.4, D.sub.4, and E.sub.4 and cylooxygenase products such as prostaglandins and thromboxane and are useful in the treatment of inflammatory and allergic disease states. The compounds have the structure indicated above wherein A is selected from (a) optinally substituted carbocyclic aryl, (b) optinally substituted furyl, (c) optinally substituted benzo[b]furyl, (d) optinally substituted thienyl, (e) optinally substituted pyridyloxy, (f) optinally substituted pyridylalkyl, (g) optinally substituted benzo[b]thienyl, (h) optinally substituted pyridyl, (i) optinally substituted quinolyl, and (j) optinally substituted indolyl; X is selected from (a) optionally substituted alkyl, (b) optinally substituted alkenyl, and (c) optinally substituted alkynyl; R.sup.1 and R.sup.Type: GrantFiled: April 12, 1995Date of Patent: May 14, 1996Assignee: Abbott LaboratoriesInventors: Clint D. W. Brooks, Andrew O. Stewart, Anwer Basha, Randy L. Bell
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Patent number: 5508432Abstract: CCK modulators, e.g. agonists or antagonists, of the following formula (I): ##STR1## or a base-addtion salt thereof.Type: GrantFiled: June 8, 1994Date of Patent: April 16, 1996Assignee: Glaxo Wellcome Inc.Inventors: Elizabeth E. Sugg, Milana Dezube, Gavin C. Hirst
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Patent number: 5504216Abstract: The invention provides a pharmaceutical composition comprising a particular physical form of N- 4- 5-(cyclopentyloxy-carbonyl)amino-1-methylindol-3-yl-methyl!-3-methox ybenzoyl!-2-methylbenzenesulphonamide and polyvinylpyrrolidone. It also provides methods for preparing this physical form, and another physical form of N- 4- 5-(cyclopentyloxycarbonyl)amino-1-methylindol-3-yl-methyl!-3-methoxy benzoyl!-2-methylbenzenesulphonamide useful in the preparation of the first mentioned physical form. The compositions are useful in the treatment of diseases in which leukotrienes are implicated, for example asthma.Type: GrantFiled: March 13, 1995Date of Patent: April 2, 1996Assignee: Zeneca LimitedInventors: James J. Holohan, Ieuan J. Edwards
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Patent number: 5482960Abstract: Novel indole and indoline nonpeptide antagonists of endothelin I are described, as well as novel intermediates used in their preparation, methods for the preparation and pharmaceutical compositions of the same, which are useful in treating elevated levels of endothelin, essential renovascular malignant and pulmonary hypertension, cerebral infarction, cerebral ischemia, congestive heart failure and subarachnoid hemorrhage.Type: GrantFiled: November 14, 1994Date of Patent: January 9, 1996Assignee: Warner-Lambert CompanyInventors: Kent A. Berryman, Amy M. Bunker, Annette M. Doherty, Jeremy J. Edmunds
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Patent number: 5482963Abstract: The invention provides a pharmaceutical composition comprising a particular physical form of N-[4-[5-(cyclopentyloxycarbonyl)amino-1-methylindol-3-yl-methyl]-3-methoxy benzoyl]-2-methylbenzenesulphonamide and polyvinylpyrrolidone. It also provides methods for preparing this physical form, and another physical form of N-[4-[5-(cyclopentyloxycarbonyl)amino-1-methylindol-3-yl-methyl]-3-methoxy benzoyl]-2-methylbenzenesulphonamide useful in the preparation of the first mentioned physical form. The compositions are useful in the treatment of diseases in which leukotrienes are implicated, for example asthma.Type: GrantFiled: September 3, 1993Date of Patent: January 9, 1996Assignee: Zeneca LimitedInventors: James J. Holohan, Ieuan J. Edwards, Robert J. Timko, Randy J. Bradway, Arlene Clements
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Patent number: 5481021Abstract: This invention relates to phenyl amidine derivatives having the following formula ##STR1## or a pharmaceutically acceptable salt which are useful in the inhibition of platelet aggregation. This invention also relates to pharmaceutical compositions of such phenyl amidine derivatives.Type: GrantFiled: December 22, 1994Date of Patent: January 2, 1996Assignee: G. D. Searle & Co.Inventors: Robert B. Garland, Masateru Miyano, Jeffery A. Zablocki, Lori A. Schretzman
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1,2-ethanediol derivative and salt thereof and cerebral function-improving agent comprising the same
Patent number: 5472984Abstract: 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: December 29, 1993Date of Patent: December 5, 1995Assignee: Toyama Chemical Co., Ltd.Inventors: Satoshi Ono, Tetsuo Yamafuji, Hisaaki Chaki, Mutsuko Maekawa, Yozo Todo, Hirokazu Narita -
Patent number: 5451605Abstract: Compounds of the formula ##STR1## where R.sub.1 -R.sub.5 are hydrogen, lower alkyl of 1-6 carbons, or halogen; A is (CH.sub.2).sub.n where n is 0-5, lower branched chain alkyl having 3-6 carbons, cycloalkyl having 3-6 carbons, alkenyl having 2-6 carbons and 1 or 2 double bonds, alkynyl having 2-6 carbons and 1 or 2 triple bonds; B is hydrogen, COOH or a pharmaceutically acceptable salt thereof, COOR.sub.8, CONR.sub.9 R.sub.10, --CH.sub.2 OH, CH.sub.2 OR.sub.11, CH.sub.2 OCOR.sub.11, CHO, CH(OR.sub.12).sub.2, CHOR.sub.13 O, --COR.sub.7, CR.sub.7 (OR.sub.12).sub.2, or CR.sub.7 OR.sub.13 O, where R.sub.7 is an alkyl, cycloalkyl or alkenyl group containing 1 to 5 carbons, R.sub.8 is an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5 to 10 carbons, or R.sub.8 is phenyl or lower alkylphenyl, R.sub.9 and R.sub.10 independently are hydrogen, an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5-10 carbons, or phenyl or lower alkylphenyl, R.sub.11 is lower alkyl, phenyl or lower alkylphenyl, R.sub.Type: GrantFiled: December 30, 1993Date of Patent: September 19, 1995Assignee: Allergan, Inc.Inventors: Roshantha A. Chandraratna, Richard L. Beard
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Patent number: 5436264Abstract: The present invention relates to novel N-aryloxyalkyl tryptamine .alpha..sub.1 -adrenergic receptor antagonists of the formula I: ##STR1## in which n is 2, 3 or 4; q is 1, 2 or 3; t is 0, 1, 2 or 3; z is 0, 1, 2 or 3; each R.sup.1 and R.sup.2 are independently hydroxy, halogen, cyano, (C.sub.1-8)alkyl, (C.sub.1-8)alkyloxy or trifluoromethyl; and R.sup.2 is hydrogen, (C.sub.1-4)alkyl, fluoro(C.sub.1-4)alkyl, difluoro(C.sub.1-4)alkyl, trifluoro(C.sub.1-4)alkyl, (C.sub.1-4)alkyloxy(C.sub.1-4)alkyl, oxo(C.sub.1-4)alkyl, (C.sub.1-8)cycloalkyl, (C.sub.1-8)cycloalkylmethyl or allyl or phenyl(C.sub.1-4)alkyl or heterocyclo(C.sub.1-8)alkyl (optionally substituted with one to two substituents independently selected from (C.sub.1-4)alkyl, (C.sub.1-4)alkyloxy, trifluoromethyl and halogen); R.sup.3 and R.sup.4 are independently hydrogen, (C.sub.1-4)alkyl, (C.sub.1-8)cycloalkyl, (C.sub.1-8)cycloalkylmethyl or allyl; and R.sup.5 is hydrogen, (C.sub.1-4)alkyl, (C.sub.1-8)cycloalkyl, (C.sub.1-8)cycloalkylmethyl, allyl, (C.Type: GrantFiled: August 19, 1993Date of Patent: July 25, 1995Assignee: Syntex (U.S.A.) Inc.Inventors: Jurg R. Pfister, David E. Clarke
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Patent number: 5420294Abstract: This invention provides a method of selectively antagonizing the 5-HT.sub.1A receptor in mammals by administering aryloxypropanolamines. Aryloxypropanolamines are also claimed.Type: GrantFiled: December 22, 1993Date of Patent: May 30, 1995Assignee: Eli Lilly and CompanyInventors: Edward E. Beedle, David W. Robertson, David T. Wong
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Patent number: 5403851Abstract: This invention relates to novel substituted tryptamine and phenalkylamine and related compounds, pharmaceutical compositions thereof and methods of using said compounds and compositions for a number of pharmaceutical indications including (but not limited to): 1. central nervous system and psychiatric disorders (e.g., sleep disorders, epilepsy and other convulsive disorders, anxiety, psychiatric diseases, neurodegenerative diseases, fever); 2. chronobiological-based disorders (e.g., jet lag, delayed sleep syndrome, shift-work, seasonal affective disorder); 3. endocrine indications (e.g., contraception and infertility, precocious puberty, premenstrual syndrome, hyperprolactinemia, growth hormone deficiency); 4. cancer and other proliferative diseases; 5. immune system disorders and conditions associated with senescence; 6. ophthalmological diseases; 7. animal breeding (e.g., regulation of fertility, puberty, pelage color).Type: GrantFiled: April 5, 1994Date of Patent: April 4, 1995Assignee: Interneuron Pharmaceuticals, Inc.Inventors: Kay J. D'Orlando, Kenneth W. Locke, Emile M. Bellott, Richard L. Gabriel, Michael D. Nohrden, Yesh P. Sachdeva, Salah A. Zahr, Emile Al-Farhan, Subramaniam Krishnananthan
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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
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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
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Patent number: 5348949Abstract: The invention relates to a method of preparing N-oxo-tetrahydro-.beta.-carbolines having formula 1. ##STR1## by an intramolecular ringclosure reaction of compounds of formula 2. ##STR2## wherein Z is an aldehyde function or acetal function, or is a functional group which can be converted into such a function during the ringclosure reaction.The eudistomin derivatives within the group of compounds having formula 1 have strong antiviral and antitumour activity.Type: GrantFiled: February 12, 1993Date of Patent: September 20, 1994Assignee: Duphar International Research B.V.Inventors: Peter H. H. Hermkens, Jan H. Van Maarseveen, Johan W. Scheeren, Cornelis G. Kruse
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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
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Patent number: 5319097Abstract: The invention provides a pharmaceutical composition comprising a particular physical form of N-[4-[5-(cyclopentyloxy-carbonyl)amino-1-methylindol-3-yl-methyl]-3-methox ybenzoyl]-2-methylbenzenesulphonamide and polyvinylpyrrolidone. It also provides methods for preparing this physical form, and another physical form of N-[4-[5-(cyclopentyloxycarbonyl)amino-1-methylindol-3-yl-methyl]-3-methoxy benzoyll-2-methylbenzenesulphonamide useful in the preparation of the first mentioned physical form. The compositions are useful in the treatment of diseases in which leukotrienes are implicated, for example asthma.Type: GrantFiled: December 11, 1991Date of Patent: June 7, 1994Assignee: Imperial Chemical Industries PLCInventors: James J. Holohan, Ieuan J. Edwards
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Patent number: 5294636Abstract: A physical form of N-[4-[5 -(cyclopentyloxycarbonyl)amino-1-methyl-indol-3-ylmethyl]-3-methoxybenzoyl ]-2-methylbenzenesulphonamide substantially free of other physical forms, which form is crystalline, has an X-ray powder diffraction pattern with specific peaks occuring at 2.theta.=8.1, 13.7, 16.4, 20.5 and 23.7.degree. and an infra-red spectrum (0.5% in KBr) having sharp peaks at 3370, 1670, 1525, 1490, 1280, 890, 870 and 550 cm.sup.-1, a process for its preparation and pharmaceutical compositions containing it. Also disclosed is a flowable preparation of the physical form which is in the form of soft pellets, and a process for obtaining this preparation.Type: GrantFiled: December 11, 1991Date of Patent: March 15, 1994Assignee: Imperial Chemical Industries plcInventors: Martin P. Edwards, John D. Sherwood
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Patent number: 5276051Abstract: The invention relates to a compound selected from those of formula (I): ##STR1## in which Ar', R.sub.1 and R.sub.2 are as defined in the specification, an optical isomer,and an addition salt thereof with a pharmaceutically-acceptable acid or base.Medicinal product which is useful in treating or in preventing a disorder of the melatoninergic system.Type: GrantFiled: August 12, 1992Date of Patent: January 4, 1994Assignee: Adir et CompagnieInventors: Daniel Lesieur, Said Yous, Patrick Depreux, Jean Andrieux, Gerard Adam, Daniel H. Caignard, Beatrice Guardiola
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Patent number: 5276190Abstract: The invention relates to a method for the preparation of an .alpha.,.alpha.-disubstituted .alpha.-amino alcohol from the corresponding amide with the aid of sodium in the presence of an alcohol as solvent. The conversion of amino acid amide to amino alcohol proceeds virtually quantitatively. Moreover, the reduction of the amino acid amide to the corresponding amino alcohol proceeds with retention of optical activity.Type: GrantFiled: September 25, 1992Date of Patent: January 4, 1994Assignee: DSM N.V.Inventors: Wilhelmus H. J. Boesten, Harold M. Moody, Quirinus B. Broxterman
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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
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Patent number: 5206377Abstract: Melatonin compounds are disclosed of the formula ##STR1## where R is hydrogen or C.sub.1 to C.sub.6 linear or branched alkylene substituted with phenyl; R.sub.1 is hydrogen, substituted benzyl, naphthylmethyl or taken together with R.sub.2 and the two carbon atoms of the five-membered hetero ring form the group ##STR2## where R.sub.1 ' is C.sub.1 to C.sub.6 linear or branched alkanoyl and R.sub.1 " is hydrogen, C.sub.1 to C.sub.6 linear or branched alkyl or phenyl optionally substituted with one or more halogen, amino, nitro, hydroxy, alkyl, alkoxy or haloalkyl; R.sub.2 is hydrogen, 1-pyrrolyl, 1-pyrrolyl substituted with one or more alkyl or alkoxy, the group --(CH.sub.2).sub.m --NHR.sub.2 '1, where m is 1 to 3 and R.sub.2 ' is phenyl sulfonyl, the phenyl group optionally substituted with alkyl, or --C(O)--R.sub.2 ", where R.sub.2 " is C.sub.1 to C.sub.Type: GrantFiled: December 5, 1991Date of Patent: April 27, 1993Assignee: Whitby Research, Inc.Inventor: Donald A. McAfee
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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
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Patent number: 5180728Abstract: A compound of the formula: ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 are each hydrogen, lower alkyl, lower alkenyl, aryl or ar(lower)alkyl,R.sup.4 is imidazolyl, which may have alkyl or imino-protective group as substituents, or pyridyl,A is lower alkylene, andis single bond or double bond, and pharmaceutically acceptable salts thereof, having 5-HT antagonism.Type: GrantFiled: August 27, 1990Date of Patent: January 19, 1993Assignee: Fujisawa Pharmaceutical Company, Ltd.Inventors: Masayuki Kato, Shigetaka Nishino, Kiyotaka Ito, Hisashi Takasugi
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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
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Patent number: 5147888Abstract: Non-peptidyl compounds characterized generally as heterocyclic acyl aminodiol .beta.-amino acid derivatives are useful as renin inhibitors for treatment of hypertension. Compounds of particular interest are of the formula ##STR1## wherein R.sub.1 is selected from ##STR2## wherein each of R.sub.2 and R.sub.4 is independently selected from hydrido and methyl; wherein R.sub.3 is selected from methyl and ethyl; wherein R.sub.5 is cyclohexylmethyl; wherein R.sub.6 is hydroxy; wherein R.sub.7 is selected from isobutyl and ethyl; wherein X is selected from ##STR3## wherein each of Y and Z is independently selected from hydrido, chloro, fluoro, methoxy and dimethylamino; and wherein n is a number selected from zero through four, inclusive; or a pharmaceutically-acceptable salt thereof.Type: GrantFiled: September 16, 1991Date of Patent: September 15, 1992Assignee: G. D. Searle & Co.Inventors: Gunnar J. Hanson, John S. Baran, Dave Weissing, Mark Russell
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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
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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
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Patent number: 5112846Abstract: The present invention includes N-hydroxyamide, N-hydroxyurea, N-hydroxythioamide, and N-hydroxythiourea derivatives of fenamates, indomethacin, cicloprofen, oxepinac, and indoprofen as dual inhibitors or selective inhibitors of cyclooxygenase and 5-lipoxygenase.Type: GrantFiled: October 16, 1990Date of Patent: May 12, 1992Assignee: Warner-Lambert CompanyInventors: Thomas R. Belliotti, Wiaczeslaw A. Cetenko, David T. Connor, Daniel L. Flynn, Catherine R. Kostlan, James B. Kramer, Jagadish C. Sircar
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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
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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
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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
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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
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Patent number: 4997845Abstract: .beta.-Alkylmelatonins are useful as ovulation inhibitors.Type: GrantFiled: May 10, 1990Date of Patent: March 5, 1991Assignee: Eli Lilly and CompanyInventor: Michael E. Flaugh
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Patent number: 4977272Abstract: This invention relates to new compounds of the formula: ##STR1## where each of R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 has zero to 10 C atoms, and no acetylenic unsaturation; each of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 is independently selected from H and hydrocarbyl; with the proviso that R.sup.6 is C.sub.1 -C.sub.10 hydrocarbyl; each of R.sup.5 and R.sup.Type: GrantFiled: June 29, 1989Date of Patent: December 11, 1990Assignee: The Standard Oil CompanyInventors: Mark C. Cesa, James E. Rinz, Gilles Klopman, Teodora T. Kopp
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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
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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
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Patent number: 4886802Abstract: A compound selected from the group consisting of all possible isomeric forms, optically active isomers and racemic mixtures of compounds of the formula ##STR1## wherein R.sub.1 and R.sub.2 are individually selected from the group consisting of hydrogen, halogen, alkyl and alkoxy of 1 to 5 carbon atoms, --OH, --CF.sub.3 and --NO.sub.2, R is selected from the group consisting of hydrogen, alkyl of 1 to 5 carbon atoms, aralkyl of 7 to 12 carbon atoms, benzoyl and acyl of an alkanoic acid of 1 to 12 alkyl carbon atoms and ##STR2## is selected from the group consisting of ##STR3## and their non-toxic, pharmaceutically acceptable acid addition salts having analgesic activity as well as cerebral oxygenating and vaso regulating activity.Type: GrantFiled: April 14, 1988Date of Patent: December 12, 1989Assignee: Roussel UclafInventors: Nurgun Aktogu, Francois Clemence
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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
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Patent number: 4849527Abstract: A process for resolving a racemic modification of .beta.-adrenergic aryl- or hetaryl-oxypropanolamines such as (.+-.)-2-[2-hydroxy-3-[[2-(1H-indol-3-yl)-)-1,1-dimethylethyl]amino]propox y]benzonitrile into its individual enantiomers is described. The process comprises converting the racemic modification into a pair of diastereomeric urea derivativesby reaction with a chiral aralkylisocyanate; separation into the individual diastereomers; and facile regeneration of the starting amine by cleavage of the intermediate urea compound using hydrazine. This final step is improved by the addition of an .alpha.-keto carboxylic acid, such as pyruvic acid, which functions as a scavenger of nucleophilic by-products.Type: GrantFiled: March 30, 1988Date of Patent: July 18, 1989Assignee: Bristol-Myers CompanyInventors: Ronald D. Dennis, Terence M. Dolak, William E. Kreighbaum
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Patent number: 4837235Abstract: This invention provides a series of novel keto sulfones of formula I ##STR1## in which the group .dbd.A-- is selected from .dbd.C(Ra)-- and .dbd.N-- and the other radicals have the meanings defined in the following specification.The compounds of formula I are leukotriene antagonists. The invention also provides pharmaceutically acceptable salts of the formula I compounds; pharmaceutical compositions containing the formula I compound, or their salts, for use in the treatment of, for example, allergic or inflammatory diseases, or endotoxic or traumatic shock conditions; and processes for the manufacture of the formula I compounds, as well as intermediates for use in such manufacture.Type: GrantFiled: October 16, 1986Date of Patent: June 6, 1989Assignee: ICI Americas Inc.Inventors: Peter R. Bernstein, Frederick J. Brown, Victor G. Matassa, Ying K. Yee
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Patent number: 4806551Abstract: New N-dihydroindolylethyl-sulphonamides are prepared from the corresponding N-indolylethyl-sulphonamides by oxidation or hydrogenation and are useful as active compounds in medicaments. These compounds exhibit a platelet aggregation-inhibiting and thromboxan A.sub.2 -antagonistic action.The N-dihydroindolylethyl-sulphonamides have the formula ##STR1## in which R.sup.1 represents hydrogen, halogen, trifluoromethyl, carboxyl or alkoxycarbonyl, or represents a group of the formula --S(O).sub.m R.sup.5,whereinR.sup.5 denotes alkyl or aryl andm denotes one of the numbers 0, 1 or 2, orR.sup.1 represents a group of the formula ##STR2## or R.sup.1 represents a group of the formula --OR.sup.8, orR.sup.1 represents optionally substituted alkyl, alkenyl or cycloalkyl,R.sup.2 represents aryl, which is optionally substituted by up to 5 substituents,R.sup.3 represents hydrogenor alkyl andR.sup.4 represents hydrogen, orR.sup.3 and R.sup.4 together bond a carbonyl oxygen.Type: GrantFiled: April 16, 1987Date of Patent: February 21, 1989Assignee: Bayer AktiengesellschaftInventors: Horst Boshagen, Ulrich Rosentreter, Folker Lieb, Hermann Oediger, Volker-Bernd Fiedler, Elisabeth Perzborn, Friedel Seuter
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Patent number: 4806655Abstract: The present invention relates to a process for the stereo-specific synthesis of indole derivatives of formula: ##STR1## which consists in using 3-tosyloxy-1,2-O-isopropylidenepropane-1,2-diol (II) in an optically pure form in order to introduce the asymetric carbon C* of compound (I). Compound (II) is condensed with a suitable primary amine in order to prepare an oxazolidinone and condensation with a suitable phenol, and the oxazolidinone ring is then opened to form an indole compound (I).Type: GrantFiled: June 29, 1987Date of Patent: February 21, 1989Assignee: Societe Anonyme: SanofiInventors: Jean Wagnon, Claude Plouzane, Bernard Tonnerre, Dino Nisato