And Is Bonded Directly To A Ring Carbon Which Is Adjacent To The Ring Nitrogen Of The Five-membered Hetero Ring (e.g., 4-hydroxy Proline, Etc.) Patents (Class 548/532)
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Patent number: 5212287Abstract: A method of synthesizing commercial quantities of the pentapeptide L-aspartyl-L-seryl-L-aspartyl-L-prolyl-L-arginine, and salts or solvates thereof, e.g., the hydrochloride or acetate salt or water solvate, compounds useful in pharmaceutical compositions for the treatment of allergic conditions, is disclosed, as are novel intermediate compounds produced in the course of the synthesis.Type: GrantFiled: December 21, 1988Date of Patent: May 18, 1993Assignee: Immunetech Pharmaceuticals, Inc.Inventors: John C. Tolle, Wenying Z. Gifford, Kenneth W. Funk
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Patent number: 5196548Abstract: Diazabicyclo[2.2.1]heptane intermediates are prepared from 4-hydroxy-L-proline in a five step procedure, or from allo-4-hydroxy-D-proline, through a novel 2-(C.sub.1 -C.sub.6)alkyl-5-substituted-2,5-diazabicyclo[2.2.1]heptane intermediate. The diazabicycloheptanes are of use in the preparation of antibiotic quinolones.Type: GrantFiled: July 2, 1992Date of Patent: March 23, 1993Assignee: Pfizer Inc.Inventors: Tamim F. Braish, Darrell E. Fox
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Patent number: 5189055Abstract: The present invention relates to phenylpyrrole compounds, pharmaceutical compositions, preparation and to their application as an active principle, especially as a drug having antimitotic activity.Type: GrantFiled: April 1, 1991Date of Patent: February 23, 1993Assignee: Centre National de la Recherche Scientifique (CNRS)Inventors: Claude Thal, Olivier Boye, Daniel Guenard, Pierre Potier
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Patent number: 5182348Abstract: Compounds of the formula (1) ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7 and R.sup.8 have the meanings given in the description, and the other radicals have the following meanings:X, Y and Z denote identical or different divalent radicals --O--, --S--, --N(R.sup.9)-- or --C(R.sup.10).dbd.C(R.sup.11)--, with the proviso that at least one of the radicals, X, Y and Z is not a radical of the formula --C(R.sup.10).dbd.C(R.sup.11)--, and whereinR.sup.9 is a hydrogen atom, a branched or unbranched C.sub.1 - to C.sub.8 -alkyl radical or an optionally substituted phenyl radical, andR.sup.10 and R.sup.11 are, in each case, identical or different radicals which have one of the meanings of R.sup.1,R.sup.7 and R.sup.8 denote identical or different radicals, that is to say hydrogen atoms or C.sub.1 - to C.sub.6 -alkyl or phenyl radicals, andn, m and o denote identical or different integers with a value of from 1 to 10.Type: GrantFiled: August 19, 1991Date of Patent: January 26, 1993Assignee: Wacker-Chemie GmbHInventors: Hermann Braeunling, Richard Becker, Georg Bloechl
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Patent number: 5142056Abstract: A retroviral protease inhibiting compound of the formulaA--X--Bor a pharmaceutically acceptable salt, prodrug or ester thereof, wherein X is a linking group; A is(1) substituted amino,(2) substituted carbonyl,(3) functionalized imino,(4) functionalized alkyl,(5) functionalized acyl,(6) functionalized heterocyclic or(7) functionalized (heterocyclic)alkyl; and B is(1) substituted carbonyl independently defined as herein,(2) substituted amino independently defined as herein,(3) functionalized imino independently defined as herein,(4) functionalized alkyl independently defined as herein,(5) functionalized acyl independently defined as herein,(6) functionalized heterocyclic independently defined as herein or(7) functionalized (heterocyclic)alkyl independently defined as herein.Type: GrantFiled: May 9, 1990Date of Patent: August 25, 1992Assignee: Abbott LaboratoriesInventors: Dale J. Kempe, Daniel W. Norbeck, John W. Erickson
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Patent number: 5136050Abstract: Novel substituted lactones of amino acids in all their possible stereoisomeric forms or mixtures thereof of the formula ##STR1## wherein A is a hydrocarbon chain of 1 to 10 chain members containing one or more heteroatoms and one or more unsaturations and the chain members being a mono- or polycyclic system or comprises a system of spiro or endo type and may contain one or more chiral atoms or the lactone copula can present a supplementary chirality due to the asymetric spatial configuration of the molecule make up and R is selected from the group consisting of ##STR2## wherein Z is the organic remainder of an amino acid of the formula ##STR3## Y is derived from a primary, secondary or tertiary alcohol of the formula Y-OH and B is the remainder of a heterocycle amino acid of 3 to 6 carbon atoms of the formula ##STR4## and their preparation and their use for the resolution of amino acids.Type: GrantFiled: February 11, 1988Date of Patent: August 4, 1992Assignee: Roussel UclafInventors: Jacques Martel, Jean Tessier, Andre Teche
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Patent number: 5106997Abstract: A novel squarylium derivative represented by general formula (I) and a process for preparing the same are described: ##STR1## wherein X and Z are defined in the specification. This squarylium derivative exhibits high nonlinearity and is excellent in thermal resistance, light resistance, storage stability and processability, so that it can be used for preparation of nonlinear optical elements.Type: GrantFiled: September 24, 1990Date of Patent: April 21, 1992Assignee: Fuji Xerox Co., Ltd.Inventor: Lyong S. Pu
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Patent number: 5102911Abstract: HMG-CoA reductase inhibitors of formulae (I) and (II) are disclosed.Type: GrantFiled: July 6, 1990Date of Patent: April 7, 1992Assignee: Merck & Co, Inc.Inventors: Ta J. Lee, Wilbur J. Holtz
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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: 5091407Abstract: Fungicidally active compounds of the formula ##STR1## and steroisomers thereof, wherein A is the group .dbd.CW--or a nitrogen atom, B is the group .dbd.CX--or a nitrogen atom, D is the group .dbd.CY--or a nitrogen atom, and E is the group .dbd.CZ--or a nitrogen atom, wherein W, X, Y and Z, which may be the same or different, are, for example, hydrogen, halogen, nitro, nitrile, or other defined groups and wherein R.sup.1 and R.sup.2 are alkyl, cycloalkyl, alkenyl, alkynyl, optionally substituted aryl, optionally substituted aralkyl, cycloalkyl groups, or optionally substituted heteroaromatic, and V is oxygen or sulfur.Type: GrantFiled: November 24, 1989Date of Patent: February 25, 1992Assignee: Imperial Chemical Industries PLCInventors: Paul deFraine, Brian K. Snell, Kevin Beautement, Vivienne M. Anthony, John M. Clough
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Patent number: 5082856Abstract: Novel pyrrolecarboxylic acid derivatives represented by the following formula: ##STR1## where R.sup.1 is a hydrogen atom, an alkyl group of 5 to 25 carbon atoms or an alkenyl group of 5 to 25 carbon atoms, R.sup.2 is a hydrogen atom, a phenyl group or an optionally substituted alkyl group of 1 to 10 carbon atoms, and R.sup.3 is a hydrogen atom, an alkyl group of 5 to 25 carbon atoms or an alkenyl group of 5 to 25 carbon atoms, or pharmaceutically acceptable salts thereof are provided.The compounds are highly effective in reducing the level of triglyceride or cholesterol in serum, and useful as an active ingredient of a pharmaceutical composition for treating hyperlipemia and arteriosclerosis.Type: GrantFiled: June 22, 1989Date of Patent: January 21, 1992Assignee: Mitsubishi Kasei CorporationInventors: Masao Taniguchi, Kohei Umezu, Tadashi Shirasaka, Shinya Inoue, Tetsuro Shinpuku, Masayuki Mitsuka, Mayumi Hirata
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Patent number: 5081252Abstract: A process for the preparation of aromatic carboxylic acids or their salts comprises heating carboxyl-free aromatic compounds and aromatic carboxylic acid salts whose basic structures differ from those of the aromatic compounds, or heating polycyclic aromatic compounds with three or more rings and monocyclic or bicyclic aromatic carboxylic acid salts, under carbon dioxide pressure in the presence of one or more metal compounds selected from group (a) of compounds of zinc, cadmium, and thallium and one or more compounds selected from group (b) of compounds of cesium, Group II metals, And Group IIIa metals to effect the intermolecular transfer of the carboxyl groups.Type: GrantFiled: June 5, 1989Date of Patent: January 14, 1992Assignees: Nippon Steel Corporation, Nippon Steel Chemical Co., Ltd.Inventors: Shuichi Mitamura, Yoshimi Kata, Koichi Fujishiro, Yasuhisa Tsutsumi
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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: 5041442Abstract: This invention is directed to compounds of formula (I): ##STR1## wherein R.sup.1 is thiocyano, --CH.sub.2 CN, --NH.sub.2, --NHR.sup.5, or --CH.sub.2 OR.sup.5 where R.sup.5 is lower alkyl;R.sup.2 is hydrogen, halo, lower alkyl, or lower alkylthio;R.sup.3 is hydrogen, halo, lower alkyl, lower alkylthio, or thiocyano;R.sup.4 is hydrogen, halo, lower alkyl, lower alkoxy, lower alkylthio, or lower alkylsulfonyl; andY is --O--CH.sub.2 --, --S--CH.sub.2 --, --CH.dbd.CH--, or --(CH.sub.2).sub.n -- where n is 0, 1, 2, 3 or 4;or a pharmaceutically acceptable salt thereof. These compounds are useful in treating mammals having disease-states characterized by excessive gastric acid secretion.Type: GrantFiled: July 31, 1990Date of Patent: August 20, 1991Assignee: Syntex (U.S.A.) Inc.Inventors: Ruth S. Romero, Fidencio Franco, Armando C. Castaneda, Joseph M. Muchowski
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Patent number: 5041554Abstract: This invention relates to novel aryl- or heteroaryl-1-alkyl-pyrrole-2-carboxylic acid compounds useful in treating interleukin-1 mediated conditions.Type: GrantFiled: February 23, 1990Date of Patent: August 20, 1991Assignee: Merrell Dow Pharmaceuticals Inc.Inventors: Roger A. Parker, George Ku
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Patent number: 5039695Abstract: This invention relates to the method of using aryl- or heteroaryl-1-alkyl-pyrrole-2-carboxylic acid compounds to treat interleukin-1 mediated conditions.Type: GrantFiled: February 27, 1990Date of Patent: August 13, 1991Assignee: Merrell Dow Pharmaceuticals Inc.Inventors: Roger A. Parker, George Ku
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Patent number: 5028718Abstract: Novel amino acid derivatives of the formula ##STR1## wherein R.sup.1 is a protecting group removable under reducing or acid conditions, and R.sup.2 and R.sup.5 are hydrogen or carboxylic protecting groups, are useful as intermediates in preparing stereospecific carbapenam/carbapenem derivatives. R.sup.1 is removed under reducing conditions to form a pyrrolidine derivative, which is further cyclized from the R.sup.5 .dbd.H compound to form a .beta.-lactam ring. Stereospecificity at the 6-position is achieved by treatment with lithium diisopropylamide (LDA) and quenching at different temperatures. Compound (I) can be prepared by treating R.sup.1 -protected R.sup.3 -pyrrolidone carboxylic acid R.sup.2 -ester with a lithium enolate of the formula R.sup.4 CHLiCO.sub.2 R.sup.5. The lithium enolate can be formed from R.sup.4 CH.sub.2 CO.sub.2 R.sup.5 by treatment with LDA.Type: GrantFiled: June 2, 1989Date of Patent: July 2, 1991Assignee: Ajinomoto Co., Inc.Inventors: Shigeo Nozoe, Tomihisa Ohta
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Patent number: 5028604Abstract: Novel condensed benzene derivatives having prolyl endopeptidase inhibitory, anti-hypoxic, and anti-amnesic activities are disclosed. The compounds are represented by the following (I), ##STR1## wherein A represents a methylene, ethylene, or propylene group, B represents a methylene or ethylene group, m denotes an integer of 0-5, X and Y, which may be same or different, individually represent a methylene group or sulfur atom, R.sup.1 represents a hydrogen atom, a carboxyl, lower alkyloxycarbonyl, hydroxymethyl, or formyl group, R.sup.2 represents a hydrogen atom, a halogen atom, a lower alkyl, lower alkoxy, nitro, or amino group, R.sup.3 represents a hydrogen atom or a lower alkyl group, and the dotted line may optionally be present. They are useful as a medicine for treating or preventing cerebral circulation disorder, cerebral metabolism disorder, or memory disturbance.Type: GrantFiled: December 1, 1989Date of Patent: July 2, 1991Assignee: Zeria Pharmaceutical Co., Ltd.Inventors: Motoki Torizuka, Tomoji Aotsuka, Mitsuo Soeda, Kuniyoshi Ogura, Yoshiaki Tanaka, Hisayoshi Kato, Naoki Nakata, Naoyoshi Miura, Hikari Morita
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Patent number: 5013842Abstract: There is disclosed a novel method for the syntheses of chiral pyrrolidines and piperidines by the intramolecular ring closure of anomeric mixtures of 4-amino- and 5-amino-2-trifluoromethanesulfonates of methyl furanosides. The novel method preferably provides for the efficient syntheses from diacetone glucose of 1,4-dideoxy-1,4-imino-D-arabinitol--known as DAB1, (2S,3R,4R)-3,4-dihydroxyproline, fagomine [1,5-imino-1,2,5-trideoxy-D-arabino-hexitol], and (2S,3R,4R)-3,4-dihydroxypipecolic acid by intramolecular nucleophilic displacement by an amino function of 2-O-trifluoromethanesulphonates of anomeric mixtures of methyl furanosides.Type: GrantFiled: January 22, 1990Date of Patent: May 7, 1991Assignee: Monsanto CompanyInventors: George W. J. Fleet, David R. Witty
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Patent number: 4990647Abstract: Unsymmetric biaryl compounds are prepared by coupling two different halogenoaromatics by reaction with a metal and carrying out the reaction in the presence of catalytic amounts of a nickel compound, a promoter and a phosphorus-containing ligand.Type: GrantFiled: April 24, 1989Date of Patent: February 5, 1991Assignee: Bayer AktiengesellschaftInventors: Thomas Himmler, Rudolf Braden
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Patent number: 4981853Abstract: The compounds of this invention are heterocyclic amides represented by the formula: ##STR1## wherein: R.sub.1 and R.sub.2 are the same or different members of the group consisting of halo, phenyl, substituted phenyl and a ##STR2## group wherein q, r and t are independently an integer of from 1 to 8 provided that q+r+t is equal to or less than 10; Y is thio, sulfinyl or sulfonyl; Alk is straight or branched chain lower alkylene, and R.sub.3 is a heterocyclic amine represented by the formula: ##STR3## wherein R.sub.4 is selected from the group consisting of hydrogen, lower alkyl, phenyl, substituted phenyl, benzyl, substituted benzyl, carboxyl or carboxyloweralkyl; X is selected from the group consisting of N-R.sub.4, O and CH.sub.2 ; m is 2 or 3; n is 2 or 3 when X is O or N-R.sup.4, and n is 1 to 3 when X is CH.sub.2 ; p is 0 to 2; and the pharmaceutically acceptable salts thereof. The compounds are anti-inflammatory and anti-allergy agents.Type: GrantFiled: November 14, 1989Date of Patent: January 1, 1991Assignee: G. D. Searle & Co.Inventors: Richard A. Mueller, Richard A. Partis
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Patent number: 4966901Abstract: Pyrrole derivatives of the general formula I ##STR1## wherein R denotes alkyl which is substituted by --NH.sub.2 or acylamino, R.sup.1 and R.sup.2 independently of one another denote hydrogen or alkyl having 1 to 4 carbon atoms, R.sup.3 denotes hydrogen, alkyl having 1 to 4 carbon atoms or a carboxylic acid grouping, R.sup.Type: GrantFiled: May 23, 1989Date of Patent: October 30, 1990Assignee: Cassella AktiengesellschaftInventors: Gerhard Zoller, Rudi Beyerle, Ursula Schindler
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Patent number: 4939164Abstract: New distrontium salt of 3-(1-carboxymethyl-2-carboxy-pyrrol-4-yl)-pentanedioic acid which can be used therapeutically especially in the treatment of osseous diseases.Type: GrantFiled: June 20, 1989Date of Patent: July 3, 1990Assignee: Adir et CompagnieInventors: Michel Wierzbicki, Jacqueline Bonnet, Yannis Tsouderos
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Patent number: 4937355Abstract: A process is provided for preparing (trans)-4-phenyl-DL-proline derivatives, which are useful in preparing certain angiotensin converting enzyme inhibitors, which process involves reacting an ester of the structure ##STR1## wherein X is a leaving group such as tosylate, R.sup.3 is lower alkyl, R is cyclohexyl, phenyl or substituted phenyl, and R.sup.1a is a protecting group, with a potassium amide base such as potassium hexamethyldisilazide under reduced temperatures to form the trans-4-substituted proline ester derivative of the structure ##STR2## then hydrolyzing the proline ester to the acid of the structure ##STR3## and removing the R.sup.Type: GrantFiled: January 17, 1989Date of Patent: June 26, 1990Assignee: E. R. Squibb & Sons, Inc.Inventors: John Kloss, David Kronenthal, Christopher M. Cimarusti, Richard H. Mueller
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Patent number: 4927809Abstract: Compounds of the formula IA--R--NH--CHR.sup.1 --(CH.sub.2).sub.a --NHC(.dbd.NH)NH.sub.2in whichR.sup.1 is the cyanide group,R is Pro or D--Phe--Pro,A is a hydrogen atom or a protective group customary in peptide chemistry, anda is an integer from 2 to 5, preferably 3 or 4,which are able to inhibit serine proteases, and a process for their preparation, are described.Agents containing compounds of this type can be used as anticoagulants.Type: GrantFiled: February 26, 1987Date of Patent: May 22, 1990Assignee: Behringwerke AktiengesellschaftInventor: Werner Stuber
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Patent number: 4923994Abstract: A process for the preparation of a 3-cyano-4-arylpyrrole of the formula ##STR1## in which Ar is optionally substituted heteroaryl or aryl, which comprises (a) reacting an .alpha.-cyanoacrylic acid derivative of the formula ##STR2## in which R.sup.1 is amino or alkoxy, with an isocyanoacetic acid ester of the formula ##STR3## in which R.sup.2 is alkyl, in the presence of a base thereby to produce a .DELTA..sup.2 -pyrroline-2-carboxylic acid derivative of the formula ##STR4## in which X represents hydrogen or an equivalent of an inorganic or organic cation,and (b) oxidatively decarboxylating the .DELTA..sup.2 -pyrroline-2-carboxylic -pyrroline-2-carboxylic acid. The end products are known fungicides and the intermediates IVa are new and themselves fungicidally active.Type: GrantFiled: May 9, 1989Date of Patent: May 8, 1990Assignee: Bayer AktienegesellschaftInventor: Detlef Wollweber
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Patent number: 4912231Abstract: A process is provided for preparing (trans)-4-phenyl-L-proline derivatives with excellent stereospecificity, which are useful in preparing certain ACE inhibitors, which process involves reacting a proline derivative of the structure ##STR1## whereing R is a nitrogen protecting group, R.sub.1 is H, aryl, arylalkyl or lower alkyl, and X is a leaving group such as fluorine, an alkyl sulfonate, arylsulfonate or cycloalkyl sulfonate is reacted with an aromatic nucleophile, such as benzene, in the presence of a Lewis acid such as AlCl.sub.Type: GrantFiled: June 17, 1988Date of Patent: March 27, 1990Assignee: E. R. Squibb & Sons, Inc.Inventors: David Kronenthal, Paula L. Kuester, Richard H. Mueller
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Patent number: 4912229Abstract: A process for the preparation of a 3-cyano-4-aryl-pyrrole of the formula ##STR1## in which Ar is optionally substituted heteroaryl or aryl, which comprises (a) reacting an .alpha.-cyanoacrylic acid derivative of the formula ##STR2## in which R.sup.1 is amino or alkoxy, with an isocyanoacetic acid ester of the formula ##STR3## in which R.sup.2 is alkyl, in the presence of a base thereby to produce a .DELTA..sup.2 -pyrroline-2-carboxylic acid derivative of the formula ##STR4## in which X represents hydrogen or an equivalent of an inorganic or organic cation,and (b) oxidatively decarboxylating the .DELTA..sup.2 -pyrroline-2-carboxylic acid. The end products are known fungicides and the intermediates IVa are new and themselves fungicidally active.Type: GrantFiled: May 19, 1988Date of Patent: March 27, 1990Assignee: Bayer AktiengesellschaftInventor: Detlef Wollweber
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Patent number: 4904679Abstract: Pyrrolophenylalkanolamines of the formula ##STR1## R.sup.1 and R.sup.2 represent hydrogen or various radicals, R.sup.3 represents hydrogen, acyl or trialkylsilyl,R.sup.4 represents hydrogen or alkyl,R.sup.5 represents hydrogen, or, together with R.sup.3, represents ##STR2## wherein R.sup.7 represents hydrogen or alkyl, andR.sup.6 represents branched or cyfclic alkyl, which is optionally substituted,and salts thereof promote the yield of animals. Many new intermediates are also shown.Type: GrantFiled: April 22, 1988Date of Patent: February 27, 1990Assignee: Bayer AktiengesellschaftInventors: Hartmund Wollweber, Jurgen Stoltefuss, Friedrich Berschauer, Ann de Jong, Martin Scheer
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Patent number: 4886908Abstract: (R)-4-amino-3-hydroxybutyric acid is prepared from the hydrochloride of the methyl ester or ethyl ester of (2S, 4R)-4-hydroxyproline via the intermediary stages of the corresponding, non-isolated (R)-4-hydroxy-1-pyrroline-2-carboxylic acid ester and the isolated (R)-4-hydroxy-2-pyrrolidone. The (R)-4-amino-3-hydroxybutyric acid which is useful for pharmacological purposes is obtainable in a high yield according to this method.Type: GrantFiled: February 29, 1988Date of Patent: December 12, 1989Assignee: Degussa AktiengesellschaftInventor: Johannes Haeusler
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Patent number: 4849524Abstract: The invention relates to a process for preparing compounds of the formula I ##STR1## in which R stands for hydrogen, alkyl or aralkyl and R.sup.1 to R.sup.5 are identical or different radicals, (substituted) alkyl, cycloalkyl or (substituted) aryl or in which the pairs of radicals R.sup.1 and R.sup.2, R.sup.2 and R.sup.3, and R.sup.4 and R.sup.5 together with the carbon atom(s) supporting them form a mono- or bicyclic ring system and the other radicals are hydrogen, by treating a compound of the formula II ##STR2## in which R and R.sup.1 and R.sup.5 have the abovementioned meaning and R.sup.6 and R.sup.7 denote alkyl or aralkyl or together with the nitrogen atom supporting them form a heterocycle which can additionally contain an oxygen atom, with a reducing agent.Type: GrantFiled: November 19, 1987Date of Patent: July 18, 1989Assignee: Hoechst AktiengesellschaftInventors: Rainer Henning, Hansjorg Urbach
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Patent number: 4847287Abstract: The invention provides pure enatiomers of 4,5-disubstituted .gamma.-butyrolactams of the general formula ##STR1## By means of the pure enantiomers of 4,5-disubstituted .gamma.-butyrolactams (I), according to the invention, it is now possible to synthesize (+)-(3R), (4S), (5S), (7R)-3-hydroxy-5-.alpha.-hydroxybenzyl-1-methyl-4-phenyl-pyrrolidin-2-one and derivatives in the form of pure enantiomers.Type: GrantFiled: May 14, 1987Date of Patent: July 11, 1989Assignees: Bayer AG, Chinese Academy of Medical SciencesInventor: Wolfgang Hartwig
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Patent number: 4824958Abstract: The present invention is for compounds having the formula of N-1H-tetrazol-5-yl-2-thiophenecarboxamides, N-1H-tetrazol-5-yl-2-pyrrolecarboxamides, N-1H-tetrazol-5-yl-2-furancarboxamides or analogs of each of the carboxamides. The compounds are useful for the treatment of allergic or inflammatory conditions or diseases. Thus, pharmaceutical compositions and methods of use are also the invention. Processes of preparation for the compounds are also the invention.Type: GrantFiled: February 16, 1988Date of Patent: April 25, 1989Assignee: Warner-Lambert CompanyInventors: Wiaczeslaw A. Cetenko, David T. Connor, Michael D. Mullican, Roderick J. Sorenson
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Patent number: 4822890Abstract: A method for the production of substantially 100% pure N.alpha.-urethane protected amino acids is disclosed. This method eliminates the formation of di-peptide and tri-peptide contaminants. Reaction of blocking reagents at the carboxylate site on a protected peptide is prevented by the application of labile amino acid esters. Subsequent removal of the ester yields, in ultra-high purity, the N.alpha.-protected amino acid. The substantially 100% pure N.alpha.-urethane protected amino acid are also disclosed.Type: GrantFiled: June 24, 1986Date of Patent: April 18, 1989Assignee: Hoffmann-La Roche Inc.Inventor: David R. Bolin
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Patent number: 4820818Abstract: The muscle relaxant (E)-3-(9-chloro-5,6-dihydro-11H-pyrrolo[2,1-b][3]benzazepin-11-ylidene-N,N -dimethyl-1-propanamine is prepared by the geometric stereoselective dehydration of the intermediate carbinol with acidic agents and organic bases and low temperatures.Type: GrantFiled: May 2, 1988Date of Patent: April 11, 1989Assignee: Merck & Co., Inc.Inventors: Ruth V. Wattley, Gerard R. Kieczykowski
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Patent number: 4810791Abstract: Compounds of the formula ##STR1## are disclosed. These compounds are useful as hypotensive agents due to their angiotensin converting enzyme inhibition activity and depending upon the definintion of X may also be useful as analgesics due to their enkephalinase inhibition activity.Type: GrantFiled: December 28, 1987Date of Patent: March 7, 1989Assignee: E. R. Squibb & Sons, Inc.Inventors: Harold N. Weller, III, Eric M. Gordon
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Patent number: 4801742Abstract: Formylating the amino nitrogen of an alkali metal salt of an amino carboxylic acid, by reacting the salt with an alkyl formate in an alkanol solvent. In one embodiment, the alkyl formate is added to the reaction as such; in another embodiment, the alkyl formate is formed in situ by reaction of carbon monoxide with the alkanol solvent in the presence of the alkali metal salt of the amino carboxylic acid. The process provides a new class of compounds, the alkali metal salts of N-formyl-aspartic acids.Type: GrantFiled: July 17, 1987Date of Patent: January 31, 1989Assignee: W. R. Grace & Co.-Conn.Inventors: Jennifer M. Quirk, Charles G. Carter, Robert J. Kupper
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Patent number: 4801721Abstract: Methods for the alkylation of substituted amines with trifluorate esters is disclosed.Type: GrantFiled: December 19, 1986Date of Patent: January 31, 1989Inventors: James W. Ryan, Alfred Chung
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Patent number: 4785109Abstract: These is described a process for producing sulfonylureas of the formula ##STR1## wherein G is an unsubstituted or substituted furanyl, thienyl, pyrrolyl, pyridinyl or phenyl radical,X is alkyl, haloalkyl, alkoxy, alkylthio, halogen, haloalkoxy, alkylamino or dialkylamino,Y is alkyl, alkoxy or haloalkoxy,Z is a nitrogen atom or the methyne group --CH.dbd..This novel process comprises reacting a sulfonamide of the formulaG--SO.sub.2 --NH.sub.2,in the presence of a base, with a chloroformic acid ester of the formulaCl--CO--Q--T,or a sulfonyl chloride of the formulaG--SO.sub.2 Cl,in the presence of a base, with a urethane of the formulaH.sub.2 N--CO--Q--T;and converting the formed carbamate of the formulaG--SO.sub.2 --NH--CO--Q--Tby reaction with an amine of the formula ##STR2## into the sulfonylurea of the above formula. There are also described novel sulfonylcarbamates of the above formula as intermediates.Type: GrantFiled: January 30, 1987Date of Patent: November 15, 1988Assignee: Ciba-Geigy CorporationInventors: Willy Meyer, Werner Fory, Werner Topfl
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Patent number: 4749786Abstract: Disclosed is the hydrocarboxylation of defined enamides with CO and a compound ROH to make amido acids or amido esters, either of which can be hydrolyzed to .alpha.-amino acids.Type: GrantFiled: April 6, 1987Date of Patent: June 7, 1988Assignee: The Standard Oil CompanyInventors: Mark C. Cesa, James D. Burrington
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Patent number: 4746350Abstract: The invention concerns novel compounds of the formula I ##STR1## wherein: Y is selected from phenyl, furyl, thienyl and pyrrolyl rings (each optionally substituted by group X), optionally branched alkylene or alkylenethio(oxy)alkylene;X which may be the same or different are independently selected from halogen, nitro, alkyl, substituted alkyl, hydroxy, alkoxy, carboxy, alkoxycarbonyl, alkylthio, sulfamoyl, substituted sulfamoyl, amino, substituted amino and alkanoyl;R.sup.1 is selected from hydrogen, acyl and an inorganic or organic cation;R.sup.2 is selected from alkyl, substituted alkyl, alkenyl, haloalkenyl and alkynyl;R.sup.3 is selected from alkyl; andR.sup.4 is selected from hydrogen, alkyl, and alkoxycarbonyl.Type: GrantFiled: April 14, 1986Date of Patent: May 24, 1988Assignee: Imperial Chemical Industries PLCInventor: Keith G. Watson
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Patent number: 4740508Abstract: Compounds of the formula ##STR1## are disclosed. These compounds are useful as hypotensive agents due to their angiotensin converting enzyme inhibition activity and depending upon the definition of X may also be useful as analgesics due to their enkephalinase inhibition activity.Type: GrantFiled: April 22, 1985Date of Patent: April 26, 1988Assignee: E. R. Squibb & Sons, Inc.Inventors: Harold N. Weller, III, Eric M. Gordon
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Patent number: 4734508Abstract: A process is provided for preparing 4-hydroxy-4-phenyl-proline derivatives of the structure ##STR1## wherein R.sub.1 is a nitrogen protecting group such as benzoyl, benzyloxycarbonyl, t-butoxycarbonyl, benzyl, benzhydryl, trityl, acetyl, trifluoromethylacetyl, sulfonamides, and the like and wherein X is OR.sub.2 and R.sub.2 is hydrogen or an acid protecting group such as lower alkyl, aryl-lower alkyl or a metal ion, such as Na or K, or X is NR.sub.3 R.sub.4 wherein R.sub.3 and R.sub.4 may be the same or different and are hydrogen, lower alkyl, aryl or arylalkyl, or R.sub.3 and R.sub.4 together with the nitrogen to which they are attached form a 5-, 6- or 7-membered ring. The process includes the steps of forming triphenylcerium [(C.sub.6 H.sub.5).sub.3 Ce], for example, by reacting cerium trichloride (CeCl.sub.3) with phenyllithium, and reacting the triphenylcerium with the keto acid ##STR2## in the presence of an inert organic solvent such as tetrahydrofuran.Type: GrantFiled: May 1, 1987Date of Patent: March 29, 1988Assignee: E. R. Squibb & Sons, Inc.Inventor: John K. Thottathil
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Patent number: 4687840Abstract: The present invention provides a hypotensive composition comprising a peptide having the structure X-Y, Y-X, or a salt thereof, wherein X is proline or proline-proline and Y is arginine, lysine, arginine-arginine, lysine-lysine, arginine-lysine, or lysine-arginine, together with a pharmaceutically suitable diluent.Type: GrantFiled: February 11, 1986Date of Patent: August 18, 1987Assignee: Texas Tech University Health Sciences CenterInventors: Peter K. T. Pang, Thomas E. Tenner, Jr.
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Patent number: 4684660Abstract: Compounds having the formula ##STR1## and alkyl esters and salts thereof. R.sub.1 is hydrogen, alkanoyl or ##STR2## R.sub.2 is hydrogen, alkyl, or phenylalkyl; n is 0 or 1; andA.sub.1 and A.sub.2 each is an .alpha.-amino or .alpha.-imino acid residue joined through a peptide bond, have useful hypotensive activity.Type: GrantFiled: May 1, 1980Date of Patent: August 4, 1987Assignee: E. R. Squibb & Sons, Inc.Inventors: Miquel A. Ondetti, Josip Pluscec
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Patent number: 4678806Abstract: Prodrugs of 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase inhibitors which are useful as antihypercholesterolemic agents and are represented by the following general structural formula (I): ##STR1## the amido ester moiety of which is in the L-configuration, and pharmaceutically acceptable salts thereof are disclosed.Type: GrantFiled: September 2, 1986Date of Patent: July 7, 1987Assignee: Merck & Co., Inc.Inventors: John J. Baldwin, Wasyl Halczenko, George Hartman, Steven M. Pitzenberger
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Patent number: 4672139Abstract: Benzoylurea compounds of the formula ##STR1## wherein the meaning of each of the symbols is described in the specification.Type: GrantFiled: July 21, 1986Date of Patent: June 9, 1987Assignee: E. I. Du Pont de Nemours and CompanyInventor: Martin Anderson
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Patent number: 4638006Abstract: A unique series of N,N-dialkylaminoalkyl-hexahydro-5-oxo-1H-pyrrolizine-3-carboxamides are disclosed. These compounds are useful as agents for the reversal of amnesia. Intermediates for preparing the compounds, pharmaceutical compositions containing them, and methods for using the pharmaceutical compositions for treating senility and for the reversal of amnesia are described.Type: GrantFiled: September 24, 1985Date of Patent: January 20, 1987Assignee: Warner Lambert CompanyInventor: Donald E. Butler
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Patent number: 4634715Abstract: There are disclosed aza analogs of carboxyalkyl dipeptide derivatives and related compounds which are useful as converting enzyme inhibitors and as antihypertensives said compounds being represented by the general formula: ##STR1## wherein A and B can be joined together to form various ring structures.Type: GrantFiled: July 27, 1983Date of Patent: January 6, 1987Assignee: Merck & Co., Inc.Inventors: William J. Greenlee, Eugene D. Thorsett
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Patent number: RE33024Abstract: A novel carbostyril derivative of the formula: ##STR1## or a pharmaceutically acceptable acid addition salt thereof, and a process for preparing same. The compound (I) shows potent bronchodilating activity and is useful as a bronchodilator.Type: GrantFiled: July 9, 1987Date of Patent: August 15, 1989Assignee: Tanabe Seiyaku Co. Ltd.Inventors: Takeo Iwakuma, Akira Tsunashima, Katsuo Ikezawa, Osasi Takaiti