Additional -c(=x) Bonded Directly To The Five-membered Hetero Ring (e.g., N N-butyryl-l-proline, Etc.) Patents (Class 548/533)
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Patent number: 5733906Abstract: The present invention provides novel HIV protease inhibitors, pharmaceutical formulations containing those compounds and methods of treating and/or preventing HIV infection and/or AIDS.Type: GrantFiled: October 12, 1993Date of Patent: March 31, 1998Assignee: Eli Lilly and CompanyInventors: Louis N. Jungheim, Timothy A. Shepherd
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Patent number: 5726311Abstract: Disclosed is a compound of the formula ##STR1## wherein R.sup.1 is H, NH.sub.2, or OCH.sub.3, R.sup.2 is an optionally substituted cyclic group optionally containing one or more heteroatoms, R.sup.3 and R.sup.4 are independently H or C.sub.1-4 alkyl, m is 0-4, n is 0-6, p is 0.1, X is CN, CSNH.sub.2, PO(OH).sub.2, COOH, SO.sub.2 NH.sub.2, NH.sub.2, OH, CNHNH.sub.2, tetrazole, triazole, or COR.sup.5 where R.sup.5 is C.sub.1-4 alkyl, CF.sub.3, NH.sub.2, or OC.sub.1-4 alkyl, and Y is O or NH that is useful as a pharmaceutical.Type: GrantFiled: June 7, 1995Date of Patent: March 10, 1998Assignee: BioCryst Pharmaceuticals, Inc.Inventors: Shri Niwas, John A. Secrist, III, John A. Montgomery, Mark David Erion, Wayne C. Guida, Steve E. Ealick
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Patent number: 5716936Abstract: Compounds of formula (I), in which R, R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, and R.sub.7 are as defined in the specification. The invention also concerns the salts of said compounds, the preparation thereof and the drugs containing same.Type: GrantFiled: December 18, 1996Date of Patent: February 10, 1998Assignee: Rhone-Poulenc Rorer S.A.Inventors: Marc Capet, Marie-Christine Dubroeucq
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Patent number: 5707991Abstract: The present invention relates to derivatives of formula: ##STR1## to their salts, to their preparation and to the medicaments containing them.Type: GrantFiled: June 28, 1995Date of Patent: January 13, 1998Assignee: Rhone-Poulenc Rorer S.A.Inventors: Marc Capet, Marie-Christine Dubroeucq, Franco Manfre
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Patent number: 5686627Abstract: A process for making pure sodium enalapril is provided which includes the step of decomplexing essentially pure sodium enalapril-sodium iodide complex to yield essentially pure sodium enalapril.Type: GrantFiled: November 22, 1996Date of Patent: November 11, 1997Assignee: Brantford Chemicals Inc.Inventors: K. S. Keshava Murthy, Andrew Burchat, Gamini Weeratunga
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Patent number: 5670655Abstract: The invention relates to a method for analyzing degenerates of enalapril maleate and enalaprilat, potent angiotensin converting enzyme inhibitors.Type: GrantFiled: September 10, 1996Date of Patent: September 23, 1997Assignee: Merck & Co. Inc.Inventors: Xue-Zhi Qin, Giuseppina Visentini, Qingxi Wang
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Patent number: 5631385Abstract: Method for the preparation of N-protected 4-ketoproline derivatives of formula I ##STR1## by oxidation of the corresponding N-protected 4-hydroxyproline derivatives of ##STR2## using the system TEMPO (2,2,6,6-tetramethylpiperidinyl oxy free radical)/NaOCl.Type: GrantFiled: June 27, 1996Date of Patent: May 20, 1997Assignee: Degussa AktiengesellschaftInventors: Karlheinz Drauz, Matthias Kottenhahn, Klaus Stingl
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Patent number: 5622970Abstract: This invention relates to a novel class of immunosuppressive compounds having an affinity for the FK-506 binding protein (FKBP). Once bound to this protein, the immunosuppressive compounds inhibit the prolyl peptidyl cis-trans isomerase (rotamase) activity of the FKBP and inhibit T cell activation. As such, the compounds of this invention can be used as immunosuppressive drugs to prevent or significantly reduce graft rejection in bone marrow and organ transplantations and for use in the treatment of a wide variety of autoimmune diseases in humans and other mammals.Type: GrantFiled: June 1, 1995Date of Patent: April 22, 1997Assignee: Vertex Pharmaceuticals, IncorporatedInventors: David A. Armistead, Joshua S. Boger, Harold V. Meyers, Jeffrey O. Saunders, Roger D. Tung
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Patent number: 5616727Abstract: A process for purifying 1-[N.sup.2 -((S)-ethoxycarbonyl)-3-phenylpropyl)-N.sup.6 -trifluoroacetyl]-1-lysyl-1-proline by extraction and crystallization. The process includes a two step extraction in a two phase aqueous/organic solvent system and crystallization from organic solvent.Type: GrantFiled: March 18, 1996Date of Patent: April 1, 1997Assignee: Degussa AktiengesellschaftInventors: Matthias Kottenhahn, Karlheinz Drauz
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Patent number: 5614547Abstract: This invention relates to neurotrophic compounds having an affinity for FKBP-type immunophilins, their preparation and use as inhibitors of the enzyme activity associated with immunophilin proteins, and particularly inhibitors of peptidyl-prolyl isomerase or rotamase enzyme activity.Type: GrantFiled: June 7, 1995Date of Patent: March 25, 1997Assignee: Guilford Pharmaceuticals Inc.Inventors: Gregory S. Hamilton, Joseph P. Steiner
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Patent number: 5610144Abstract: This invention relates to compositions of formula: ##STR1## and their salts, their preparation and the medicaments containing them.Type: GrantFiled: June 27, 1994Date of Patent: March 11, 1997Assignee: Rhone-Poulenc Rorer S.A.Inventors: Marc Capet, Claude Cotrel, Claude Guyon, Michel Joannic, Franco Manfre, G erard Roussel, Marie-Christine Dubroeuco, Michel Cheve, Gilles Dutruc-Rosset
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Patent number: 5591867Abstract: This invention provides a process for preparing kainic acid and provides intermediates in the synthesis thereof.Type: GrantFiled: October 30, 1995Date of Patent: January 7, 1997Assignee: Eli Lilly and CompanyInventor: James A. Monn
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Patent number: 5543521Abstract: Compounds of formula (I) and pharmaceutical compositions containing the compounds of formula (I): ##STR1## are provided. In formula (I): Ar is a substituted or unsubstituted aromatic or heterocyclic group; R is H or a substituted or unsubstituted straight or branched chain, cyclic or mixture of straight branched and cyclic alkyl, alkenyl, or alkynyl group having from 1-20 carbon atom; A is a functional group that bears a polar moiety; R.sub.1 is R, R--C=0, R substituted with one or more heteroatoms, a substituted or unsubstituted aryl group, or is aryl-(CH.sub.2).sub.n ; R.sub.2 is (CH.sub.2).sub.n, CHR, C(R).sub.2, COO, OCO, NHCO, CONH, SO, SO.sub.2 or NR; R.sub.3 and R.sub.4, which are the same or different or each may be absent, and are .dbd.O, H, O-aryl, OR, O-alkyl or alkyl, aryl, SR, S-aryl, NHR, NH-aryl, NR, or are other heteroaromatic groups; R.sub.5 is H, OH or R; E and F, which are the same or are different, are either N or (CH.sub.2).sub.Type: GrantFiled: January 12, 1994Date of Patent: August 6, 1996Assignee: Immunopharmaceutics, Inc.Inventors: Ming F. Chan, Vitukudi N. Balaji
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Patent number: 5534515Abstract: Compounds of formula (I) ##STR1## wherein R1 stands for alkyl or R5-substituted alkylene; R2 stands for alkyl; R3 stands for hydrogen, halogen, --CHO (formyl), hydroxymethyl, nitro, amino, or the substituent --CH.sub.2 O--COR7; R4 stands for halogen or the substituent --A--B--R6; R5 stands for furyl, thienyl, tetrahydrofuryl, phenyl or phenyl substituted by one or two identical or different substituents from the group composed of halogen, alkyl, alkoxy, nitro, --NH--CO--NH.sub.2 (ureido), amino, alkylcarbonyl-amino and alkoxycarbonylamino; R7 stands for alkyl, alkoxy-alkyl, alkoxycarbonyl-alkyl or carboxy-alkyl; A stands for O (oxygen) or NH; B stands for a bond, --CH.sub.2 -- (methylene) or --CH.sub.2 CH.sub.2 -- (1,2-ethylene); and n stands for the number 0 or 1; are useful for preventing and treating gastrointestinal disorders.Type: GrantFiled: April 25, 1994Date of Patent: July 9, 1996Assignee: BYK Gulden Lomberg Chemische Fabrik GmbHInventor: Gerhard Grundler
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Patent number: 5525735Abstract: Disclosed are methods for synthesizing very large collections of diverse pyrrolidine compounds and derivatives thereof on solid supports and synthetic compound libraries comprising pyrrolidine groups and derivatives thereof prepared by such methods.Type: GrantFiled: December 12, 1994Date of Patent: June 11, 1996Assignee: AFFYMAX Technologies NVInventors: Mark A. Gallop, Martin A. Murphy
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Patent number: 5525623Abstract: Compositions and methods for the prevention and treatment of immunomediated inflammatory disorders, especially for those disorders associated with the respiratory tract, are provided. More particularly, a tryptase inhibitor, typically a hydroxyaroyl or hydroxyheteroaroyl substituted dipeptide, is administered. Also provided by this invention are pharmaceutical compositions, typically aerosol or topical, as well as aerosol devices for administering these compositions intranasally.Type: GrantFiled: March 11, 1994Date of Patent: June 11, 1996Assignee: Arris Pharmaceutical CorporationInventors: Kerry Spear, Charles Johnson, Heinz W. Gschwend
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Patent number: 5525734Abstract: Disclosed are methods for synthesizing very large collections of diverse pyrrolidine compounds on solid supports and synthetic compound libraries comprising pyrrolidine groups prepared by such methods.Type: GrantFiled: June 22, 1994Date of Patent: June 11, 1996Assignee: Affymax Technologies N.V.Inventors: Mark A. Gallop, Martin A. Murphy
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Patent number: 5519146Abstract: A process for crystallizing N.sup.2 -((S)-1-ethoxycarbonyl-3-phenylpropyl)-N.sup.6 -trifluoroacetyl-L-lysyl-L-proline using one or a mixture of at least two kinds of compound having the general formula: CR.sup.1 R.sup.2 R.sup.3 R.sup.4 as a crystallizing solvent, optionally with an auxiliary solvent which controls crystallization condition.Type: GrantFiled: August 26, 1994Date of Patent: May 21, 1996Assignee: Kanegafuchi Kagaku Kogyo Kabushiki KaishaInventors: Yasuyoshi Ueda, Hajime Manabe
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Patent number: 5518735Abstract: D,L-, L- and D-phenyl alanine derivatives of formula (I) defined in claim 1 in which R.sub.1 is an amidino-, guanidino-, oxamidino-, aminomethyl- or amino group have been discovered which effectively prevent blood coagulation or thrombosis. The antithrombotically active compounds have low toxicity and may be administered by mouth, subcutaneously or intravenously.Type: GrantFiled: February 10, 1993Date of Patent: May 21, 1996Assignee: Pentapharm AGInventors: Jorg Sturzebecher, Helmut Vieweg, Peter Wikstroem
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Patent number: 5473081Abstract: An L-proline derivative represented by: ##STR1## wherein R.sub.2 represents a lower alkyl group is prepared by reacting L-proline with a D-.alpha.-alkyl-.beta.-acylthiopropionic acid halide, ##STR2## wherein R.sub.1 represents an acyl group, X represents a halogen atom and R.sub.2 has the same meaning as defined above. The halide is added to an aqueous medium containing L-proline and a condensation agent for deacidification. The halide and L-proline are reacted while the reaction temperature and pH are maintained at 12.degree. C. or lower and within a range of 10.5-11.5, whereby a compound represented by: ##STR3## wherein R.sub.1 and R.sub.2 have the same meanings as defined above is obtained. The resulting compound is then subjected to deacylation under strong alkaline conditions without being isolated from the reaction mixture, thereby yielding the target L-proline derivative.Type: GrantFiled: January 13, 1994Date of Patent: December 5, 1995Assignee: Mitsubishi Rayon Co., Ltd.Inventors: Yoshimasa Kobayashi, Kaori Tosa, Akihiro Sakimae, Ryozo Numazawa
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Patent number: 5453424Abstract: This invention is concerned with novel compounds represented by structural formulae I and II. ##STR1## which are useful in the treatment of cardiac arrhythmia.Type: GrantFiled: November 22, 1993Date of Patent: September 26, 1995Assignee: Merck & Co., Inc.Inventors: Gerald S. Ponticello, John J. Baldwin, David C. Remy
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Patent number: 5439930Abstract: A novel class of substances of N-acyl-prolyldipeptides, which possess psychotropic activity and particularly facilitate learning and memory are described. The N-acyl-prolyldipeptides of the invention have the formula: ##STR1## wherein R.sup.1 =(C.sub.4 -C.sub.5) alkyl, cycloalkyl, aralkyl, or aryl; R.sup.2 =H.sub.1 (C.sub.1 -C.sub.4) alkyl, carbamidoalkyl, or carbalkoxyalkyl; R.sup.3 =NH.sub.2, NH(alkyl), N(alkyl).sub.2, OH, or alkoxy; and n=0-3, preferably 0-2.Type: GrantFiled: October 14, 1992Date of Patent: August 8, 1995Assignee: Russian-American Institute for New Drug DevelopmentInventors: Sergei B. Seredenin, Tatiana A. Voronina, Tatiana A. Gudasheva, Rita U. Ostrovskaya, Grigori G. Rozantsev, Alexander P. Skoldinov, Sergei S. Trophimov, James A. Halikas, Taisija L. Garibova
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Patent number: 5424454Abstract: L-alanyl-L-proline is stereoselectively prepared catalytically hydrogenating an N-(2-iminopropionyl)-L-proline in the presence of a metal hydrogenolysis catalyst and at a pH of less than about 4. Also disclosed are improved processes for production of N-pyruvyl-L-proline in which L-proline and a 2,2-disubstituted propionyl halide are allowed to react at a pH of at least 9 to produce an L-proline intermediate which is hydrolyzed at a pH range of from about 6.5 to about 8.5 to yield N-pyruvyl-L-proline.Type: GrantFiled: May 26, 1994Date of Patent: June 13, 1995Assignee: Celgene CorporationInventors: Beverly W. Burbaum, Chunshi Li, George W. Matcham
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Patent number: 5418236Abstract: Aroyl(piperidinyl and piperazinyl)acyl pyrroles of the following formula have anxiolytic activity: ##STR1## wherein, Y is selected from the group consisting of N, CH or COH;A.sup.1 is selected from the group consisting of ##STR2## n is an integer from 1 to 5;R.sup.1 is selected from the group consisting of H and C.sub.1-4 alkyl;R.sup.2 and R.sup.3 are selected from the group consisting of H and C.sub.1-4 alkyl;R.sup.4 is selected from the group consisting of halo, C.sub.1-4 alkyl, hydroxy, C.sub.1-4 alkoxy, nitro, amino, C.sub.1-4 acylamino, cyano, trihaloC.sub.1-4 alkyl, C.sub.1-4 alkylsulfonyl, C.sub.1-4 alkylsulfinyl and C.sub.1-4 acyl; andR.sup.5 is selected from the group consisting of halo, C.sub.1-4 alkyl, hydroxy, C.sub.1-4 alkoxy, nitro, amino, C.sub.1-4 acylamino, cyano, trihaloC.sub.1-4 alkyl, C.sub.1-4 alkylsulfonyl, C.sub.1-4 alkylsulfinyl and C.sub.1-4 acyl; and acid addition salts thereof.Type: GrantFiled: December 23, 1993Date of Patent: May 23, 1995Assignee: Ortho Pharmaceutical CorporationInventors: Richard J. Carmosin, John R. Carson, Philip Pitis
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Patent number: 5387697Abstract: The intermediate 1-[3-acetylthio-2(s)-methylpropanoyl]-1-proline is prepared by reacting L-proline with (R)-3-acetylthio-2-methyl propanoyl chloride at 0-5.degree. C., with pH controlled at 7.5-8.5, using 2.5M potassium hydroxide and potassium phosphate buffer, which gives >97% pure material after crystallizing from the reaction mixture.Type: GrantFiled: June 13, 1994Date of Patent: February 7, 1995Assignee: Merck & Co., Inc.Inventor: Azucena C. Hen
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Patent number: 5387696Abstract: N-substituted .alpha.-amino acids and dipeptides are valuable intermediate products for the production of inhibitors of the angiotensin converting enzyme (ACE); representatives are e.g. enalapril and ramipril. These compounds are prepared by means of hydrogenolytic conversion of a primary amine with a ketone with the addition of an organic or inorganic base; among the inorganic bases, basic aluminum oxide is preferred. The use of chiral organic bases favors the production of a diastereomer.Type: GrantFiled: July 13, 1992Date of Patent: February 7, 1995Assignee: DeGussa AktiengesellschaftInventors: Matthias Kottenhahn, Karlheinz Drauz, Horst Harr
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Patent number: 5380875Abstract: Provided are N-(9-fluorenylmethoxycarbonyl)-4-substituted proline derivatives represented by the following formula (I): ##STR1## wherein Q is O or S, R represents a particular monovalent group, and T represents H or --C(CH.sub.3).sub.3. Where T is H, the derivatives can each be prepared by reacting a corresponding electron attractive compound with N-(9-fluorenylmethoxycarbonyl)-4-hydroxyproline in the presence of a coupling reagent. The derivatives in which T stands for --(CH.sub.3).sub.3 can each be prepared by reacting the corresponding N-(9-fluorenylmethoxy-carbonyl)-4-hydroxyproline derivative with isobutylene in the presence of a catalytic amount of sulfuric acid. The staring material, N-(9-fluorenylmethoxycarbonyl)-4-hydroxyproline, can be purified by adsorbing it on anhydrous magnesium sulfate.Type: GrantFiled: May 4, 1994Date of Patent: January 10, 1995Assignee: Hitachi Chemical Company, Ltd.Inventors: Yasuo Yamamoto, Yoshiaki Harushima, Akira Nagai
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Patent number: 5359086Abstract: A process for preparing N-[1(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanine N-carboxy anhydride from N-[1(S)-ethoxycarbonyl-3 -phenylpropyl]-L-alanine and N,N'-carbonyldiimidazole and the condensation thereof with L-proline silyl ester hydrochloride. The condensation product is used as an angiotensin converting enzyme (ACE) inhibitor.Type: GrantFiled: September 16, 1993Date of Patent: October 25, 1994Assignee: KRKA, Pharmaceutical & Chemical WorksInventors: Marjo Merslavic, Janja Crinski
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Patent number: 5319098Abstract: L-Alanyl-L-proline is stereoselectively prepared catalytically hydrogenating an N-(2-iminopropionyl)-L-proline in the presence of a metal hydrogenolysis catalyst and at a pH of less than about 4. Also disclosed are improved processes for production of pyruvylproline in which L-proline and a 2,2-disubstituted propionyl halide are allowed to react at a pH of at least 9 to produce an L-proline intermediate which is hydrolyzed at a pH range of from about 6.5 to about 8.5 to yield N-pyruvyl-L-proline.Type: GrantFiled: May 18, 1993Date of Patent: June 7, 1994Assignee: Celgene CorporationInventors: Beverly W. Burbaum, Chunshi Li, George W. Matcham
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Patent number: 5304570Abstract: A pharmaceutical composition is described comprising ibopamine and an ACE-inhibitor. Such composition is useful in the treatment of cardiovascular diseases, more particularly of hypertension and heart insufficiency even when the latter is associated with or caused by hypertension.Type: GrantFiled: July 11, 1989Date of Patent: April 19, 1994Assignee: Zambon Group S.P.A.Inventors: Cesare Casagrande, Luciano Licciardello
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Patent number: 5276207Abstract: The invention relates to a novel process for preparing 1-[/2S/-methyl-3-mercaptopropionyl]-pyrrolidine-/2S/-carboxylic acid of the formula I ##STR1## in which 1-[/2S/-methyl-3-thiocyanatopropionyl]-pyrrolidine-/2S/-carboxylic acid of the formula II ##STR2## is dissolved in an aqueous mineral acid, the solution obtained is diluted with water and the 1-[/2S/-methyl-3-carbamoylthiopropionyl]-pyrrolidine-/2S/-carboxylic acid of the formula III ##STR3## that forms is hydrolized with an aqueous solution of a base.Type: GrantFiled: March 1, 1993Date of Patent: January 4, 1994Assignee: Egis Gyogyszergyar Rt.Inventors: Geza Schneider, Gabor Blasko, Agnes Kovacs nee Palotai, Gabriella rmos nee Lassu, Ilma Dinnyes nee Nagy, Ivan Beck, Elemer Jakfalvi, Andras Dietz
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Patent number: 5268472Abstract: Nitrogen-containing heterocyclic (poly) peroxycarboxylic acid monopersulfates which have the formula: ##STR1## wherein the symbols have the following meanings: R represents a hydrogen atom or an alkyl, (hetero)cycloalkyl, (hetero)aryl, alkyl-aryl or arylalkyl group, wherein said groups are optionally substituted, or a carboxylic group or a peroxycarboxylic group, or any other substituents non-reactive in the presence of the peroxycarboxylic group;R.sup.1 represents an alkyl group > C.sub.5 ;n is a number selected from 0,1 and 2;m is a number selected from 1, 2 and 3;and the heterocyclic ring may be in its turn condensed with at least one further (hetero) aromatic or (hetero)cycloalkylic ring. The invention relates to a preparation process for, and to their use, as bleaching agents.Type: GrantFiled: October 5, 1992Date of Patent: December 7, 1993Assignee: Ausimont S.p.A.Inventors: Carlo Venturello, Claudio Cavallotti, Fiorella Achilli
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Patent number: 5235066Abstract: An intermediate, useful in the conversion of FK-506 to FK-525 and analogous 23-membered ring macrolides, of the structure: ##STR1##Type: GrantFiled: February 19, 1992Date of Patent: August 10, 1993Assignee: Merck & Co., Inc.Inventors: David Askin, Daisy Joe, Ralph P. Volante, Ichiro Shinkai
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Patent number: 5227497Abstract: A process for producing N.sup.2 -(1-(S)-carboxy-3-phenylpropyl)-L-lysil-L-proline of formula (VIII); ##STR1## N.sup.2 -(1-substituted-3-phenylpropyl)-L-lysil-L-proline derivative of formula (VII); ##STR2## and N.sup.2 -(1-carbonyl-3-phenylpropyl)-L-lysil-L-proline derivative of formula (XXVI); ##STR3## is disclosed.Type: GrantFiled: December 19, 1991Date of Patent: July 13, 1993Assignee: Kanegafuchi Kagaku Kogyo Kabushiki KaishaInventors: Kenji Inoue, Satomi Takahashi
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Patent number: 5206384Abstract: A novel actinonin derivative and a salt thereof are provided, which are useful as enzyme inhibitors and particularly have strong inhibitory activities against enkephalinase and angiotensin-converting enzymes. This actinonin derivative is represented by general formula (I): ##STR1## wherein R.sup.1 is sulfoxymethyl or carboxyl or a substituted carboxyl group selected from carboxamide, hydroxyaminocarbonyl and alkoxycarbonyl groups; and R.sup.2 is hydroxyl, alkoxy, hydroxyamino or sulfoxyamino group.Type: GrantFiled: September 4, 1991Date of Patent: April 27, 1993Assignees: Zaidan Hojin Biseibutsu Kagaku Kai, Meiji Seika Kaisha Ltd.Inventors: Seiji Shibahara, Yoshiyuki Koyama, Shigeharu Inoue, Mitsugu Hachisu, Shinichi Kondo, Takaaki Aoyagi, Tomio Takeuchi
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Patent number: 5202443Abstract: The invention relates to a novel process for preparing 1-[(2S)-3-mercapto-2-methyl-1-oxopropyl]-L-proline (captopril) of formula (I). ##STR1## which comprises hydrogenolysing 1-[(2S)-2-methyl-1-oxo-3-rhodanidopropyl]-L-proline of formula (II) ##STR2## in an inert solvent, in the presence of a catalyst, at a temperature of 50.degree. to 120.degree. C. under a pressure of 10.sup.5 to 10.sup.7 Pa.The above compound of formula (II) is new and can be prepared by acylating L-proline with a reactive acylating derivative of (2S)-2-methyl-3-rhodanido-propionic acid of formula (III).Type: GrantFiled: September 20, 1991Date of Patent: April 13, 1993Assignee: EGIS GyogyszergyarInventors: Geza Schneider, Gabor Blasko, Agnes Kovacs nee Palotai, Gabriella rmos nee Lassu, Judit Kun, Ilma Dinnyes nee Nagy, Ivan Beck, Elemer Jakflavi, Andras Dietz
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Patent number: 5192773Abstract: This invention relates to a novel class of immunosuppressive compounds having an affinity for the FK-506 binding protein (FKBP). Once bound to this protein, the immunosuppressive compounds inhibit the prolyl peptidyl cis-trans isomerase (rotamase) activity of the FKBP and inhibit T cell activation. As such, the compounds of this invention can be used as immunosuppressive drugs to prevent or significantly reduce graft rejection in bone marrow and organ transplantations and for use in the treatment of a wide variety of autoimmune diseases in humans and other mammals.Type: GrantFiled: July 2, 1990Date of Patent: March 9, 1993Assignee: Vertex Pharmaceuticals, Inc.Inventors: David A. Armistead, Joshua S. Boger, Harold V. Meyers, Jeffrey O. Saunders, Roger D. Tung
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Patent number: 5187290Abstract: Compounds of the formula ##STR1## wherein Z is oxygen or sulfur are disclosed. These compounds are useful as hypotensive agents due to their angiotensin converting enzyme inbitition activity and depending upon the definition of X may also be useful as analgesics due to their enkephalinase inhibition activity.Type: GrantFiled: September 29, 1986Date of Patent: February 16, 1993Assignee: E. R. Squibb & Sons, Inc.Inventor: Eric M. Gordon
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Patent number: 5166361Abstract: This invention relates to novel methods for converting a diastereomeric mixture of S-protected derivatives of an orally active inhibitor of an angiotensin-converting enzyme (ACE) and its analogues into its separate optically resolved diastereomeric components. Specifically the invention relates to methods for the preparation of optically purified captopril and its analogs from racemic precursors. This resolution process is achieved through the fractional crystallization of S-protected derivatives of captopril and its precursors, which derivatives are useful for the reason that they are (1) easily prepared from novel precursors, (2) resolvable to their optically purified stereoisomeric species and (3) convertible to non-derivatized stereoisomeric species which correspond to the pharmacologically active inhibitor and its analogues. Novel methods for preparing the derivatives and their precursors are also noted herein. In addition, the novel derivatives and their precursors are also described herein.Type: GrantFiled: September 25, 1991Date of Patent: November 24, 1992Assignee: Sepracor, Inc.Inventor: Charles M. Zepp
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Patent number: 5151433Abstract: Stabilized compounds of the formula I ##STR1## in which R, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 have the stated meanings, and a process for the preparation thereof, are described. The stabilized compounds are suitable for the manufacture of medicinal formulations.Type: GrantFiled: November 22, 1988Date of Patent: September 29, 1992Assignee: Hoechst AktiengesellschaftInventors: Werner Fulbreth, Richard Leeb, Manfred Radau, Willi Stammberger
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Patent number: 5142065Abstract: An acylamino ester of the formula ##STR1## wherein X is C.sub.1-6 alkyl, or halogen,Y is hydrogen, C.sub.1-6 alkyl, halogen, or C.sub.1-3 halogenalkyl,Z is C.sub.1-6 alkyl, or halogen,n is 0 to 3,provided that when n is O,Y is not hydrogen, andR.sup.3 is C.sub.1-6 alkyl.Type: GrantFiled: June 5, 1991Date of Patent: August 25, 1992Assignee: Bayer AktiengesellschaftInventors: Reiner Fischer, Hermann Hagemann, Andreas Krebs, Albrecht Marhold, Klaus Lurssen, Robert R. Schmidt, Hans-Joachim Santel, Benedikt Becker, Klaus Schaller, Wilhelm Stendel
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Patent number: 5118811Abstract: Amino acid derivatives of the formula ##STR1## wherein: Q is W--(CH.sub.2).sub.m --(A).sub.n --CO--B-- whereinA is oxygen atom or --NH--;B is ##STR2## or --(CH.sub.2).sub.l -- wherein X is sulfur atom or --CH.sub.2 --, and l is an integer from 1 to 3;W is ##STR3## wherein Hal is halogen atom; n is an integer of 0 or 1; andm is an integer from 0 to 3;Y is sulfur atom or --CH.sub.2 --; andR is hydrogen atom, formyl group, C.sub.1-5 alkoxycarbonyl group, --C.tbd.N or ##STR4## wherein R.sup.1 is hydrogen atom, andR.sup.2 is hydroxyl group, C.sub.1-5 alkylcarboxy group, phenylcarboxy group, C.sub.1-5 alkoxy group or phenyl C.sub.1-5 alkoxy group;with the proviso that when R is hydrogen atom, formyl group or C.sub.1-5 alkoxycarbonyl group, W is ##STR5## The compounds mentioned above specifically inhibit prolyl endopeptidase activity and are useful as agents for the treatment and prevention of dementia and amnesia.Type: GrantFiled: December 12, 1990Date of Patent: June 2, 1992Assignees: Japan Tobacco Inc., Yoshitomi Pharmaceutical Industries, Ltd.Inventors: Itsuo Uchida, Koji Kobayashi, Kazuhiko Nishii, Kunio Iwata, Shin Hara, Koretake Anami
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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: 5097043Abstract: An optically active amine compound and a method for preparing same are provided which compound has the structure ##STR1## in the form of its R-(+) enantiomer or S-(-) enantiomer, wherein R and R.sup.1 are independently H, lower alkyl or halogen, R.sup.2 is H or lower alkyl and R.sup.3 is lower alkyl, the optically active amine is useful in the optical resolution of DL-3-acylthio-2-methylpropanoic acid wherein acyl is acetyl or benzoyl. The optically active D-(+)-3-acylthio-2-methylpropanoic acids are used as intermediates for preparing antihypertensive agents, such as captopril.Type: GrantFiled: November 5, 1990Date of Patent: March 17, 1992Assignee: E. R. Squibb & Sons, Inc.Inventors: Patrick A. MacManus, Peter Walsh, Adrian J. Kilbane
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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: 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: 5028704Abstract: The present invention relates to compounds of the formula ##STR1## wherein R.sub.c is carboxy, esterified carboxy or amidated carboxy;R.sub.2 is hydrogen or lower alkyl or joins with R.sub.a and R.sub.b and the atoms therebetween to form a fused ring ##STR2## and either R.sub.a is methyl and R.sub.b is ##STR3## or R.sub.2 and R.sub.b and the atoms therebetween form a group wherein R.sub.3 and R.sub.4 are either both hydrogen, or together are propylene, butylene, or with the two atoms to which they are attached form a benzene ring. Methods of manufacture and use thereof in the production of angiotensin converting enzyme inhibitors are disclosed.Type: GrantFiled: February 8, 1990Date of Patent: July 2, 1991Assignee: Ciba-Geigy CorporationInventor: Stephen K. Boyer
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Patent number: 5026873Abstract: A process is disclosed for direct isolation of captopril from a substrate of the formula ##STR1## wherein R is lower alkyl or lower alkoxy. In this process, the substrate is first treated with an aqueous alkali metal hydroxide capable of forming a water-soluble salt of the substrate, wherein the alkali metal hydroxide has a concentration of 4M or greater. The substrate is then neutralized, preferably with a mineral acid. By this process, captopril may be directly crystallized from an aqueous solution, avoiding the prior art use of organic solvents and zinc treatment to reduce levels of sulfide and disulfide impurities, respectively. In an alternative embodiment, neutralization is carried out by use of a hydrogen-supplying ion exchange resin.Type: GrantFiled: November 6, 1989Date of Patent: June 25, 1991Assignee: E. R. Squibb & Sons, Inc.Inventors: Neal G. Anderson, David A. Lust, Barbara J. Bennett, Alan F. Feldman, Robert E. Polomski
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Patent number: 5025001Abstract: The invention relates to novel S-nitroso derivatives of ACE inhibitors and to pharmaceutical compositions comprising the S-nitrosothiol derivatives of the invention together with a pharmaceutically acceptable carrier.The invention also relates to methods for treating various pathophysiological conditions including acute myocardial infarction, left ventricular dysfunction without overt heart failure, hypertension, pulmonary hypertension, congestive heart failure, angina pectoris, vascular thrombosis, Raynauds syndrome, scleroderma, toxemia of pregnancy, acute renal failure, diabetic nephropathy, and renal artery stenosis, and to methods of inhibiting ACE and effecting vasodilation comprising administering the S-nitrosothiol derivatives of the ACE inhibitors of the invention to an animal.Type: GrantFiled: March 24, 1989Date of Patent: June 18, 1991Assignee: Brigham and Women's HospitalInventors: Joseph Loscalzo, John Cooke