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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Publication number: 20020049165Abstract: A novel dipeptide compound inhibiting the enzymatic activity of HIV protease, an anti-AIDS medicine comprising this dipeptide compound as an effective component.Type: ApplicationFiled: August 27, 2001Publication date: April 25, 2002Inventors: Tsutomu Mimoto, Keisuke Terashima, Haruso Takaku, Shinji Matsumoto, Makoto Shintani, Satoshi Nojima
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Publication number: 20020040048Abstract: The present invention relates to a pyrrolidine compound and pharmaceutically acceptable esters and/or salts thereof. The compounds are useful as inhibitors of metalloproteases, e.g. zinc proteases, particularly zinc hydrolases, and which are effective in treating disease states are associated with vasoconstriction of increasing occurrences.Type: ApplicationFiled: July 6, 2001Publication date: April 4, 2002Inventors: Johannes Aebi, Henrietta Dehmlow, Eric A. Kitas
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Patent number: 6350882Abstract: The instant invention is directed to a process for synthesizing substituted prolines, in particular, optically pure substituted prolines, which comprises the steps of: a) adding an unsubstituted or substituted proline alkali salt and an alkali halide to a solution of dialkylacylamidomalonate; and b) adding &agr;, &bgr; unsaturated aldehyde to produce an adduct.Type: GrantFiled: May 5, 2000Date of Patent: February 26, 2002Assignee: Merck & Co., Inc.Inventors: Khateeta Emerson, Guo-Jie Ho
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Publication number: 20020019371Abstract: There is provided compounds of formula I, 1Type: ApplicationFiled: April 30, 2001Publication date: February 14, 2002Applicant: AstraZeneca ABInventors: David Gustafsson, Jan-Erik Nystrom
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Publication number: 20020007073Abstract: This invention relates to the synthesis of novel cationic, amphiphilic lipids and their application as gene transfer vehicles in vitro and in vivo. For this a series of different lipids (diglycerides, steroids) were synthesized by modification with variable cationic molecules (amino acids, biogenic amines). Compounds of this kind are, due to their capability of producing complexes with polynucleotides (DNA, RNA, Antisense oligonucleotides, ribozymes etc) suitable as vectors for gene transfer (transfection).Type: ApplicationFiled: July 3, 2001Publication date: January 17, 2002Applicant: Max-Delbruck-Centrum fur molekulare MedizinInventors: Manfred Schneider, Oliver Keil, Regina Reszka, Detlef Groth
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Patent number: 6335453Abstract: There is provided a process for preparing a pharmacologically acceptable salt of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid which comprises condensing an amino acid and N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanine.N-carboxyanhydride under basic condition, carrying out decarboxylation under between neutral and acidic condition to obtain N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid, and forming a pharmacologically acceptable salt thereof, wherein the production of a by-product (3): is suppressed by carrying out in an aqueous liquid a series of operations till formation of the pharmacologically acceptable salt or till isolation of the pharmacologically acceptable salt. The present invention enables to prepare the pharmacologically acceptable salt of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid having high quality, in a commercial scale with high yield and economical efficiency.Type: GrantFiled: March 19, 1999Date of Patent: January 1, 2002Assignee: Kaneka CorporationInventors: Yasuyoshi Ueda, Koichi Kinoshita, Tadashi Moroshima, Yoshifumi Yanagida, Yoshihide Fuse
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Patent number: 6329418Abstract: The invention provides compounds which are potent inhibitors of metalloproteases and which are effective in treating conditions characterized by excess activity of these enzymes. In particular, the present invention relates to compounds having a structure according to the following Formula (I): wherein R1, R2, X, Z, m, and n are defined below. to This invention also includes optical isomers, diastereomers and enantiomers of the formula above, and pharmaceutically-acceptable salts, biohydrolyzable amides, esters, and imides thereof. The compounds of the present invention are useful for the treatment of diseases and conditions which are characterized by unwanted metalloprotease activity. Accordingly, the invention further provides pharmaceutical compositions comprising these compounds. The invention still further provides methods of treatment for metalloprotease-related maladies using these compounds or the pharmaceutical compositions containing them.Type: GrantFiled: March 23, 1999Date of Patent: December 11, 2001Assignee: The Procter & Gamble CompanyInventors: Menyan Cheng, Michael George Natchus, Biswanath De, Neil Gregory Almstead, Yetunde Olabisi Taiwo, Stanislaw Pikul
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Patent number: 6313159Abstract: The present invention relates to metabotropic glutamate receptor ligand derivatives and methods of using the same to inhibit NAALADase enzyme activity, to effect neuronal activities, to inhibit angiogenesis, and to treat glutamate abnormalities, compulsive disorders, pain, diabetic neuropathy, and prostate diseases, as well as pharmaceutical compositions comprising the same.Type: GrantFiled: August 20, 1999Date of Patent: November 6, 2001Assignee: Guilford Pharmaceuticals Inc.Inventors: Paul F. Jackson, Barbara S. Slusher
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Patent number: 6271393Abstract: The process for producing N2-(1(S)-carboxy-3-phenylpropyl)-L-lysyl-L-proline in a simple, efficient and industrially advantageous manner, including the following steps: 1) subjecting N2-(1(S)-alkoxycarbonyl-3-phenylpropyl)-N6-trifluoroacetyl-L-lysyl-L-proline (1) to alkali hydrolysis in a mixed solution composed of water and a hydrophilic organic solvent using an inorganic base in an amount of n molar equivalents (n ≧ 3) per mole of the above compound (1), 2) neutralizing the hydrolysis product using an inorganic acid in an amount of (n − 1) to n molar equivalents (n ≧ 3) to form a compound (2) and removing the inorganic salt formed by causing the same to precipitate out from a solvent system suited for decreasing the solubility of the inorganic salt, and 3) causing the compound (2) existing in the mixture after removal of the inorganic salt to crystallize out at the isoelectric point thereof and thereby recovering the compound (2) in the form of crystals while retaining the salts including theType: GrantFiled: July 17, 2000Date of Patent: August 7, 2001Assignee: Kaneka CorporationInventors: Tadashi Moroshima, Yoshifumi Yanagida, Yoshihide Fuse, Yasuyoshi Ueda
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Patent number: 6262089Abstract: New compounds have the formula: wherein R, R1, X and Y have the meanings described herein. Methods are set forth for synthesizing these compounds and using these compounds to treat diseases associated with amyloidosis, such as Alzheimer's disease, maturity onset diabetes mellitus, familial amyloid polyneuropathy, scrapie, and Kreuzfeld-Jacob disease.Type: GrantFiled: February 16, 2000Date of Patent: July 17, 2001Assignee: Hoffman-La Roche Inc.Inventors: Cornelia Hertel, Torsten Hoffmann, Roland Jakob-Roetne, Roger David Norcross
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Patent number: 6258959Abstract: A process for the preparation of 2,4-dimethyl-3,5-bisalkoxycarbonylpyrrole is described, in which an acetoacetic alkyl ester is nitrosated to give the 2-nitrosoacetoacetic alkyl ester, the nitroso compound is reduced using hydrogen in the presence of a noble metal catalyst to give the amine, and the resulting amino compound is condensed without isolation in the presence of the corresponding non-nitrosated acetoacetic alkyl ester to give the 2,4-dimethyl-3,5-bisalkoxycarbonylpyrrole. The process makes it possible to work under conditions which are milder than in the prior art and to avoid the formation of by-products.Type: GrantFiled: December 13, 1999Date of Patent: July 10, 2001Assignee: BASF AktiengesellschaftInventors: Carsten Gröning, Reinhard Kemper, Markus Frede, Klaus Ebel
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Patent number: 6242476Abstract: The present invention relates to leukotriene A4 hydrolase inhibitors containing compounds represented by the formula [I] or salts thereof as active ingredients, wherein R1 represents hydrogen, alkyl, phenylalkyl, alkanoyl or benzoyl; R2 and R3 each represent hydrogen or alkyl; R4 represents hydroxyl, alkoxy, phenylalkoxy, amino, alkylamino or phenylalkylamino; R5 represents phenylalkyl or naphthylalkyl; “Z” represents sulfur or oxygen; “A” represents alkylene; and “n” represents 0, 1 or 2; providing that the phenyl ring in R1 can be substituted by alkyl, alkoxy or halogen, and that the phenyl ring or the naphthyl ring in R5 can be substituted by alkyl, cycloalkyl, alkoxy, alkylthio or halogen.Type: GrantFiled: September 17, 1999Date of Patent: June 5, 2001Assignee: Santen Pharmaceutical Co., Ltd.Inventors: Shiro Mita, Masato Horiuchi, Masakazu Ban, Ken-ichi Fujimura, Hiroshi Suhara
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Patent number: 6239146Abstract: The present invention relates to the design, synthesis, and the peptidyl-prolyl isomerase (PPIase or rotamase) inhibitory activity of novel &agr;,&agr;-difluoroacetamido compounds that are neurotrophic agents (i.e. compounds capable of stimulating growth or proliferation of nervous tissue) and that bind to immunophilins such as FKBP12 and inhibit their rotamase activity. This invention also relates to pharmaceutical compositions comprising these compounds.Type: GrantFiled: June 9, 2000Date of Patent: May 29, 2001Assignee: Bristol-Myers Squibb CompanyInventors: Vivekananda M. Vrudhula, Gene M. Dubowchik, Bireshwar Dasgupta, Dolatrai M. Vyas
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Patent number: 6232467Abstract: Amines and amino acids are prepared by reacting an amine, a carbonyl derivative, and an organoboron compound under mild conditions.Type: GrantFiled: June 27, 1997Date of Patent: May 15, 2001Assignee: University of Southern CaliforniaInventors: Nicos A. Petasis, Ilia A. Zavialov
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Patent number: 6218417Abstract: Compounds having platelet anti-aggregating activity and antihypertension activity having reduced branchial side effects.Type: GrantFiled: November 8, 1999Date of Patent: April 17, 2001Assignee: Nicox, S.A.Inventor: Piero Del Soldato
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Patent number: 6218551Abstract: Combination chemical libraries of Formula I and methods for preparation are disclosed. The libraries allow one to screen large numbers of compounds for a desired biological activity with relative ease. The libraries may be tagged or untagged. In preferred libraries, Y is the residue of an N-acylated amino acid, a substituted 4-aminoproline or substituted piperazinealkanoic acid. The use of the libraries to discover biologically active compounds is also disclosed.Type: GrantFiled: June 21, 1999Date of Patent: April 17, 2001Assignee: Pharmacopeia, Inc.Inventors: Roland Ellwood Dolle, III, Tao Guo, Theodore Otto Johnson, Jr., Hitesh K. Patel, Shiwei Tao, Zhen Min He
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Patent number: 6204393Abstract: A process for simply and easily crystallizing a maleate salt of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-L-proline (enalapril) having a high quality out of an aqueous liquid, which comprises mixing an aqueous liquid having a pH of not less than 4 and containing N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-L-proline, maleic acid and a base with an amount of an acid sufficient to convert substantially all the base into a neutral salt.Type: GrantFiled: March 17, 2000Date of Patent: March 20, 2001Assignee: Kaneka CorporationInventors: Koichi Kinoshita, Tadashi Moroshima, Yoshifumi Yanagida, Yoshihide Fuse, Yasuyoshi Ueda
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Patent number: 6187932Abstract: A process for producing captopril of the following formula (1) comprising subjecting a substrate compound of the following general formula (2) to a hydrolysis reaction in aqueous medium to remove the RCO group and isolating the product compound, said hydrolysis reaction in aqueous medium being conducted in the presence of a strong acid at pH not over 1 and a reaction temperature not below 40° C.Type: GrantFiled: August 3, 1998Date of Patent: February 13, 2001Assignee: Kaneka CorporationInventors: Koichi Kinoshita, Fumihiko Kano, Takahiro Okubo, Yasuyoshi Ueda
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Patent number: 6150527Abstract: New compounds are disclosed for multimerizing immunophilins and proteins containing immunophilin or immunophilin-related domains.Type: GrantFiled: February 28, 1997Date of Patent: November 21, 2000Assignee: Ariad Pharmaceuticals, Inc.Inventors: Dennis A. Holt, Terence P. Keenan, Tao Guo, Edgardo Laborde, Wu Yang
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Patent number: 6147189Abstract: Homologs and analogs of naturally-occurring polypeptides contain one or more interaction sites of the natural counterpart. The interaction sites are flanked by conformation-constraining moieties, such as proline or cysteine.Type: GrantFiled: September 19, 1997Date of Patent: November 14, 2000Assignee: Virginia Commonwealth UniversityInventors: Herbert J. Evans, R. Manjunatha Kini
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Patent number: 6133456Abstract: New compounds are disclosed for multimerizing immunophilins and proteins containing immunophilin or immunophilin-related domains. The compounds are of the formulaM.sup.1 --L--M.sup.2where M.sup.1 and M.sup.2 are independently moieties of the formula: ##STR1## in which B.sup.1, B.sup.2, B.sup.3, R.sup.1, R.sup.2, n, W, X and Y are as defined.Type: GrantFiled: February 28, 1997Date of Patent: October 17, 2000Assignee: ARIAD Gene Therapeutics, Inc.Inventors: Dennis A. Holt, Terence P. Keenan, Tao Guo, Edgardo Laborde, Wu Yang
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Patent number: 6111069Abstract: Homologs and analogs of naturally-occurring polypeptides contain one or more interaction sites of the natural counterpart. The interaction sites are flanked by conformation-constraining moieties, such as proline or cysteine.Type: GrantFiled: September 19, 1997Date of Patent: August 29, 2000Assignee: Virginia Commonwealth UniversityInventors: Herbert J. Evans, R. Manjunatha Kini
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Patent number: 6100044Abstract: Homologs and analogs of naturally occurring polypeptides contain one or more interaction sites of the natural counterpart. The interaction sites are identified by the presence of flanking conformation-constraining moieties, such as proline or cysteine.Type: GrantFiled: September 19, 1997Date of Patent: August 8, 2000Assignee: Virginia Commonwealth UniversityInventors: Herbert J. Evans, R. Manjunatha Kini
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Patent number: 6096762Abstract: The present invention relates to the design, synthesis, and the peptidyl-prolyl isomerase (PPIase or rotamase) inhibitory activity of novel .alpha.,.alpha.-difluoroacetamido compounds that are neurotrophic agents (i.e. compounds capable of stimulating growth or proliferation of nervous tissue) and that bind to immunophilins such as FKBP12 and inhibit their rotamase activity. This invention also relates to pharmaceutical compositions comprising these compounds.Type: GrantFiled: May 21, 1999Date of Patent: August 1, 2000Assignee: Bristol-Myers Squibb CompanyInventors: Vivekananda M. Vrudhula, Gene M. Dubowchik, Bireshwar Dasgupta, Dolatrai M. Vyas
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Patent number: 6084066Abstract: Homologs and analogs of naturally-occurring stem cell factor polypeptides contain one or more interaction sites of the natural counterpart. The interaction sites are flanked by conformation-constraining moieties, such as proline or cysteine.Type: GrantFiled: January 15, 1999Date of Patent: July 4, 2000Assignee: Virginia Commonwealth UniversityInventors: Herbert J. Evans, R. Manjunatha Kini
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Patent number: 6063931Abstract: A process of synthesizing a compound of the formula 1: ##STR1## is described. A compound of the formula 2: ##STR2## is reacted with diphenylphosphinic chloride to activate the carboxylic acid group, and then reacted with methanesulfonyl chloride to produce a compound of formula 4: ##STR3## Compound 4 is then reacted with a group II metal sulfide source in water to produce a compound of formula 1.Type: GrantFiled: June 29, 1998Date of Patent: May 16, 2000Assignee: Merck & Co., Inc.Inventors: Karel M. J. Brands, John M. Williams, Ulf H. Dolling, Ronald B. Jobson, Antony J. Davies, Ian F. Cottrell, Mark Cameron, Michael S. Ashwood
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Patent number: 6039939Abstract: N-Acyl-hydroxyamino acid alkyl esters help to strengthen the natural barrier function of the skin against environmental influences and external irritation. They improve the suppleness and the elasticity of skin and hair, help to increase the moisture content and protect skin and hair from drying out.Type: GrantFiled: March 13, 1998Date of Patent: March 21, 2000Assignee: Haarmann & Reimer GmbHInventors: Jakob Ley, Roland Langner
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Patent number: 6031112Abstract: Process for the production of alkoxycarbonyldipeptides intermediates in the synthesis of the lisinopril which comprises protecting both amino functions of the L-lysine with an alkoxycarbonyl group, subsequently making the N-carboxyanhydride of the N6-[alkoxycarbonyl]-L-lysine by treatment with thionyl chloride and making the desired alkoxycarbonyldipeptide by reaction with L-proline in alkaline medium.Type: GrantFiled: January 25, 1999Date of Patent: February 29, 2000Assignee: P.F.C. Italiana S.r.l.Inventors: Vincenzo Cannata, Valeriano Merli, Stefano Saguatti
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Patent number: 6025500Abstract: The invention relates to an improved stereoselective heterogenous catalytic reductive amination between ethyl 2-oxo-4-phenylbutyrate and alanylproline using hydrogen, a catalyst and one or more additives to produce the ACE inhibitor, enalapril.Type: GrantFiled: September 17, 1999Date of Patent: February 15, 2000Assignee: Merck & Co., Ltd.Inventors: Mark A. Huffman, Paul J. Reider, Carl Leblond, Yongkui Sun
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Patent number: 5990131Abstract: This invention relates to neurotrophic low molecular weight, small molecule heterocyclic thioesters and ketones having an affinity for FKBP-type immunophilins, and their use as inhibitors of the enzyme activity associated with immunophilin proteins, particularly peptidyl-prolyl isomerase, or rotamase, enzyme activity.Type: GrantFiled: August 1, 1997Date of Patent: November 23, 1999Assignee: Gpi Nil Holdings Inc.Inventors: Gregory S. Hamilton, Jia-He Li
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Patent number: 5977380Abstract: A process for synthesizing N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanine derivatives of the following formula (I): ##STR1## in which the definition of R has the same meaning as given in the description by using a sulfite derivative to activate the C-terminus of the three dimensional structure of an amino acid of N-[1-(S)-ethoxycarbonyl-3- phenylpropyl]-L-alanine, which can effectively couple with another amino acid to form a dipeptide of formula (I). The compound of fomula (I) is an inhibitor of ACE.Type: GrantFiled: February 17, 1999Date of Patent: November 2, 1999Assignee: Everlight USA, Inc.Inventors: Suh-Wan Yang, Yu-An Chang, Yu-Liang Liu
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Patent number: 5965698Abstract: Homologs and analogs of naturally-occurring polypeptides contain one or more interaction sites of the natural counterpart. The interaction sites are flanked by conformation-constraining moieties, such as proline or cysteine.Type: GrantFiled: May 3, 1996Date of Patent: October 12, 1999Assignee: Virginia Commonwealth UniversityInventors: Herbert J. Evans, R. Manjunatha Kini
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Patent number: 5962696Abstract: There is provided a process for the work-up of this material having the formula ##STR1## because of its poor crystallizability has heretofore been available only with large yield losses. The yield losses are due to the fact that the crystals of this compound are associated with large amounts of residual solvent material which gives rise to complex and expensive drying procedures. In accordance with the present invention the crude LPE is dried by means of fluid or supercritical carbon dioxide which maces it possible to reduce drying times from the previous range of about 124 hours to about 10 hours for the same amount of product and thus produce a dry LPE which has smaller amounts of residual solvent, as well as smaller by-products than that obtained by conventional drying.Type: GrantFiled: June 9, 1998Date of Patent: October 5, 1999Assignee: Degussa AktiengesellschaftInventors: Herbert Tanner, Karlheinz Drauz, Klaus Stingl, Gerhard Sator, Horst Bethge, Roland Moller, Thomas Tacke, Claus Rehren
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Patent number: 5952465Abstract: The present invention relates to method of producing a conformationally-constrained polypeptide that mimics the activity of an immunomodulator peptide, wherein the method comprises: producing the conformationally-constrained polypeptide, wherein the conformationally-constrained polypeptide contains a protein--protein interaction site of said immunomodulator peptide adjacently flanked on both termini by proline residues in a manner distinct from the manner found in the naturally occurring immunomodulator peptide.Type: GrantFiled: December 9, 1998Date of Patent: September 14, 1999Assignee: Virginia Commonwealth UniversityInventors: Herbert J. Evans, R. Manjunatha Kini
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Patent number: 5948887Abstract: Homologs and analogs of naturally-occurring polypeptides contain one or more interaction sites of the natural counterpart. The interaction sites are flanked by conformation-constraining moieties, such as proline or cysteine.Type: GrantFiled: September 19, 1997Date of Patent: September 7, 1999Assignee: Virginia Commonwealth UniversityInventors: Herbert J. Evans, R. Manjunatha Kini
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Patent number: 5935989Abstract: This invention relates to neurotrophic low molecular weight, small molecule N-linked ureas and carbamates of heterocyclic thioesters having an affinity for FKBP-type immunophilins, and their use as inhibitors of the enzyme activity associated with immunophilin proteins, particularly peptidyl-prolyl isomerase, or rotamase, enzyme activity.Type: GrantFiled: December 31, 1996Date of Patent: August 10, 1999Assignee: GPI NIL Holdings Inc.Inventors: Gregory S. Hamilton, Jia-He Li, Wei Huang
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Patent number: 5917055Abstract: A highly convenient and efficient process for economically producing in a high yield high-quality captopril which is remarkably reduced in the content of impurities and has a high melting point and intermediates for synthesizing the same which contain only a small amount of precursors as impurities and have excellent qualities. The process comprises subjecting an acid halide and an L-proline to the Schotten-Baumann reaction and eliminating the impurities formed as the by-products in the form of the precursors represented by general formula (5) or (6) by treating, during or after the Schotten-Baumann reaction, the aqueous medium solution with active carbon or crystallization followed by deacylation. In the formula, R.sup.1 represents acyl and n represents an integer of from 2 to 4.Type: GrantFiled: July 31, 1997Date of Patent: June 29, 1999Assignee: Kaneka CorporationInventors: Yasuyoshi Ueda, Fumihiko Kanou, Koichi Kinoshita, Takahiro Okubo
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Patent number: 5907044Abstract: A method of isolating 1-?N.sup.2 -((S)-ethoxycarbonyl)-3-phenylpropyl)-N.sup.6 -trifluoroacetyl!-L-lysyl-L-proline (lisinopril (TFA) ethyl ester, LPE). The solvent or solvent mixture used for the extraction is also a main constituent of the solvent or solvent mixture from which the crystallization takes place. High yield as well as good purity of the end product are obtained, without distillation. 1-?N.sup.2 -((S)-ethoxycarbonyl)-3-phenylpropyl)-N.sup.6 -trifluoroacetyl!-L-lysyl-L-proline (lisinopril (TFA) ethyl ester, LPE) is described as a precursor for producing an ACE inhibitor.Type: GrantFiled: October 16, 1997Date of Patent: May 25, 1999Assignee: Degussa AktiengellschaftInventors: Matthias Kottenhahn, Roland Moller, Michael Kraft, Karlheinz Drauz, Klaus Stingl
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Patent number: 5907043Abstract: The present invention relates to pyrrolidine derivatives, and more particularly to the compound (S)-1-?(S)-2-(4-methoxybenzamido)-3-methylbutyryl!-N-?(S)-2-methyl-1-(trif luoroacetyl)propyl!pyrrolidine-2-carboxamide, shown by formula I, and solvates thereof. The present invention also provides pharmaceutical compositions, intermediates and methods of preparation of the compound. The compound of formula I is an inhibitor of human neutrophil elastase and is useful in the treatment of diseases in which the enzyme is implicated, such as, for example, emphysema and acute respiratory distress syndrome (ARDS).Type: GrantFiled: January 27, 1998Date of Patent: May 25, 1999Assignee: Zeneca LimitedInventors: Stephen John Pegg, George Joseph Sependa, Elwyn Peter Davies, Chris Allan Veale
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Patent number: 5898076Abstract: Process for preparing N-pyruvyl-L-proline by reaction of L-proline with methyl pyruvate dimethyl ketal in the presence of an alkali metal alkoxide, subsequent acid hydrolysis and extraction of 1-pyruvyl-L-proline.Type: GrantFiled: August 6, 1998Date of Patent: April 27, 1999Assignee: DSM Chemie Linz GmbHInventors: Karlheinz Giselbrecht, Curt Zimmermann
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Patent number: 5869671Abstract: A process for preparing an angiotensin converting enzyme inhibitor. Phosphorus pentachloride is reacted with the carboxylic acid group of an amino acid to form an acyl chloride hydrochloride. The resulting hydrochloride salt is then coupled with a silylated amino acid in a non-aqueous medium to form a high yield peptide. The peptide is used as an angiotensin converting enzyme (ACE) inhibitor.Type: GrantFiled: June 29, 1998Date of Patent: February 9, 1999Assignee: Industrial Technology Research InstituteInventors: Shin-Shin Wang, Hui-Ping Tsai
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Patent number: 5861428Abstract: Inhibitors for matrix metalloproteases, pharmaueutical compositions containing them, and a process for using them to treat a variety of physiological conditions. The compounds of the invention have the generalized formula ##STR1## wherein each Tis a substituent group; x is 0, 1, or 2; the group D represents ##STR2## the group R6 reresents a variety of possible substituent groups on the carbon chain between D and G, and the group G represents M, ##STR3## in which M represents --CO.sub.2 H, --CON(R.sup.11).sub.2, or --CO.sub.2 R.sup.12, and R.sup.13 represents any of the side chains of the 19 noncyclic naturally occurring amino acids.Type: GrantFiled: May 30, 1997Date of Patent: January 19, 1999Assignee: Bayer CorporationInventors: Harold Clinton Eugene Kluender, Brian Richard Dixon, Michael Christopher VanZandt, Scott McClelland Wilhelm, Donald John Wolanin, Jill Elizabeth Wood
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Patent number: 5859031Abstract: This invention relates to neurotrophic N-glyoxyl-prolyl ester 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: May 21, 1996Date of Patent: January 12, 1999Assignee: GPI NIL Holdings, Inc.Inventors: Gregory S. Hamilton, Joseph P. Steiner
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Patent number: 5859047Abstract: Inhibitors for matrix metalloproteases, pharmaceutical compositions containing them, and a process for using them to treat a variety of physiological conditions. The compounds of the invention have the generalized formula ##STR1## wherein each T is a substituted group; x is 0, 1, or 2; the group D represents ##STR2## the group R6 represents a variety of possible substituent groups on the carbon chain between D and G, and the group G represents M, ##STR3## in which M represents --CO.sub.2 H, --CON(R.sup.11).sub.2, or --CO.sub.2 R.sup.12 ; and R.sup.13 represents any of the side chains of the 19 noncyclic naturally occurring amino acids.Type: GrantFiled: May 30, 1997Date of Patent: January 12, 1999Assignee: Bayer CorporationInventors: Harold Clinton Eugene Kluender, David Ross Brittelli, William Harrison Bullock, Kerry Jeanne Combs, Brian Richard Dixon, Michael Christopher VanZandt, Scott McClelland Wilhelm, Donald John Wolanin
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Patent number: 5852047Abstract: Salicylates of esterifiable ACE-inhibitors, especially captopril-S-aspirinate, and processes for their preparation are described. Such compounds are useful as analgesics, in the process of anti-clotting and as anti-hypertensive pharmaceutical reagents.Type: GrantFiled: July 29, 1996Date of Patent: December 22, 1998Assignee: Cal International LimitedInventors: William Byrne, Andrew Rynne
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Patent number: 5801251Abstract: 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: May 3, 1996Date of Patent: September 1, 1998Assignee: Kanegafuchi Kagaku Kogyo Kabushiki KaishaInventors: Yasuyoshi Ueda, Hajime Manabe
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Patent number: 5795908Abstract: This invention relates to neurotrophic N-glyoxyl-prolyl ester 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: January 23, 1997Date of Patent: August 18, 1998Assignee: GPI Nil Holdings, Inc.Inventors: Gregory S. Hamilton, Joseph P. Steiner
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Patent number: 5789434Abstract: Inhibitors for matrix metalloproteases, pharmaceutical compositions containing them, and a process for using them to treat a variety of physiological conditions. The presently claimed compounds have the generalized formula ##STR1## in which each T represents a substituent group; x is 0, 1, or 2; D represents ##STR2## .delta. is 0 or 1; U' represents O, S, or N, with the proviso that when U' is N, then .delta.=0, and when U' is O or S, then .delta.=1; R.sup.14 is any of a variety of substituent groups; and G represents M, ##STR3## in which M represents --CO.sub.2 H, --CON(R.sup.11).sub.2, or --CO.sub.2 R.sup.12, R.sup.11 represents H or an alkyl group, R.sup.12 represents an alkyl group, and R.sup.13 represents any of the side chains of the 19 noncyclic naturally occurring amino acids; and pharmaceutically acceptable salts thereof.Type: GrantFiled: November 6, 1995Date of Patent: August 4, 1998Assignee: Bayer CorporationInventors: Harold Clinton Eugene Kluender, Guenter Hans Heinz Herbert Benz, David Ross Brittelli, William Harrison Bullock, Kerry Jeanne Combs, Brian Richard Dixon, Stephan Schneider, Jill Elizabeth Wood, Michael Christopher VanZandt, Donald John Wolanin, Scott M. Wilhelm
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Patent number: 5786378Abstract: This invention relates to neurotrophic low molecular weight, small molecule heterocyclic thioesters and ketones having an affinity for FKBP-type immunophilins, and their use as inhibitors of the enzyme activity associated with immunophilin proteins, particularly peptidyl-prolyl isomerase, or rotamase, enzyme activity.Type: GrantFiled: September 25, 1996Date of Patent: July 28, 1998Assignee: GPI Nil Holdings, Inc.Inventors: Gregory S. Hamilton, Jia-He Li
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Patent number: 5744487Abstract: A prolineamide derivative represented by the formula (I): ##STR1## or a salt or hydrate thereof or a pharmaceutically acceptable salt thereof, which has a protease inhibition activity and is useful as an active ingredient of pharmaceutical compositions is provided.Type: GrantFiled: January 26, 1995Date of Patent: April 28, 1998Assignee: Mitsubishi Chemical CorporationInventors: Masahiro Ohshima, Norimichi Iwase, Shigeo Sugiyama, Koichi Sugawara, Misao Okitsu, Yoshikuni Tamao, Yasuhiro Morinaka