The Acyclic Carbon Or Acyclic Carbon Chain Is Further Unsubstituted Or Alkyl Substituted Only (e.g., Tryptophane, Etc.) Patents (Class 548/496)
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Patent number: 5650508Abstract: A novel class of peptide .alpha.-ketoamides useful for selectively inhibiting serine proteases, selectively inhibiting cysteine proteases, generally inhibiting all serine proteases, and generally inhibiting all cysteine proteases, having the formula M.sub.1 --AA--NH--CHR.sub.2 --CO--CO--NR.sub.3 R.sub.4, M.sub.1 --AA.sub.2 --AA.sub.1 --CO--NR.sub.3 R.sub.4, M.sub.1 --AA--AA--AA--CO--NR.sub.3 R.sub.4, M.sub.1 --AA--AA--AA--AA--CO--NR.sub.3 R.sub.4, or M.sub.1 --AA--CO--NR.sub.3 R.sub.4.Type: GrantFiled: October 6, 1995Date of Patent: July 22, 1997Assignee: Georgia Tech Research CorporationInventor: James C. Powers
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Patent number: 5646301Abstract: D-2-Alkyl Tryptophan compounds for incorporation into various peptides during manufacture thereof or for substitution for D-Tryptophan residues in such peptides to provide a D-2-alkyl Tryptophan residue therein which enhances the stability and biological activity of the peptide.Type: GrantFiled: April 4, 1996Date of Patent: July 8, 1997Assignee: Romano DeghenghiInventor: Romano Deghenghi
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Patent number: 5639781Abstract: The present invention provides a cathepsin L inhibitor containing a compound of the formula: ##STR1## wherein R.sup.1 is a hydrogen atom or an arylalkyl, heterocyclic-alkyl or lower alkyl group which may be substituted; R.sup.2 and R.sup.3 independently are a hydrogen atom or a hydrocarbon residue which may be substituted; R.sup.4 is an alkanoyl, sulfonyl, carbonyloxy, carbamoyl or thiocarbamoyl group which may be substituted; X is formula: --CHO or --CH.sub.2 OB (wherein B is a hydrogen atom or a protecting group of hydroxyl group); m and n independently are an integer of 0 or 1; provided that R.sup.4 is an alkanoyl group substituted by aryl, a sulfonyl group substituted by aryl having more than 9 carbon atoms or by lower alkyl, or a carbamoyl or thiocarbamoyl group which may be substituted when R.sup.1 is an unsubstituted lower alkyl, arylalkyl on methylthioethyl group, R.sup.2 and R.sup.3 independently are a lower alkyl or arylalkyl, X is --CHO, m is 1 and n is 0 or 1, or a salt thereof.Type: GrantFiled: June 27, 1995Date of Patent: June 17, 1997Assignee: Takeda Chemical Industries, Ltd.Inventors: Takashi Sohda, Yukio Fujisawa, Tsuneo Yasuma, Junji Mizoguchi, Masakuni Kori, Masayuki Takizawa
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Patent number: 5635379Abstract: Peptides containing in its amino acid chain a D-2-alkylTryptophan residue wherein the alkyl group has between one and three carbon atoms and having pharmacological activity similar to that of analogous peptides containing natural unsubstituted D-Tryptophan residues in place of the D-2-alkylTryptophan. These new peptides are more resistant to oxidative degradation which usually takes place, for example, in the presence of reactive radicals or during high energy sterilization than unsubstituted Tryptophan containing peptides. Specific peptides include His-D-2-alkyl-Trp-Ala-Trp-D-Phe-Lys-NH.sub.2, Ala-His-D-2-alkyl-Trp-Ala-Trp-D-Phe-Lys-NH.sub.2, Pyro-Glu-His-Trp-Ser-Tyr-D-2-alkyl-Trp-Leu-Arg-Pro-Gly-NH.sub.2, Pyro-Glu-His-Ser-Tyr-D-2-alkyl-Trp-Leu-Arg-Pro-NHCH.sub.2 CH.sub.3, D-Pro-Gln-Gln-D-Trp-Phe-D-Trp-2-alkyl-Trp-Met-NH.sub.2, Arg-D-Trp-N-methyl-Phe-D-2-alkyl-Trp-Leu-Met-NH.sub.2, D-Phe-Cys-Phe-D-2-alkyl-Trp-Lys-Thr-Cys-NHCH(CH.sub.2 OH)CHOHCH.sub.3 and D-Phe-Cys-Tyr-D-2-alkyl-Trp-Lys-Val-Cys-Trp-NH.sub.2.Type: GrantFiled: October 30, 1995Date of Patent: June 3, 1997Assignee: Romano DeghenghiInventor: Romano Deghenghi
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Patent number: 5631281Abstract: Novel unnatural dipeptoids of .alpha.-substituted Trp-Phe derivatives useful as agents in the treatment of obesity, hypersecretion of gastric acid in the gut, gastrin-dependent tumors, colorectal tumors, or as antipsychotics are disclosed. Further the compounds are antianxiety agents, antiulcer agents, antidepressant agents, and are agents useful for preventing the withdrawal response produced by chronic treatment or use followed by chronic treatment followed by withdrawal from nicotine, diazepam, alcohol, cocaine, caffeine, or opiods. Also disclosed are pharmaceutical compositions and methods of treatment using the dipeptoids as well as processes for preparing them and novel intermediates useful in their preparation. An additional feature of the invention is the use of the subject compounds to prepare pharmaceutical and diagnostic compositions.Type: GrantFiled: April 28, 1994Date of Patent: May 20, 1997Assignee: Warner-Lambert CompanyInventors: David C. Horwell, Martyn C. Pritchard, Edward Roberts, Reginald S. Richardson, Julian Aranda
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Patent number: 5622983Abstract: Novel unnatural dipeptoids of .alpha.-substituted Trp-Phe derivatives useful as agents in the treatment of obesity, hypersecretion of gastric acid in the gut, gastrin-dependent tumors, colorectal tumors, or as antipsychotics are disclosed. Further the compounds are antianxiety agents, antiulcer agents, antidepressant agents, and are agents useful for preventing the withdrawal response produced by chronic treatment or use followed by chronic treatment followed by withdrawal from nicotine, diazepam, alcohol, cocaine, caffeine, or opiods. Also disclosed are pharmaceutical compositions and methods of treatment using the dipeptoids as well as processes for preparing them and novel intermediates useful in their preparation. An additional feature of the invention is the use of the subject compounds to prepare pharmaceutical and diagnostic compositions.Type: GrantFiled: May 22, 1995Date of Patent: April 22, 1997Assignee: Warner-Lambert CompanyInventors: David C. Horwell, Martyn C. Pritchard, Edward Roberts, Reginald S. Richardson, Julian Aranda
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Patent number: 5620998Abstract: The invention relates to N-acyl-N-heterocyclylalkylamino acids of the formula ##STR1## wherein Y.sub.1 is O, S or N(R) and R is hydrogen or C.sub.1 -C.sub.7 alkyl;X.sub.1 is --CO-- or --S(O).sub.m -- and the index m is 0, 1 or 2;one of the variables X.sub.2 and X.sub.4 is C.sub.1 -C.sub.4 alkylene and the other of the variables X.sub.2 and X.sub.4 is a bond; or each of the variables X.sub.2 and X.sub.4 is a bond;X.sub.3 is C.sub.3 -C.sub.7 cycloalkylidene or the structural element --C(X.sub.a)(X.sub.b)-- and X.sub.a is hydrogen or C.sub.1 -C.sub.7 alkyl and X.sub.b is C.sub.1 -C.sub.7 alkyl;and the rings A, B and C, with the exception of the substituents indicated in the formula, and also aromatic substituents are, independently of one another, unsubstituted or mono- or poly-substituted by substituents selected from the group consisting of halogen, C.sub.1 -C.sub.7 alkyl, C.sub.1 -C.sub.7 alkoxy, C.sub.2 -C.sub.7 alkenyloxy, phenoxy, benzyloxy, trifluoromethyl and S(O).sub.Type: GrantFiled: June 7, 1995Date of Patent: April 15, 1997Assignee: Ciba-Geigy CorporationInventors: Tibur Schmidlin, Paul Zbinden, Peter B uhlmayer
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Patent number: 5610297Abstract: A novel class of peptide .alpha.-ketoamides useful for selectively inhibiting serine proteases, selectively inhibiting cysteine proteases, generally inhibiting all serine proteases, and generally inhibiting all cysteine proteases, having the formula M.sub.1 -AA-NH--CHR.sub.2 --CO--CO--NR.sub.3 R.sub.4, M.sub.1 -AA.sub.2 -AA.sub.1 -CO--NR.sub.3 R.sub.4, M.sub.1 -AA-AA-AA-CO--NR.sub.3 R.sub.4, M.sub.1 -AA-AA-AA-AA-CO--NR.sub.3 R.sub.4, or M.sub.1 -AA-CO--NR.sub.3 R.sub.4.Type: GrantFiled: October 6, 1995Date of Patent: March 11, 1997Assignee: Georgia Tech Research Corp.Inventor: James C. Powers
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Patent number: 5610177Abstract: Novel acylated amino acids which are antagonists of endothelin are described. Methods for their preparation and pharmaceutical compositions containing them are also included. The compounds are expected to be useful in treating elevated levels of endothelin, acute and chronic renal failure, hypertension, myocardial infarction, myocardial ischemia, cerebral vasospasm, cirrhosis, septic shock, congestive heart failure, endotoxic shock, subarachnoid hemorrhage, arrhythmias, asthma, preeclampsia, atherosclerotic disorders including Raynaud's disease and restenosis, angina, cancer, pulmonary hypertension, ischemic disease, gastric mucosal damage, hemorrhagic shock, ischemic bowel disease, diabetes, head injury, and stroke.Type: GrantFiled: August 8, 1994Date of Patent: March 11, 1997Assignee: Warner-Lambert CompanyInventors: Annette M. Doherty, Harriet W. Hamilton, James S. Kaltenbronn, John Quin, III
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Patent number: 5608078Abstract: Dipeptide compounds and analogs thereof having a phosphonomethyl moiety are disclosed. These compounds inhibit Endothelin Converting Enzyme and are thus useful in treating conditions responsive to inhibition of production of Endothelin.Type: GrantFiled: November 13, 1995Date of Patent: March 4, 1997Assignee: Merrell Pharmaceuticals Inc.Inventors: Hugues d'Orchymont, Marc Bigaud
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Patent number: 5599947Abstract: Novel derivatives of fatty acid analogs that have from one to three heteroatoms in the fatty acid moiety which can be oxygen, sulfur or nitrogen, are disclosed in which the carboxy-terminus has been modified to form various amides, esters, ketones, alcohols, alcohol esters and nitriles thereof.These compounds are useful as substrates for N-myristoyltransferase (NMT) and/or its acyl coenzyme, and as anti-viral and anti-fungal agents or pro-drugs of such agents. Illustrative of the disclosed compounds are fatty acid amino acid analogs of the structure ##STR1## in which X is the ethyl or t-butyl ester of an amino acid such as Gly, L--Ala, L--Ile, L--Phe, L--Trp, L--Thr or an amide such as NHCH.sub.2 C.sub.6 H.sub.5 or NH(CH.sub.2).sub.2 C.sub.6 H.sub.Type: GrantFiled: March 24, 1995Date of Patent: February 4, 1997Assignee: G. D. Searle & Co.Inventors: Sean T. Nugent, Richard A. Mueller
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Patent number: 5593967Abstract: Novel cholecystokinin antagonists useful as agents in the treatment of obesity, hypersecretion of gastric acid in the gut, gastrin-dependent tumors, or as antipsychotics are disclosed. Further, the compounds are antianxiety agents and antiulcer agents. They are agents useful for preventing the response to the withdrawal from chronic treatment with use of nicotine, diazepam, alcohol, cocaine, coffee, or opioids. The compounds of the invention are also useful in treating and/or preventing panic. Also disclosed are pharmaceutical compositions and methods of treatment using the antagonists as well as processes for preparing them and novel intermediates useful in their preparation. An additional feature of the invention is the use of the subject compounds in diagnostic compositions.Type: GrantFiled: April 1, 1993Date of Patent: January 14, 1997Assignee: Warner-Lambert CompanyInventors: David C. Horwell, Edward Roberts, Ann Holmes, Janak K. Padia, William H. Roark, Bruce D. Roth, Bharat K. Trivedi, Jurgen Kleinschroth, David C. Rees, Reginald S. Richardson
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Patent number: 5594022Abstract: The invention concerns tachykinin antagonists. The compounds are nonpeptides which have utility in treating disorders mediated by tachykinins. Such disorders are respiratory, inflammatory, gastrointestinal, ophthalmic, allergies, pain, vascular, diseases of the central nervous system, and migraine. Methods of preparing compounds and novel intermediates are also included.The compounds are expected to be especially useful in asthma and rheumatoid arthritis.Type: GrantFiled: November 29, 1994Date of Patent: January 14, 1997Assignee: Warner-Lambert CompanyInventors: David C. Horwell, William Howson, Martyn C. Pritchard, Edward Roberts, David C. Rees
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Patent number: 5591768Abstract: A method for treating circadian rhythm phase disorders is described. The invention provides methods to specifically advance or delay the phase of certain circadian rhythms in humans. The disclosed methods relate to the administration of melatonin at times determined with relation to the time of dim light endogenous melatonin onset. Embodiments capable of alleviating the effects of jet lag, winter depression and shift-work sleep disturbance are provided.Type: GrantFiled: August 24, 1993Date of Patent: January 7, 1997Assignee: State of Oregan, Acting by and Through the Oregon State Board of Higher Education on Behalf of the Oregon Health Sciences UniversityInventors: Alfred J. Lewy, Robert L. Sack
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Patent number: 5554767Abstract: The invention covers a novel series of .alpha.-mercaptoacrylic acid derivatives that inhibit both calpain I and calpain II with a high affinity and selectivity. The compounds are useful in the treatment of neurodegenerative disorders including cerebrovascular disorders, brain injury, spinal cord, and peripheral nerve injury, cardiac infarction, cataracts, inflammation, restenosis, muscular dystrophy, and platelet aggregation. Pharmaceutical compositions, methods of using processes for preparing and novel intermediates useful in the processes are also disclosed.Type: GrantFiled: May 21, 1993Date of Patent: September 10, 1996Assignee: Warner-Lambert CompanyInventors: Kevin K. Wang, Po-Wai Yuen
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Patent number: 5554644Abstract: The compounds of the instant invention are ligands for the NK.sub.2 receptor. The compounds are modified at the C-terminus to provide various amide isostere derivatives expected to be useful in treating obesity, anxiety, gastrointestinal ulcers, pain, stroke, and inflammation. Pharmaceutical compositions and methods of using the compounds are also included.Type: GrantFiled: June 8, 1994Date of Patent: September 10, 1996Assignee: Warner-Lambert CompanyInventors: David C. Horwell, William Howson, Simon Osborne
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Patent number: 5543397Abstract: Novel N-acyl depeptides of the formula:R.sup.2 --NH--CHR.sup.1 --CO--ASin which AS, R.sup.1 and R.sup.2 have certain, more precisely defined meanings. These N-acyl dipeptides are more stable under conditions of sterilization (121.degree. C.) than corresponding, non-acylated dipeptides. On the other hand, they are cleaved more rapidly and more completely at the peptide bond in the living organism than the cleavage of the acyl group from simple N-acyl amino acids takes place. They can therefore be used with advantage as a source for the carbon terminal amino acid in mixtures and solutions for artificial nutrition or in culture media for cell cultures.Type: GrantFiled: June 7, 1994Date of Patent: August 6, 1996Assignee: Degussa AktiengesellschaftInventors: Karlheinz Drauz, G unter Knaup, Ulrich Groeger
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Patent number: 5538950Abstract: A compound of the formula: ##STR1## in which R.sup.3 is hydrogen or lower alkyl, R.sup.4 is pyridyl (lower) alkyl; andR.sup.1, R.sup.2, R.sup.5 and A are defined in the description;or a pharmaceutically acceptable salt thereof, which have endothelin antagonistic activity.Type: GrantFiled: May 12, 1994Date of Patent: July 23, 1996Assignee: Fujisawa Pharmaceutical Co., Ltd.Inventors: Keiji Hemmi, Masahiro Neya, Naoki Fukami, Masashi Hashimoto, Hirokazu Tanaka, Natsuko Kayakiri
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Patent number: 5536815Abstract: The present invention is directed to the use of a cyclopropylmethyl derivative as a protecting group for compounds containing an amino group, carboxy group, amido group, mercapto group or hydroxy group and to the compounds formed having the cyclopropylmethyl moiety as the protecting group.Type: GrantFiled: March 31, 1994Date of Patent: July 16, 1996Assignee: Research Corporation Technologies, Inc.Inventors: Louis A. Carpino, Hann-Guang Chao
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Patent number: 5510353Abstract: Compounds of formulaA--X--Y--NH--Bwherein A is derived from optionally substituted benzothiophene, indole, 4-aza-and 7-aza-benzothiophene or-indole, A bearing in position 5 hydrogen, halogen, optionally substituted alkyl, hydroxy, nitro, amino, alkylamino, acylamino, alkoxycarbonyl, sulfamoyl, cyano, trimethylsilyl, carboxy, carbamoyl, phosphate, oxycarbamoyl, heterocyclic radical or ether or ester group, X-Y is --CR.sub.8 .dbd.N-- or CH(R.sub.8)--NH-- wherein R.sub.8 is -H or alkyl and attached at position 3 of A, and B is a heterocyclic radical or a residue ##STR1## wherein R.sub.10 is H, optionally substituted alkyl, cycloalkyl, aryl, adamantyl, acyl or carbamoyl and X.sub.2 is alkylthio or NR.sub.3 R.sub.10 wherein R.sub.3 is H or alkyl or R.sub.3 and R.sub.10 together with the nitrogen atom to which they are attached form a heterocyclic radical, in free form or in salt form, have pharmacological activity, e.g. for treating gastrointestinal disorders.Type: GrantFiled: January 9, 1995Date of Patent: April 23, 1996Assignee: Sandoz Ltd.Inventors: Rudolf K. A. Giger, Henri Mattes
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Patent number: 5506362Abstract: An .alpha.-amino acid amide is prepared by reaction of an N.sup..alpha. -aryloxycarbonylamino acid with a compound containing a free amino group. This process makes it possible readily to prepare peptides, by direct reaction between the carboxyl group of the N.sup..alpha. -aryloxycarbonyl derivative of an amino acid and the free amino group of a second amino acid or of a peptide fragment, without requiring protection of the carboxyl function of the second amino acid or of the peptide fragment, nor a coupling agent nor a deprotection step.Type: GrantFiled: June 9, 1994Date of Patent: April 9, 1996Assignee: Solvay (Societe Anonyme)Inventors: Roland Callens, Georges Blondeel
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Patent number: 5496928Abstract: Peptides having the formula: ##STR1## inhibit the binding of endothelin and are useful in treating diseases associated with excess production or secretion of endothelin.Type: GrantFiled: April 20, 1994Date of Patent: March 5, 1996Assignee: Banyu Pharmaceutical Co., Ltd.Inventors: Kiyofumi Ishikawa, Takehiro Fukami, Takashi Hayama, Kenji Niiyama, Toshio Nagase, Toshiaki Mase, Kagari Fujita, Masaki Ihara, Fumihiko Ikemoto, Mitsuo Yano, Masaru Nishikibe
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Patent number: 5484814Abstract: The present invention is directed to a class of 4,6-disubstituted tryptophan derivatives, 4,6-disubstituted kynurenines, their use as NMDA antagonists and to pharmaceutical compositions containing these compounds.Type: GrantFiled: December 10, 1993Date of Patent: January 16, 1996Assignee: Merrell Dow Pharmaceuticals Inc.Inventors: Michael G. Palfreyman, Ian Alexander McDonald, Francesco G. Salituro, Robert Schwarcz
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Patent number: 5444152Abstract: Peptides having the formula ##STR1## inhibit the binding of endothelin to its receptor and are useful in treating diseases associated with excess production or secretion of endothelin.Type: GrantFiled: March 21, 1994Date of Patent: August 22, 1995Assignee: Banyu Pharmaceutical Co., Ltd.Inventors: Kiyofumi Ishikawa, Takehiro Fukami, Takashi Hayama, Kenji Niiyama, Toshio Nagase, Toshiaki Mase, Kagari Fujita, Masaki Ihara, Fumihiko Ikemoto, Mitsuo Yano
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Patent number: 5432186Abstract: Disclosed are the compounds of formula I ##STR1## wherein R represents hydrogen, lower alkyl, carbocyclic or heterocyclic aryl-lower alkyl or cycloalkyl-lower alkyl;R.sub.1 represents hydrogen, lower alkyl, cycloalkyl, carbocyclic aryl or heterocyclic aryl, or biaryl;R.sub.3 represents hydrogen or acyl;R.sub.4 represents hydrogen, lower alkyl, carbocyclic or heterocyclic aryl, carbocyclic or heterocyclic aryl-lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, biaryl or biaryl-lower alkyl;R.sub.Type: GrantFiled: November 19, 1993Date of Patent: July 11, 1995Assignee: Ciba-Geigy CorporationInventor: Cynthia A. Fink
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Patent number: 5380872Abstract: CCK modulators, e.g. agonists or antagonists, of the following formula (I): ##STR1## or a base-addtion salt thereof.Type: GrantFiled: July 14, 1992Date of Patent: January 10, 1995Assignee: Glaxo Inc.Inventors: Elizabeth E. Sugg, Milana Dezube, Gavin C. Hirst
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Patent number: 5360814Abstract: The present invention is directed to a class of 4,6-disubstituted tryptophan derivatives, 4,6-disubstituted kynurenines, their use as NMDA antagonists and to pharmaceutical compositions containing these compounds.Type: GrantFiled: January 25, 1994Date of Patent: November 1, 1994Assignee: Merrell Dow Pharmaceuticals Inc.Inventors: Michael G. Palfreyman, Ian A. McDonald, Francesco G. Salituro, Robert Schwarcz, Bruce M. Baron
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Patent number: 5359128Abstract: The invention comprises compositions and methods for the treatment of psoriasis.Type: GrantFiled: February 11, 1993Date of Patent: October 25, 1994Inventor: Izhak Blank
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Patent number: 5354738Abstract: This invention relates to compounds having the following formula ##STR1## or a pharmaceutically acceptable salt thereof which are useful in the inhibition of platelet aggregation, to pharmaceutical compositions including the compounds, and to a method of inhibiting platelet aggregation in mammals by administering such compounds and compositions.Type: GrantFiled: September 4, 1992Date of Patent: October 11, 1994Assignees: G. D. Searle & Co., The Monsanto CompanyInventors: Foe S. Tjoeng, Jeffery A. Zablocki
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Patent number: 5348949Abstract: The invention relates to a method of preparing N-oxo-tetrahydro-.beta.-carbolines having formula 1. ##STR1## by an intramolecular ringclosure reaction of compounds of formula 2. ##STR2## wherein Z is an aldehyde function or acetal function, or is a functional group which can be converted into such a function during the ringclosure reaction.The eudistomin derivatives within the group of compounds having formula 1 have strong antiviral and antitumour activity.Type: GrantFiled: February 12, 1993Date of Patent: September 20, 1994Assignee: Duphar International Research B.V.Inventors: Peter H. H. Hermkens, Jan H. Van Maarseveen, Johan W. Scheeren, Cornelis G. Kruse
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Patent number: 5329013Abstract: The present invention provides a process for the preparation of tricyclo- [3.3.1.1.sup.3,7 ]dec-2-yl-[R-(R*,R*)]-3-(1H-indol-3-ylmethyl)-3-methyl-4,9-dioxo-7,11-diph enyl-10-oxa-2,5,8-triazaundecanate, an important compound in the preparation of a new class of cholecystokinin inhibitors, wherein N-[(benzyloxy)carbonyl]-(R)-.beta.-amino-1-azido-2-phenylethane is hydrogenated, and subsequently, by means of carbon dioxide, the resulting N.sup..beta. -[(benzyloxy)-carbonyl]-(R)-.beta.-amino-2-phenylethylamine carbonate is precipitated out. This is coupled by the carbodiimide process with N-[(2-adamantyloxy)-carbonyl]-.alpha.-methyl-R-tryptophane.Type: GrantFiled: October 26, 1992Date of Patent: July 12, 1994Assignee: Godecke AktiengesellschaftInventors: Wolfgang Herrmann, Klaus Steiner, Hans-Joachim Witzke
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Patent number: 5300653Abstract: A method is provided for the separation of at least one aromatic amino acid from an aqueous solution of mixed amino acids including the aromatic amino acid. The aqueous solution is brought into contact with a strongly acidic gel-type cation exchange resin which has been converted into a salt with an alkali metal or an alkaline earth metal, whereby the aromatic amino acid is selectively sorbed by the cation exchange resin. The aromatic amino acid thus sorbed can then be desorbed from the ion exchange resin, preferably with water.Type: GrantFiled: December 23, 1992Date of Patent: April 5, 1994Assignee: Mitsui Toatsu Chemicals, IncorporatedInventors: Shohei Nozaki, Naohiro Murata, Kiyoo Miyazaki
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Patent number: 5283343Abstract: This invention relates to novel melatonin derivatives, such as 2-aryl substituted N-acetyltryptamines, having pharmacological activity, e.g., melatonin antagonist activity, and methods for the synthesis thereof.Type: GrantFiled: June 18, 1991Date of Patent: February 1, 1994Assignee: Whitby Research, Inc.Inventors: Margarita L. Dubocovich, Vithal J. Rajadhyaksha, James V. Peck, Atef A. Helmy
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Patent number: 5278316Abstract: Novel unnatural dipeptoids of .alpha.-substituted Trp-Phe derivatives useful as agents in the treatment of obesity, hypersecretion of gastric acid in the gut, gastrin-dependent tumors, or as antipsychotics are disclosed. Further the compounds are antianxiety agents, antiulcer agents, antidepressant agents, and are agents useful for preventing the withdrawal response produced by chronic treatment or use followed by chronic treatment followed by withdrawal from nicotine, diazepam, alcohol, cocaine, caffeine, or opiods. Also disclosed are pharmaceutical compositions and methods of treatment using the dipeptoids as well as processes for preparing them and novel intermediates useful in their preparation. An additional feature of the invention is the use of the subject compounds to prepare pharmaceutical and diagnostic compositions.Type: GrantFiled: December 19, 1990Date of Patent: January 11, 1994Assignee: Warner-Lambert CompanyInventors: David C. Horwell, Martyn C. Pritchard, Reginald S. Richardson, Edward Roberts, Julian Aranda
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Patent number: 5266576Abstract: The invention relates to a compound of formula (I): ##STR1## which can be used as N-myristoyltransferase inhibitors, in which R.sub.1 represents hydrogen, substituted or unsubstituted (C.sub.1 -C.sub.6) alkyl, substituted or unsubstituted phenyl, (C.sub.3 -C.sub.7) cycloalkyl methyl, substituted or unsubstituted (imidazolyl-2-yl)methyl, substituted or unsubstituted (indol-3-yl)methyl or (1-azaindolizin-2-yl)methyl,R.sub.2, R.sub.3, which are identical or different, represent hydrogen or (Cl-C6) alkyl,or when R.sub.1 represents hydrogen, R.sub.2 and R.sub.3 form with the carbon and nitrogen atoms to which they are attached, a mono-, bi- or tricyclic heterocycle,X represents --CO--, --SO.sub.2 --, --PO(OH)--,Y represents --COR.sub.5 or --POR.sub.6 R.sub.6 ',R.sub.4 represents substituted or unsubstituted, linear or branched (C.sub.6 -C.sub.Type: GrantFiled: February 10, 1992Date of Patent: November 30, 1993Assignee: Adir et CompagnieInventors: Michel Vincent, Georges Remond, Bernard Portevin, Jean-Albert Boutin, Ghanem Atassi
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Patent number: 5246950Abstract: Thioformamide derivatives of the formula (I) ##STR1## wherein R represents an alkyl group; A represents either:(1) a phenyl group which is optionally substituted; or(2) heteroaromatic group (e.g. pyrid-3-yl, quinolin-3-yl);Y represents:an ethylene or methylene group or a direct bond; and B represents either:a) a phenyl, pyridyl, furyl or thienyl group, each of which may be optionally substituted, orb) a straight- or branched-chain alkyl, alkenyl, or cycloalkyl group, each of which may be optionally substituted.These compounds may be formulated into pharmaceutical preparations and have utility in the treatment of disorders associated with smooth muscle contraction.Type: GrantFiled: March 30, 1990Date of Patent: September 21, 1993Assignee: Rhone-Poulenc SanteInventors: Terance W. Hart, Bernard Y. J. Vacher, Brian W. Sharp
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Patent number: 5244915Abstract: Novel .alpha.-substituted Trp dipeptoid derivatives cyclized at the C-terminal useful as agents in the treatment of obesity, hypersecretion of gastric acid in the gut, gastrin-dependent tumors, or as antipsychotics are disclosed. Further, the compounds are antianxiety agents and antiulcer agents. They are agents useful for preventing the response to the withdrawal from chronic treatment with or use of nicotine, diazepam, alcohol, cocaine, caffeine, or opioids. The compounds of the invention are also useful in treating and/or preventing panic attacks. Also disclosed are pharmaceutical compositions and methods of treatment using the compounds as well as processes for preparing them and novel intermediates useful in their preparation. An additional feature of the invention is the use of the compounds in diagnostic compositions.Type: GrantFiled: July 12, 1991Date of Patent: September 14, 1993Assignee: Warner-Lambert CompanyInventors: David C. Horwell, Martyn C. Pritchard, Reginald S. Richardson, Edward Roberts
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Patent number: 5239083Abstract: The present invention provides Indole derivatives represented by the formula (I) ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 independently represent hydrogen or lower alkyl;R.sup.4 represents hydrogen, lower alkyl or cycloalkyl;R.sup.5 represents hydrogen, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl,--CHR.sup.7 R.sup.8 where R.sup.7 and R.sup.8 independently represent hydrogen, alkyl, alkenyl, alkynyl, substituted or unsubstituted cycloalkyl, --(CH.sub.2).sub.m OR.sup.9 (wherein m is an integer of 1-3 and R.sup.9 is lower alkyl), substituted or unsubstituted aryl, substituted or unsubstituted pyridyl, substituted or unsubstituted furyl, or substituted or unsubstituted thienyl], ##STR2## (wherein Y is CH.sub.2, O, S, CH.sub.2 --CH.sub.2, CH.dbd.CH, CH.sub.2 --O or CH.sub.2 --S); R.sup.Type: GrantFiled: March 10, 1992Date of Patent: August 24, 1993Assignee: Kyowa Hakko Kogyo Co., Ltd.Inventors: Toshiaki Kumazawa, Hitoshi Takami, Hiroyuki Obase, Nobuyuki Kishibayashi, Akio Ishii
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Patent number: 5239078Abstract: Compounds of the formulas ##STR1## wherein each R.sup.1 is independently H or alkyl (1-8C) and R.sup.2 is alkyl (1-8C) or wherein the proximal R.sup.1 and R.sup.2 taken together are --(CH.sub.2).sub.p -- wherein p=3-5;R.sup.3 is H or alkyl (1-4C);R.sup.4 is fused or conjugated unsubstituted or substituted bicycloaryl methylene;n is 0, 1 or 2;m is 0 or 1; andx is OR.sup.5 or NHR.sup.5, wherein R.sup.5 is H or substituted or unsubstituted alkyl (1-12C), aryl (6-12C), aryl alkyl (6-16C); orX is an amino acid residue or amide thereof; orX is the residue of a cyclic amine or heterocyclic amine;Y is selected from the group consisting of R.sup.7 ONR.sup.6 CONR.sup.6 -, R.sup.6.sub.2 NCONOR.sup.7 -, and R.sup.6 CONOR.sup.7 -, wherein each R.sup.6 is independently H or lower alkyl (1-4C); R.sup.7 is lower alkyl (1-4C) or an acyl group; andwherein --CONR.sup.3 -- is optionally in modified isoteric form are inhibitors of matrix metalloproteases.Type: GrantFiled: August 20, 1991Date of Patent: August 24, 1993Assignee: Glycomed IncorporatedInventors: Richard E. Galardy, Damian Grobelny, John H. Musser
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Patent number: 5210215Abstract: 3-indolepyruvic acid derivatives substituted on the benzene moiety show good antagonizing activity on excitatory aminoacids and on free radicals, for which reason they are therapeutic agents in cerebral and peripheral degenerative pathologies. Their method of production by passage through the corresponding substituted triptophane.Type: GrantFiled: September 18, 1990Date of Patent: May 11, 1993Assignee: Polifarma S.p.A.Inventors: Vincenzo Politi, Giovanna De Luca, Giovanni Di Stazio, Mario Materazzi
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Patent number: 5206218Abstract: Methods of reducing post-prandial fluctuations in plasma levels of large, neutral amino acids (LNAA), as well as compositions useful in that method. The foods and compositions comprise a carbohydrate to protein ratio of from about 3:1 to about 6:1 and, in a specific embodiment, a ratio of 4:1, which results in minimizing the variability in responses individuals exhibit to drugs which are LNAA.Type: GrantFiled: April 3, 1989Date of Patent: April 27, 1993Assignee: Interneuron Pharmaceuticals, Inc.Inventors: Richard J. Wurtman, Judith J. Wurtman
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Patent number: 5189179Abstract: The present invention is directed to a new class of serotonin 5HT.sub.1A agonists.Type: GrantFiled: July 30, 1991Date of Patent: February 23, 1993Assignee: Merrell Dow Pharmaceuticals Inc.Inventors: Ian A. McDonald, Ronald C. Bernotas, Mark W. Dudley, Jeffrey S. Sprouse
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Patent number: 5189178Abstract: Compounds of the formulas ##STR1## wherein each R.sup.1 is independently H or alkyl (1-8C) and R.sup.2 is alkyl (1-8C) or wherein the proximal R.sup.1 and R.sup.2 taken together are --(CH.sub.2).sub.p -- wherein p=3-5;R.sup.3 is H or alkyl (1-4C);R.sup.4 is fused or conjugated unsubstituted or substituted bicycloaryl methylene;n is 0, 1 or 2;m is 0 or 1; andX is OR.sup.5 or NHR.sup.5, wherein R.sup.5 is H or substituted or unsubstituted alkyl (1-12C), aryl (6-12C), aryl alkyl (6-16C); orX is an amino acid residue or amide thereof; orX is the residue of a cyclic amine or heterocyclic amine;wherein R.sup.6 is H or lower alkyl (1-4C) and R.sup.7 is H, lower alkyl (1-4C) or an acyl group, and wherein --CONR.sup.3 -- is optionally in modified isosteric formare useful for treating conditions which are characterized by unwanted matrix metalloprotease activities.Type: GrantFiled: August 20, 1991Date of Patent: February 23, 1993Inventors: Richard E. Galardy, Damian Grobelny
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Patent number: 5187270Abstract: This invention pertains to amino acids attached to a solid support in a racemization free manner and to a method of covalently linking amino acids to solid supports for use in solid phase peptide syntheses.Type: GrantFiled: January 6, 1989Date of Patent: February 16, 1993Assignee: Millipore CorporationInventor: Michael S. Bernatowicz
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Patent number: 5149692Abstract: The invention concerns novel renin-inhibitory peptides which are useful for treating renin-associated hypertension, congestive heart failure, hyperaldosteronism, glaucoma, and diseases caused by retroviruses including HTLV-I, -II, -III. Processes for preparing the peptides, novel intermediates useful in the preparation thereof, compositions containing them, and methods of using them are included. Also included is a diagnostic method which uses the compounds to determine the presence of renin-associated hypertension, congestive heart failure, or hyperaldosteronism.Type: GrantFiled: December 21, 1989Date of Patent: September 22, 1992Assignee: Warner-Lambert CompanyInventors: Annette M. Doherty, Harriet W. Hamilton, Bruce A. Steinbaugh
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Patent number: 5122537Abstract: The invention relates to new arylvinylamide derivatives of formula ##STR1## wherein Y is a bicyclic ring system chosen from (A), (B), (C), (D), and (E); ##STR2## in which m is zero, 1 or 2; R is hydrogen, a C.sub.1 -C.sub.6 alkyl or C.sub.1 -C.sub.6 alkanoyl group;R.sub.1 is hydrogen or C.sub.1 -C.sub.6 alkyl;R.sub.2 is hydrogen, halogen, cyano or C.sub.1 -C.sub.6 alkyl; andn is an integer of 1 to 3; and wherein each of the substituents --CH.dbd.CHNHCOR.sub.1, OR and R.sub.2 may be independently on either of the aryl and heteroaryl moieties of the bicyclic ring system (A), (C), (D) and (E); whereas only the benzene ring may be substituted in the bicyclic ring system (B),which are useful as tyrosine kinase inhibitors.Type: GrantFiled: November 2, 1990Date of Patent: June 16, 1992Assignee: Farmitalia Carlo Erba S.r.l.Inventors: Franco Buzzetti, Angelo Crugnola
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Patent number: 5110797Abstract: Peptide compounds of formula (I): ##STR1## wherein A is hydrogen or an amino-protecting group; X is a member selected from the group consisting of Gly, Glu, Tyr, Asp, Phe, Ile, Ala, Pro, Leu, Hyp, Val, His, Arg, Ser, Thr, Pyr, Trp, 5-HTP, Cys, Met, .tau.-Glu, .beta.-Asp; Y is a (CH.sub.2).sub.3-6 or (CH.sub.2).sub.3-6 having an hydroxy group; R is an hydroxy group or an oxygen atom with a carboxy-protecting group; are useful as neurotropic agents.Type: GrantFiled: April 29, 1988Date of Patent: May 5, 1992Assignee: Nippon Zoki Pharmaceutical Co., Ltd.Inventors: Kazuharu Ienaga, Kunihiko Higashiura
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Patent number: 5101036Abstract: The invention relates to a process for the preparation of N-hydroxy-alpha-amino acids and the derivatives thereof by reacting a derivative of an alpha-amino acid with an aromatic aldehyde to form a Schiff base, oxidizing the Schiff base to an oxaziridine and converting the oxaziridine into the corresponding N-hydroxy-alpha-amino acid derivative and, if so desired, converting that derivative into the acid or a different derivative, in which an alpha-amino acid amide is used as starting material.Type: GrantFiled: September 20, 1990Date of Patent: March 31, 1992Assignee: Stamicarbon B.V.Inventors: Johan Kamphuis, Wilhelmus H. J. Boesten
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Patent number: 5096700Abstract: The subject invention involves halogenated amino acid derivatives useful as antimicrobial agents having the structure: ##STR1## wherein --R is hydrogen or 2-aminoethyl; --R' is hydroxy, alkoxy, aryloxy, or an amino acid residue bonded at the amino nitrogen; --R" is hydrogen or an amino acid residue bonded at the carbonyl carbon; --X is halogen; and --Y is hydrogen or halogen.Type: GrantFiled: September 28, 1990Date of Patent: March 17, 1992Assignee: The Procter & Gamble CompanyInventors: William L. Seibel, Joseph H. Gardner
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Patent number: 5095031Abstract: Substituted indolyl compounds of the formula ##STR1## are potent inhibitors of the lipoxygenase enzymes and are useful as agents for the treatment of allergies and inflammatory disease states.Type: GrantFiled: August 20, 1990Date of Patent: March 10, 1992Assignee: Abbott LaboratoriesInventors: Dee W. Brooks, George W. Carter, Joseph F. Dellaria, Robert G. Maki, Karen E. Rodriques