The Chalcogen And The Nitrogen Are In The 1,5-positions Of The Bicyclo Ring System (e.g., 1,5-benzothiazepinone, Etc.) Patents (Class 540/491)
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Patent number: 7141562Abstract: Compound of the Formula: and pharmaceutically acceptable salts or prodrugs thereof, wherein: X is CH or N, Y is C or S, Z is —SO2— or —(CRaRb)r—, n is 1 or 2, R2 is aryl or heteroaryl, and R1, R3, R4, R5, R6, R7, R8, R9, Ra, Rb, m, p, q and r, are as defined herein. The compounds are modulators of the 5-HT6 receptor and are useful for treatment of central nervous system disorders. Also provided are methods for preparing, compositions comprising, and methods for using Compounds of Formula I.Type: GrantFiled: November 6, 2003Date of Patent: November 28, 2006Assignee: Roche Palo Alto LLCInventors: Hans Maag, Meng Sui, Shu-Hai Zhao
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Patent number: 7101909Abstract: Novel multibinding compounds are disclosed. The compounds of this invention comprise 2–10 ligands covalently connected, each of the ligands being capable of binding to a ligand binding site in a Ca++ channel, thereby modulating the biological activities thereof.Type: GrantFiled: June 25, 2004Date of Patent: September 5, 2006Assignee: Theravance, Inc.Inventors: Yu-Hua Ji, Maya Natarajan, John H. Griffin, Thomas E. Jenkins
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Patent number: 7011960Abstract: The present invention relates to a new process for the preparation compounds of formula I wherein R1, R2, R3 and n are as described in the description which process comprises reacting compounds of formula II wherein R1, R2, R3, n and R4 are as described in the description, with a protease in an aqueous system containing an organic co-solvent. The compound of formula I are useful for the preparation of 1,5-benzothiazepines which are useful as enzyme inhibitors, such as protease, interleukin-1?-converting enzyme, elastase or angiotensin converting enzyme, GPCR antagonists (cholecystokinin, angiotensin II receptor).Type: GrantFiled: September 23, 2002Date of Patent: March 14, 2006Assignee: Hoffmann-La Roche Inc.Inventors: Konrad Bleicher, Scott Borthwick, Hans Iding, Mark Rogers-Evans, Stefan Schmid, Han Min Tong, Beat Wirz
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Patent number: 7001901Abstract: This invention relates to novel tetrazolyl-propionamides in which the amide group comprises an aminoazepinone, and related structures, of Formula (I): or pharmaceutically acceptable salt or prodrug forms thereof, their pharmaceutical compositions and methods of use. These novel compounds inhibit the processing of amyloid precursor protein and, more specifically, inhibit the production of A?-peptide, thereby resulting in prevention and treatment of the neuropathology associated with production of A?-peptide. More particularly, the present invention relates to the treatment of neurological disorders related to ?-amyloid production such as Alzheimer's disease.Type: GrantFiled: August 27, 2003Date of Patent: February 21, 2006Assignee: Bristol-Myers Squibb CompanyInventor: Michael G. Yang
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Patent number: 6924277Abstract: Compounds having the general formula wherein R1a, R1b, R1c, X1, X2, R2, R3, R4, R5, R6, n, Y and Z are as defined in the specification, methods of using such compounds for the treatment of diseases and pharmaceutical composition comprising such compounds.Type: GrantFiled: September 27, 2001Date of Patent: August 2, 2005Assignee: AstraZeneca ABInventor: Peter Bernstein
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Patent number: 6906056Abstract: Disclosed are compounds which inhibit ?-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions that include a compound which inhibits ?-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.Type: GrantFiled: March 20, 2003Date of Patent: June 14, 2005Assignees: Elan Pharmaceuticals, Inc., Eli Lilly & CompanyInventors: Richard C. Thompson, Stephen Wilkie, Douglas R. Stack, Eldon E. Vanmeter, Qing Shi, Thomas C. Britton, James E. Audia, Jon K. Reel, Thomas E. Mabry, Bruce A. Dressman, Cynthia L. Cwi, Steven S. Henry, Stacey L. McDaniel, Russell D. Stucky, Warren J. Porter
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Patent number: 6897305Abstract: Novel multibinding compounds are disclosed. The compounds of this invention comprise 2-10 ligands covalently connected, each of the ligands being capable of binding to a ligand binding site in a Ca++ channel , thereby modulating the biological activities thereof.Type: GrantFiled: December 8, 1999Date of Patent: May 24, 2005Assignee: Theravance, Inc.Inventors: Yu-Hua Ji, Maya Natarajan, John H. Griffin, Thomas E. Jenkins
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Patent number: 6881839Abstract: The present invention comprises a simplified synthesis of (+)-diltiazem through IE-PdOsW wherein IE is ion-exchanger, catalyzed three-component coupling reaction and Fe3+-exchanged clay catalyzed ring opening of sulfite with 2-aminothiophenol followed by cyclization as key steps.Type: GrantFiled: December 31, 2002Date of Patent: April 19, 2005Assignee: Council of Scientific and Industrial ResearchInventors: Boyapati M. Choudary, Naidu S. Chowdari, Sateesh Madhi, Lakshmi K. Mannepalli
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Patent number: 6864250Abstract: Compounds of structural Formula (I) where A is a lipophilic group including an aliphatic bridging group, B is a lipophilic group, D is a group having at least one amino or substituted amino group and R is hydrogen, alkyl or cycloalkyl, and pharmaceutically acceptable salts and individual isomers thereof, which have growth hormone releasing activity in humans or animalsType: GrantFiled: August 20, 1998Date of Patent: March 8, 2005Assignees: Kaken Pharmaceutical Co., Ltd., Molecular Research InstituteInventors: Hidenori Funamizu, Nobuo Ishiyama, Satoru Ikegami, Tadashi Okuno, Kiyoshi Inoguchi, Ping Huang, Gilda Loew
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Patent number: 6777550Abstract: N-formyl hydroxylamines are provided which have the structure wherein R is H, alkyl, alkenyl, aryl-(CH2)p—, heteroaryl-(CH2)p— or cycloheteroalkyl-(CH2)p— R1 is H or COR2 where R2 is alkyl, aryl-(CH2)p—, cycloheteroalkyl-(CH2)p—, heteroaryl-(CH2)p—, alkoxy or cycloalkyl-(CH2)p—, p is 0 to 8, and A is a dipeptide derived from an amino acid or is a conformationally restricted dipeptide mimic. The above compounds are useful in treating hypertension congestive heart failure, renal failure, and hepatic cirrhosis.Type: GrantFiled: April 4, 1997Date of Patent: August 17, 2004Assignee: Bristol-Myers Squibb CompanyInventor: Jeffrey A. Robl
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Patent number: 6759404Abstract: Novel cyclic malonamides having the formula (I): and their pharmaceutical compositions. These novel compounds inhibit the processing of amyloid precursor protein and, more specifically, inhibit the production of A&bgr;-peptide, thereby acting to prevent the formation of neurological deposits of amyloid protein.Type: GrantFiled: April 3, 2001Date of Patent: July 6, 2004Inventors: Richard E. Olson, Michael G. Yang
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Publication number: 20040127704Abstract: The present invention comprises a simplified synthesis of (+)-diltiazem through IE-PdOsW wherein IE is ion-exchanger, catalyzed three-component coupling reaction and Fe3+-exchanged clay catalyzed ring opening of sulfite with 2-aminothiophenol followed by cyclization as key steps.Type: ApplicationFiled: December 31, 2002Publication date: July 1, 2004Applicant: COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCHInventors: Boyapati M. Choudary, Naidu S. Chowdari, Sateesh Madhi, Lakshmi K. Mannepalli
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Publication number: 20040121996Abstract: The present invention provides compounds of Formula I 1Type: ApplicationFiled: December 8, 2003Publication date: June 24, 2004Inventors: Nicole Barvian, Christine Nylund Kolz, Kimberly Suzanne Para, William Chester Patt, Melean Visnick
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Patent number: 6664249Abstract: Compounds according to general formula (1), and pharmaceutically acceptable salts thereof, wherein V is a covalent bond or NH, X is selected from CH2, O and N-alkyl, Z is either S or —CH═CH—, R1 and R2 are independently selected from H, F, Cl, Br and alkyl, R3 is selected from OH, O-alkyl and NR4R5, R4 and R5 are each independently H or alkyl, or together are —(CH2)q—, p is 0, 1, 2, 3 or 4, and q is 4 or 5, are new. They are agonists at the asopressin V2 receptor and are useful as antidiuretics and pro-coagulants.Type: GrantFiled: June 10, 2002Date of Patent: December 16, 2003Assignee: Ferring BVInventors: Doreen Mary Ashworth, Gary Robert William Pitt, Peter Hudson, Christopher Martyn Yea, Richard Jeremy Franklin
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Patent number: 6602865Abstract: Pyridazino(4,5-b)(1,5)oxazepinone, thiazepinone and diazepinone compounds of formula(I) and their tautomers and the acid-addition salts of all these compounds show memory-enhancing and neuroprotective properties.Type: GrantFiled: November 15, 1999Date of Patent: August 5, 2003Assignee: IVAX Drug Research Institute, Ltd.Inventors: Ferenc Andrasi, Agnes Angyal nee Pataky, Pal Berzsenyi, Sandor Boros, Laszlo Harsing, Katalin Horvath, Peter Matyus, Imre Moravcsik, Agnes Papp nee Behr, Antal Simay, Erzsebet Szabo nee Bagdy, Katalin Szabo nee Pusztai, Istvan Tarnawa, Ildiko Varga
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Publication number: 20030119152Abstract: The present invention relates to a new process for the preparation compounds of formula I 1Type: ApplicationFiled: September 23, 2002Publication date: June 26, 2003Inventors: Konrad Bleicher, Scott Borthwick, Hans Iding, Mark Rogers-Evans, Stefan Schmid, Han Min Tong, Beat Wirz
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Patent number: 6503897Abstract: Compounds of formula (I) are antibacterial agents wherein: R3 and R4, taken together with the carbon atoms to which they are respectively attached, form an optionally substituted saturated carbocyclic or heterocyclic ring of 5 to 16 atoms, which may be benz-fused or fused to a second optionally substituted saturated carbocyclic or heterocyclic ring of 5 to 16 atoms; and R1 and R2 are as defined in the specification.Type: GrantFiled: August 22, 2001Date of Patent: January 7, 2003Assignee: British Biotech Pharmaceuticals Ltd.Inventors: Raymond Paul Beckett, Mark Whittaker, Zoe Marie Spavold
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Patent number: 6455522Abstract: The present application describes novel lactams and derivatives thereof of formula I: or pharmaceutically acceptable salt forms thereof, wherein rings ring B is a 4-8 membered cyclic sulfonamide containing from 0-3 additional heteroatoms selected from N, O, and S, which are useful as metalloprotease inhibitors.Type: GrantFiled: February 10, 1999Date of Patent: September 24, 2002Assignee: Bristol-Myers Squibb Pharma CompanyInventors: Jingwu Duan, Lihua Chen, Robert J. Cherney, Carl P. Decicco, Matthew E. Voss
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Patent number: 6258948Abstract: The present invention relates to novel classes of compounds which are inhibitors of interleukin-IB converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against IL-1-, apoptosis-, IGIF-, and IFN-&ggr;-mediated diseases, inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, degenerative diseases, and necrotic diseases. This invention also relates to methods for inhibiting ICE activity, for treating interleukin-1-, apoptosis-, IGIF- and IFN-&ggr;-mediated diseases and decreasing IGIF and IFN-&ggr; production using the compounds and compositions of this invention.Type: GrantFiled: September 21, 1999Date of Patent: July 10, 2001Assignee: Vertex Pharmaceuticals, IncorporatedInventors: Mark James Batchelor, David Bebbington, Guy W. Bemis, Wolf Herman Fridman, Roger John Gillespie, Julian M. C. Golec, Yong Gu, David J. Lauffer, David J. Livingston, Saroop Singh Matharu, Michael D. Mullican, Mark A. Murcko, Robert Murdoch, Philip Nyce, Andrea L. C. Robidoux, Michael Su, M. Woods Wannamaker, Keith P. Wilson, Robert E. Zelle
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Patent number: 6232308Abstract: The present invention relates to benzazepine derivatives and their use as &agr;v integrin receptor antagonists. More particularly, the compounds of the present invention are antagonists of the integrin receptors &agr;v&bgr;3, &agr;v&bgr;5, and/or &agr;v&bgr;6 and are useful for inhibiting bone resorption, treating and preventing osteoporosis, and inhibiting vascular restenosis, diabetic retinopathy, macular degeneration, angiogenesis, atherosclerosis, inflammation, wound healing, viral disease, tumor growth, and metastasis.Type: GrantFiled: February 2, 2000Date of Patent: May 15, 2001Assignee: Merck & Co., Inc.Inventor: Ben C. Askew
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Patent number: 6197953Abstract: Methods for the preparation of (2S,3S)-1,5-benzothiazepine derivatives of the formula (II) and isomers thereof, and for the preparation of (2R,3R)-1,5-benzothiazepine derivatives of the formula (III) and isomers thereof, wherein ring A and ring B are independently a substituted or unsubstituted benzene ring, and R2 is a 2-(dimethylamino)ethyl group or a group of the formula: or a pharmaceutically acceptable salt thereof.Type: GrantFiled: April 16, 1999Date of Patent: March 6, 2001Assignee: Tanabe Seiyaku Co., Ltd.Inventors: Masakatsu Furui, Toshiyuki Furutani
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Patent number: 6187936Abstract: A process for the preparation of I: in which R and R1 have the meanings reported in the description, that comprises the enzymatic kinetic resolution by transesterification with aminoalcohols of 3-phenylglycidates of formula I: is described.Type: GrantFiled: September 20, 1999Date of Patent: February 13, 2001Assignee: Zambon Group S.p.A.Inventors: Marco Villa, Dario Tentorio, Angelo Restelli, Sergio Riva
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Patent number: 6180785Abstract: A process for preparing a 2R-hydroxy-3-[(2-amino-phenylthio)]-3-[(p-alkoxyaryl)] propanoic acid alkyl ester of formula (V) wherein R is an alkyl, or benzoyl residue, R1 is hydrogen, an alkyl, alkoxy, aryloxy, phenyl, naphthyl, or hydroxy residue, and R2 and R3 are independently of each other hydrogen, and alkyl, alkoxy, alkylamino, alkylthio, aryl, or halogen residue, which comprises refluxing 2-aminothiophenol, or 2-aminothionaphthol with a compound of Formula (IV) that is 5S-(p-alkoxyphenyl)-4R-carboalkoxy-1,3,2-dioxathiolane-2-oxide when X is S, or the corresponding cyclic carbonate, in the presence of an organic solvent and an inert atmosphere, and recovering the resultant compound of Formula (V).Type: GrantFiled: January 28, 1999Date of Patent: January 30, 2001Inventors: Lohray Braj Bhushan, Balakrishnan Ezhuthachan Jayachandran, Lohray Vidya Bhushan, Ravindranathan Thottappillil
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Patent number: 6114523Abstract: A process which allows the re-use of compounds of formula ##STR1## in diltiazem synthesis through a process of conversion to a mixture of enantiomers III-(2R,3R) and III-(2S,3S) is described.Type: GrantFiled: October 21, 1998Date of Patent: September 5, 2000Assignee: Zamon Group S.p.A.Inventors: Pietro Allegrini, Gaetano Marchioro, Giuseppe Barreca, Marco Villa, Laura Russo
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Patent number: 5998400Abstract: The invention is concerned with novel hypolipidemic compounds of formula (I), with processes and novel intermediates for their preparation, pharmaceutical compositions containing them and with their use in medicine, particularly in the prophylaxis and treatment of hyperlipidemic conditions, and associated diseases such as atherosclerosis.Type: GrantFiled: May 1, 1997Date of Patent: December 7, 1999Assignee: Glaxo Wellcome Inc.Inventors: Lawrence Edward Brieaddy, Anthony Louis Handlon, Gordon Lewis Hodgson, Jr.
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Patent number: 5968924Abstract: There are disclosed certain novel compounds identified as benzo-fused lactams which promote the release of growth hormone in humans and animals. This property can be utilized to promote the growth of food animals to render the production of edible meat products more efficient, and in humans, to increase the stature of those afflicted with a lack of a normal secretion of natural growth hormone. Growth promoting compositions containing such benzo-fused lactams as the active ingredient thereof are also disclosed.Type: GrantFiled: March 18, 1997Date of Patent: October 19, 1999Assignee: Merck & Co., Inc.Inventors: Matthew Wyvratt, Robert Devita, Richard Bochis, William Schoen
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Patent number: 5945533Abstract: Powdery aggregate of 2-phenyl-1,5-benzothiazepin-3,4(2H,5H)-dione compound: ##STR1## wherein Ring A and Ring B are benzene ring having optionally substituent selected from lower alkyl, lower alkoxy and halogen, which is prepared by admixing solution of the compound (II) in polar organic solvent with solvent which does not substantially dissolve the compound (II) but is miscible with said polar organic solvent, and separating and collecting the resultant particles of the compound (II). Said aggregate of the compound (II) can be converted into optically active 3-hydroxy-2-phenyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-one compounds (I) on industrial scale, which are useful as intermediate for various medicaments.Type: GrantFiled: August 14, 1997Date of Patent: August 31, 1999Assignee: Tanabe Seiyaku Co., Ltd.Inventors: Tadashi Kometani, Hiroaki Matsumae, Takeji Shibatani
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Patent number: 5874424Abstract: The present invention relates to novel classes of compounds which are inhibitors of interleukin-1.beta. converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against an IL-1 mediated disease, an apoptosis mediated disease, AML, CML, melanoma, myeloma, Kaposi's sarcoma, graft vs host disease, rheumatoid arthritis, inflammatory bowel disorder, psoriasis, osteoarthritis, myeloma, apoptosis, sepsis, rheumatoid arthritis, asthma, Alzheimer's disease, Parkinson's disease, and ischemic heart disease diseases. This invention also relates to methods for inhibiting ICE activity and methods for treating interleukin-1 mediated diseases using the compounds and compositions of this invention.Type: GrantFiled: February 8, 1996Date of Patent: February 23, 1999Assignee: Vertex Pharmaceuticals IncorporatedInventors: Mark James Batchelor, David Bebbington, Guy W. Bemis, Wolf Herman Fridman, Roger John Gillespie, Julian M. C. Golec, David J. Lauffer, David J. Livingston, Saroop Singh Matharu, Michael D. Mullican, Mark A. Murcko, Robert Murdoch, Robert E. Zelle
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Patent number: 5859239Abstract: Compounds of the formula ##STR1## wherein X.sub.1 is ##STR2## are disclosed. These compounds possess inhibitory activity against angiotensin converting enzyme and neutral endopeptidase and thus useful as cardiovascular agents.Type: GrantFiled: September 30, 1997Date of Patent: January 12, 1999Assignee: E. R. Squibb & Sons, Inc.Inventors: Donald S. Karanewsky, Jeffrey A. Robl
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Patent number: 5854233Abstract: Liver diseases, such as cirrhosis of the liver, toxic and medicamentary liver damage, a liver-parenchymic disorder or hepatitis, are treated by administering to a human or animal subject in need thereof a therapeutically active or prophylactically effective low dose amount of a vasodilating agent which selectively increases the supply of oxygenated blood to the liver by increasing hepatic arterial inflow. Suitable vasodilating agents include calcium blockers, such as a benzothiazepine derivative, nifedipine, felodipine or verapamil.Type: GrantFiled: June 20, 1996Date of Patent: December 29, 1998Assignee: Pharmacy and Therapeutic Advisory Consultancy Ltd.Inventor: Allan Joseph McLean
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Patent number: 5847122Abstract: A novel process for preparing 1,5-benzothiazepine derivative ?II!: ##STR1## wherein Ring A and Ring B are substituted or unsubstituted benzene ring, and R.sup.3 is H, (di-lower alkylamino)-lower alkyl or substituted or unsubstituted piperazinyl-lower alkyl, or a salt thereof, in high yield and in a single step from a novel 3-(2-amino-substituted or unsubstituted phenylthio)-2-hydroxy-3-substituted or unsubstituted phenylpropionamide compound. Said 1,5-benzothiazepine derivative ?II! is useful as an intermediate for preparing medicaments such as diltiazem hydrochloride.Type: GrantFiled: February 21, 1997Date of Patent: December 8, 1998Assignee: Tanabe Seiyaku Co., Ltd.Inventors: Shinichi Yamada, Ryuzo Yoshioka, Takeji Shibatani
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Patent number: 5846967Abstract: A compound having the formula I ##STR1## in which R.sub.1, R.sub.2 independently are OH, OOC--R.sub.3 or O--R.sub.3, andR.sub.3 is an unsubstituted or substituted C.sub.1 -C.sub.6 alkyl, alkenyl, alkynyl or phenyl group.The compound is useful as a natriuretic and anti-hypertensive agent.Type: GrantFiled: March 24, 1997Date of Patent: December 8, 1998Assignee: Loma Linda University Medical CenterInventors: William J. Wechter, E. David Murray, Jr., Darko Kantoci
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Patent number: 5817602Abstract: Thiadiazabicyclodecanes of formula (I) wherein, Z is oxygen or sulfur; R is an optional substituent and W is an optionally condensed or substituted phenyl radical and the salts, complexes and stereisomers thereof, have good selective pre- and post-emergence herbicidal properties.Type: GrantFiled: December 21, 1995Date of Patent: October 6, 1998Assignee: Novartis CorporationInventors: Georg Pissiotas, Hans Moser, Hans-Georg Brunner
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Patent number: 5789587Abstract: There are disclosed certain novel compounds identified as heterocyclic-fused lactams which promote the release of growth hormone in humans and animals. This property can be utilized to promote the growth of food animals to render the production of edible meat products more efficient, and in humans, to increase the stature of those afflicted with a lack of a normal secretion of natural growth hormone. Growth promoting compositions containing such heterocyclic-fused lactams as the active ingredient thereof are also disclosed.Type: GrantFiled: November 6, 1996Date of Patent: August 4, 1998Assignee: Merck & Co., Inc.Inventors: Michael H. Fisher, Helmut Mrozik, William R. Schoen, Thomas L. Shih, Matthew J. Wyvratt
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Patent number: 5726307Abstract: There are disclosed certain novel compounds identified as benzo-fused lactams which promote the release of growth hormone in humans and animals. This property can be utilized to promote the growth of food animals to render the production of edible meat products more efficient, and in humans, to increase the stature of those afflicted with a lack of a normal secretion of natural growth hormone. Growth promoting compositions containing such benzo-fused lactams as the active ingredient thereof are also disclosed.Type: GrantFiled: December 15, 1994Date of Patent: March 10, 1998Assignee: Merck & Co., Inc.Inventors: William R. Schoen, Matthew J. Wyvratt
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Patent number: 5723458Abstract: The invention provides novel 1,4-benzothiazepine compounds substituted with hydroxy or a group containing hydroxy, compositions comprising such compounds and their use in the treatment or prophylaxis of treating clinical conditions in which inhibition of bile acid uptake is indicated, for example, hyperlipidemia and atherosclerosis.Type: GrantFiled: August 15, 1995Date of Patent: March 3, 1998Assignee: Glaxo Wellcome Inc.Inventors: Lawrence Edward Brieaddy, Gordon Lewis Hodgson, Jr.
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Patent number: 5705638Abstract: An optical resolution process of the compound of the formula (1): ##STR1## wherein Ring A and Ring B are a substituted or unsubstituted benzene ring and R.sup.1 and R.sup.2 are the same or different and a lower alkyl group, by utilizing difference in solubility between the two diastereoisomeric salts prepared by treating the racemic compound (1) with an acidic resolution agent. The present process is industrially advantageous with compared to conventional processes for preparing an optically active 3-hydroxy-1,5-benzothiazepine derivative which are useful as an intermediate for preparing medicines.Type: GrantFiled: November 6, 1996Date of Patent: January 6, 1998Assignee: Tanabe Seiyaku Co., Ltd.Inventors: Ryuzo Yoshioka, Shin-ichi Yamada, Takeji Shibatani
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Patent number: 5677297Abstract: Compounds with neutral endopeptidase (NEP) inhibitory activity corresponding to the formula I ##STR1## in which R.sup.1 is a lower alkoxy-lower-alkyl group whose lower alkoxy radical is substituted by a lower alkoxy group, or a phenyl-lower-alkyl or phenyloxy-lower-alkyl group which can optionally be substituted in the phenyl ring by lower alkyl, lower alkoxy or halogen, or a naphthyl-lower-alkyl group,A is CH.sub.2, O or S,R.sup.2 is hydrogen or halogen,R.sup.3 is hydrogen or halogen,R.sup.4 is hydrogen or a group forming a biolabile ester, andR.sup.5 is hydrogen or a group forming a biolabile ester, and the physiologically acceptable acid addition salts thereof.Type: GrantFiled: March 22, 1996Date of Patent: October 14, 1997Assignee: Solvay Pharmaceuticals GmbHInventors: Harald Waldeck, Dagmar Hoeltje, Josef Messinger, Jochen Antel, Michael Wurl, Dirk Thormaehlen
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Patent number: 5663332Abstract: A method for the preparation of 3-hydroxy-5-[2-(dimethylamino)ethyl]-2,3-dihydro-2-(4-methoxyphenyl)-1,5-b enzothiazepine-4(5H)-one and use of the product prepared by this method for making pharmaceutical compositions and pharmaceutically active compounds is disclosed starting with N-alkylation of 3-hydroxy-2,3-dihydro-4-(methoxyphenyl)-1,5-benzothiazepin-4(5H)-one with a (dimethylamino)ethyl halide wherein the N-alkylation reaction is carried out in a reaction mixture comprising 2-butanone and water. The product of this reaction and its salts have utility as pharmaceutically active compounds and as intermediates for making pharmaceutically active compounds. The disclosed method and use is simpler, more efficient and safer than prior known methods and produces a product of superior purity.Type: GrantFiled: September 15, 1995Date of Patent: September 2, 1997Assignee: Orion Corporation FermionInventor: Martti Hytonen
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Patent number: 5644054Abstract: A process is provided for preparing cis-(+)-hydroxy-5-[2-(dimethylamine)ethyl]-2,3-dihydro-2-(4-methoxyphenyl) -benzothiazepin-4(5H)-one that is a useful intermediate in the preparation of diltiazem. It has been found that the requisite N-alkylation reaction proceeds rapidly and with an excellent yield when the solvent is a mixture of toluene and N-methylpyrrolidin-2-one and the base is finely-divided sodium carbonate under anhydrous conditions. Such diltiazem commonly is used in the treatment of angina pectoris.Type: GrantFiled: February 14, 1996Date of Patent: July 1, 1997Assignee: Orion-Yhtyma Oy FermionInventor: Martti Hytonen
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Patent number: 5635502Abstract: The present invention relates to certain novel mercaptoacetylamide bicyclic lactam derivatives useful as inhibitors of enkephalinase and of ACE.These mercaptoacetylamide bicyclic lactam derivatives can be described by the following formula: ##STR1## wherein R is hydrogen, a C.sub.1 -C.sub.4 alkyl, an Ar--Y--group, --CH.sub.2 O--C(O)C(CH.sub.3).sub.3 or diphenylmethyl;R.sub.1 is hydrogen, acetyl, --CH.sub.2 O--C(O)C(CH.sub.3).sub.3, benzoyl or a group of the formula ##STR2## R.sub.2 is hydrogen, C.sub.1 -C.sub.8 alkyl, --CH.sub.2 OCH.sub.2 CH.sub.2 OCH.sub.3 or an Ar--Y--group;A is --CH.sub.2 --, --O--, or --S--;B is --S--or --O--; andpharmaceutically acceptable salts thereof.Type: GrantFiled: April 3, 1995Date of Patent: June 3, 1997Assignee: Merrell Pharmaceuticals Inc.Inventor: Gary A. Flynn
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Patent number: 5610153Abstract: The invention relates to substituted 3-amino-1-arylalkyl-benzazepin-2-ones of the general formula ##STR1## wherein Ar is aryl;X is --O-- or --S(O).sub.n -- and n is 0, 1 or 2;X.sub.1 is C.sub.1 -C.sub.2 alkylene or a direct bond;R.sub.1 is hydrogen, lower alkyl, aryl-lower alkyl or acyl;R.sub.2 is lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, aryl-lower alkoxy-lower alkyl, aryl-lower alkyl or C.sub.3 -C.sub.7 cycloalkyl-lower alkyl;R.sub.3 is carboxy; lower alkoxycarbonyl; lower alkoxy-lower alkoxycarbonyl; aryl-lower alkoxycarbonyl; aryloxycarbonyl; carbamoyl; carbamoyl that (i) is monosubstituted by hydroxy, lower alkanesulfonyl, halo-lower alkanesulfonyl or by arylsulfonyl, (ii) is monosubstituted or disubstituted, the substituents being independent of one another, by lower alkyl, lower alkenyl, lower alkynyl or by phenyl-lower alkyl or (iii) is disubstituted by lower alkylene or by lower alkylene-Z.sub.1 -lower alkylene, Z.sub.1 being O, S or NH; 5-tetrazolyl; PO.sub.2 H.sub.2 ; PO.sub.3 H.Type: GrantFiled: July 12, 1994Date of Patent: March 11, 1997Assignee: Ciba-Geigy CorporationInventors: Peter Buhlmayer, Pascal Furet
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Patent number: 5597922Abstract: Methods of treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia and surgery, as well as treating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease and Down's syndrome, treating or preventing the adverse consequences of the hyperactivity of the excitatory amino acids, as well as treating anxiety, chronic pain, convulsions and inducing anesthesia are disclosed by administering to an animal in need of such treatment a compound which has high binding to the glycine receptor.Type: GrantFiled: July 29, 1994Date of Patent: January 28, 1997Assignees: State of Oregon, Acting by and through the Oregon State Board of Higher Education, Acting for and on Behalf of the Oregon Health Sciences University and the University of Oregon, Acea Pharmaceuticals, Inc., The Regents of the University of CaliforniaInventors: Sui X. Cai, John F. W. Keana, Eckard Weber
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Patent number: 5571807Abstract: This invention relates to diltiazem analogs having the formula: ##STR1## where the substituents are defined in the specification. These compounds are useful in treating cardiovascular problems. The invention also relates to a process for preparing the compounds and to pharmaceutical compositions containing the compounds.Type: GrantFiled: March 31, 1995Date of Patent: November 5, 1996Assignee: Istituto Luso Farmaco d'Italia S.p.A.Inventors: Aldo Salimbeni, Saturnino Caliari, Francesco Fici, Elso Manghisi
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Patent number: 5559229Abstract: A process for the manufacture of Diltiazem or deacetyl-Diltiazem, which comprises the use of MIBK as solvent and NaOH as base.Type: GrantFiled: June 1, 1995Date of Patent: September 24, 1996Assignee: ACIC (Canada) Inc.Inventors: Keshava Murthy, Gamini Weeratunga, Burchat Andrew
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Patent number: 5495013Abstract: A process for the preparation of Diltiazem of formula (I) ##STR1## starting from the corresponding benzothiazepine and carried out throughout a 11 the steps in a single solvent.Type: GrantFiled: October 20, 1994Date of Patent: February 27, 1996Assignee: Profarmaco Nobel S.r.l.Inventors: Fulvio L. Piselli, Piermarino Boschi, Claudio Navoni
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Patent number: 5473066Abstract: Process for stereoselectivity preparing a cis-form of 5-(aminoalkylamino)-1,5-benzothiazepine derivative represented by formula (VI): ##STR1## is provided, said process comprising carrying out a stereoselective addition reaction of an o-(aminoalkylamino) thiophenyl derivative with a trans-substituted glycidic ester at an elevated temperature in a nonpolar solvent in the presence of a divalent or trivalent iron ion to prepare a threo-form intermediate, hydrolyzing the ester group of said intermediate, acetylating the hydroxyl group of said hydrolyzed compound, and subjecting said acetylated compound to a ring closure reaction to obtain the objective compound (VI).Type: GrantFiled: January 19, 1994Date of Patent: December 5, 1995Assignee: Shionogi & Co., Ltd.Inventors: Teruo Yamamori, Hiroshi Harada, Eiichi Oosugi, Katsunori Sakai
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Patent number: 5462936Abstract: A compound of the formula: ##STR1## wherein X is .dbd.N--A--R.sup.1 or .dbd.C(R.sup.1)R.sup.2 ; A is a single bond, polymethylerie or --CO--; R.sup.1 and R.sup.2 are each hydrogen, C.sub.1-6 alkyl, C.sub.3-7 cycloalkyl, unsubstituted or substituted phenyl, optionally substituted benzhydryl, or optionally substituted 5 to 6 membered heterocyclic group; Y is hydrogen, halogen, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, C.sub.1-6 alkoxy, optionally substituted phenoxy, optionally substituted benzyloxy, or optionally substituted benzyl; Z is hydrogen or acyl; n is an integer of from 2 to 6, and pharmaceutically acceptable salt thereof. A pharmaceutical composition containing the compound, which is useful for treating hypertension and cardiac diseases, is also provided.Type: GrantFiled: August 22, 1994Date of Patent: October 31, 1995Assignee: Shionogi & Co., Ltd.Inventors: Teruo Yamamori, Hiroshi Harada, Katsunori Sakai, Kazumi Iwaki, Kazuki Matsunaga
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Patent number: 5413998Abstract: Compounds characterized generally as benzo-fused thiazopinyl-terminated alkylamino ethynyl alanine amino diol derivatives are useful as renin inhibitors for the treatment of hypertension. Compounds of particular interest are those of Formula I ##STR1## wherein A is selected from CO and SO.sub.2 ; wherein X is selected from oxygen atom and methylene; wherein B is a benzo-fused thiazopinyl group; wherein R.sub.1 is selected from hydrido, methyl, ethyl, isopropyl and n-propyl; wherein R.sub.2 is phenylmethyl; wherein each of R.sub.3 and R.sub.5 is hydrido; wherein R.sub.4 is selected from ##STR2## wherein V is selected from hydrido and methyl; wherein R.sub.6 is cyclohexylmethyl; wherein R.sub.7 is selected from isobutyl, cyclopropyl and cyclopropylmethyl; wherein q is a number selected from zero through three, inclusive; and wherein n is a number selected from zero through three, inclusive; or a pharmaceutically-acceptable salt thereof.Type: GrantFiled: February 22, 1994Date of Patent: May 9, 1995Assignee: G. D. Searle & Co.Inventors: Gunnar J. Hanson, Robert E. Manning
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Patent number: RE34935Abstract: 2-Aminothiophenol is reacted with methyl (-)-(2R,3S)-2,3-epoxy-3-(4-methoxyphenyl)propionate, and the intermediate methyl (2S,3S)-3-[(2-aminophenyl)thio]-2-hydroxy-3-(4-methoxyphenyl)propionate is cyclized in the presence of methanesulfonic acid, in the same vessel and without isolating said intermediate product, using e.g. chlorobenzene as a solvent.Type: GrantFiled: April 29, 1993Date of Patent: May 9, 1995Assignee: SynthelaboInventors: Guy Rossey, Isaac Chekroun, Antonio Ugolini, Alexander Wick, Bernard Gerin, Andre Bourbon, Jean-Baptiste Graux