S-triazolo(4,3-a)(1,4)-benzodi-azepines (including Hydrogenated) Patents (Class 540/563)
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Patent number: 11040977Abstract: The invention provides processes to manufacture substituted 1-[4-(Pyridin-2-yloxy)-cyclohexyl]-5,6-dihydro-4H-2,3,5,10b-tetraaza-benzo[e]azulenes. Also disclosed are compounds useful as intermediates in the methods of the invention.Type: GrantFiled: March 4, 2019Date of Patent: June 22, 2021Assignee: Hoffmann-La Roche Inc.Inventors: Benno Rothenhaeusler, Rene Trussardi, Fabienne Hoffmann-Emery, Urs Schwitter, Jean-Michel Adam, Olaf Grassmann, Thomas Hartung, Frederic Ran, Ralph Diodone, Christophe Pfleger, Bjorn Bartels
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Patent number: 11021448Abstract: The present invention provides compounds that are muscarinic M1 receptor positive allosteric modulators (PAM) and useful in the treatment of diseases, mediated by the muscarinic M1 receptor, such as Alzheimer's disease, cognitive impairment, schizophrenia, pain or sleep disorders, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances.Type: GrantFiled: April 30, 2019Date of Patent: June 1, 2021Assignee: Hoffmann-La Roche Inc.Inventor: Alexander Flohr
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Patent number: 8835424Abstract: In preferred embodiments, the present invention provides methods of treatment and pharmaceutical compositions for the suppression, alleviation and prevention of the often chronic, severe and debilitating pain that can accompany inflammatory diseases and neuropathic insults, pain that is often unresponsive to conventional analgesic treatment. The preferred embodiments of the present invention further relate to methods of treatment and pharmaceutical compositions using benzodiazepine derivatives that provide suppression, alleviation and prevention of neuropathic pain, migraine-related pain and inflammatory pain with reduced sedative and ataxic side effects.Type: GrantFiled: May 13, 2010Date of Patent: September 16, 2014Assignee: Wisconsin Alumni Research FoundationInventors: James Cook, Shengming Huang, Rahul Edwankar, Ojas A. Namjoshi, Zhi-Jian Wang
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Patent number: 8664216Abstract: The present invention is concerned with spiro-dihydrotetraazabenzoazulenes, i.e. spiro-5,6-dihydro-4H-2,3,5,10b-tetraaza-benzo[e]azulenes of formula I wherein R1, R2, R3, X, Y, Z, m and n are as described herein. The compounds according to the invention act as V1a receptor modulators and are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.Type: GrantFiled: November 6, 2009Date of Patent: March 4, 2014Assignee: Hoffmann-La Roche Inc.Inventors: Caterina Bissantz, Erwin Goetschi, Roland Jakob-Roetne, Raffaello Masciadri, Emmanuel Pinard, Hasane Ratni, Mark Rogers-Evans, Patrick Schnider
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Patent number: 8642590Abstract: The present invention is concerned with alkylcyclohexylethers of dihydro-tetraazabenzoazulenes, i.e. alkylcyclohexylethers of 5,6-dihydro-4H-2,3,5,10b-tetraaza-benzo[e]azulene s of formula I wherein R1, R2 and R3 are as described herein, their manufacture, and pharmaceutical compositions containing them. The compounds according to the invention act as V1a receptor modulators, and in particular as V1a receptor antagonists. The compounds are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.Type: GrantFiled: November 12, 2009Date of Patent: February 4, 2014Assignee: Hoffmann-La Roche Inc.Inventor: Patrick Schnider
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Patent number: 8513238Abstract: The present invention provides heteroaryl-cyclohexyl-tetraazabenzo[e]azulenes of formula I wherein R1, R2 and R3 are as described herein. The compounds according to the invention act as V1a receptor modulators, and in particular as V1a receptor antagonists, their manufacture, pharmaceutical compositions containing them and their use as medicaments. The active compounds of the present invention are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.Type: GrantFiled: May 5, 2011Date of Patent: August 20, 2013Assignee: Hoffmann-La Roche Inc.Inventors: Cosimo Dolente, Patrick Schnider
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Patent number: 8492376Abstract: The present invention is concerned with heteroaryl-cyclohexyl-tetraazabenzo[e]azulenes of formula I wherein R1, R2 and R3 are as described herein. The compounds according to the invention act as V1a receptor modulators, and in particular as V1a receptor antagonists, their manufacture, pharmaceutical compositions containing them and their use as medicaments. The active compounds of the present invention are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.Type: GrantFiled: April 14, 2011Date of Patent: July 23, 2013Assignee: Hoffmann-La Roche Inc.Inventors: Cosimo Dolente, Patrick Schnider
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Patent number: 8481528Abstract: The present invention relates to heterobiaryl-cyclohexyl-tetraazabenzo[e]azulenes of formula I wherein R1, R2 and R3 are as described herein. The compounds according to the invention act as V1a receptor modulators, and in particular as V1a receptor antagonists, their manufacture, pharmaceutical compositions containing them and their use as medicaments. The active compounds of the present invention are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.Type: GrantFiled: April 19, 2011Date of Patent: July 9, 2013Assignee: Hoffmann-La Roche Inc.Inventors: Cosimo Dolente, Patrick Schnider
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Patent number: 8461152Abstract: The present invention is concerned with arylcyclohexylethers of dihydro-tetraazabenzoazulenes, i.e. arylcyclohexylethers of 5,6-dihydro-4H-2,3,5,10b-tetraaza-benzo[e]azulenes of formula I wherein R1, R2 and R3 are as described herein, their manufacture, and pharmaceutical compositions containing them. The compounds according to the invention act as V1a receptor modulators, and in particular as V1a receptor antagonists. The active compounds of the present invention are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.Type: GrantFiled: May 15, 2012Date of Patent: June 11, 2013Assignee: Hoffmann-La Roche Inc.Inventor: Patrick Schnider
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Patent number: 8461151Abstract: The present invention is concerned with aryl-/heteroaryl-cyclohexenyl-tetraazabenzo[e]azulenes of formula I wherein R1, R2 and R3 are as described herein. The invention further provides methods for the manufacture of such compounds and pharmaceutical compositions containing them. The compounds according to the invention act as V1a receptor modulators, and in particular as V1a receptor antagonists, their manufacture, pharmaceutical compositions containing them and their use as medicaments. The active compounds of the present invention are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.Type: GrantFiled: April 4, 2011Date of Patent: June 11, 2013Assignee: Hoffmann-La Roche Inc.Inventors: Cosimo Dolente, Patrick Schnider
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Patent number: 8455479Abstract: The present invention relates to novel compounds of Formula I, their pharmaceutically acceptable derivatives, tautomeric forms, stereoisomers including R and S isomers, polymorphs, prodrugs, metabolites, salts or solvates thereof. The invention also relates to the processes for the synthesis of novel compounds of Formula I, their pharmaceutically acceptable derivatives, tautomeric forms, stereoisomers, polymorphs, prodrugs, metabolites, salts or solvates thereof. The present invention also provides pharmaceutical compositions comprising compounds of Formula I and methods of treating or preventing one or more conditions that may be regulated or normalized via inhibition of dipeptidyl peptidase IV (DPP-IV).Type: GrantFiled: January 23, 2009Date of Patent: June 4, 2013Assignee: Panacea Biotec LimitedInventors: Rajesh Jain, Sanjay Trehan, Jagattaran Das, Nishan Singh, Gurmeet Kaur Nanda, Sitaram Kumar Magadi, Sudhir Kumar Sharma
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Patent number: 8420633Abstract: The present invention is concerned with aryl-cyclohexyl-tetraazabenzo[e]azulenes of formula I wherein R1, R2 and R3 are as described herein. The invention further provides methods for the manufacture of such compounds and pharmaceutical compositions containing them. The compounds according to the invention act as V1a receptor modulators, and in particular as V1a receptor antagonists. The compounds are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.Type: GrantFiled: March 24, 2011Date of Patent: April 16, 2013Assignee: Hoffmann-La Roche Inc.Inventors: Cosimo Dolente, Patrick Schnider
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Patent number: 8278297Abstract: In one aspect, the invention provides compounds of Formula I or pharmaceutically acceptable salts thereof. In another aspect, the invention provides methods for treatment of diseases or disorders mediated by a protein kinase, comprising administering a therapeutically effective amount of a compound of this invention.Type: GrantFiled: December 23, 2010Date of Patent: October 2, 2012Assignee: Vertex Pharmaceuticals IncorporatedInventors: Jean-Damien Charrier, Steven Durrant
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Patent number: 8252787Abstract: In one aspect, the invention provides compounds of Formula I or pharmaceutically acceptable salts thereof. In another aspect, the invention provides methods for treatment of diseases or disorders mediated by a protein kinase, comprising administering a therapeutically effective amount of a compound of this invention.Type: GrantFiled: December 23, 2010Date of Patent: August 28, 2012Assignee: Vertex Pharmaceuticals IncorporatedInventors: Jean-Damien Charrier, Steven Durrant
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Patent number: 8227458Abstract: The present invention is concerned with arylcyclohexylethers of dihydro-tetraazabenzoazulenes, i.e. arylcyclohexylethers of 5,6-dihydro-4H-2,3,5,10b-tetraaza-benzo[e]azulenes of formula I wherein R1, R2 and R3 are as described herein, their manufacture, and pharmaceutical compositions containing them. The compounds according to the invention act as V1a receptor modulators, and in particular as V1a receptor antagonists. The active compounds of the present invention are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.Type: GrantFiled: November 19, 2009Date of Patent: July 24, 2012Assignee: Hoffmann-La Roche Inc.Inventor: Patrick Schnider
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Patent number: 8093240Abstract: Novel triazole derivatives are inhibitors of TGF-beta receptor I kinase, and can be employed, inter alia, for the treatment of tumours.Type: GrantFiled: November 24, 2006Date of Patent: January 10, 2012Assignee: Merck Patent GmbHInventors: Bertram Cezanne, Christiane Amendt, Hartmut Greiner, Ulrich Graedler, Guenter Hoelzemann
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Publication number: 20110263573Abstract: The present invention relates to heterobiaryl-cyclohexyl-tetraazabenzo[e]azulenes of formula I wherein R1, R2 and R3 are as described herein. The compounds according to the invention act as V1a receptor modulators, and in particular as V1a receptor antagonists, their manufacture, pharmaceutical compositions containing them and their use as medicaments. The active compounds of the present invention are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.Type: ApplicationFiled: April 19, 2011Publication date: October 27, 2011Inventors: Cosimo Dolente, Patrick Schnider
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Publication number: 20110263578Abstract: The present invention is concerned with heteroaryl-cyclohexyl-tetraazabenzo[e]azulenes of formula I wherein R1, R2 and R3 are as described herein. The compounds according to the invention act as V1a receptor modulators, and in particular as V1a receptor antagonists, their manufacture, pharmaceutical compositions containing them and their use as medicaments. The active compounds of the present invention are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.Type: ApplicationFiled: April 14, 2011Publication date: October 27, 2011Inventors: Cosimo Dolente, Patrick Schnider
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Publication number: 20110251183Abstract: The present invention is concerned with aryl-/heteroaryl-cyclohexenyl-tetraazabenzo[e]azulenes of formula I wherein R1, R2 and R3 are as described herein. The invention further provides methods for the manufacture of such compounds and pharmaceutical compositions containing them. The compounds according to the invention act as V1 a receptor modulators, and in particular as V1 a receptor antagonists, their manufacture, pharmaceutical compositions containing them and their use as medicaments. The active compounds of the present invention are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.Type: ApplicationFiled: April 4, 2011Publication date: October 13, 2011Inventors: Cosimo Dolente, Patrick Schnider
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Publication number: 20110245237Abstract: The present invention is concerned with aryl-cyclohexyl-tetraazabenzo[e]azulenes of formula I wherein R1, R2 and R3 are as described herein. The invention further provides methods for the manufacture of such compounds and pharmaceutical compositions containing them. The compounds according to the invention act as V1a receptor modulators, and in particular as V1a receptor antagonists. The compounds are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.Type: ApplicationFiled: March 24, 2011Publication date: October 6, 2011Inventors: Cosimo Dolente, Patrick Schnider
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Patent number: 7947678Abstract: Compounds of formula I: (where variables R2, R7, D, W, X, Y and Z are as described herein) which are antagonists of CGRP receptors and which are useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.Type: GrantFiled: July 25, 2006Date of Patent: May 24, 2011Assignee: Merck Sharp & Dohme Corp.Inventor: Theresa M. Williams
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Publication number: 20100137286Abstract: The present invention is concerned with arylcyclohexylethers of dihydro-tetraazabenzoazulenes, i.e. arylcyclohexylethers of 5,6-dihydro-4H-2,3,5,10b-tetraaza-benzo[e]azulenes of formula I wherein R1, R2 and R3 are as described herein, their manufacture, and pharmaceutical compositions containing them. The compounds according to the invention act as V1a receptor modulators, and in particular as V1a receptor antagonists. The active compounds of the present invention are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.Type: ApplicationFiled: November 19, 2009Publication date: June 3, 2010Inventor: Patrich Schnider
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Publication number: 20100125066Abstract: The present invention is concerned with alkylcyclohexylethers of dihydro-tetraazabenzoazulenes, i.e. alkylcyclohexylethers of 5,6-dihydro-4H-2,3,5,10b-tetraaza-benzo[e]azulene s of formula I wherein R1, R2 and R3 are as described herein, their manufacture, and pharmaceutical compositions containing them. The compounds according to the invention act as V1a receptor modulators, and in particular as V1a receptor antagonists. The compounds are useful as therapeutics acting peripherally and centrally in the conditions of dysmenorrhea, male or female sexual dysfunction, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior.Type: ApplicationFiled: November 12, 2009Publication date: May 20, 2010Inventor: Patrick Schnider
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Patent number: 7473689Abstract: The present invention provides a compound of formula (I): wherein all variables are as defined herein, pharmaceutical formulations containing the same, processes for preparing the same and their use therapy.Type: GrantFiled: January 5, 2007Date of Patent: January 6, 2009Assignee: CeNes LimitedInventors: Paul L. Feldman, David Kendall Jung, Istvan Kaldor, Gregory J. Pacofsky, Jeffrey A. Stafford, Jeffrey H. Tidwell
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Publication number: 20080306042Abstract: Novel triazole derivatives are inhibitors of TGF-beta receptor I kinase, and can be employed, inter alia, for the treatment of tumours.Type: ApplicationFiled: November 24, 2006Publication date: December 11, 2008Inventors: Bertram Cezanne, Christiane Amendt, Hartmut Greiner, Ulrich Graedler, Guenter Hoelzemann
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Patent number: 7238685Abstract: The invention relates to novel benzo-fused heterocycles and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as endothelin receptor antagonists.Type: GrantFiled: July 31, 2002Date of Patent: July 3, 2007Assignee: Actelion Pharmaceuticals Ltd.Inventors: Martin Bolli, Christoph Boss, Martine Clozel, Walter Fischli, Thomas Weller, Judith Marfurt
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Patent number: 5753649Abstract: A therapeutic agent for osteoporosis, comprising an azepine compound of the formula ##STR1## wherein each symbol is as defined in the specification, or a pharmaceutically acceptable salt thereof as an active ingredient, a method for treating osteoporosis comprising administering said compound and a use of said compound for the production of a therapeutic agent for osteoporosis. The compounds of the formula (I) have superior bone resorption-inhibitory activity and act to reduce the increased amount of calcium in blood serum, which is caused by bone resorption.Type: GrantFiled: August 30, 1996Date of Patent: May 19, 1998Assignees: Yoshitomi Pharmaceutical Industries, Ltd., Japan Tobacco, Inc.Inventors: Tetsuya Tahara, Minoru Moriwaki, Kenji Chiba, Shunichi Manabe, Masanori Shindo, Takashi Nakagawa, Takeshi Nakamura
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Patent number: 5679672Abstract: Compounds of structures (I) and (Ia) are Class III antiarrhythmic agents ##STR1##Type: GrantFiled: May 14, 1996Date of Patent: October 21, 1997Assignee: Merck & Co., Inc.Inventors: John J. Baldwin, David A. Claremon, Jason M. Elliott, Nigel Liverton, David C. Remy, Harold G. Selnick
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Patent number: 5516774Abstract: Tricyclic diazepines of the formula: ##STR1## wherein A, B, D, E, F, Y and Z are defined in the specification which compounds have vasopressin and oxytocin antagonist activity.Type: GrantFiled: June 13, 1994Date of Patent: May 14, 1996Assignee: American Cyanamid CompanyInventors: Jay D. Albright, Marvin F. Reich, Fuk-Wah Sum, Efren G. Delos Santos
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Patent number: 5116971Abstract: The invention relates to new 1,4-diazepines of the general formula ##STR1## in which R.sub.1, R.sub.2 R.sub.3, X and A have the meaning indicated in the specification.The new compounds are intended for use for the treatment of pathological states and diseases in which PAF (platelet activating factor) is involved.Type: GrantFiled: September 19, 1990Date of Patent: May 26, 1992Assignee: Boehringer Ingelheim KGInventors: Albrecht Harreus, Karl-Heinz Weber, Werner Stransky, Gerhard Walther, Gojko Muacevic, Jorge C. Stenzel, Wolf-Dietrich Bechtel
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Patent number: 5008263Abstract: Platelet activating factor antagonists of formula (I), (II) or (III): ##STR1## where A is optionally substituted benzene, pyridine, naphthalene, quinoline, thiophene, benzothiophene, pyrazole or isothiazole,X is O, S or NHY is 1,4 phenylene or a group of formula ##STR2## R.sup.1 is H or optionally substituted C.sub.1 -C.sub.4 alkyl, R.sup.2 and R.sup.3 are H or C.sub.1 -C.sub.4 alkyl,B is an optionally fused 5- or 6-membered ring containing nitrogen atoms,Het is an optionally substituted 5-membered heterocyclic ring containing nitrogen or a pyridine ring, the ring optionally being fused to benzene or nitrogen-containing heterocyclic ring.Type: GrantFiled: March 20, 1990Date of Patent: April 16, 1991Assignee: Pfizer Inc.Inventors: Kelvin Cooper, Michael J. Fray
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Patent number: 4987131Abstract: Novel 4H-triazolo[4,3-a][1,4]benzodiazepines of the formula ##STR1## wherein R.sub.1 and R.sub.2 are individually selected from the group consisting of hydrogen and alkyl of 1 to 5 carbon atoms and R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are individually selected from the group consisting of hydrogen, --OH, alkyl and alkoxy of 1 to 4 carbon atoms, --NH.sub.2, --NHalk wherein alk is alkyl of 1 to 4 carbon atoms, ##STR2## and alk.sub.1 and alk.sub.2 are individually alkyl of 1 to 4 carbon atoms, halogen, --NO.sub.2 and --CF.sub.3 in any position of the benzene rings with the proviso that R.sub.5 and R.sub.6 are not both hydrogen and their non-toxic, pharmaceutically acceptable acid addition salts having good analgesic activity.Type: GrantFiled: March 8, 1990Date of Patent: January 22, 1991Assignee: Roussel UclafInventors: Francois Clemence, Odile Le Martret, Francois Delevallee
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Patent number: 4959361Abstract: The invention relates to compounds of the formula ##STR1## wherein X is --CH.dbd.CH-- or S; R.sub.1 is lower alkyl, lower alkoxy or trifluoromethyl;R.sub.2 is hydrogen, lower alkyl, lower alkoxy, hydroxy or alkanoyloxy;R.sub.3 and R.sub.4, independently, are hydrogen, chlorine, fluorine, lower alkyl or lower alkoxy;s is an integer from 0 to 1, provided that when s is 1,R.sub.2 cannot be hydroxy, lower alkoxy or alkanoyloxy;R.sub.5 is a radical of the formula R.sub.6 --(CH.sub.2).sub.n -- or R.sub.7 --O--(CH.sub.2).sub.m --wherein R.sub.6 and R.sub.7 are aryl or a heterocyclic radical, n is an integer of from 0 to 2 and m is an integer of from 1 to 2, provided that, when n is 0, R.sub.6 must be attached through a carbon to carbon bond, and provided that R.sub.7 is always attached through a carbon to oxygen bond,and, when at least one asymmetric carbon is present, its enantiomers and racemates, and pharmaceutically acceptable acid addition salts thereof.Type: GrantFiled: October 3, 1988Date of Patent: September 25, 1990Assignee: Hoffmann-La Roche Inc.Inventor: Armin Walser
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Patent number: 4902794Abstract: 1-Substituted-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines of the formula (III): ##STR1## wherein R is selected from the group consisting of hydroxy, esters thereof, and alkoxy, in which the alkyl group is of 1 to 3 carbon atoms, inclusive; wherein R.sub.1 is selected from the group consisting of hydrogen and alkyl of 1 to 3 carbon atoms, inclusive; and wherein R.sub.2, R.sub.3, R.sub.4, and R.sub.5 are selected from the group consisting of hydrogen, alkyl of 1 to 3 carbon atoms, inclusive, halogen, nitro, cyano, trifluoromethyl, and alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoylamino, and dialkylamino in which the carbon chain moieties are of 1 to 3 carbon atoms, inclusive, are produced by condensing a 1,3-dihydro-5-phenyl-2H-1,4-benzodiazepine-2-thione of the formula (I): ##STR2## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R.sub.Type: GrantFiled: July 20, 1983Date of Patent: February 20, 1990Assignee: The Upjohn CompanyInventor: Jackson B. Hester, Jr.
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Patent number: 4831161Abstract: Prepare N-(amidoalkyl)imides by contacting an imide with a 2-oxazoline under reaction conditions, optionally in the presence of a solvent.Type: GrantFiled: June 24, 1987Date of Patent: May 16, 1989Assignee: The Dow Chemical CompanyInventors: Pen-Chung Wang, Steven P. Crain
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Patent number: 4739049Abstract: Compounds of the general formula ##STR1## are reacted with a strong base followed by a phosphorylating agent, such as dicyclicaminophosphinic halide or bis-di-lower alkylaminophosphinic halide to produce an imine of the formula ##STR2## wherein R is dicyclicaminophosphinyloxy or bis-di-lower alkylaminophosphinyloxy.R represents a leaving group which will undergo nucleophilic displacement with nitrogen, oxygen, sulfur and carbon containing nucleophiles, that is, nucleophiles which have, as a reactive site, a nitrogen, oxygen, sulfur or carbon atom, such that, when the cyclic imine undergoes nucleophilic displacement, there is formed C--N, C--O, C--S and C--C bonds between the carbon atom of the cyclic imine and the nucleophilic group.The end products may be utilized as intermediates in the production of pharmaceutically valuable compounds and, in some instances, are pharmaceutically valuable compounds per se.Type: GrantFiled: August 15, 1986Date of Patent: April 19, 1988Assignee: Hoffmann-La Roche Inc.Inventors: Robert Y. Ning, Pradeep B. Madan
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Patent number: 4689413Abstract: Triazolo-benzodiazepine-1-ethanamines of the formulas ##STR1## where R, R.sub.1, R.sub.2, R.sub.3, R.sub.4 and Ring A are as defined in the specification, e.g., 8-chloro-N,N-dimethyl-.beta.,6-diphenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benz odiazepine-1-ethanamine, and pharmacologically acceptable salts thereof, have been found to have substantial diuretic, natriuretic, but little, if any, kaliuretic activity, which can be used alone, or concomittently with other diuretic drugs such as furosemide or hydrochlorothiazide and/or with antihypertensive agents such as propranolol, captopril, minoxidil, prazosin, guanadrel sulfate, whose actions are supplemented by the action of a diuretic drug.Type: GrantFiled: January 31, 1985Date of Patent: August 25, 1987Assignee: The Upjohn CompanyInventors: Jackson B. Hester, Jr., James H. Ludens
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Patent number: 4663321Abstract: Triazolobenzodiazepines of the formula: ##STR1## are disclosed which are antagonists of cholecystokinin (CCK).Type: GrantFiled: June 10, 1985Date of Patent: May 5, 1987Assignee: Merck & Co., Inc.Inventors: Mark G. Bock, Ben E. Evans, Roger M. Freidinger
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Patent number: 4663454Abstract: .alpha.-Halomethylbenzodiazepines (II) are produced by direct halogenation of methylbenzodiazepines (I) using sulfuryl halide.Type: GrantFiled: April 17, 1985Date of Patent: May 5, 1987Assignee: The Upjohn CompanyInventor: Joel E. Huber