Abstract: The present invention is directed to compounds which inhibit farnesyl-protein transferase (FPTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.
Type:
Grant
Filed:
March 22, 1994
Date of Patent:
July 25, 1995
Assignee:
Merck & Co., Inc.
Inventors:
Sheo B. Singh, Barry A. Katz, Russell B. Lingham, Isabel Martin, Keith C. Silverman
Abstract: The present invention relates to a novel oral dosage form of a bisphosphonic active ingredient for use in treatment of diseases involving bone resorption and formulated in an enteric-coated form for administration to subjects exhibiting upper gastrointestinal tract sensitivity to bisphosphonic acid compounds.
Abstract: A class of pyrrolo[2,3-b]pyridine derivatives, substituted at the 3-position by a substituted piperazinylmethyl moiety, are antagonists of dopamine receptor subtypes within the brain, having a selective affinity for the dopamine D.sub.4 receptor subtype over other dopamine receptor subtypes, and are accordingly of benefit in the treatment and/or prevention of psychotic disorders such as schizophrenia while manifesting fewer side-effects than those associated with classical neuroleptic drugs.
Type:
Grant
Filed:
February 22, 1994
Date of Patent:
July 11, 1995
Assignee:
Merck Sharpe & Dohme Ltd.
Inventors:
Raymond Baker, Janusz J. Kulagowski, Neil R. Curtis, Paul D. Leeson, Mark P. Ridgill
Abstract: The present invention is directed to water-soluble derivatives of antibiotic lipopeptides. The derivatives have good solubility properties in aqueous medium, rendering them more useful as therapeutic agents.
Abstract: A process for producing an antibiotic compound which is normally a minor component in the cultivation of Z. arboricola to be the major product is described.
Type:
Grant
Filed:
February 14, 1994
Date of Patent:
June 20, 1995
Assignee:
Merck & Co, Inc.
Inventors:
Jimmy M. Fountoulakis, Prakash S. Masurekar, Louis Kaplan
Abstract: A class of 4-hydroxy-pyrrolo[1,2-b]pyridazin-2(1H)-one derivatives, substituted at the 3-position by an optionally substituted aryl substituent, are selective non-competitive antagonists of NMDA receptors and/or are antagonists of AMPA receptors, and are therefore of utility in the treatment of conditions, such as neurodegenerative disorders, convulsions or schizophrenia, which require the administration of an NMDA and/or AMPA receptor antagonist.
Abstract: This invention relates to a method for the preparation of a compound of formula I: ##STR1## a key intermediate in the synthesis of a series of Angiotensin II receptor antagonists. The invention also relates to a selective reagent for conducting the Hofmann rearrangement, particularly in the formation of a pyridinoimidazolone, which is a percursor to the formation of an imidazopyfidine of formula I. This invention also relates to a method for the preparation of imidazolutidine, a key intermediate in the synthesis of 3-(2'-(N-benzoyl)sulfonamidobiphen-4-yl)-methyl-5,7 -dimethyl-2-ethyl-3H-imidazo[4,5-b]pyridine, using pyridinoimidazolone, an unreactive urea.
Type:
Grant
Filed:
May 26, 1994
Date of Patent:
June 13, 1995
Assignee:
Merck & Co., Inc.
Inventors:
Laura E. Fredenburgh, Robert D. Larsen, Ji Liu, Robert A. Reamer, Chris H. Senanayake, Thomas R. Verhoeven
Abstract: A class of 4-hydroxy-2(1H)-pyrrolone derivatives, substituted at the 3-position by an optionally substituted aryl substituent, are selective non-competitive antagonists of NMDA receptors and/or are antagonists of AMPA receptors, and are therefore of utility in the treatment of conditions, such as neurodegenerative disorders, convulsions or schizophrenia, which require the administration of an NMDA and/or AMPA receptor antagonist.
Type:
Grant
Filed:
May 10, 1993
Date of Patent:
May 30, 1995
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Janusz J. Kulagowski, Paul D. Leeson, Ian M. Mawer
Abstract: This invention relates to pharmaceutical compounds of structural formulae (I) and (II): ##STR1## and compositions and methods of treatment utilizing these compounds to inhibit farnesyl protein transferase and farnesylation of the oncogene protein Ras.
Type:
Grant
Filed:
December 16, 1991
Date of Patent:
May 30, 1995
Assignee:
Merck & Co., Inc.
Inventors:
Sheo B. Singh, Gerald F. Bills, Russell B. Lingham, Keith C. Silverman, Deborah L. Zink
Abstract: The present invention is directed to compounds which inhibit farnesyl-protein transferase (FPTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting famesyl-protein transferase and the famesylation of the oncogene protein Ras.
Type:
Grant
Filed:
April 4, 1994
Date of Patent:
May 30, 1995
Assignee:
Merck & Co., Inc.
Inventors:
Sheo B. Singh, Gerald F. Bills, Russell B. Lingham, Isabel Martin, Keith C. Silverman, Jack L. Smith
Abstract: Phenoxyphenylacetic acids and derivatives of general structural formula I ##STR1## have endothelin antagonist activity and are therefore useful in treating cardiovascular disorders, such as hypertension, postischemic renal failure, vasospasm, cerebral and cardiac ischemia, myocardial infarction, inflammatory diseases, Raynaud's disease, and endotoxic shock, and asthma.
Type:
Grant
Filed:
March 19, 1993
Date of Patent:
May 30, 1995
Assignee:
Merck & Co., Inc.
Inventors:
Daljit S. Dhanoa, Kenneth J. Fitch, Daniel F. Veber, Thomas F. Walsh, David L. Williams, Jr.
Abstract: Heterocyclic compounds of structural formula: ##STR1## wherein A, B, C, and D are independently carbon atoms or nitrogen atoms are angiotensin II antagonists useful in the treatment of hypertension and congestive heart failure.
Type:
Grant
Filed:
September 2, 1992
Date of Patent:
May 2, 1995
Assignee:
Merck & Co., Inc.
Inventors:
Prasun K. Chakravarty, William J. Greenlee, Dooseop Kim, Nathan B. Mantlo, Arthur A. Patchett, Ralph A. Rivero
Abstract: Avermectin derivatives, wherein the C-17-21-25-dioxaspirane substructure has been modified to include substitutions of heteratomic nucleophilic thiols at the 23,24-.alpha.-epoxide. These compounds can be similarly substituted at the 4"-, 5-, 13, and 25-positions. The new C-23 and C-24 substituted avermectin derivatives are potent anthelmintic, insecticidal and acaricidal agents.
Abstract: There is disclosed a slow release drug delivery device for the prolonged administration of topically active medicines which consists of a vehicle in which water is soluble and in which is dissolved the topically active drug which is formed into a stable organogel with a polymer matrix with a very low water absorbing capability. The organogel, in the presence of water or atmospheric water vapor, slowly imbibes such water into the vehicle and by doing so the vehicle becomes incompatible with the matrix and is slowly expelled therefrom. The vehicle dissolves the drug and the vehicle/drug combination is slowly pumped out of the polymeric matrix with substantially linear drug delivery occurring for periods in excess of 6 months. The drug delivery device may be used to administer drugs topically, as a collar or trans dermal patch, orally, as a slow delivery device, particularly as a ruminal bolus, or as a suppository or a subcutaneous implant.
Abstract: There are disclosed new substituted triazolinone, triazolinethione, and triazolinimine compounds which are useful as angiotensin II antagonists. These compounds have the general formula: ##STR1## wherein G is R.sup.
Type:
Grant
Filed:
December 21, 1992
Date of Patent:
May 2, 1995
Assignee:
Merck & Co., Inc.
Inventors:
Wallace T. Ashton, Linda L. Chang, Malcolm MacCoss, Prasun K. Chakravarty, William J. Greenlee, Arthur A. Patchett, Kelly Flanagan