Abstract: The present invention is concerned with novel processes for the preparation of (2R, 2-alpha-R, 3a)-2-[1-[3,5-bis(trifluoromethyl)phenyl]ethoxy-3-(4-fluorophenyl)-1,4-oxazine. This compound is useful as an intermediate in the synthesis of compounds which possess pharmacological activity.
Type:
Grant
Filed:
June 8, 2001
Date of Patent:
July 29, 2003
Assignee:
Merck & Co., Inc.
Inventors:
Karel M. Jos Brands, Fuh-Rong Tsay, Karen M. Conrad, Matthew M. Zhao
Abstract: Substituted 4-hydroxy-2-furoic acids are obtained by the fermentation of an asterriquinone, which is a natural product having a 2,5-dioxy-3,6-bis(indolyl)quinone structure. The compounds modulate insulin receptor tyrosine kinase activity and may be useful in the treatment of diabetes and other diseases or conditions characterized by impaired endogenous insulin production or an impaired response to endogenous insulin.
Type:
Grant
Filed:
October 18, 2002
Date of Patent:
July 22, 2003
Assignee:
Merck & Co. Inc.
Inventors:
Shieh-Shung Tom Chen, Bei B. Zhang, Xiaohua Li
Abstract: A class of pyrido[2,3-d]pyridazine derivatives, possessing an optionally substituted cycloalkyl, phenyl or heteroaryl substituent at the 8-position, a substituted alkoxy moiety at the 2-position, and a range of substituents at the 3-position, are selective ligands for GABAA receptors, in particular having high affinity for the &agr;2 and/or &agr;3 and/or &agr;5 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety, convulsions and cognitive disorders.
Type:
Grant
Filed:
February 20, 2002
Date of Patent:
July 15, 2003
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
William Robert Carling, Jose Luis Castro Pineiro, Andrew Mitchinson, Leslie Joseph Street
Abstract: The present invention is directed to compounds of the formula I:
(wherein R1, R3, R4, R5, R6, R7, R8, X, n, x and y are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.
Type:
Grant
Filed:
February 14, 2002
Date of Patent:
July 15, 2003
Assignee:
Merck & Co. Inc.
Inventors:
Paul E. Finke, Kerry A. Hilfiker, Malcolm MacCoss, Kevin T. Chapman, Jennifer L. Loebach, Sander G. Mills, Ravi N. Guthikonda, Shrenik K. Shah, Dooseop Kim, Dong-Ming Shen, Bryan Oates
Abstract: Certain &agr;-hydroxy-&ggr;-[[(carbocyclic- or heterocyclic-substituted)amino]carbonyl]alkanamide derivatives are described as inhibitors of HIV protease and inhibitors of HIV replication. These compounds are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described. These compounds are effective against HIV viral mutants which are resistant to HIV protease inhibitors currently used for treating AIDS and HIV infection.
Type:
Grant
Filed:
April 16, 2002
Date of Patent:
July 8, 2003
Assignee:
Merck & Co., Inc.
Inventors:
James R Tata, Zhijian Lu, Subharekha Raghavan, Tracy T. Huening, Thomas A. Rano, Mark G. Charest
Abstract: The invention encompasses the novel class of compounds represented by formula I which are inhibitors of the PTP-1B enzyme.
The invention also encompasses pharmaceutical compositions and methods of treating or preventing PTP-1B mediated diseases, including diabetes, obesity, and diabetes-related diseases.
Type:
Grant
Filed:
December 21, 2000
Date of Patent:
June 24, 2003
Assignee:
Merck Erosst Canada & Co.
Inventors:
Yves Leblanc, Claude Dufresne, Scheigetz John, Cheuk Kun Lau, Chun Sing Li, Patrick Roy, Michael Boyd, Zhaoyin Wang
Abstract: This invention is concerned with a novel polymorphic form of the compound 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)-phenyl)-ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine which is a tachykinin receptor antagonist useful in the treatment or prevention of disorders of the central nervous system, inflammatory diseases, pain or migraine, asthma, and emesis. The instant polymorphic form has advantages over the other known forms of 2-(R)-(1-(R)-(3,5-bis(trifluoro-methyl)-phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine in terms of thermodynamic stability and suitability for inclusion in pharmaceutical formulations.
Abstract: 1,2,4-triazolo[4,3-b]pyridazine derivatives, possessing a fluoro-substituted phenyl ring at the 3-position and a heteroaryl-alkoxy moiety at the 6-position, are selective ligands for GABAA receptors, in particular having high affinity for the &agr;2 and/or &agr;3 subunit thereof, are useful in the treatment of anxiety and convulsions.
Type:
Grant
Filed:
June 28, 2000
Date of Patent:
June 17, 2003
Assignee:
Merck Sharp & Dohme Limited
Inventors:
William Robert Carling, Jose Luis Castro Pineiro, Ian James Collins, Alexander Richard Guiblin, Timothy Harrison, Andrew Madin, Kevin William Moore, Michael Geoffrey Russell, Gayle Scott, Leslie Joseph Street
Abstract: This invention relates to the use of a tachykinin receptor antagonist for treating a psychosomatic or a psychoimmunological disorder in a patient.
Abstract: A class of aryloxyacetic acids comprises compounds that are potent agonists of PPAR alpha and/or gamma, and are therefore useful in the treatment, control or prevention of non-insulin dependent diabetes mellitus (NIDDM), hyperglycemia, dyslipidemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, atherosclerosis, obesity, vascular restenosis, inflammation, and other PPAR alpha and/or gamma mediated diseases, disorders and conditions.
Abstract: The present invention relates to a process for producing optically active diols represented by the general formula (II):
wherein R1 represents (CH2)n, CH═CH, O, S or NH whereupon n is an integer of 1 to 4, and R2 represents hydrogen, C1-6 alkyl, C1-6 alkoxy, (C1-6 alkoxy)-carbonyl, hydroxy, carboxy, halogen, nitro or amino, which comprises treating compounds represented by the general formula (I):
wherein R1 and R2 have the same meanings as defined above, with a culture of a microorganism belonging to the genus Rhodococcus, Bacillus, Brevibacterium or Gordona and being capable of stereoselectively diolating a double bond in ring A, or with a culture of Mortierella vinacea, or with said microorganism itself, or with a treated material from said microorganism.
Abstract: The instant invention provides methods and pharmaceutical compositions for inhibiting HMG-CoA reductase, as well as for treating and/or reducing the risk for diseases and conditions affected by inhibition of HMG-CoA reductase, comprising orally administering a therapeutically effective amount of a compound selected from a dihydroxy open acid statin and a pharmaceutically acceptable salt or ester thereof in a delayed-release pharmaceutical dosage form to a patient in need of such treatment wherein substantial release of the compound from the dosage form is delayed until after passage of the dosage form through the stomach.
Type:
Grant
Filed:
April 26, 2000
Date of Patent:
May 27, 2003
Assignee:
Merck & Co., Inc.
Inventors:
Richard D. Tillyer, Paul J. Reider, Edward J. J. Grabowski, Feng Xu, Jose M. Vega, Mandana Asgharnejad
Abstract: A class of phenylsulphonyl derivatives wherein the sulphonyl moiety is also attached to an N-arylalkyl-substituted azetidine, pyrrolidine or piperidine ring are selective antagonists of the human 5-HT2A receptor and are therefore useful as pharmaceutical agents, especially in the treatment and/or prevention of adverse conditions of the central nervous system, including schizophrenia and depression.
Type:
Grant
Filed:
September 27, 2001
Date of Patent:
May 6, 2003
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Peter Blurton, Frank Burkamp, Susan Koon-Fung Cheng, Stephen Robert Fletcher, Angus Murray MacLeod, Daniel Spinks, Monique Bodil Van Niel
Abstract: The present invention relates compounds of the formula (I):
wherein
X represents hydrogen or a C1-4alkyl group optionally substituted by a hydroxy group;
Y represents hydrogen, C1-6alkyl or C3-7cycloalkyl;
Z is —CR9R10CH2— or —CH2CR9R10—;
R represents hydrogen, fluorine, hydroxy, C1-6alkyl or C1-6alkoxy;
and R1, R2, R3, R4, R5 and R6 are as defined herein.
The compounds are of particular use in the treatment of depression, anxiety, pain, inflammation, migraine, emesis or postherpetic neuralgia.
Type:
Grant
Filed:
April 1, 2002
Date of Patent:
April 29, 2003
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Janusz Jozef Kulagowski, Piotr Antoni Raubo, Christopher George Thomson
Abstract: A thrombin receptor antagonist having the formula
useful for inhibiting the aggregation of blood platelets. The compounds can be used in a method of acting upon a thrombin receptor which comprises administering a therapeutically effective but non-toxic amount of such compound to a mammal, preferably a human.
Type:
Grant
Filed:
October 27, 2000
Date of Patent:
April 8, 2003
Assignee:
Merck & Co., Inc.
Inventors:
Harold G. Selnick, Philippe G. Nantermet, James C. Barrow, Roger M. Freidinger, Thomas Connolly
Abstract: A class of substituted and/or ring-fused pyrazolo[3,4-b]pyridine derivatives, possessing an optionally substituted cycloalkyl, phenyl or heteroaryl substituent on the pyrazole nitrogen atom adjacent the pyridine nucleus, and an optionally substituted cycloalkyl-alkoxy, aryl-alkoxy or heteroaryl-alkoxy substituent on the carbon atom adjacent the pyridine ring nitrogen atom, are selective ligands for GABAA receptors, in particular having high affinity for the &bgr;2 and/or &bgr;3 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of adverse neurological disorders, including anxiety and convulsions.
Type:
Grant
Filed:
June 14, 2002
Date of Patent:
April 1, 2003
Assignee:
Merck Sharp & Dohme Limited
Inventors:
Ian James Collins, Linda Elizabeth Keown, Leslie Joseph Street
Abstract: Compounds useful in the inhibition of HIV integrase, the prevention or treatment of infection by HIV and the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines are described. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described. The culture Cytospora sp. MF 6608 (ATCC PTA-1691) is also disclosed, as well as processes for making a compound of the present invention employing the culture.
Type:
Grant
Filed:
August 9, 2001
Date of Patent:
April 1, 2003
Assignee:
Merck & Co., Inc.
Inventors:
Sheo Bux Singh, Hiranthi Jayasuriya, Ziqiang Guan, Keith C. Silverman, Russell B. Lingham, Anne W. Dombrowski, Daria J. Hazuda, Jon D. Polishook
Abstract: The present invention is a method for diagnosing a patient at risk to thrombocytopenia induced by administration of a GP IIb/IIIa receptor antagonist, which comprises combining
i) a plasma sample of the patient;
ii) detectable monoclonal antibody which recognizes induced binding sites formed on the GP IIb/IIIa receptor following association of a fibrinogen receptor antagonist with the GP IIb/IIIa receptor; and
iii) GP IIb/IIIa receptor:GP IIb/III receptor antagonist complex,
and determining association of the detectable monoclonal antibody with the complex in the presence of the plasma.
Type:
Grant
Filed:
March 30, 2001
Date of Patent:
March 25, 2003
Assignee:
Merck & Co., Inc.
Inventors:
Bohumil Bednar, Daniel M. Bollag, Robert J. Gould
Abstract: The present in to s directed to compounds of the formula I:
(wherein R1, R2, R3, R7, R8, X, Y, Z, x and y are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-5 and/or CCR-3.
Type:
Grant
Filed:
June 8, 2000
Date of Patent:
March 25, 2003
Assignee:
Merck & Co., Inc.
Inventors:
Paul E. Finke, Malcolm Maccoss, Sander G. Mills, Bryan Oates