Abstract: Indazole compounds that modulate and/or inhibit the activity of certain protein kinases are described. These compounds and pharmaceutical compositions containing them are capable of mediating tyrosine kinase signal transduction and thereby modulate and/or inhibit unwanted cell proliferation. The invention is also directed to the therapeutic or prophylactic use of pharmaceutical compositions containing such compounds, and to methods of treating cancer and other disease states associated with unwanted angiogenesis and/or cellular proliferation, such as diabetic retinopathy, neovascular glaucoma, rheumatoid arthritis, and psoriasis, by administering effective amounts of such compounds.
Type:
Grant
Filed:
February 15, 2003
Date of Patent:
May 10, 2005
Assignee:
Agouron Pharmaceuticals, Inc.
Inventors:
Robert Steven Kania, Steven Lee Bender, Allen J. Borchardt, Stephan James Cripps, Ye Hua, Michael David Johnson, Theodore Otto Johnson, Jr., Hiep The Luu, Cynthia Louise Palmer, Siegfried Heinz Reich, Anna Maria Tempczyk-Russell, Min Teng, Christine Thomas, Michael David Varney, Michael Brennan Wallace, Michael Raymond Collins
Abstract: Indazole compounds that modulate and/or inhibit the activity of certain protein kinases are described. These compounds and pharmaceutical compositions containing them are capable of mediating tyrosine kinase signal transduction and thereby modulate and/or inhibit unwanted cell proliferation. The invention is also directed to the therapeutic or prophylactic use of pharmaceutical compositions containing such compounds, and to methods of treating cancer and other disease states associated with unwanted angiogenesis and/or cellular proliferation, such as diabetic retinopathy, neovascular glaucoma, rheumatoid arthritis, and psoriasis, by administering effective amounts of such compounds.
Type:
Grant
Filed:
February 13, 2003
Date of Patent:
April 26, 2005
Assignee:
Agouron Pharmaceuticals, Inc.
Inventors:
Robert Steven Kania, Steven Lee Bender, Allen J. Borchardt, Stephan James Cripps, Ye Hua, Michael David Johnson, Theodore Otto Johnson, Jr., Hiep The Luu, Cynthia Louise Palmer, Siegfried Heinz Reich, Anna Marie Tempczyk-Russell, Min Teng, Christine Thomas, Michael David Varney, Michael Brennan Wallace, Michael Raymond Collins
Abstract: Compounds of formula I are hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) inhibitors, and are useful in therapeutic and prophylactic treatment of persons infected with hepatitis C virus
Abstract: Compounds of the formula: where the formula variables are as defined in the disclosure, advantageously inhibit or block the biological activity of the picornaviral 3C protease. These compounds, as well as pharmaceutical compositions containing these compounds, are useful for treating patients or hosts infected with one or more picornaviruses, such as RVP. Intermediates and synthetic methods for preparing such compounds are also described.
Type:
Grant
Filed:
May 12, 2003
Date of Patent:
March 29, 2005
Assignee:
Agouron Pharmaceuticals, Inc.
Inventors:
Theodore O. Johnson, Jr., Ye Hua, Hiep T. Luu, Peter S. Dragovich
Abstract: The invention relates to compounds represented by the formula I and to prodrugs or metabolites thereof, or pharmaceutically acceptable salts or solvates of said compounds, said prodrugs, and said metabolites, wherein Z, Y, R11 and R14, R15, R16, and R17 are as defined herein. The invention also relates to pharmaceutical compositions containing the compounds of formula I and to methods of treating hyperproliferative disorders in a mammal by administering the compounds of formula I.
Type:
Grant
Filed:
June 11, 2003
Date of Patent:
March 22, 2005
Assignee:
Agouron Pharmaceuticals, Inc.
Inventors:
Michael Collins, Stephan Cripps, Judith Deal, Robert Steven Kania, Jihong Lou, Mingying He, Cynthia Louise Palmer, William Henry Romines, III, Ru Zhou
Abstract: The present invention provides compounds of formula (I) wherein X, Y, R1, R2 and R3 are as defined hereinabove. The compounds of the present invention are modulators, especially antagonists, of the activity of chemokine CCR5 receptors. Modulators of the CCR5 receptor may be useful in the treatment of various inflammatory diseases and conditions, and in the treatment of infection by HIV and genetically related retroviruses.
Type:
Grant
Filed:
April 7, 2003
Date of Patent:
February 15, 2005
Assignee:
Agouron Pharmaceuticals, Inc.
Inventors:
Patricia Ann Basford, Peter Thomas Stephenson, Stefan Colin John Taylor, Anthony Wood
Abstract: The present invention relates to novel dihydropyrones with tethered heterocycles having improved pharmacologic properties which potently inhibit the HIV aspartyl protease blocking HIV infectivity. The dihydropyrones are useful in the development of therapies for the treatment of viral infections and diseases, including AIDS. The present invention is also directed to methods of synthesis of the dihydropyrones and intermediates useful in the preparation of the final compounds.
Type:
Grant
Filed:
November 19, 2002
Date of Patent:
February 8, 2005
Assignee:
Agouron Pharmaceuticals, Inc.
Inventors:
Frederick Earl Boyer, Jr., John Michael Domagala, Edmund Lee Ellsworth, Christopher Andrew Gajda, Susan Elizabeth Hagen, Michael James Lovdahl, Elizabeth Ann Lunney, Larry James Markoski, Josyula Venkata Nagendra Vara Prasad, Bradley Dean Tait
Abstract: A 2.4 ? crystal structure of a protein construct containing the catalytic kinase domain of vascular endothelial growth factor receptor 2 (VEGFR2/KDR), a key enzyme in angiogenesis, has been determined in an unliganded, phosphorylated state. This protein construct, contains a modified catalytic linker and has comparable in vitro kinase activity to constructs containing the entire KID. The resulting construct retains comparable in vitro kinase activity to that of the wild-type KID, and more importantly, allows complete crystallization of the protein such that it may be characterized by X-ray crystallography. The present invention further discloses the use of the x-ray crystallographic data for identification and construction of possible therapeutic compounds in the treatment of various disease conditions.
Type:
Grant
Filed:
August 28, 2001
Date of Patent:
February 1, 2005
Assignee:
Agouron Pharmaceuticals, Inc.
Inventors:
Michele A. McTigue, Chris Pinko, Camran V. Parast, Michael R. Gehring, Chen-Chen Kan, Krzysztof Appelt, John A. Wickersham, Richard E. Showalter, Anna M. Tempcyzk-Russell, Barbara Mroczkowski, Jesus E. Villafranca
Abstract: There are disclosed novel neuropeptide Y ligands having the general formula I Wherein the symbols W, A, D, R1, R2, R3, R4 are further defined in the description. Compounds of formula I are agonists and antagonists of neuropeptide Y, and are therefore useful as regulators.
Type:
Grant
Filed:
August 22, 1997
Date of Patent:
February 1, 2005
Assignee:
Agouron Pharmaceuticals, Inc.
Inventors:
Yufeng Hong, Vlad Edward Gregor, Anthony Lai Ling, Eileen Valenzuela Tompkins
Abstract: The invention relates to compounds of the formula 1: wherein: Z is O or S; V is a divalent radical which together with C* and N forms a ring having six ring atoms, where each of said ring atoms other than C* and N independently is unsubstituted or substituted by a suitable substituent, and at least one of said other ring atoms is a heteroatom selected from O, N and S, and the remainder are carbon atoms; and Ar is an aryl or heteroaryl group; and pharmaceutically acceptable prodrugs, salts and solvates thereof. The invention further relates to pharmaceutically acceptable prodrugs, salts and solvates of these compounds. The invention also relates to methods of inhibiting the activity of metalloproteinases by administering a compound of the formula I or a prodrug, salt or solvate thereof. The invention further relates to pharmaceutical compositions comprising an effective amount of these compounds, prodrugs, salts, and solvates.
Type:
Grant
Filed:
November 18, 2002
Date of Patent:
February 1, 2005
Assignee:
Agouron Pharmaceuticals, Inc.
Inventors:
Scott E. Zook, Raymond Dagnino, Jr., Michael E. Deason, Steven L. Bender, Michael J. Melnick
Abstract: The invention relates to processes for the preparation of a key intermediate in the synthesis of a GARFT inhibitor of formula (Ia) containing a 4-methyl-substituted thiophene core: 1
Type:
Application
Filed:
June 16, 2004
Publication date:
December 30, 2004
Applicant:
AGOURON PHARMACEUTICALS, INC.
Inventors:
Wolfgang Reinhard Ludwig Notz, Carlos Alberto Martinez
Abstract: The invention relates to processes for the preparation of a GARFT inhibitor containing a methyl substituted thiophene core having the following structure: 1
Type:
Application
Filed:
June 23, 2004
Publication date:
December 30, 2004
Applicant:
AGOURON PHARMACEUTICALS, INC.
Inventors:
Elena Dovalsantos, Erik Jon Flahive, Brian John Halden, Mark Bryan Mitchell, Wolfgang Reinhard Ludwig Notz, Stacy Ann O'Neill-Slawecki, Qingping Tian
Abstract: The invention relates to compounds represented by the formula I
and to prodrugs thereof, pharmaceutically acceptable salts or solvates of said compounds or said prodrugs, wherein X, R1 and R11 are as defined herein. The invention also relates to pharmaceutical compositions containing the compounds of formula I and to methods of treating hyperproliferative disorders in a mammal by administering the compounds of formula I.
Type:
Grant
Filed:
February 21, 2003
Date of Patent:
December 21, 2004
Assignee:
Agouron Pharmaceuticals, Inc.
Inventors:
William Henry Romines, III, Robert Steven Kania, Jihong Lou, Stephan Cripps, Ru Zhou, Mingying He
Abstract: Pharmaceutically acceptable salts of compounds of the formula below are poly(ADP-ribosyl)transferase (PARP) inhibitors, and are useful as therapeutics in treatment of cancers and the amelioration of the effects of stroke, head trauma, and neurodegenerative disease. As cancer therapeutics, the compounds of the invention may be used, e.g., in combination with cytotoxic agents and/or radiation.
Type:
Application
Filed:
March 29, 2004
Publication date:
December 9, 2004
Applicant:
Agouron Pharmaceuticals, Inc.
Inventors:
Stacie Canan-Koch, Jan-Jon Chu, Jia Liu, Jean Matthews
Abstract: The invention relates to methods of inhibiting SARS-related coronavirus viral replication activity comprising contacting a SARS-related coronavirus protease with a therapeutically effective amount of a rhinovirus protease inhibitor, and compositions comprising the same.
Type:
Application
Filed:
April 27, 2004
Publication date:
November 25, 2004
Applicant:
Agouron Pharmaceuticals, Inc.
Inventors:
Shella Fuhrman, David A. Matthews, Amy Karen Patick, Paul Rejto
Abstract: The invention relates to a method for identifying a therapeutic having analogous activity to a thiazolidinedione by contacting a cell containing a PPAR&ggr; receptor with a candidate therapeutic; and determining the level of a selected gene expression; to indicate that the candidate therapeutic is a therapeutic for treating a disease associated with a PPAR&ggr; receptor. The invention also relates to a composition comprising a plurality of selected genes or gene fragments, or a plurality of proteins or proteins fragments selected from proteins encoded by the selected genes thereof. The invention further relates to a method for determining whether a subject is responsive to treatment with a therapeutic having analogous activity to a thiazolidinedione.
Type:
Application
Filed:
March 3, 2004
Publication date:
November 25, 2004
Applicants:
Agouron Pharmaceuticals, Inc., The Regents of the University of California
Inventors:
Justin Chapman, Michael North, Jerrold Olefsky, Dorothy Worrall
Abstract: The invention relates to methods of inhibiting HCV viral replication activity comprising contacting an HCV polymerase with a therapeutically effective amount of a hydroxamate MMP inhibitor, and compositions comprising the same.
Abstract: The present invention relates to pharmaceutical compositions and to methods for their use in decreasing cytochrome P450 (CYP450) enzyme activity. The present invention also relates to methods of increasing the bioavailability of a compound in a mammal. Additionally, the present invention relates to methods of decreasing the metabolism of certain compounds in a mammal that are metabolized by the cytochrome P450 enzyme. Furthermore, the present invention relates to pharmaceutical compositions comprising at least one compound metabolized by at least one cytochrome P450 enzyme and a cytochrome P450 enzyme-inhibiting amount of a compound of formula (I).
Type:
Application
Filed:
February 17, 2004
Publication date:
November 11, 2004
Applicant:
Agouron Pharmaceuticals, Inc.
Inventors:
Allen J. Borchardt, Peter Scott Dragovich, Javier Gonzalez, Hui Li, Maria Angelica Linton, John Howard Tatlock
Abstract: The invention relates to a reporter-selectable hepatitis C virus (HCV) replicon, and use of the replicon to generate stable, human hepatoma cell lines. The replicon and cell lines are useful in the compound screening process in HCV drug discovery.
Type:
Application
Filed:
April 24, 2003
Publication date:
October 28, 2004
Applicant:
Agouron Pharmaceuticals, Inc.
Inventors:
Rohit Duggal, Amy Karen Patick, Jie Zhang, Weidong Zhao