Abstract: The present invention relates to pyrrole substituted 2-indolinone compounds and their pharmaceutically acceptable salts which modulate the activity of protein kinases and therefore are expected to be useful in the prevention and treatment of protein kinase related cellular disorders such as cancer.
Type:
Grant
Filed:
April 5, 2004
Date of Patent:
May 30, 2006
Assignee:
Sugen, Inc.
Inventors:
Connie Li Sun, Chung Chen Wei, Peng Cho Tang, Marcel Koenig, Yong Zhou, Tomas Vojkovsky, Asaad S. Nematalla
Abstract: The present invention relates to compounds of the Formulae (I) and (II), wherein R1-R10 and G are defined herein, and their pharmaceutically acceptable salts. These compounds modulate the activity of c-Met and are therefore expected to be useful in the prevention and treatment of c-Met related disorders such as cancer.
Type:
Grant
Filed:
June 29, 2004
Date of Patent:
May 2, 2006
Assignee:
Sugen, Inc.
Inventors:
Tomas Vojkovsky, Marcel Koenig, Fang-Jie Zhang, Jingrong Cui
Abstract: The present invention provides 2-thia-1,6,8-triaza-naphthalene-2,2-dioxide inhibitors of cyclin-dependent kinases, uses thereof and pharmaceutical compositions thereof. These compounds are useful for treating cell proliferative disorders, such as cancer, atherosclerosis, and restenosis. These compounds are potent inhibitors of kinases such as cyclin-dependent (cdks) and growth factor-mediated kinases.
Abstract: 3,5 disubstituted indazole compounds that modulate and/or inhibit cell proliferation, such as the activity of protein kinases are described. These compounds and pharmaceutical compositions containing them are capable of mediating CDK dependent diseases to 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 as well as 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:
June 10, 2004
Date of Patent:
March 7, 2006
Assignee:
Agouron Pharmaceuticals, Inc.
Inventors:
Susan Elizabeth Kephart, Indrawan James McAlpine, Siegfried Heinz Reich
Abstract: The present invention is directed to 1-pyrrolidin-1-ylmethyl-3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives that modulate the activity of protein kinases (“PKs”). Pharmaceutical compositions comprising these compounds, methods of treating diseases related to abnormal PK activity utilizing pharmaceutical compositions comprising these compounds and methods of preparing them are also disclosed.
Type:
Grant
Filed:
May 5, 2003
Date of Patent:
March 7, 2006
Assignee:
Pharmacia & Upjohn Company
Inventors:
Malcolm Wilson Moon, Walter Morozowich, Ping Gao
Abstract: Diarylamines, such as 5-amide substituted diarylamines of formula (I) or formula (II) wherein A is hydroxy, C1-6 alkoxy, or NR6OR7; X is OR12, NR13R12, or NR14; inhibitors of MEK and are useful in the treatment of a variety of proliferative disease states, such as conditions related to the hyperactivity of MEK, as well as diseases modulated by the MEK cascade.
Type:
Grant
Filed:
March 12, 2001
Date of Patent:
February 21, 2006
Assignee:
Warner-Lambert Company
Inventors:
Cathlin Biwersi, Haile Tecle, Joseph Scott Warmus
Abstract: This invention provides quinazolines that are useful for treating cell proliferative diseases and disorders, such as cardiovascular diseases, infections, cancers, autoimmune diseases, gout, kidney disease, and neurodegenerative diseases and disorders such as Alzheimer's disease. We have now discovered a group of 2-arylamino-7-(alkyl)oxy-8-alkylquinazolines and 8-alkyl-2-arylamino-quinazoline 2,7-diamines that are potent inhibitors of cyclin-dependent kinases (cdks). The compounds are readily synthesized and can be administered by a variety of routes, including orally, and have sufficient bioavailability. This invention also provides pharmaceutical formulations comprising at least one of the quinazoline compounds together with a pharmaceutically acceptable carrier, diluent, or excipient therefor. The invention further provide useful intermediates generated during the production of the quinazoline compounds.
Type:
Grant
Filed:
November 3, 2000
Date of Patent:
January 3, 2006
Assignee:
Warner-Lambert Company
Inventors:
Mark Robert Barvian, Ellen Myra Dobrusin, James Stanley Kaltenbronn, Peter L. Toogood, Roy Thomas Winters, Inderjit S. Sidhu, Rajeshwar Singh, Yadagiri Bathini, Ronald George Micetich
Abstract: 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:
Grant
Filed:
December 3, 2004
Date of Patent:
December 20, 2005
Assignees:
Agouron Pharmacetucals, Inc., Cancer Research Campaign Technology Limited
Inventors:
Stephen Evan Webber, Stacie S. Canan-Koch, Jayashree Tikhe, Lars Henrik Thoresen
Abstract: Protein kinase, such as CHK-1, inhibiting tricyclic compounds of the following formula (wherein R2, R3 and R4 are as defined in the specification) pharmaceutical compositions containing effective amounts of said compounds or their salts are useful as a single agent or in combination with an anti-neoplastic agent or therapeutic radiation having an anti-neoplastic effect for treating diseases or conditions such as cancers.
Type:
Grant
Filed:
January 9, 2004
Date of Patent:
November 22, 2005
Assignee:
Agouron Pharmaceuticals Inc.
Inventors:
Suzanne Benedict, Michael Bennett, Sacha Ninkovic, Min Teng, Yuanjin Rui, Fen Wang, Yong Wang, Jinjiang Zhu
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: Non-peptide GnRH agents that inhibit the effect of gonadotropin-releasing hormone are described. Such agents are useful for treating mammalian reproductive disorders and steroid hormone-dependent tumors as well as for regulating fertility, where suppression of gonadotropin release is indicated.
Type:
Grant
Filed:
February 11, 2003
Date of Patent:
December 21, 2004
Assignee:
Pfizer, Inc.
Inventors:
Lance C. Christie, Mark B. Anderson, Jun Feng, Yufeng Hong, Ved P. Pathak, Ranjan J. Rajapakse, Eileen V. Tompkins, Haresh Vazir, Haitao Li
Abstract: The present invention provides a compound of formula as described herein, which are useful as antiviral agents, in particular, as agents against viruses of the herpes family.
Type:
Grant
Filed:
August 27, 2003
Date of Patent:
December 14, 2004
Assignee:
Pharmacia & Upjohn
Inventors:
Mark E. Schnute, Fred L. Ciske, Michael J. Genin, Joseph Walter Strohbach, Suvit Thaisrivongs
Abstract: The present invention provides a compound of formula I
These compounds are useful as antiviral agents, in particular, as agents against viruses of the herpes family.
Abstract: The present invention provides a compound of the formula and pharmaceutically acceptable salts having useful antiviral activity against viruses of the herpes family.
Wherein:
X=O, (CH2)m, S, SO, SO2, NH, NR8;
Y=O, (CH2)m, S, SO, SO2, NH, NR8 or a chemical bond;
Z=NH, O, NR8, S, SO, SO2;
The remaining substituents are described in the specification.
Type:
Grant
Filed:
July 5, 2002
Date of Patent:
October 5, 2004
Assignee:
Warner Lambert Company
Inventors:
Richard John Booth, Vara Prasad Venkata Nagendra Josyula, Annette Lynn Meyer, Bruce Allan Steinbaugh
Abstract: A 2.4 Å 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 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:
September 21, 2004
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: The invention provides compounds of formula I,
R1—OP(O)(OH)2 I
wherein R1 represents the non-hydroxy portion of a triazole antifungal compound of the type comprising a tertiary hydroxy group; or a pharmaceutically acceptable salt thereof.
The compounds of the invention are useful in the treatment of fungal infections, and have good aqueous solubility.
Type:
Grant
Filed:
January 9, 2003
Date of Patent:
September 14, 2004
Assignee:
Pfizer, Inc.
Inventors:
Stuart Green, Peter T. Stephenson, Charles W. Murtiashaw
Abstract: A cell-based assay system in which the detection of the reporter gene activity, or secreted alkaline phosphatase (SEAP), is dependent upon the protease activity of the Hepatitis C virus NS3 gene product. This system can be used to assess the activity of candidate protease inhibitors in a mammalian cell-based assay system. The assay system is simpler than previously described assays due to the use of SEAP which allows the reporter gene activity to be quantified by measuring the amount of secreted gene product in the cell media by monitoring the conversion of luminescent or calorimetric alkaline phosphatase substrate.
Type:
Grant
Filed:
July 10, 2002
Date of Patent:
September 14, 2004
Assignee:
Agouron Pharmaceuticals, Inc.
Inventors:
Karen Elizabeth Potts, Roberta Lynn Jackson, Amy Karen Patick
Abstract: A 2.4 Å 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 x-ray crystallographic data for identification and construction of possible therapeutic compounds in the treatment of various disease conditions.
Type:
Grant
Filed:
February 18, 2000
Date of Patent:
August 31, 2004
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: Efficient synthetic routes for the preparation of rhinovirus protease inhibitors of formula I, as well as key intermediates useful in those synthetic routes. These compounds of formula I, as well as pharmaceutical compositions that contain these compounds, are suitable for treating patients or hosts infected with one or more picornaviruses.
Type:
Grant
Filed:
October 30, 2001
Date of Patent:
August 10, 2004
Assignee:
Agouron Pharmaceuticals, Inc.
Inventors:
Qingping Tian, Naresh K. Nayyar, Srinivasan Babu, Junhua Tao, Terence Jarold Moran, Raymond Dagnino, Jr., Lennert J. Mitchell, Jr., Travis Paul Remarchuk, Michael Joseph Melnick, Steven Lee Bender