Plural Ring Nitrogens In The Bicyclo Ring System Patents (Class 514/234.5)
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Publication number: 20120129853Abstract: This invention pertains to methods of treating systemic lupus erythematosus, lupus nephritis or Sjogren's Syndrome with compounds that selectively inhibit the activity of Bcl-2 anti-apoptotic proteins. Specifically, the current invention is directed to treatment with compounds that selectively inhibit the activity of Bcl-2 proteins, with a lesser affinity for inhibiting the activity of other BCL-2 family proteins, including Bcl-xL.Type: ApplicationFiled: November 22, 2011Publication date: May 24, 2012Applicant: Abbott LaboratoriesInventors: Steven Elmore, Andrew Souers, Li Chun Wang, Tariq Ghayur, Stuart J. Perper
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Publication number: 20120129845Abstract: This application discloses 5-phenyl-1H-pyridin-2-one and 6-phenyl-2H-pyridazin-3-one derivatives according to generic Formulae I-IV: wherein, variables R, X, Y1, Y2, Y2?, Y3, Y4, n and m are defined as described herein, which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are further useful to treat inflammatory and auto immune diseases associated with aberrant B-cell proliferation such as rheumatoid arthritis. Also disclosed are compositions comprising compounds of Formulae I-IV and at least one carrier, diluent or excipient.Type: ApplicationFiled: January 26, 2012Publication date: May 24, 2012Inventors: Nolan James Dewdney, Rama K. Kondru, Bradley E. Loe, Yan Lou, Joel McIntosh, Timothy D. Owens, Michael Soth
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Publication number: 20120129855Abstract: A compound of the formula (I): wherein: A and B together represent an optionally substituted, fused aromatic ring; X and Y are selected from CH and CH, CF and CH, CH and CF and N and CH respectively; RC is selected from H, C1-4 alkyl; and R1 is selected from C1-7 alkyl, C3-20 heterocyclyl and C5-20 aryl, which groups are optionally substituted; or RC and R1 together with the carbon and oxygen atoms to which they are attached form a spiro-C5-7 oxygen-containing heterocyclic group, which is optionally substituted or fused to a C5-7 aromatic ring.Type: ApplicationFiled: January 30, 2012Publication date: May 24, 2012Inventors: Keith Allan Menear, Muhammad Hashim Javaid, Sylvie Gomez, Marc Geoffrey Hummersone, Carlos Fernandez Lence, Niall Morrison Barr Martin, David Alan Rudge, Craig Anthony Roberts, Kevin Blades
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Publication number: 20120122817Abstract: Compounds of formula (IA) and their pharmaceutically acceptable salts are described. Processes for their preparation, pharmaceutical compositions containing them, their use as medicaments and their use in the treatment of bacterial infections are also described.Type: ApplicationFiled: May 28, 2010Publication date: May 17, 2012Applicant: ASTRAZENECA ABInventors: Neil Bifulco, Allison Laura Choy, Olga Quiroga, Brian Alan Sherer
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Publication number: 20120122863Abstract: Disclosed are small molecule inhibitors which are useful in treating various diseases and conditions involving Chymase.Type: ApplicationFiled: August 12, 2008Publication date: May 17, 2012Applicant: BOEHRINGER INGELHEIM INTERNATIONAL GMBHInventors: Xin Guo, Ho Yin Lo, Chuk Chui Man, Hidenori Takahashi
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Publication number: 20120122860Abstract: Solid forms of phenyl sulfonamide compounds of formula (I) active on protein kinases, including Raf protein kinases, are described, as well as methods of using such solid forms to treat diseases and conditions associated with activity of protein kinases, e.g. Raf protein kinases, including pain, polycystic kidney disease, melanoma and colorectal cancer.Type: ApplicationFiled: May 4, 2010Publication date: May 17, 2012Inventors: Gary Conard Visor, Prabha N. Ibrahim, Wayne Spevak, Hanna Cho, Songyuan Shi, Guoxian Wu
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Publication number: 20120122864Abstract: Provided herein are compounds, pharmaceutical compositions and combination therapies for inhibition of hepatitis C.Type: ApplicationFiled: December 2, 2009Publication date: May 17, 2012Applicant: PRESIDIO PHARMACEUTICALS, INC.Inventors: Min Zhong, Leping Li
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Publication number: 20120122847Abstract: The present invention relates to chemical compounds having a general formula I wherein A1-8, D?, L1, L2, R1, R6-8 and n are defined herein, and synthetic intermediates, which are capable of modulating various protein kinase receptor enzymes and, thereby, influencing various disease states and conditions related to the activities of such kinases. For example, the compounds are capable of modulating Aurora kinase thereby influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of Aurora kinase.Type: ApplicationFiled: June 9, 2011Publication date: May 17, 2012Applicant: Amgen Inc.Inventors: Victor Cee, Holly Deak, Bingfan Du, Stephanie Geuns-Meyer, Zihao Hua, Matthew Martin, Issac Marx, Hanh Nho Nguyen, Philip Olivieri, Kathleen Panter, Karina Romero, Laurie Schenkel, Ryan White
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Publication number: 20120122838Abstract: Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.Type: ApplicationFiled: November 10, 2011Publication date: May 17, 2012Inventors: Pingda Ren, Yi Liu, Liansheng Li, Katrina Chan, Troy Edward Wilson, Alfredo C. Castro, Catherine A. Evans, Daniel A. Snyder
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Patent number: 8178532Abstract: The present invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. More specifically, the invention provides quinazolines and quinolines which inhibit, regulate, and/or modulate kinase receptor, particularly c-Met, KDF, c-Kit, flt-3 and flt-4, signal transduction pathways related to the changes in cellular activities as mentioned above, compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions. The present invention also provides methods for making compounds as mentioned above, and compositions which contain these compounds.Type: GrantFiled: May 24, 2007Date of Patent: May 15, 2012Assignee: Exelixis, Inc.Inventors: Lynne Canne Bannen, Diva Sze-Ming Chan, Timothy Patrick Forsyth, Richard George Khoury, James William Leahy, Morrisson B. Mac, Larry W. Mann, John M. Nuss, Jason Jevious Parks, Yong Wang, Wie Xu
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Patent number: 8178694Abstract: Heterocyclylaminoalkyl Substituted Benzimidazoles Inhibitors of RSV replication of formula (I): The salts and stereochemically isomeric forms thereof, wherein Q is hydrogen, C1-6alkyl optionally substituted with a heterocycle or Q is C1-6alkyl substituted with both —OR4 and a heterocycle; wherein said heterocycle is oxazolidine, thiazolidine, 1-oxo-thiazolidine, 1,1-dioxothiazolidine, morpholinyl, thiomorpholinyl, 1-oxo-thiomorpholinyl, 1,1-dioxothiomorpholinyl, hexahydrooxazepine, hexahydrothiazepine, 1-oxo-hexahydrothiazepine, 1,1-dioxo-hexahydrothiazepine, pyrrolidine, piperidine, homopiperidine, piperazine; which heterocyle may be substituted with 1-2 substituents; each Alk is C1-6alkanediyl; R1 is Ar or optionally substituted piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, furanyl, tetrahydrofuranyl, thienyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl, isothiazolyl, pyrazolyl, isoxazo lyl, oxadiazolyl, quinolinyl, quinoxalinyl, benzofuranyl, benzothienType: GrantFiled: June 20, 2006Date of Patent: May 15, 2012Assignee: Tibotec Pharmaceuticals Ltd.Inventors: Jean-François Bonfanti, Philippe Muller, Jérôme Michel Claude Fortin, Frédéric Marc Maurice Doublet
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Publication number: 20120115861Abstract: Compounds of the formula (I), in which R1, R2, R3, R4, R7 and Y have the meanings indicated in Claim 1, are inhibitors of PDK1 and cell proliferation/cell vitality and can be employed for the treatment of tumours and for the treatment of inflammatory diseases.Type: ApplicationFiled: June 17, 2010Publication date: May 10, 2012Applicant: MERCK PATENT GESELLSCHAFT MIT BESCHRANKTER HAFTUNGInventors: Michel Calderini, Margarita Wucherer-Plietker, Ulrich Graedler, Christina Esdar
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Publication number: 20120114643Abstract: Disclosed are compounds of Formula (I): and salts thereof. Also, disclosed are methods of using the compounds in the treatment of proliferative diseases, such as cancer, and to pharmaceutical compositions comprising at least one compound of Formula (I) or a pharmaceutically acceptable salt.Type: ApplicationFiled: January 12, 2012Publication date: May 10, 2012Inventors: Robert M. Borzilleri, Zhen-Wei Cai
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Publication number: 20120115856Abstract: A compound depicted by the formula below, or a pharmaceutically acceptable salt or solvate thereof. wherein, R1 represents (1) a C3-6 alkyl group, (2) a C1-6 alkyl group substituted with one or more substituent group(s) selected from those consisting a halogen atom, etc., (3) a C3-10 non-aromatic cyclic hydrocarbon group or a 5- to 6-membered non-aromatic heterocyclic group which respectively is optionally substituted with one or more substituent group(s) selected from those consisting an oxo group, etc., (4) an aromatic cyclic hydrocarbon group substituted with one or more substituent selected from the group consisting halogen atom and C1-4 alkoxy group; X represents NH, O, or S; Y represents CH or N; Z represents N or a C—R2; R2 represents (1) hydrogen atom, (2) a C1-6 alkyl group, a C2-6 alkenyl group or a C2-6 alkynyl group that respectively is optionally substituted with one or more substituent group(s) selected from among those consisting (a) a halogen atom, etc.Type: ApplicationFiled: May 28, 2010Publication date: May 10, 2012Inventors: Junichi Ishikawa, Koichi Saito, Norihisa Ohe, Kentaro Kobayashi
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Patent number: 8173635Abstract: The present invention relates to compounds useful as inhibitors of protein kinase. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders. The invention also provides processes for preparing compounds of the inventions.Type: GrantFiled: October 31, 2008Date of Patent: May 8, 2012Assignee: Vertex Pharmaceuticals IncorporatedInventors: Juan-Miguel Jimenez, Michael Mortimore, Andrew Miller, Philip Collier, Stephen Young, Guy Brenchley, Chris Davis, Heather Twin, Chau Mak, Dean Boyall, Shazia Keily, Luca Settimo
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Publication number: 20120107312Abstract: Disclosed are pharmaceutical compositions for the treatment of diseases which involve cell proliferation. Also disclosed are methods for the treatment of said diseases, comprising co-administration of a compound 1 of Formula (I) wherein the groups L, R1, R2, R3, R4 and R5 have the meanings given herein and of an effective amount of an active compound 2 and/or co-treatment with radiation therapy, in a ratio which provides an additive and synergistic effect, and to the combined use of a compound 1 of Formula (I) and of an effective amount of an active compound 2 and/or radiotherapy for the manufacture of corresponding pharmaceutical combination preparations.Type: ApplicationFiled: January 3, 2012Publication date: May 3, 2012Applicant: BOEHRINGER INGELHEIM INTERNATIONAL GMBHInventors: Gerd MUNZERT, Martin STEEGMAIER, Anke BAUM
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Publication number: 20120108534Abstract: The invention relates to new dihydrothienopyrimidine of formula 1, as well as pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof, wherein X is SO or SO2, but preferably SO, and wherein R1, R2 and R3 have the meanings given in the description, and which are suitable for the treatment of respiratory or gastrointestinal complaints or diseases, inflammatory diseases of the joints, skin or eyes, diseases of the peripheral or central nervous system or cancers, as well as pharmaceutical compositions which contain these compounds.Type: ApplicationFiled: January 4, 2012Publication date: May 3, 2012Inventors: Pascale POUZET, Christoph HOENKE, Rolf GOEGGEL, Birgit JUNG, Peter NICKOLAUS, Dennis FIEGEN, Thomas FOX
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Publication number: 20120108590Abstract: A pro-apoptotic solid dispersion comprises, in essentially non-crystalline form, a Bcl-2 family protein inhibitory compound of Formula I as defined herein, dispersed in a solid matrix that comprises (a) a pharmaceutically acceptable water-soluble polymeric carrier and (b) a pharmaceutically acceptable surfactant. A process for preparing such a solid dispersion comprises subjecting to elevated temperature the compound of Formula I, the water-soluble polymeric carrier and the surfactant, to provide an extrudable semi-solid mixture; extruding the semi-solid mixture; and cooling the resulting extrudate to to provide a solid matrix comprising the polymeric carrier and the surfactant and having the compound dispersed in essentially non-crystalline form therein. The solid dispersion is suitable for oral administration to a subject in need thereof for treatment of a disease characterized by overexpression of one or more anti-apoptotic Bcl-2 family proteins, for example cancer or an immune or autoimmune disease.Type: ApplicationFiled: October 5, 2011Publication date: May 3, 2012Applicant: ABBOTT LABORATORIESInventors: Esther Birtalan, Peter Hoelig, David J. Lindley, Yeshwant D. Sanzgiri, Ping Tong
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Publication number: 20120101096Abstract: Described herein are compounds, and pharmaceutically acceptable salts and prodrugs thereof, which are useful as inhibitors of IMPDH. In certain embodiments, a compound of the invention selectively inhibits a parasitic IMPDH versus a host IMPDH. Further, the invention provides pharmaceutical compositions comprising one or more compounds of the invention. The invention also relates to methods of treating various parasitic and bacterial infections in mammals. Moreover, the compounds may be used alone or in combination with other therapeutic or prophylactic agents, such as anti-virals, anti-inflammatory agents, antimicrobials and immunosuppressants.Type: ApplicationFiled: March 22, 2010Publication date: April 26, 2012Applicants: University of Georgia Foundation, Inc., Brandeis UniversityInventors: Lizbeth K. Hedstrom, Gregory D. Cuny, Deviprasad R. Gollapalli, Sivapriya Kirubakaran, Sushil Kumar Maurya, Boris Striepen, Suresh Kumar Gorla, Corey Robert Johnson, Mandapati Kavitha, Jihan Khan
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Publication number: 20120101064Abstract: The invention provides compounds of the formula (I): and salts, tautomers, solvates and N-oxides thereof; wherein Q is CH or N; X is N, N+—O? or CR3; Y is N, N+—O? or CR3a; R1 and R2 are independently selected from hydrogen and various substituents as defined in the claims; or R1 and R2 together with the atoms to which they are attached, link to form an optionally substituted carbocyclic or heterocyclic aromatic or non-aromatic ring of 4 to 7 members; R3 is selected from hydrogen and various substituents; and R3a is selected from hydrogen and various substituents as defined in the claims. Also provided are pharmaceutical compositions containing the compounds of formula (I), processes for making the compounds and the medical uses of the compounds. The compounds of formula (I) have activity as inhibitors of CDK kinases and are useful in the treatment of inter alia proliferative diseases such as cancers.Type: ApplicationFiled: April 30, 2010Publication date: April 26, 2012Applicants: Astex Therapeutics Limited, Novartis AGInventors: Steven Howard, Paul Neil Mortenson, Steven Douglas Hiscock, Alison Jo-Anne Woolford, Andrew James Woodhead, Gianni Chessari, Marc O'reilly, Miles Stuart Congreve, Claudio Dagostin, Young Shin Cho, Fan Yang, Christine Hiu-Tung Chen, Christopher Thomas Brain, Bharat Lagu, Yaping Wang, Sunkyu Kim, John Grialdes, Michael Joseph Luzzio, Lawrence Blas Perez
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Patent number: 8163743Abstract: The invention is directed to certain novel compounds. Specifically, the invention is directed to compounds of formula (I) and salts thereof. The compounds of the invention are inhibitors of P13-kinase activity.Type: GrantFiled: June 3, 2009Date of Patent: April 24, 2012Assignee: GlaxoGroupLimitedInventors: Ian Robert Baldwin, Kenneth David Down, Paul Faulder, Simon Gaines, Julie Nicole Hamblin, Katherine Louise Jones, Joelle Le, Christopher James Lunniss, Nigel James Parr, Timothy John Ritchie, Christian Alan Paul Smethurst, Yoshiaki Washio
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Publication number: 20120094972Abstract: Substituted bicyclic heteroaryls and compositions containing them, for the treatment of general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, including but not restricted to autoimmune diseases such as systemic lupus erythematosis (SLE), myestenia gravis, rheumatoid arthritis, acute disseminated encephalomyelitis, idiopathic thrombocytopenic purpura, multiples sclerosis, Sjoegren's syndrome and autoimmune hemolytic anemia, allergic conditions including all forms of hypersensitivity, The present invention also enables methods for treating cancers that are mediated, dependent on or associated with p110 activity, including but not restricted to leukemias, such as Acute Myeloid leukaemia (AML) Myelo-dysplastic syndrome (MDS) myelo-proliferative diseases (MPD) Chronic Myeloid Leukemia (CML) T-cell Acute LymphobType: ApplicationFiled: June 25, 2010Publication date: April 19, 2012Applicant: AMGEN INC.Inventors: Matthew Brown, Yi Chen, Timothy David Cushing, Felix Gonzalez Lopez De Turiso, Xiao He, Todd J. Kohn, Julia Winslow Lohman, Vatee Pattaropong, Jennifer Seganish, Youngsook Shin, Jillian L. Simard
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Publication number: 20120094997Abstract: This invention provides compounds of formula (I): wherein R1a, R1b, Ra, R2a, R2b, R1, and X have values as described in the specification, useful as inhibitors of HDAC6. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of proliferative, inflammatory, infectious, neurological or cardiovascular diseases or disorders.Type: ApplicationFiled: October 14, 2011Publication date: April 19, 2012Applicant: Millennium Pharmaceuticals, Inc.Inventors: Dylan B. England, Kenneth M. Gigstad, Alexandra E. Gould, Liting Ma, He Xu
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Patent number: 8158647Abstract: Provided herein are substituted pyrrolopyridine heterocycles and substituted pyrazolopyridine heterocycles, pharmaceutical compositions comprising said heterocycles and methods of using said heterocycles in the treatment of disease. The heterocycles disclosed herein function as kinase modulators and have utility in the treatment of diseases such as cancer, allergy, asthma, inflammation, obstructive airway disease, autoimmune diseases, metabolic disease, infection, CNS disease, brain tumor, obesity, asthma, hematological disorder, degenerative neural disease, cardiovascular disease, or disease associated with angiogenesis, neovascularization, or vasculogenesis.Type: GrantFiled: May 29, 2008Date of Patent: April 17, 2012Assignee: SGX Pharmaceuticals, Inc.Inventors: Jeffrey M. Blaney, Andreas Gosberg, Stefan N. Gradl, Gavin Hirst, Stephanie A. Hopkins, Paul A. Sprengeler, Ruo W. Steensma, Johnny Uy
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Patent number: 8158624Abstract: Purine compounds of Formula I, and including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting lipid kinases including p110 alpha and other isoforms of PI3K, and for treating disorders such as cancer mediated by lipid kinases. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.Type: GrantFiled: May 29, 2009Date of Patent: April 17, 2012Assignee: Genetech, Inc.Inventors: Georgette Castanedo, Irina Chuckowree, Adrian Folkes, Daniel P. Sutherlin, Nan Chi Wan
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Publication number: 20120087914Abstract: The present invention provides methods to treat cancers using inhibitors of the TRIM62 protein and methods to identify inhibitors and other modulators of the TRIM62 protein. Pharmaceutical compositions that contain an inhibitor of a TRIM62 protein are also provided.Type: ApplicationFiled: March 25, 2009Publication date: April 12, 2012Inventors: James M. Roberts, Erik Eide, Claire Faltermeier
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Publication number: 20120088767Abstract: This invention relates to the use of benzimidazole derivatives for the modulation, notably the inhibition of the activity or function of the phosphoinositide 3? OH kinase family (hereinafter PI3 kinases), suitably, PI3K?, PI3K?, PI3K?, and/or PI3K?. Suitably, the present invention relates to the use of benzimidazoles in the treatment of one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries. More suitably, the present invention relates to PI3K? selective benzimidazoles compounds for treating cancer.Type: ApplicationFiled: October 3, 2011Publication date: April 12, 2012Inventors: Junya Qu, Ralph Rivero, Robert Sanchez, Rosanna Tedesco
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Publication number: 20120088752Abstract: Heterocyclic compounds that modulate the hedgehog signaling pathway, pharmaceutical composition thereof and their therapeutic applications.Type: ApplicationFiled: June 9, 2010Publication date: April 12, 2012Applicant: SIENA BIOTECH S.p.A.Inventors: J. Russell Thomas, Gal.la Pericot Mohr, Chiara Caramelli, Giacomo Minetto, Marta Bellini
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Patent number: 8153629Abstract: Fused pyrimidines of formula (I): wherein R1-R3, A and n have any of the values described in the specification; and pharmaceutically acceptable salts thereof; have activity as inhibitors of PI3K and may thus be used to treat diseases and disorders arising from abnormal cell growth, function or behavior associated with PI3 kinase such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine disorders and neurological disorders. Processes for synthesizing the compounds are also described.Type: GrantFiled: May 28, 2010Date of Patent: April 10, 2012Assignee: F. Hoffmann-La Roche AGInventors: Stephen J. Shuttleworth, Adrian J. Folkes, Irina S. Chuckowree, Nan Chi Wan, Timothy C. Hancox, Stewart J. Baker, Sukhjit Sohal, Mohammed A. Latif
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Publication number: 20120083493Abstract: Provided are small-molecule Trp-p8 modulators, including Trp-p8 agonists and Trp-p8 antagonists, and compositions comprising small-molecule Trp-p8 agonists as well as methods for identifying and characterizing novel small-molecule Trp-p8 modulators and methods for decreasing viability and/or inhibiting growth of Trp-p8 expressing cells, methods for activating Trp-p8-mediated cation influx, methods for stimulating apoptosis and/or necrosis, and related methods for the treatment of diseases, including cancers such as lung, breast, colon, and/or prostate cancers as well as other diseases, such as benign prostatic hyperplasia, that are associated with Trp-p8 expression.Type: ApplicationFiled: August 9, 2010Publication date: April 5, 2012Applicant: Dendreon CorporationInventors: Ofir Moreno, Sateesh Natarajan, David F. Duncan
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Publication number: 20120077811Abstract: The invention provides novel prodrug compounds comprising a kinase inhibitor and a reductively-activated fragmenting aromatic nitroheterocycle or aromatic nitrocarbocycle trigger, where the compound carries a positive charge. In preferred embodiments, the compounds are of Formula I: where: X is any negatively charged counterion; R1 is a group of the formula —(CH2)nTr, where Tr is an aromatic nitroheterocycle or aromatic nitrocarbocycle and —(CH2)nTr acts as a reductively-activated fragmenting trigger; and n is an integer from 0 to 6; R2, R3 and R4 may each independently be selected from aliphatic or aromatic groups of a tertiary amine kinase inhibitor (R2)(R3)(R4)N, or two of R2, R3, and R4 may form an aliphatic or aromatic heterocyclic amine ring of a kinase inhibitor, or one of R2, R3 and R4 may be absent and two of R2, R3 and R4 form an aromatic heterocyclic amine ring of a kinase inhibitor. The compounds of the invention are useful in treating proliferative diseases such as cancer.Type: ApplicationFiled: March 11, 2010Publication date: March 29, 2012Inventors: Jeffrey Bruce Smaill, Adam Vorn Patterson, Michael Patrick Hay, William Alexander Denny, William Robert Wilson, Guo-Liang Lu, Robert Forbes Anderson, Ho Huat Lee, Amir Ashoorzadeh
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Publication number: 20120076775Abstract: The present invention is directed toward a method of treating cancer by administering to a patient an inhibitor of Hepatocyte Growth Factor and an inhibitor of, e.g., Epidermal Growth Factor.Type: ApplicationFiled: December 8, 2010Publication date: March 29, 2012Inventors: John Laterra, Bachchu Lal, Kyung Jin Kim
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Patent number: 8143250Abstract: In view of the great potential the quinazoline class of compounds offer, we started the synthesis and screening of a large number of new chemical entities with novel structural features. It has been surprisingly and unexpectedly found that quinazolines having 3-Ethynyl anilino group at the 4th position and specifically substituted alkoxy groups in the 6 and 7 positions, impart much enhanced and special anti-proliferative properties when compared to other prominent members of the quinazoline class of drugs. Also, surprisingly the compounds of this invention are much less toxic and the safety profile is exceedingly beneficial for therapeutic applications. The novel chemical entities described in this invention are designated by the general structure (I) and have not been synthesized earlier nor investigated for their therapeutic benefits and safety profile. Compound (I) is NRC-2694, when structure (A).Type: GrantFiled: January 18, 2008Date of Patent: March 27, 2012Assignee: Natco Pharma LimitedInventors: Ramanadham Jyothi Prasad, Bhujanga Rao Adibhatla Kali Satya, Bollepalli Nageshwara Rao, Nannapaneni Venkaiah Chowdary
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Patent number: 8142782Abstract: Compositions and methods for promoting neural regeneration in a patient determined to have a lesion in a mature CNS neuron are disclosed. The method comprises the step of contacting the neuron with an EGFR inhibitor sufficient to promote regeneration of the neuron.Type: GrantFiled: February 18, 2009Date of Patent: March 27, 2012Assignee: Children's Medical Center CorporationInventors: Zhigang He, Vuk Koprivica
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Publication number: 20120071435Abstract: The present invention relates to the field of oncology and provides compositions and methods for treating specific cancers, including non small cell lung cancer, breast cancer, thyroid cancer, pancreatic cancer, colon cancer, melanoma, hepatoma and adenocarcinoma. Particularly, compositions and methods involving administration, either simultaneously or sequentially, of pharmaceutical combinations comprising (S)—N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide with other compounds, to patients suffering from cancer are described.Type: ApplicationFiled: March 11, 2010Publication date: March 22, 2012Applicant: Ardea Biosciences, Inc.Inventor: Mark Chapman
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Publication number: 20120070442Abstract: Provided herein are methods for identifying a cancer patient responsive to treatment with an EGFR tyrosine kinase inhibitor. One method comprises obtaining a biopsy from the patient and measuring the number of copies of miR-128b in DNA extracted from the biopsy. A patient responsive to EGFR tyrosine kinase inhibitor treatment has a cancer with less than two copies of miR-128b DNA. Another method comprises measuring miR-128b or miR-128a level in a biopsy obtained from the patient and comparing that level to miR-128b or miR-128a level in a normal tissue sample. A patient responsive to treatment with an EGFR tyrosine kinase inhibitor has a cancer expressing a lower level of miR-128b or miR-128a relative to normal tissue. Further provided herein are methods for treating cancer in a patient in need thereof. One method comprises measuring the level of miR-128b or miR-128a in a biopsy obtained from the patient and administering to the patient an EGFR tyrosine kinase inhibitor.Type: ApplicationFiled: August 11, 2008Publication date: March 22, 2012Applicant: The Regents of the University of Colorado, a body corporateInventors: Glen Joel Weiss, Lynne Bemis, Paul A. Bunn, JR., Wilber A/ Franklin
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Publication number: 20120071477Abstract: The invention relates to the compounds and methods for inhibiting the Cyclin-Dependent Kinase Inhibitor (CDKI) pathway. More particularly, the invention relates to compounds and methods for inhibiting the CDKI pathway for studies of and intervention in senescence-related and other CDKI-related diseases.Type: ApplicationFiled: November 30, 2010Publication date: March 22, 2012Applicant: Senex Biotechnology, Inc.Inventors: Donald C. Porter, Igor B. Roninson, Mark P. Wentland
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Patent number: 8138177Abstract: This invention relates to compounds of the formula (I): or pharmaceutically acceptable salts thereof, wherein: A, B, R1, R2 and R3 are each as described herein, and compositions containing such compounds and the use of such compounds in the treatment of a condition mediated by CB2 receptor binding activity such as, but not limited to, inflammatory pain, nociceptive pain, neuropathic pain, fibromyalgia, chronic low back pain, visceral pain, acute cerebral ischemia, pain, chronic pain, acute pain, post herpetic neuralgia, neuropathies, neuralgia, diabetic neuropathy, HIV-related neuropathy, nerve injury, rheumatoid arthritic pain, osteoarthritic pain, back pain, cancer pain, dental pain, fibromyalgia, neuritis, sciatica, inflammation, neurodegenerative disease, cough, broncho constriction, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), colitis, cerebrovascular ischemia, emesis such as cancer chemotherapy-induced emesis, rheumatoid arthritis, asthma, Crohn's disease, ulcerative colitis, asthmaType: GrantFiled: March 2, 2006Date of Patent: March 20, 2012Assignee: Pfizer Inc.Inventors: Kazuo Ando, Makoto Kawai, Tsutomu Masuda, Hirofumi Omura
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Publication number: 20120064072Abstract: A method of treating cancer comprising: (a) identifying a patient having cancer that initially responded to IRS1 agent therapy and that has resumed progression; (b) administering an effective regimen comprising the same or a different IRS1 agent and an IGF-1 R inhibitor administered together or sequentially.Type: ApplicationFiled: March 18, 2010Publication date: March 15, 2012Inventors: Maryland Franklin, Robert Wild
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Publication number: 20120065191Abstract: The invention relates to compounds and compositions for inhibiting the enzyme fatty acid amide hydrolase (FAAH), the use of the compounds in therapy and, in particular, for treating or preventing conditions whose development or symptoms are linked to substrates of the FAAH enzyme, and methods of treatment or prevention using the compounds and compositions.Type: ApplicationFiled: December 23, 2009Publication date: March 15, 2012Applicant: BIAL - PORTELA & Cª, S.A.Inventors: Laszlo Erno Kiss, David Alexander Learmonth, Carla Patrícia da Costa Pereira Rosa, Rita Gusmão de Noronha, Pedro Nuno Leal Palma, Patrício Manuel Vieira Araújo Soares da Silva, Alexander Beliaev
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Publication number: 20120064025Abstract: Compounds, pharmaceutical compositions and methods for modulating the activity of nuclear receptors are provided. In particular, quinazolinones are provided for modulating the activity of farnesoid X receptor (FXR) and/or orphan nuclear receptors.Type: ApplicationFiled: September 28, 2011Publication date: March 15, 2012Applicant: EXELIXIS, INC.Inventors: Richard Martin, Jeffrey D. Kahl, Brenton T. Flatt, Ronald Griffith
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Publication number: 20120059003Abstract: This invention describes the development of targeted small molecule inhibitors of the inv(16) fusion, the causative agent in ˜12% of acute myeloid leukemia (AML). The inv(16) fusion results in expression of the CBF?-SMMHC fusion protein in the blood cells of afflicted patients. The present invention provides compounds which inhibit the function of both CBF? and the CBF?-SMMHC fusion. These compounds block the growth of an inv(16) leukemia cell line as well as increase its apoptosis, while showing minimal effects against non inv(16) cell lines. As a mechanism to develop inhibitors with selectivity for the CBF?-SMMHC fusion protein, the present invention further provides dimeric derivatives of these compounds which show both increased potency as well selectivity for CBF?-SMMHC. These compounds show potent inhibition of an inv(16) leukemia cell line with minimal effects on non inv(16) cell lines.Type: ApplicationFiled: May 13, 2010Publication date: March 8, 2012Applicant: UNIVERSITY OF VIRGINIA PATENT FOUNDATIONInventors: John H. Bushweller, Jolanta Grembecka, Anuradha Illendula, Lauren Dixon
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Publication number: 20120059002Abstract: Disclosed are methods of regulating interleukin-6 (IL-6) and/or vascular cell adhesion molecule-1 (VCAM-1) and methods of treating and/or preventing cardiovascular and inflammatory diseases and related disease states, such as, for example, atherosclerosis, asthma, arthritis, cancer, multiple sclerosis, psoriasis, and inflammatory bowel diseases, and autoimmune disease(s) by administering a naturally occurring or synthetic quinazolone derivative. The invention provides novel synthetic quinazolone compounds, as well as pharmaceutical compositions comprising those compounds.Type: ApplicationFiled: April 21, 2010Publication date: March 8, 2012Inventors: Henrik C. Hansen, Gregory S. Wagner, Sarah C. Attwell, Kevin G. McLure, Ewelina B. Kulikowski
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Publication number: 20120058107Abstract: The present invention relates to pyrrolo[3,2-c]pyridine-4-one 2-indolinone compounds of Formula (I) and their pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8 X, Y and have the meaning cited in the specification. Also disclosed are the pharmaceutical compositions containing the foregoing compounds, methods for the preparation and pharmaceutical use thereof, particularly as protein kinase inhibitors. Formula (I).Type: ApplicationFiled: August 2, 2011Publication date: March 8, 2012Applicant: Shanghai Hengrui Pharmaceutical Co., Ltd.Inventors: Peng Cho TANG, Yidong Su, Lei Zhang, Lu Xiao
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Publication number: 20120058987Abstract: The subject matter of the present invention is the use of compounds of formula (I) in the form of a base, a hydrate or a solvate, or of mixtures thereof, as a medicament or for preparing a medicament intended for the treatment and/or prevention of disorders associated with the central nervous system (abbreviated to CNS) and/or associated with the peripheral nervous system (abbreviated to PNS).Type: ApplicationFiled: March 25, 2010Publication date: March 8, 2012Applicant: SANOFIInventors: Gilbert Marciniak, Jean-Francois Nave, Fabrice Viviani
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Publication number: 20120052062Abstract: The present invention provides methods of treating non-small cell lung cancer by administering to a subject in need thereof a therapeutically effective amount of a pyrroloquinolinyl-pyrrole-2,5-dione compound in combination with a therapeutically effective amount of an epidermal growth factor tyrosine kinase inhibitorType: ApplicationFiled: August 31, 2011Publication date: March 1, 2012Applicant: ArQule, Inc.Inventors: Yinpu Chen, Edward G. Garmey, Brian Schwartz
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Publication number: 20120053178Abstract: Compounds of the formula (I), in which R1, R2 and R3 have the meanings indicated in claim (1), are inhibitors of PDK1 and cell proliferation/cell vitality and can be employed for the treatment of tumours.Type: ApplicationFiled: April 8, 2010Publication date: March 1, 2012Applicant: MERCK PATENT GESELLSCHAFT MIT BESCHRANKTER HAFTUNGInventors: Dieter Dorsch, Margarita Wucherer-Plietker, Thomas J.J. Mueller, Eugen Merkul
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Publication number: 20120053166Abstract: The invention is directed to certain novel compounds. Specifically, the invention is directed to compounds of formula (I): and salts thereof. The compounds of the invention are inhibitors of kinase activity, in particular PI3-kinase activity.Type: ApplicationFiled: March 5, 2010Publication date: March 1, 2012Inventors: Julie Nicole Hamblin, Zoe Alicia Harrison, Paul Spencer Jones, Suzanne Elaine Keeling, Joelle Le, Christopher James Lunniss, Nigel James Parr
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Publication number: 20120053176Abstract: Provided herein is a method of preventing, treating, or ameliorating one or more symptoms of an adenosine A3-mediated condition, disorder, or disease, with a compound of Formula I. Also provided herein is a method of preventing, treating, or ameliorating one or more symptoms of glaucoma or ocular hypertension. Further provided herein is a method of modulating the activity of an adenosine A3 receptor.Type: ApplicationFiled: August 31, 2011Publication date: March 1, 2012Applicant: AMBIT BIOSCIENCES CORP.Inventors: Robert C. Armstrong, Barbara Belli, Mark W. Holladay, Martin W. Rowbottom
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Publication number: 20120053177Abstract: Compounds active on protein kinases are described, as well as methods of using such compounds to treat diseases and conditions associated with aberrant activity of protein kinases.Type: ApplicationFiled: September 23, 2011Publication date: March 1, 2012Inventors: Prabha N. Ibrahim, Dean R. Artis, Ryan Bremer, Gaston Habets, Shumeye Mamo, Marika Nespi, Chao Zhang, Jiazhong Zhang, Yong-Liang Zhu, Rebecca Zuckerman, Brian West, Yoshisa Suzuki, James Tsai, Klaus-Peter Hirth, Gideon Bollag, Wayne Spevak, Hanna Cho, Samuel J. Gillette, Guoxian Wu, Hongyao Zhu, Shenghua Shi