Nitrogen Bonded Directly To Ring Carbon Of The 1,3-diazine Ring Of The Quinazoline Ring System Patents (Class 514/266.4)
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Publication number: 20130018033Abstract: Compounds of Formula I are useful for inhibition of Raf kinases. Methods of using compounds of Formula I and stereoisomers, tautomers, prodrugs and pharmaceutically acceptable salts thereof, 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: ApplicationFiled: August 27, 2010Publication date: January 17, 2013Applicant: ARRAY BIOPHARMA INC.Inventors: Ignacio Aliagas, Stefan Gradl, Janet Gunzner, Wendy Lee, Simon Mathieu, Joachim Rudolph, Zhaoyang Wen, Guiling Zhao, Alexandre J. Buckmelter, Jonas Grina, Joshua D. Hansen, Ellen Laird, David Moreno, Li Ren, Steven Mark Wenglowsky
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Publication number: 20130018040Abstract: Compositions and methods for the treatment of toxoplasmosis, caused by the infectious eukaryotic parasite Toxoplasma gondii (T. gondii) and for the treatment of cryptosporidiosis, caused by the infectious eukaryotic parasites Cryptosporidium parvum (C. parvum) and Cryptosporidium hominus (C. hominus) are described. In particular, the present disclosure is directed to compositions and methods for inhibiting either T. gondii calcium dependent protein kinases (TgCDPKs) or C. parvum and C. hominus calcium dependent protein kinases (CpCDPKs) using pyrazolopyrimidine and/or imidazo[1,5-a]pyrazine inhibitors, of the formula, wherein the variables X, Y, Z, L, R1, and R3 are defined herein.Type: ApplicationFiled: July 30, 2012Publication date: January 17, 2013Applicant: University of Washington through its Center for CommercializationInventors: Wesley C. VAN VOORHIS, Wilhelmus G.J. HOL, Eric T. LARSON, Dustin James MALY, Ethan MERRITT, Kayode K. OJO
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Publication number: 20130011408Abstract: The current disclosure provides for specific peptides from the Epidermal Growth Factor Receptor (EGFR) protein and the derived ionization characteristics of those peptides that are advantageous for quantifying the EGFR directly in formalin fixed biological samples by the method of Selected Reaction Monitoring (SRM) mass spectrometry. Such fixed biological samples include: formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and formalin fixed and paraffin embedded tissue culture cells. EGFR protein is quantitated in biological samples by the method of SRM/MRM mass spectrometry by quantitating one or more of the peptides described herein. The peptides can be quantitated if they reside in a modified or an unmodified form. Examples of potentially modified forms of an EGFR peptides include those bearing phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.Type: ApplicationFiled: June 21, 2012Publication date: January 10, 2013Applicant: EXPRESSION PATHOLOGY, INC.Inventors: David B. Krizman, Todd Hembrough, Sheeno Thyparambil
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Publication number: 20130012528Abstract: This invention relates to novel compounds and hydrochloric acid salts thereof. More specifically, this invention relates to novel compounds and hydrochloric acid salts thereof derived from erlotinib. This invention also provides compositions comprising one or more compounds of this invention and a carrier and the use of the disclosed compounds and compositions in methods of treating diseases and conditions that are beneficially treated by administering an epidermal growth factor receptor tyrosine kinase (EGFR) inhibitor, such as erlotinib.Type: ApplicationFiled: July 5, 2011Publication date: January 10, 2013Inventor: Xueheng Cheng
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Patent number: 8349854Abstract: The present invention relates to salt forms of N-{4-[3-chloro-4-(3-fluoro-benzyloxy)phenylamino]-quinazolin-6-yl}-acrylamide as exemplified by formula (I), methods of preparation thereof, pharmaceutical compositions comprising the same and their use thereof. The salt forms of the present invention, which possess excellent tumor inhibitory activity, good bioavailability and low toxicity in an animal body, are suitable for use of preparation of anti-tumor medicaments.Type: GrantFiled: February 4, 2008Date of Patent: January 8, 2013Assignee: Shanghai Allist Pharmaceuticals, Inc.Inventors: Jianhui Guo, Yong Jiang
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Patent number: 8349855Abstract: The present invention relates to three novel crystalline forms of Erlotinib hydrochloride and method of preparation thereof. Erlotinib hydrochloride is N-(3-ethynylphenyl)-6,7-bis(2-methoxy ethoxy)-4-quinazolinamine hydrochloride of formula-(I). The present invention provides stable novel crystalline forms of Erlotinib hydrochloride designated as Form-M, Form-N and Form-P, and processes for the preparation of the same. Erlotinib hydrochloride can be used as medicament for the treatment of hyperproliferative disorders, such as cancers, in humans.Type: GrantFiled: September 11, 2007Date of Patent: January 8, 2013Assignee: Natco Pharma LimitedInventors: Ramanadham Jyothi Prasad, Bhujanga rao Adibhatla Kali Satya, Nannapaneni Venkaiah Chowdary
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Patent number: 8349856Abstract: The present invention relates to quinazoline containing zinc-binding moiety based derivatives of formula I that have enhanced and unexpected properties as inhibitors of epidermal growth factor receptor tyrosine kinase (EGFR-TK) and their use in the treatment of EGFR-TK related diseases and disorders such as cancer.Type: GrantFiled: June 8, 2011Date of Patent: January 8, 2013Assignee: Curis, Inc.Inventors: Changgeng Qian, Xiong Cai
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Patent number: 8349857Abstract: A compound which inhibits both of EGF receptor tyrosine kinase and HER2 tyrosine kinase is provided. A compound represented by the general formula (I): wherein RX is a group represented by the formula: wherein R1 is a hydrogen atom, optionally substituted alkyl, etc.; Z is —O—, —N(R10)—, etc.; R10 is a hydrogen atom, alkyl, etc.; R2 is a hydrogen atom, optionally substituted alkyl, etc.; R18 is a hydrogen atom, optionally substituted alkyl, etc.; R19 is optionally substituted alkyl, etc.; W1 is an optionally substituted non-aromatic nitrogen-containing group; R17 is a hydrogen atom, optionally substituted alkyl, etc.; R3 and R4 are independently a hydrogen atom, optionally substituted alkyl, etc.; X is —O—, —S—, or —N(R12)—, etc.; R12 is a hydrogen atom, alkyl, etc.; and A is phenyl optionally having a substituent, etc., its pharmaceutically acceptable salt, or a solvate thereof.Type: GrantFiled: January 26, 2012Date of Patent: January 8, 2013Assignee: Shionogi & Co., Ltd.Inventors: Masaharu Kume, Kenji Matsuo, Naoki Omori, Masami Takayama, Aiko Omori, Takeshi Endo
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Publication number: 20130005726Abstract: A method for treating in a subject with an inflammatory disorder and/or immunological disorder associated with NOD2 activation includes administering to the subject a therapeutically effective amount of at least one tyro sine kinase inhibitor that substantially inhibits nucleotide-binding oligomerization domain containing 2 (NOD2):receptor-interacting protein 2 (RIP2) signaling in a NOD2-bearing cell and is not cytotoxic to the cell.Type: ApplicationFiled: March 8, 2011Publication date: January 3, 2013Inventors: Derek Abbott, Justine Tigno-Aranjuez
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Patent number: 8343982Abstract: The present invention relates methods for treating disease conditions selected from the list consisting of benign or malignant tumors, diseases of the airways and lungs, diseases of the gastrointestinal tract, the bile duct and the gall bladder by administration to a patient in need thereof of a therapeutically effective amount of a bicyclic heterocyclic groups of general formula wherein said substituents are as defined herein.Type: GrantFiled: December 6, 2010Date of Patent: January 1, 2013Assignee: Boehringer Ingelheim Pharma GmbH & Co. KGInventors: Frank Himmelsbach, Birgit Jung, Flavio Solca
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Publication number: 20120321637Abstract: Embodiments are directed to compositions and methods related combination therapy with HERV inhibition.Type: ApplicationFiled: June 18, 2012Publication date: December 20, 2012Applicant: The Board of Regents of the University of Texas SystemInventors: Jianli Dong, Gengming Huang
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Publication number: 20120321615Abstract: Disclosed herein is a method for predicting the prognosis, the likelihood of metastasis in, or the desirability of administering an aggressive therapy to, a subject with colorectal cancer, comprising determining, in a sample from the subject, the level of phosphorylation of one or more of certain proteins compared to a positive and/or negative reference standard; or the total amount of COX-2 protein compared to a positive and/or negative reference standard. Also described are methods for treating subjects likely to develop metastatic colorectal carcinoma, and pharmaceutical compositions and kits for implementing the methods of the invention.Type: ApplicationFiled: May 25, 2012Publication date: December 20, 2012Inventors: Emanuel Petricoin, III, Lance A. Liotta, Mariaelena Pierobon, Valerie Calvert
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Publication number: 20120322792Abstract: The present invention relates to anti-cancer therapeutics. In certain aspects, cancers are treated with a combination of an anti-EGFR agent and an agent that increases the activity of the KLF6 tumor suppressor gene and/or an agent that increases activity of the FOXO1 tumor suppressor gene. In a preferred aspect, the anti-EGFR agent erlotinib a tricyclic agent compound, are used in combination to treat non-small cell lung cancer in a patient with primary or acquired drug resistance to erlotinib, and wherein the tricyclic agent is administered in an amount that does not lead to a substantial central nervous system effect. In additional aspects, the invention relates to compositions and kits useful for treating cancers, methods for screening for compounds that enhance the activity of anti-EGFR agent, and methods for determining whether a patient will respond to anti-EGFR therapy.Type: ApplicationFiled: January 11, 2012Publication date: December 20, 2012Applicant: MOUNT SINAI SCHOOL OF MEDICINEInventors: Goutham Narla, Michael Ohlmeyer, Matthew David Galsky
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Publication number: 20120316187Abstract: The invention relates to a method for predicting the response to the treatment with an EGFR tyrosine kinase inhibitor of a patient suffering lung cancer an carrying a mutation in the EGFR gene based on the expression levels in a sample of said patient of the BRCA1 gene wherein low BRCA1 expression levels are indicative of a positive response of a patient. This positive response is also observed in patients showing the T790M mutation in the EGFR gene which is usually associated with resistance to EGFR tyrosine kinase inhibitors.Type: ApplicationFiled: November 15, 2010Publication date: December 13, 2012Applicant: PANGAEA BIOTECH, S.L.Inventors: Rafael Rosell Costa, Miguel Tarón Roca
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Publication number: 20120315247Abstract: The present invention provides novel compounds useful in modulating the protein tyrosine kinase activity, and in modulating inter- and/or intra-cellular signaling. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.Type: ApplicationFiled: August 17, 2012Publication date: December 13, 2012Applicants: SUNSHINE LAKE PHARMA CO., LTD.Inventor: Ning Xi
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Publication number: 20120316164Abstract: The present invention provides a method for inhibiting the growth of cancer stem cells, particularly colorectal cancer stem cells, liver cancer stem cells, lung cancer stem cells or breast cancer stem cells, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of antimycin A or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier.Type: ApplicationFiled: June 13, 2011Publication date: December 13, 2012Inventors: CHI-YING HUANG, CHI-TAI YEH, CHUN-HUNG WU, YU-WEN LIU
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Publication number: 20120302572Abstract: The present invention provides diagnostic methods for assessing the EMT status of tumor cells, and for predicting the effectiveness of treatment of a cancer patient with an EGFR or IGF-1R kinase inhibitor, utilizing an EMT gene signature index score. The present invention further provides methods for treating patients with cancer that incorporate these methods.Type: ApplicationFiled: April 25, 2012Publication date: November 29, 2012Applicants: AVEO PHARMACEUTICALS, INC., OSI Pharmaceuticals, LLCInventors: Julie Kan, Stuart Thomson, Gretchen M. Argast, Matthew E. O'Connor, Murray Robinson, Bin Feng, Joerg Heyer, Maria I. Chiu, Richard Nicoletti
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Patent number: 8318752Abstract: The invention concerns quinazoline derivatives of Formula (I): wherein each of R1, X1, R2, R3, R5, n and m have any of the meanings defined in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use as an antiproliferative agent in the prevention or treatment of tumors which are sensitive to inhibition of EGF and erbB receptor tyrosine kinases.Type: GrantFiled: September 15, 2004Date of Patent: November 27, 2012Assignee: Astrazeneca ABInventor: Bernard Barlaam
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Publication number: 20120294872Abstract: A signature for breast cancer tissue derived from a patient is established that is indicative of the virulence and risk of lung metastasis by determining the expression levels to define a sample signature, and comparing this sample signature to a reference signature. This determination is used to define appropriate treatment and monitoring options for the patient. Risk of metastasis to the lung can be reduced by treatment with a therapeutic combination that either (1) contains a first agent effective to inhibit epiregulin activity and a second agent effective to inhibit activity of a protein selected from the group consisting of MMP1, MMP2 and PTGS2, or (2) contains a therapeutic agent or combination of agents effective to inhibit activity MMP1, MMP2 and PTGS2. Agents that inhibit the CXCL1 pathway also can be used individually or in combination with these combinations.Type: ApplicationFiled: April 16, 2012Publication date: November 22, 2012Applicant: SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCHInventors: Gaorav P. Gupta, Joan Massague, Andy J. Minn
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Patent number: 8309563Abstract: he present invention has disclosed a compound of formula I and a pharmaceutically acceptable salt or a solvate thereof, wherein the substituents are as defined in the description. The invention has also disclosed a method for preparing the compound of formula I, the pharmaceutical compositions comprising the same and their uses in the preparation of an anti-tumor medicament.Type: GrantFiled: June 14, 2011Date of Patent: November 13, 2012Assignee: Shanghai Allist Pharmaceuticals, Inc.Inventors: Jianhui Guo, Meng Wang, Yong Jiang, Xiaofang Zhang
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Patent number: 8309562Abstract: Disclosed are 4-arylamino-quinazolines and analogs thereof that are effective as activators of caspases and inducers of apoptosis. The compounds of this invention are useful in the treatment of a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.Type: GrantFiled: July 10, 2009Date of Patent: November 13, 2012Assignee: Myrexis, Inc.Inventors: Mark B. Anderson, J. Adam Willardsen, Warren S. Weiner, Ashantai Yungai, Robert J. Halter, Yevgeniya Klimova, Kazuyuki Suzuki, Matthew Reeder
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Patent number: 8304420Abstract: This invention relates to the discovery of prodrugs of 3-or 5-substituted analogues of the selective platelet lowering agent anagrelide which have reduced potential for cardiovascular side-effects and which should therefore lead to improved patient compliance and safety in the treatment of myeloproliferative diseases. More specifically, the present invention relates to prodrugs of certain imidazoquinazoline derivatives which have utility as platelet lowering agents in humans. The compounds of the present invention function by inhibiting the formation of blood platelets. An example of a compound of the present invention is methyl 2-(2-amino-5,6- dichloroquinazolin-3 (4H)-yl)-2-methylpropanoate or the 3,3-demethyl anagrelide open-ringed analog.Type: GrantFiled: November 28, 2007Date of Patent: November 6, 2012Assignee: Shire LLCInventors: Richard Franklin, Bernard T. Golding, Peter A. Cicala
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Publication number: 20120276093Abstract: The present invention provides a therapeutic combination comprising (a) a compound of formula (I) as set forth in the specification and (b) one or more antineoplastic agents selected from the group consisting of an alkylating or alkylating-like agent, an antimetabolite agent, a topoisomerase I inhibitor, a topoisomerase 11 inhibitor, an inhibitor of a growth factor or of a growth factor receptor, an antimitotic agent, a proteasome inhibitor, an inhibitor of an anti-apoptotic protein and an antibody directed against a cell surface protein, wherein the active ingredients are present in each case in lice form or in the form of a pharmaceutically acceptable salt or any hydrate thereof.Type: ApplicationFiled: November 17, 2010Publication date: November 1, 2012Applicant: NERVIANO MEDICAL SCIENCES S.R.L.Inventors: Dario Ballinari, Antonella Ciavolella, Enrico Pesenti, Alessia Montagnoli
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Publication number: 20120263716Abstract: The method of treating a person having a cancer selected from carcinoma, sarcoma or hematopoietic cancer by administering (a) an effective amount of at least one anti-cancer drug selected from the group consisting of an epidermal growth factor receptor (EGFR) inhibitor, a vascular endothelial growth factor receptor (VEGFR) inhibitor and a Raf kinase inhibitor and (b) an effective amount of 5-(4-(6-(4-amino-3,5-dimethyl-phenoxy)-1-methyl-1H-benzimidazol-2-ylmethoxy)-benzyl)-thiazolidine-2,4-dione.dihydrochloride provided that said carcinoma is not lung cancer when an EGFR inhibitor is erlotinib. The invention also provides a pharmaceutical composition that may be used in practicing said method.Type: ApplicationFiled: June 19, 2012Publication date: October 18, 2012Applicant: DAIICHI SANKYO COMPANY, LIMITEDInventors: Kosaku FUJIWARA, Naomi Shimazaki
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Patent number: 8288398Abstract: The present invention is related to a novel series of pyrimidyl or fused pyrimidyl hydrazones. Compounds of Formula (I) wherein A is selected from the group consisting of Formulas (A1), (A2), (A3), (A4), (A5) are useful for the treatment and/or prevention of a proliferative disease.Type: GrantFiled: December 8, 2006Date of Patent: October 16, 2012Assignee: Merck Serono SAInventors: Brian Healey, Zhong Zhao, Amanda Sutton, Matthias Schwarz
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Publication number: 20120258975Abstract: Certain aspects of the invention relates to small molecule autophagy inhibitors of the formula (I), and their use for treatment and prevention of cancers and acute pancreatitis. As disclosed herein, a small molecule inhibitor of autophagy was been identified from an image-based screen in a known bioactive library. It was found that this autophagy inhibitor functions by promoting the degradation of type III PI3 kinase complex which is required for initiating autophagy. Medicinal chemistry studies led to small molecular autophagy inhibitors with improved potency and selectivity.Type: ApplicationFiled: July 21, 2010Publication date: October 11, 2012Applicants: Shanghai Institute of Organic Chemistry, President and Fellows of Harvard CollegeInventors: Junying Yuan, Dawei Ma, Junli Liu, Lihong Zhang
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Patent number: 8278314Abstract: This invention provides quinazoline analogs of Formula I: where A is bonded to at least one of the carbons at the 5, 6, 7 or 8 position of the bicyclic ring, and the ring is substituted by up to two independent R3 groups. The invention also includes methods of using compounds of Formula I as type I receptor tyrosine kinase inhibitors and for the treatment of hyperproliferative diseases such as cancer.Type: GrantFiled: October 10, 2008Date of Patent: October 2, 2012Assignee: Array BioPharma Inc.Inventors: Eli Wallace, George Topalov, Joseph Lyssikatos, Alexandre Buckmelter, Qian Zhao
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Publication number: 20120245139Abstract: The present invention is directed to a compound of Formula I or a single isomer thereof; where the compound is optionally as a pharmaceutically acceptable salt, hydrate, solvate or combination thereof, in addition to methods of preparing a Compound of Formula I, and methods of using a Compound of Formula I to treat cancer.Type: ApplicationFiled: June 4, 2012Publication date: September 27, 2012Applicant: EXELIXIS PATENT COMPANY LLCInventors: Suleyman Bahceci, William Bajjalieh, Jeff Chen, Sergey Epshteyn, Timothy Patrick Forsyth, Tai Phat Huynh, Byung Gyu Kim, James W. Leahy, Matthew Sangyup Lee, Gary L. Lewis, Morrison B. Mac, Grace Mann, Charles K. Marlowe, Brian Hugh Ridgway, Joan C. Sangalang, Xian Shi, Craig Stacy Takeuchi, Yong Wang
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Publication number: 20120238570Abstract: The present invention is directed to a compound of Formula I or a single isomer thereof; where the compound is optionally as a pharmaceutically acceptable salt, hydrate, solvate or combination thereof, in addition to methods of preparing a Compound of Formula I, and methods of using a Compound of Formula I to treat cancer.Type: ApplicationFiled: June 4, 2012Publication date: September 20, 2012Applicant: EXELIXIS PATENT COMPANY LLCInventors: Suleyman Bahceci, William Bajjalieh, Jeff Chen, Sergey Epshteyn, Timothy Patrick Forsyth, Tai Phat Huynh, Byung Gyu Kim, James W. Leahy, Matthew Sangyup Lee, Gary L. Lewis, Morrison B. Mac, Grace Mann, Charles K. Marlowe, Brian Hugh Ridgway, Joan C. Sangalang, Xian Shi, Craig Stacy Takeuchi, Yong Wang
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Publication number: 20120238575Abstract: The present invention is related to a novel series of pyrimidyl or fused pyrimidyl hydrazones. Compounds of Formula (I) wherein A is selected from the group consisting of Formulas (A1), (A2), (A3), (A4), (A5) are useful for the treatment and/or prevention of a proliferative disease.Type: ApplicationFiled: May 31, 2012Publication date: September 20, 2012Applicant: MERCK SERONO SAInventors: BRIAN HEALEY, Zhong Zhao, Amanda Sutton, Matthias Schwarz
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Publication number: 20120237508Abstract: The present invention relates to HSP90 inhibitors containing fused amino pyridine core that are useful as inhibitors of HSP90 and their use in the treatment of HSP90 related diseases and disorders such as cancer, an autoimmune disease, or a neurodegenerative disease.Type: ApplicationFiled: March 20, 2012Publication date: September 20, 2012Inventors: Xiong Cai, Changgeng Qian, Haixiao Zhai
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Patent number: 8268843Abstract: The present disclosure relates to 5,8-difluoro-4-(2-(4-(heteroaryloxy)-phenyl)ethylamino)quinazolines and their use as agrochemicals and animal health products.Type: GrantFiled: August 31, 2009Date of Patent: September 18, 2012Assignee: Dow AgroSciences, LLC.Inventors: William K. Brewster, Carla J. R. Klittich, Chenglin Yao, Yuanming Zhu, Brent J. Rieder
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Patent number: 8268825Abstract: A method of treating an anthrax infection wherein a compound of formula I wherein R1 and R2 represent, independently of one another unsubstituted or specifically substituted C1-4alkoxy; and R3 represents hydrogen; cyano; unsubstituted or specifically substituted C1-6alkyl; C3-6cycloalkyl; C2-6alkenyl; C7-18bicyclyl; aryl, aryl-C1-4alkyl, aryl-Q-C1-4alkyl heteroaryl, heterocyclyl or heterocyclyl-C1-6alkyl, wherein aryl denotes a mono- or poly-nucleous group with 6 to 14 ring carbon atoms; heterocyclyl denotes a 4- to 6-membered non-aromatic heterocyclic group comprising 1 to 3, nitrogen, oxygen and/or sulfur atoms; heteroaryl denotes a mono- or polynuclear heteroaromatic group consisting 5- and/or 6-membered rings and comprising 5 to 13 carbon atoms and 1 to 4, nitrogen, oxygen and/or sulfur atoms; and Q means —SO— or —SO2—; or a pharmaceutically acceptable salt, solvate or hydrate or a prodrug thereof; is administered to said subject in a quantity effective to inhibit, suppress, or expel an anthrax infType: GrantFiled: September 25, 2006Date of Patent: September 18, 2012Assignee: The Board of Regents for Oklahoma State UniversityInventors: Jurg Dreier, William Barrow, Esther Barrow
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Publication number: 20120225870Abstract: Provided herein are methods for treating cancer that is resistant to treatment with an anti-ErbB therapeutic agent and which is associated with an activating MET gene mutation or a MET gene amplification. The methods involve administering to a subject a combination of an anti-ErbB therapeutic and an anti-MET therapeutic. Also provided are methods for reducing ErbB mediated signaling or PI3 kinase mediated signaling in a cancer cell.Type: ApplicationFiled: April 11, 2008Publication date: September 6, 2012Inventors: Pasi A. Janne, Jeffrey Engelman, Lewis C. Cantley
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Patent number: 8258145Abstract: Disclosed are 4-arylamino-quinazolines and analogs thereof effective as activators of caspases and inducers of apoptosis. The compounds of this invention are useful in the treatment of a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs, and in particular to the use of these compounds in treating brain cancer.Type: GrantFiled: July 3, 2007Date of Patent: September 4, 2012Assignee: Myrexis, Inc.Inventors: Sui Xiong Cai, Mark B. Anderson, Adam Willardsen, Nilantha Sudath Sirisoma
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Publication number: 20120220588Abstract: Disclosed are compounds having the formula: wherein R1, R2, R3, R4, R5, R6 and R7 are as defined herein, and methods of making and using the same.Type: ApplicationFiled: November 1, 2010Publication date: August 30, 2012Inventors: Lara S. Kallander, Brian Griffin Lawhorn, Joanne Philp
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Publication number: 20120214829Abstract: Herein is described the use of a collection of 50 breast cancer cell lines to match responses to 77 conventional and experimental therapeutic agents with transcriptional, proteomic and genomic subtypes found in primary tumors. Almost all compounds produced strong differential responses across the cell lines produced responses that were associated with transcriptional and proteomic subtypes and produced responses that were associated with recurrent genome copy number abnormalities. These associations can now be incorporated into clinical trials that test subtype markers and clinical responses simultaneously.Type: ApplicationFiled: February 21, 2012Publication date: August 23, 2012Applicant: The Regents of the University of CaliforniaInventors: Paul T. Spellman, Joe W. Gray, Anguraj Sadanandam, Laura M. Heiser, William J. Gibb, Wen-Lin Kuo, Nicholas J. Wang
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Publication number: 20120214830Abstract: The present invention provides diagnostic methods for predicting the effectiveness of treatment of an hepatocellular carcinoma (HCC) patient with an IGF-1R kinase inhibitor by assessing whether the HCC tumor cells express a high level of AFP, or whether serum levels of AFP protein are high. The present invention also provides diagnostic methods for predicting the effectiveness of treatment of cancer patients with IGF-1R kinase inhibitors, based on a determination of the expression level of IR, IGF-2, IGFBP3 or IGFBP7 in tumor cells, or a 4-gene index calculated using the expression vales for each of these four genes, which can be used to identify tumors that will be sensitive to IGF-1R kinase inhibitors, and also those that will be insensitive. Improved methods for treating cancer patients with IGF-1R kinase inhibitors that incorporate the above methods are also provided.Type: ApplicationFiled: February 22, 2012Publication date: August 23, 2012Inventors: Elizabeth A. Buck, Hui Zhao
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Publication number: 20120214828Abstract: The present invention relates to prognostic methods for identifying tumors that are not susceptible to B-Raf inhibitor treatment by detecting mutations in a K-ras gene or protein or by detecting overexpression of RTKs and/or their ligands. Kits are also disclosed for carrying out the methods.Type: ApplicationFiled: August 24, 2010Publication date: August 23, 2012Inventors: Georgia Hatzivassiliou, Shiva Malek
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Patent number: 8247423Abstract: Described herein are compositions and methods for using these compositions in the treatment of cancer, tumors, and tumor-related disorders in a subject.Type: GrantFiled: July 11, 2008Date of Patent: August 21, 2012Assignee: Tragara Pharmaceuticals, Inc.Inventors: Thomas M. Estok, Sara L. Zaknoen, Robert K. Mansfield, Tracy Lawhon
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Publication number: 20120207751Abstract: The invention relates to a combination comprising compounds of formula (I) and one or more other antiproliferative compounds, hormones or radiation, pharmaceutical preparations comprising the combination thereof, and the application thereof in a process for the treatment of tumors.Type: ApplicationFiled: April 23, 2012Publication date: August 16, 2012Applicant: NOVARTIS AGInventors: Carlos Garcia-Echeverria, Frédéric Stauffer, Pascal Furet
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Patent number: 8232284Abstract: Disclosed are compounds of the following formula and their pharmaceutically-acceptable salts, which have an effect of glucokinase activation and are useful in the field of medicines for treatment for diabetes, obesity, etc. (wherein ring A represents a pyrazolyl group optionally having a lower alkyl group, etc.; ring B represents a heteroaryl group; R represents a lower alkyl group, etc.; R1 represents a group of a formula: (wherein R11 and R12 each independently represent a hydrogen atom, etc.; m indicates an integer of from 2 to 6), etc.; R2 represents a lower alkyl group, etc.; r indicates an integer of from 0 to 3; k indicates an integer of from 0 to 4).Type: GrantFiled: November 10, 2008Date of Patent: July 31, 2012Assignee: MSD K. K.Inventors: Tomoharu Iino, Akio Ohno, Norikazu Otake, Takuya Suga, Masanori Asai
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Publication number: 20120190620Abstract: The present invention discloses methods to identify targets, pathways and molecules regulating purinosomes and their uses for treating pathophysiological disorders associated with purinosomes. Disclosed are methods related to both label-free cellular assays and fluorescence imaging to confirm the regulatory roles of various targets and molecules in purinosome dynamics. Disclosed are methods to classify molecules and the uses of these molecules for different indications. Specifically, the purinosome-disrupting molecules can be used for improved prevention and treatment of cancer development.Type: ApplicationFiled: July 18, 2011Publication date: July 26, 2012Inventors: Stephen Benkovic, Ye Fang, Songon An, Florence Verrier
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Publication number: 20120184523Abstract: 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: ApplicationFiled: March 22, 2012Publication date: July 19, 2012Applicant: Exelixis, Inc.Inventors: Lynne Canne Bannen, Diva Sze-Ming Chan, Jeff Chen, Lisa Esther Dalrymple, Timothy Patrick Forsyth, Tai Phat Huynh, Vasu Jammalamadaka, Richard George Khoury, James William Leahy, Morrison B. Mac, Grace Mann, Larry W. Mann, John M. Nuss, Jason Jevious Parks, Craig Stacy Takbuchi, Yong Wang, Wei Xu
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Patent number: 8222264Abstract: The present invention relates to substituted amino-quinazolinones of general formula (I) wherein the groups R1 to R14 and A, are defined as in the specification and claims and the use thereof for the treatment of Alzheimer's disease (AD) and similar diseases.Type: GrantFiled: July 3, 2008Date of Patent: July 17, 2012Assignee: Boehringer Ingelheim International GmbHInventors: Klaus Fuchs, Niklas Heine, Christian Eickmeier, Sandra Handschuh, Cornelia Dorner-Ciossek, Stefan Hoerer
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Publication number: 20120177641Abstract: Disclosed is the identification, provision and use of a panel of biomarkers that predict sensitivity or resistance to EGFR inhibitors, and products and processes related thereto. In one embodiment, a method is described for selecting a cancer patient who is predicted to benefit from therapeutic administration of an EGFR inhibitor, an agonist thereof, or a drug having substantially similar biological activity as EGFR inhibitor. Also described is a method to identify molecules that interact with the EGFR pathway to allow or enhance responsiveness to EGFR inhibitors, as well as a plurality of polynucleotides or antibodies for detection of the expression of genes that are indicative of sensitivity or resistance to EGFR inhibitors, an agonist thereof, or a drug having substantially similar biological activity as EGFR inhibitors. A method to identify a compound with the potential to enhance the efficacy of EGFR inhibitors is also described.Type: ApplicationFiled: March 12, 2012Publication date: July 12, 2012Inventors: Paul A. BUNN, Christopher D. COLDREN, Wilbur A. FRANKLIN, Mark W. GERACI, Barbara A. HELFRICH, Fred R. HIRSCH, Razvan LAPADAT, Michio SUGITA, Samir E. WITTA
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Publication number: 20120178622Abstract: The invention relates to aminoquinazoline compounds or the enantiomers or veterinarily acceptable salts thereof which are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to methods for controlling invertebrate pests by using these compounds and to plant propagation material and to agricultural and veterinary compositions comprising said compounds. wherein A1, A2, A3, A4, R1, R2, R3, R4, R5a, R5b, R5c, R5d and p are defined as in the description.Type: ApplicationFiled: September 15, 2010Publication date: July 12, 2012Applicant: BASF SEInventors: Steffen Gross, Matthias Pohlman, Arun Narine, Claudia Rosenbaum, Prashant Deshmukh, Joachim Dickhaut, Nina Gertrud Bandur, Karsten Koerber, Florian Kaiser, Wolfgang Von Deyn, Juergen Langewald, Deborah L. Culbertson, Cecille Ebuenga
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Publication number: 20120156197Abstract: Provided is a method of treating a proliferative disease, condition, or disorder in a subject by administering a combination of an inhibitor of p53 and MDM2 binding and an EGFR inhibitor. Various embodiments of the disclosed methods provide a synergistic anti-proliferative or anti-apoptotic effect compared to administration of one agent alone.Type: ApplicationFiled: July 21, 2011Publication date: June 21, 2012Inventors: Joseph P. Errico, Benjamin Mugrage, Ignatius Turchi, Matthew Sills, Jane Ong, John Allocco, Pam Wines
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Publication number: 20120156228Abstract: The invention features methods, kits, and compositions for generating new hair follicles and growing hair on a subject.Type: ApplicationFiled: September 9, 2011Publication date: June 21, 2012Applicants: Follica, Inc., The Trustees Of The University of PennsylvaniaInventors: David Steinberg, Kevin Pojasek, Stephen Prouty, George Cotsarelis, Mayumi Ito
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Publication number: 20120157480Abstract: The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a cancer patient with an EGFR kinase inhibitor. Methods are provided for predicting the sensitivity of tumor cell growth to inhibition by an EGFR kinase inhibitor, comprising assessing whether the tumor cell has undergone an epithelial to mesenchymal transition (EMT), by determining the expression level of epithelial and/or mesenchymal biomarkers, wherein tumor cells that have undergone an EMT are substantially less sensitive to inhibition by EGFR kinase inhibitors. Improved methods for treating cancer patients with EGFR kinase inhibitors that incorporate the above methodology are also provided. Additionally, methods are provided for the identification of new biomarkers that are predictive of responsiveness of tumors to EGFR kinase inhibitors.Type: ApplicationFiled: December 12, 2011Publication date: June 21, 2012Inventors: John D. Haley, Graeme Griffin, Lukas A. Amler, David A. Eberhard, Robert L. Yauch