Abstract: The invention discloses an improved process for the preparation of 2,2,5,5-tetrasubstituted hexane-1,6-dicarbonyl compounds, and in particular diethyl 2,2,5,5-tetramethylhexanedioate and dimethyl 2,2,5,5-tetramethylhexanedioate, by the alkylation of 1,2-difunctional ethane compounds with enolates of carbonyl compounds. The process provides higher yields and greater synthetic brevity than existing processes.
Type:
Application
Filed:
December 21, 2010
Publication date:
October 18, 2012
Applicant:
THE UNIVERSITY OF READING
Inventors:
Francis William Lewis, Laurence Marius Harwood, Michael James Hudson
Abstract: The present invention provides compounds of Formula (I), pharmaceutical compositions thereof, and method of using the same in the treatment or prevention of diseases mediated by the activation of ?3-adrenoceptor.
Type:
Application
Filed:
June 20, 2012
Publication date:
October 11, 2012
Inventors:
Richard Berger, Lehua Chang, Scott D. Edmondson, Stephen D. Goble, Sookhee Nicole Ha, Nam Fung Kar, Ihor E. Kopka, Bing Li, Gregori J. Morriello, Chris R. Moyes, Dong-Ming Shen, Liping Wang, Cheng Zhu
Abstract: Specified phenylalanine derivatives and analogues thereof have an antagonistic activity to ?4 integrin. They are used as therapeutic agents for various diseases concerning ?4 integrin.
Abstract: This invention provides novel compounds that are modulators of gamma secretase. The compounds have the Formula I: Also disclosed are methods of modulating gamma secretase activity and methods of treating Alzheimer's Disease using the compounds of Formula I.
Type:
Application
Filed:
June 15, 2010
Publication date:
September 27, 2012
Inventors:
Xianhai Huang, Zhaoning Zhu, William J. Greenlee, Anandan Palani, Robert G. Aslanian
Abstract: The invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit tyrosine kinase activity of Trk receptors such as TrkA, TrkB, TrkC or Flt-3 thereby making them useful as anticancer agents.
Abstract: A compound of formula (I): wherein all symbols have the same meanings as defined in the specification; a salt thereof, a solvate thereof, an N-oxide thereof, or a prodrug thereof, has a Btk inhibitory activity, and is useful as a method for preventing and/or treating a rheumatoid arthritis, an autoimmune disease, a B cell lymphoma of cancer, and the like.
Type:
Application
Filed:
April 28, 2010
Publication date:
September 13, 2012
Applicant:
LOCUS PHARMACEUTICALS, INC.
Inventors:
Kevin J. Moriarty, Dora Do-York Wong, Zenon Konteatis, Kristofer Moffett, Younghee Lee, Wenchun Chao
Abstract: The invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit tyrosine kinase activity thereby making them useful as anticancer agents and for the treatment of Alzheimer's Disease.
Type:
Grant
Filed:
January 28, 2011
Date of Patent:
September 11, 2012
Assignee:
Bristol-Myers Squibb Company
Inventors:
Mark D. Wittman, Kurt Zimmermann, Xiaopeng Sang
Abstract: The present invention discloses triazene analogs of the general formula (I) and formula (II), their tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, and pharmaceutically acceptable salts thereof for the metastatic malignant melanoma and other cancers including but not limited to lymphomas, sarcomas, carcinomas, and gliomas. The invention further discloses a process for the preparation of the above said triazene analogs of formula (I) and formula (II), and their pharmaceutically acceptable compositions.
Abstract: Heterocyclic compounds derived from benzotriazine, triazines, triazoles and oxadiazoles are disclosed. The methods of synthesis and of use of such heterocyclic compounds are also provided.
Abstract: Disclosed herein are solubility changeable dye compositions, methods of preparing such compositions and methods of using them. The composition includes a dye component linked via a linker moiety to a stimulus responsive hydrophobic moiety which modulates the solubility of the dye, wherein the hydrophobic moiety is configured to be de-linked from the dye component on exposure to a stimulus and render the dye component more hydrophilic.
Abstract: A compound having an anti-viral activity, particularly a HIV integrase inhibitory activity, and a pharmaceutical composition, particularly an anti-HIV agent, of the formula: wherein R1, R2, R3, R4, B1 and B2 are defined in the specification.
Abstract: The present invention provides compounds useful as inhibitors of PDK1. The present invention also provides compositions thereof, and methods of treating PDK1-mediated diseases.
Type:
Application
Filed:
October 5, 2010
Publication date:
August 16, 2012
Inventors:
Joseph Arndt, Timothy Chan, Kevin Guckian, Gnanasambandam Kumaravel, Wen-Cherng Lee, Edward Yin-Shiang Lin, Daniel Scott, Lihong Sun, Jermaine Thomas, Kurt van Vloten, Deping Wang, Lei Zhang, Daniel Erlanson
Abstract: The present invention is directed to metabolites of (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan-2-ol, the compound of formula (I), pharmaceutical compositions thereof, and to methods of using the metabolites and the pharmaceutical compositions in the treatment of cancer.
Type:
Application
Filed:
October 4, 2010
Publication date:
August 2, 2012
Applicant:
Bristol-Myers Squibb Company
Inventors:
Jiachang Gong, Lisa J. Christopher, Vinod Kumar Arora
Abstract: An electron transport material based on fused aromatic electron-deficient compounds. The accumulation of aromatic rings with an electron deficiency allows free-radical anions to be stabilized very efficiently in these systems.
Abstract: This invention provides compounds having antiviral activities especially inhibiting activity for influenza virus, more preferably provides substituted 3-hydroxy-4-pyridone derivatives having cap-dependent endonuclease inhibitory activity.
Abstract: Specified phenylalanine derivatives and analogues thereof have an antagonistic activity to ?4 integrin. They are used as therapeutic agents for various diseases concerning ?4 integrin.
Abstract: The invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit protein kinase activity thereby making them useful as anticancer agents.
Abstract: This invention relates to novel pyrrozolotriazine compounds, pharmaceutical compositions containing such compounds and the use of those compounds and compositions for the prevention and/or treatment of hyper-proliferative disorders and diseases associated with angiogenesis.
Type:
Application
Filed:
March 7, 2012
Publication date:
June 28, 2012
Applicant:
Bayer HealthCare LLC
Inventors:
Julie Dixon, Barton Phillips, Yamin Wang, Tindy Li, Kyle Parcella, Jason Newcom, Harold C.E. Kluender, Zhenqiu Hong, Brent Chandler, Zhonghua Zhang, Steven Magnuson, Kristen M. Allegue, Zheng Liu
Abstract: 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:
Application
Filed:
August 27, 2010
Publication date:
June 21, 2012
Applicants:
GENENTECH, INC., ARRAY BIOPHARMA INC.
Inventors:
Ignacio Aliagas, Stefan Gradl, Janet Gunzner, Simon Mathieu, Rebecca Pulk, Joachim Rudolph, Zhaoyang Wen, Jonas Grina, Joshua D. Hansen, Ellen Laird, David Moreno, Li Ren, Steven Mark Wenglowsky
Abstract: The invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit tyrosine kinase activity thereby making them useful as anti-cancer agents and for the treatment of Alzheimer's Disease.
Abstract: Is to provide a novel compound having an anti-viral activity, particularly a HIV integrase inhibitory activity, and a pharmaceutical composition, particularly an anti-HIV agent. (wherein R1 is hydrogen or lower alkyl; X is lower alkylene etc.; R2 is optionally substituted aryl; R3 is hydrogen, halogen, hydroxy, optionally substituted lower alkyl etc.; R4 is hydrogen, optionally substituted lower alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkyl lower alkyl, optionally substituted aryl, optionally substituted aryl lower alkyl, optionally substituted heterocyclic group, optionally substituted heterocyclic lower alkyl etc.; A broken line indicates the presence or absence of a bond; B1 and B2 are such that any one of them is CR20R21, and the other is NR22 and, in this case, there is no broken line.
Abstract: In its many embodiments, the present invention provides a novel class of heterocyclic compounds of the formula: as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.
Type:
Application
Filed:
November 5, 2009
Publication date:
May 24, 2012
Inventors:
Zhaoning Zhu, William J. Greenlee, Mihir Baran Mandal, Duane A. Burnett, Chad E. Bennett, Troy McCracken
Abstract: Processes are provided for selectively preparing novel stable crystalline salt forms, selectively and consistently, namely, preparing Form N-1 of the methanesulfonic acid salt, and Form N-1 and Form N-4 of the hydrochloric acid salt of the p38 kinase inhibitor 4-[[5-[(cyclopropylamino)carbonyl]-2-methylphenyl]amino]-5-methyl-N-propylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide. The processes preferably employ solvent systems including formic acid/acetone and formic acid/methylethyl ketone which produce crystals having suitable flow properties and desired particle size, and solvents such as N,N-dimethylformamide and N,N-dimethylacetamide may be employed as well. Novel Form N-1 crystals of the Form N-1 and Form N-4 crystals of the hydrochloride salt and Form N-1 crystals of the methanesulfonic acid salt of the above free base, pharmaceutical compositions containing such novel forms and a method of treating p38 kinase associated conditions, including rheumatoid arthritis are also provided.
Type:
Application
Filed:
November 10, 2011
Publication date:
May 3, 2012
Inventors:
Soojin Kim, Mary F. Malley, Zhongping Shi
Abstract: This invention provides novel compounds that are modulators of gamma secretase. The compounds have the formula (I). Also disclosed are methods of modulating gamma secretase activity and methods of treating Alzheimer's Disease using the compounds of formula (I).
Type:
Application
Filed:
November 3, 2008
Publication date:
May 3, 2012
Inventors:
William J. Greenlee, Zhaoning Zhu, Theodros Asberom, Xianhai Huang, Hubert B. Josien
Abstract: Provided are methods for treating Orthomyxoviridae virus infections by administering ribosides, riboside phosphates and prodrugs thereof, of Formula I: wherein R2 is halogen. The compounds, compositions, and methods provided are particularly useful for the treatment of Human Influenza virus infections.
Type:
Application
Filed:
September 12, 2011
Publication date:
May 3, 2012
Applicant:
Gilead Sciences, Inc.
Inventors:
Michael O'Neil Hanrahan Clarke, Choung U. Kim, Willard Lew
Abstract: The invention relates to 2,4-dibromoropyrrolo[1,2-f][1,2,4]triazine, which is an intermediate useful in preparing 2,4-disubstituted pyrrolotriazine compounds, and a process for preparing the intermediate.
Abstract: The invention relates to 4-chloro-2-iodopyrrolo[1,2-f][1,2,4]triazine, which is an intermediate useful in preparing 2,4-disubstituted pyrrolotriazine compounds, and a process for preparing said intermediate.
Abstract: The disclosure provides biologically active compounds of formula (I): and pharmaceutically acceptable salts thereof, compositions containing these compounds, and methods of using these compounds in a variety applications, such as treatment of diseases or disorders associated with E1 type activating enzymes, and with Nedd8 activating enzyme (NAE) in particular.
Type:
Application
Filed:
September 12, 2011
Publication date:
March 29, 2012
Inventors:
Zhong Wang, Emilie D. Smith, James M. Veal, Kenneth H. Huang, Robert N. Atkinson, Rong Jiang
Abstract: This invention relates to novel pyrrozolotriazine compounds, pharmaceutical compositions containing such compounds and the use of those compounds or compositions for treating hyper-proliferative and/or angiogenesis disorders, as a sole agent or in combination with other active ingredients.
Type:
Grant
Filed:
December 1, 2006
Date of Patent:
March 27, 2012
Assignee:
Bayer HealthCare LLC
Inventors:
Julie A. Dixon, Barton Phillips, Furahi Achebe, Harold C. E. Kluender, Jason Newcom, Kyle Parcella, Steven Magnuson, Zhenqiu Hong, Zhonghua Zhang, Zheng Liu, Uday Khire, Lei Wang, Martin Michels, Brent Chandler, Stephen O'Connor
Abstract: The invention provides compounds of the formula (1): or salts or tautomers thereof; wherein X1 is N or N+(O?); X2 is N or CH; Q is a C1-3 alkylene group; R1 is selected from hydrogen, C1-4 hydrocarbyl and hydroxy-C2-4 hydrocarbyl; R2, R3 and R4 are the same or different and each is selected from hydrogen, fluorine, chlorine and methyl; Ar1 is an optionally substituted monocyclic 5 or 6-membered aryl or heteroaryl ring containing 0, 1 or 2 heteroatom ring members selected from O, N and S, or a naphthyl ring and Ar2 is an optionally substituted monocyclic 5 or 6-membered heteroaryl ring containing 1, 2 or 3 heteroatom ring members selected from O, N and S. The compounds of formula (1) are inhibitors of p70S6 kinase and are useful in the treatment of proliferative diseases.
Type:
Application
Filed:
May 26, 2010
Publication date:
March 22, 2012
Applicant:
Sentinel Oncology Limited
Inventors:
Robert George Boyle, David Winter Walker
Abstract: This invention relates to novel compounds and processes for their preparation, methods of treating diseases, particularly Cancer, comprising administering said compounds, and methods of making pharmaceutical compositions for the treatment or prevention of disorders, particularly Cancer.
Type:
Grant
Filed:
September 22, 2008
Date of Patent:
March 20, 2012
Assignee:
Bayer HealthCare LLC
Inventors:
Steven Magnuson, Philip Wickens, Zhonghua Zhang, Ning Qi, Xin Ma
Abstract: This invention relates to novel pyrrozolotriazine compounds, pharmaceutical compositions containing such compounds and the use of those compounds and compositions for the prevention and/or treatment of hyper-proliferative disorders and diseases associated with angiogenesis.
Type:
Grant
Filed:
November 30, 2006
Date of Patent:
March 13, 2012
Assignee:
Bayer HealthCare LLC
Inventors:
Julie Dixon, Steven Magnuson, Barton Phillips, Yamin Wang, Tandy Li, Kyle Parcella, Jason Newcom, Harold Kluender, Zhenqiu Hong, Brent Chandler, Zhonghua Zhang, Kristen Allegue, Zheng Liu
Abstract: This invention relates to novel pyrrozolotriazine compounds, pharmaceutical compositions containing such compounds and the use of those compounds or compositions for treating hyper-proliferative and/or angiogenesis disorders, as a sole agent or in combination with other active ingredients.
Type:
Grant
Filed:
September 2, 2009
Date of Patent:
March 6, 2012
Assignee:
Bayer HealthCare LLC
Inventors:
Julie A. Dixon, Barton Phillips, Furahi Achebe, Harold C. E. Kluender, Jason Newcom, Kyle Parcella, Steven Magnuson, Zhenqiu Hong, Zhonghua Zhang, Zheng Liu, Uday Khire, Lei Wang, Martin Michels, Brent Chandler, Stephen O'Connor
Abstract: Compounds that inhibit Aurora-kinases, compositions containing the compounds and methods of treating diseases using the compounds are disclosed.
Abstract: The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds are ligands for the nicotinic ?7 receptor and may be useful for the treatment of various disorders of the central nervous system, especially affective and neurodegenerative disorders.
Type:
Application
Filed:
October 10, 2011
Publication date:
February 9, 2012
Inventors:
James H. Cook, II, Ivar M. McDonald, Dalton King, Richard E. Olson, Nenghui Wang, Christiana I. Iwuagwu, F. Christopher Zusi, John E. Macor
Abstract: The present invention provides a compound of formula I or a salt form thereof, wherein Q1, Q2, Q3, and Q4 are as defined herein. The compound of formula I has ALK and/or JAK2 inhibitory activity, and may be used to treat proliferative disorders.
Type:
Application
Filed:
June 15, 2011
Publication date:
February 2, 2012
Applicant:
CEPHALON, INC.
Inventors:
Henry J. Breslin, Sankar Chatterjee, James L. Diebold, Bruce D. Dorsey, Derek D. Dunn, Diane E. Gingrich, Greg A. Hostetler, Robert L. Hudkins, Rachael Hunter, Kurt A. Josef, Joseph Lisko, Eugen F. Mesaros, Karen L. Milkiewicz, Gregory R. Ott, Babu G. Sundar, Jay P. Theroff, Tho Thieu, Rabindranath Tripathy, Theodore L. Underiner, Linda Weinberg, Gregory J. Wells, Craig A. Zificsak
Abstract: The present invention provides a pyrone derivative and a pyridone derivative, which are novel intermediates for synthesizing an anti-influenza drug, a method of producing the same, and a method of using the same.
Abstract: Described herein are antagonists of PGD2 receptors. Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such antagonists of PGD2 receptors, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other PGD2-dependent or PGD2-mediated conditions or diseases.
Abstract: A method for the treatment of nocturia which consists of administering to a mammal in need of such treatment a therapeutically effective amount of a nonsteroidal anti-inflammatory drug consisting of loxoprofen or a pharmacologically acceptable salt thereof, wherein the mammal is a human who has a neurogenic bladder.
Abstract: This invention relates to novel compounds of formula (I). Formula (I) in which the variable groups are as defined in the specification and claims, to pharmaceutical compositions containing them, and to a method of treatment using them for treatment of cancer.
Type:
Application
Filed:
November 2, 2006
Publication date:
December 1, 2011
Applicant:
BAYER HEALTHCARE AG
Inventors:
Stephen O'Connor, Jacques Dumas, Wendy Lee, Julie Dixon, David Cantin, David Gunn, Jennifer Burke, Barton Phillips, Derek Lowe, Tatiana Shelekhin, Gan Wang, Xin Ma, Shihong Ying, Andrea McClure, Furahi Achebe, Mario Lobell, Frederick Ehrgott, Christiana Iwuagwu, Kyle Parcella
Abstract: The present invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit tyrosine kinase activity of such as Jak2 and CK2, thereby making them useful as antiproliferative agents for the treatment of cancer and other diseases.
Type:
Application
Filed:
October 8, 2009
Publication date:
December 1, 2011
Inventors:
Ashok Vinayak Purandare, David B. Frennesson, Muthoni G. Kamau, Lalgudi S. Harikrishnan, Mark G. Saulnier
Abstract: The invention provides benzotriazine compounds having formula (I). The benzotriazine compounds of the invention are capable of inhibiting kinases, such members of the Src kinase family, and various other specific receptor and non-receptor kinases.
Type:
Application
Filed:
December 28, 2010
Publication date:
December 1, 2011
Applicant:
TargeGen, Inc.
Inventors:
Xianchang Gong, Kathy Barrett, Jianguo Cao, Colleen Gritzen, John D. Hood, Chi Ching Mak, Andrew McPherson, Ved Prakash Pathak, Joel Renick, Richard M. Soll, Ute Splittgerber, Wolfgang Wrasidlo, Ningning Zhao, Elena Dneprovskaia, Binqi Zeng, Glenn Noronha
Abstract: Crystalline forms of (3R,4R)-4-amino-1-[[4-[(3-methoxyphenyl)amino]pyrrolo[2,1-f][1,2,4]triazin-5-yl]methyl]piperidin-3-ol of the formula are provided. Also provided is a pharmaceutical composition comprising one or more crystalline forms of (3R,4R)-4-amino-1-[[4-[(3-methoxyphenyl)amino]pyrrolo[2,1-f][1,2,4]triazin-5-yl]methyl]piperidin-3-ol, as well as a method of using one or more crystalline forms of (3R,4R)-4-amino-1-[[4-[(3-methoxyphenyl)amino]pyrrolo[2,1-f][1,2,4]triazin-5-yl]methyl]piperidin-3-ol in the treatment of cancer and other proliferative diseases.
Abstract: Provided herein are pyrrolotriazine compounds for treatment of JAK kinase, including JAK2 kinase mediated diseases. Also provided are pharmaceutical compositions comprising the compounds and methods of using the compounds and compositions.
Type:
Application
Filed:
July 2, 2009
Publication date:
November 3, 2011
Inventors:
Sunny Abraham, Qi Chao, Michael Hadd, Mark Holladay, Gang Liu, Mitchell Nambu, Eduardo Setti
Abstract: The disclosure provides compounds of formula I, including Ia, Ib, Ic, or Id, including their salts, as well as compositions and methods of using the compounds. The compounds are ligands for the nicotinic ?7 receptor and may be useful for the treatment of various disorders of the central nervous system, especially affective and neurodegenerative disorders.
Type:
Application
Filed:
October 19, 2010
Publication date:
October 27, 2011
Inventors:
Ivar M. McDonald, Robert A. Mate, James H. Cook, II, Dalton King, Richard E. Olson, Nenghui Wang, Christiana I. Iwuagwu, F. Christopher Zusi, Matthew D. Hill, Haiquan Fang, John E. Macor
Abstract: The invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit tyrosine kinase activity of Trk receptors such as TrkA, TrkB, TrkC or Flt-3 thereby making them useful as anticancer agents.
Abstract: The present application provides compounds that are useful as MCHR1 antagonists, especially for the treatment of obesity, including all stereoisomers, solvates, prodrugs and pharmaceutically acceptable forms thereof according to Formula I wherein the variables are defined herein.
Type:
Application
Filed:
October 8, 2009
Publication date:
September 8, 2011
Inventors:
Pratik Devasthale, William N. Washburn, Kishore V. Renduchintala, Radhakrishnan Sridhar
Abstract: The invention relates to novel tricyclic 1,2,4-triazine-1-oxides and novel tricyclic 1,2,4-triazine-1,4-dioxides of formula I and to related analogues, to their preparation, and to their use as hypoxia-selective drugs and radiosensitizers for cancer therapy, both alone or in combination with radiation and/or other anticancer drugs.
Type:
Grant
Filed:
March 31, 2006
Date of Patent:
August 2, 2011
Assignee:
Auckland Uniservices Limited
Inventors:
Michael Patrick Hay, Adrian Blaser, William Alexander Denny, Kevin Owen Hicks, Ho Huat Lee, Karin Pchalek, Frederik Bastiaan Pruijn, Bronwyn Gae Siim, William Robert Wilson, Shangjin Yang