- Preparation method of flumatinib intermediate
-
The invention relates to a preparation method of a flumatinib intermediate, and particularly relates to a synthesis process of an antitumor drug flumatinib intermediate. The preparation method specifically comprises the steps of firstly, synthesizing 4-((4-methylpiperazine-1-yl)methyl)-3-(trifluoromethyl)benzamide(III); secondly, synthesizing 5-bromine-2-methyl-3-nitropyridine(VI); and thirdly, synthesizing N-(6-methyl-5-nitropyridine-3-yl)-4-((4-methylpiperazine-1-yl)methyl)-3-(trifluoromethyl)benzamide(VII). The invention aims to provide a preparation method of the flumatinib intermediate,which is simple to operate, available in raw materials, short in reaction steps, high in yield and environment-friendly.
- -
-
-
- HEPARAN SULFATE BIOSYNTHESIS INHIBITORS FOR THE TREATMENT OF DISEASES
-
Described herein are compounds of Formula I, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or conditions in need of inhibition of heparan sulfate biosynthesis.
- -
-
-
- 5-Alkynyl-pyridines
-
This invention relates to 5-alkynyl-pyridine of general formula (I) their use as inhibitors of the activity of PI3Kalpha, pharmaceutical compositions containing them, and their use as a medicaments for the treatment and/or prevention of diseases characterized by excessive or abnormal cell proliferation and associated conditions such as cancer. The groups R1 to R6 and n have the meanings given in the claims and in the specification
- -
-
-
- SUBSTITUTED BENZOFURAN COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES
-
The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.
- -
-
-
- NEW 5-ALKYNYL-PYRIDINES
-
5-alkynyl-pyridine of general formula (I) which are inhibitors of the activity of PI3K alpha, and their use in the treatment of diseases characterized by excessive or abnormal cell proliferation, such as cancer.
- -
-
-
- SUBSTITUTED BENZOFURAN COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES
-
The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5B polymerase inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5B polymerase activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.
- -
-
-
- Discovery of a potent and orally bioavailable benzolactam-derived inhibitor of polo-like kinase 1 (MLN0905)
-
This article describes the discovery of a series of potent inhibitors of Polo-like kinase 1 (PLK1). Optimization of this benzolactam-derived chemical series produced an orally bioavailable inhibitor of PLK1 (12c, MLN0905). In vivo pharmacokinetic-pharmacodynamic experiments demonstrated prolonged mitotic arrest after oral administration of 12c to tumor bearing nude mice. A subsequent efficacy study in nude mice achieved tumor growth inhibition or regression in a human colon tumor (HT29) xenograft model.
- Duffey, Matthew O.,Vos, Tricia J.,Adams, Ruth,Alley, Jennifer,Anthony, Justin,Barrett, Cynthia,Bharathan, Indu,Bowman, Douglas,Bump, Nancy J.,Chau, Ryan,Cullis, Courtney,Driscoll, Denise L.,Elder, Amy,Forsyth, Nancy,Frazer, Jonathan,Guo, Jianping,Guo, Luyi,Hyer, Marc L.,Janowick, David,Kulkarni, Bheemashankar,Lai, Su-Jen,Lasky, Kerri,Li, Gang,Li, Jing,Liao, Debra,Little, Jeremy,Peng, Bo,Qian, Mark G.,Reynolds, Dominic J.,Rezaei, Mansoureh,Scott, Margaret Porter,Sells, Todd B.,Shinde, Vaishali,Shi, Qiuju Judy,Sintchak, Michael D.,Soucy, Francois,Sprott, Kevin T.,Stroud, Stephen G.,Nestor, Michelle,Visiers, Irache,Weatherhead, Gabriel,Ye, Yingchun,Damore, Natalie
-
p. 197 - 208
(2012/03/10)
-
- 2-ARYLIMIDAZO[1,2-B]PYRIDAZINE, 2-PHENYLIMIDAZO[1,2-A]PYRIDINE, AND 2-PHENYLIMIDAZO[1,2-A]PYRAZINE DERIVATIVES
-
Disclosed are compounds of formula (I): (Formula (I) where X, Y, X, A, R1; R2, and R3 are defined herein. Also disclosed are pharmaceutically acceptable salts of the compounds, compositions containing the compounds, and methods of using the compounds to treat, e.g., cancer.
- -
-
-
- PYRAZOLOPIPERIDINE COMPOUNDS AS CCR1 RECEPTOR ANTAGONISTS
-
Disclosed are compounds of the formula (I), useful for treating a variety of diseases and disorders that are mediated or sustained through the activity of CCR1 including autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis. Also disclosed are methods of making and methods of using same.
- -
-
-
- NEW 5-ALKYNYL-PYRIDINES
-
This invention relates to 5-alkynyl-pyridine of general formula (I) their use as inhibitors of the activity of PI3Kalpha, pharmaceutical compositions containing them, and their use as a medicaments for the treatment and/or prevention of diseases characterized by excessive or abnormal cell proliferation and associated conditions such as cancer. The groups R1 to R6 and n have the meanings given in the claims and in the specification.
- -
-
-
- NEW 5-ALKYNYL-PYRIDINES
-
This invention relates to 5-alkynyl-pyridine of general formula (I) their use as inhibitors of the activity of P13Kalpha, pharmaceutical compositions containing them, and their use as a medicaments for the treatment and/or prevention of diseases characterized by excessive or abnormal cell proliferation and associated conditions such as cancer. The groups R1 to R6 and n have the meanings given in the claims and in the specification.
- -
-
-
- N1/N2-Lactam Acetyl-CoA carboxylase inhibitors
-
The invention provides a compound of Formula (I) or a pharmaceutically acceptable salt thereof; wherein G is R1, R2 and R3 are as described herein; pharmaceutical compositions thereof; and the use thereof in treating diseases, conditions or disorders modulated by the inhibition of an acetyl-CoA carboxylase enzyme(s) in an animal
- -
-
-
- Discovery and optimization of a series of benzothiazole phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) dual inhibitors
-
Phosphoinositide 3-kinase α (PI3K-α) is a lipid kinase that plays a key regulatory role in several cellular processes. The mutation or amplification of this kinase in humans has been implicated in the growth of multiple tumor types. Consequently, PI3K- has become a target of intense research for drug discovery. Our studies began with the identification of benzothiazole compound 1 from a high throughput screen. Extensive SAR studies led to the discovery of sulfonamide 45 as an early lead, based on its in vitro cellular potency. Subsequent modifications of the central pyrimidine ring dramatically improved enzyme and cellular potency and led to the identification of chloropyridine 70. Further arylsulfonamide SAR studies optimized in vitro clearance and led to the identification of 82 as a potent dual inhibitor of PI3K and mTOR. This molecule exhibited potent enzyme and cell activity, low clearance, and high oral bioavailability. In addition, compound 82 demonstrated tumor growth inhibition in U-87 MG, A549, and HCT116 tumor xenograft models.
- D'Angelo, Noel D.,Kim, Tae-Seong,Andrews, Kristin,Booker, Shon K.,Caenepeel, Sean,Chen, Kui,D'Amico, Derin,Freeman, Dan,Jiang, Jian,Liu, Longbin,McCarter, John D.,San Miguel, Tisha,Mullady, Erin L.,Schrag, Michael,Subramanian, Raju,Tang, Jin,Wahl, Robert C.,Wang, Ling,Whittington, Douglas A.,Wu, Tian,Xi, Ning,Xu, Yang,Yakowec, Peter,Yang, Kevin,Zalameda, Leeanne P.,Zhang, Nancy,Hughes, Paul,Norman, Mark H.
-
p. 1789 - 1811
(2011/05/16)
-
- N1-PYRAZOLOSPIROKETONE ACETYL-COA CARBOXYLASE INHIBITORS
-
The invention provides a compound of Formula (I) or a pharmaceutically acceptable salt of the compound, wherein R1, R2, R3 and R4 are as described herein; pharmaceutical compositions there-of; and the use thereof in treating diseases, conditions or disorders modulated by the inhibition of an acetyl- CoA carboxylase enzyme(s) in an animal
- -
-
-
- N2-PYRAZOLOSPIROKETONE ACETYL-COA CARBOXYLASE INHIBITORS
-
The invention provides a compound of Formula (I) or a pharmaceutically acceptable salt of said compound, wherein R1, R2, R3 and R4 are as described herein; pharmaceutical compositions thereof; and the use thereof in treating diseases, conditions or disorders modulated by the inhibition of an acetyl- CoA carboxylase enzyme(s) in an animal.
- -
-
-
- AZAINDOLE DERIVATIVES AS KINASE INHIBITORS
-
This invention relates to compounds of the general formula (I) in which the variable groups are as defined herein, and to their preparation and use.
- -
-
Page/Page column 78
(2010/07/02)
-
- 5, 7-DIHYDRO- 6H-PYRIMIDO [ 5, 4-D] [ 1 ] BENZAZEPIN-6-THIONES AS PLK INHIBITORS
-
This invention provides compounds of formula I: wherein R1, R2, R3, R4, R5, and R6 are as described in the specification. The compounds are inhibitors of PLK and are thus useful for treating proliferative, inflammatory, or cardiovascular disorders.
- -
-
Page/Page column 89-90
(2010/06/20)
-
- 1H-IMIDAZO[4,5-c]QUINOLINONE DERIVATIVES
-
The invention relates to the use of 1H-imidazo[4,5-c]quinolinone derivatives and salts thereof in the treatment of protein and/or lipid kinase dependent diseases and for the manufacture of pharmaceutical preparations for the treatment of said diseases; 1H-imidazo[4,5-c] quinolinone derivatives for use in the treatment of protein and/or lipid kinase dependent diseases; a method of treatment against said diseases, comprising administering the 1H- imidazo[4,5-c] quinofinone derivatives to a warm-blooded animal, especially a human; pharmaceutical preparations comprising an 1H-imidazo[4,5-c] quinolinone derivative, especially for the treatment of a protein and/or lipid kinase dependent disease; novel 1 H- imidazo[4,5-c] quinolinone derivatives; and a process for the preparation of the novel 1H- imidazo[4,5-c] quinolinone derivatives.
- -
-
Page/Page column 184-185
(2010/12/29)
-
- 1H-IMIDAZO[4, 5-c]QUINOLINONE COMPOUNDS, USEFUL FOR THE TREATMENT OF PROLIFERATIVE DISEASES
-
The invention relates to the use of 1 H-imidazo[4,5-c]quinolinone compounds and salts thereof in the treatment of protein and/or lipid kinase dependent diseases and for the manufacture of pharmaceutical preparations for the treatment of said diseases; 1 H-imidazo[4,5-c]quinolinone compounds for use in the treatment of protein and/or lipid kinase dependent diseases; a method of treatment against said diseases, comprising administering the 1 H-imidazo[4,5-c]quinolinone compounds to a warm-blooded animal, especially a human; pharmaceutical preparations comprising an 1 H-imidazo[4,5-c]quinolinone compounds, especially for the treatment of a protein and/or lipid kinase dependent disease; novel 1 H-imidazo[4,5-c]quinolinone compounds; and a process for the preparation of the novel 1 H-imidazo[4,5-c]quinolinone compounds.
- -
-
Page/Page column 119; 129-130
(2010/12/29)
-
- PI3 KINASE MODULATORS AND METHODS OF USE
-
The present invention comprises a new class of compounds capable of modulating the activity of PI3 kinase and, accordingly, useful for treatment of PI3 kinase mediated diseases, including melanomas, carcinomas and other cancer-related conditions. The compounds have a general Formula I wherein each of A1, A2, A3, A4, X, R1 and R2 are defined herein. The invention further comprises pharmaceutical compositions, methods for treatment of PI3 kinase mediated diseases, and intermediates and processes useful for the preparation of compounds of the invention.
- -
-
Page/Page column 73-74
(2009/03/07)
-
- PYRIDOSULFONAMIDE DERIVATIVES AS PI3 KINASE INHIBITORS
-
Invented is a method of inhibiting the activity/function of PB kinases using pyridosulfonamide derivatives. Also invented is a method of treating 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 by the administration of pyridosulfonamide derivatives.
- -
-
Page/Page column 77-78
(2009/05/30)
-
- Aminopyrimidine Derivatives With Tie2 Inhibiting Activity
-
The invention relates to a compound of the Formula I or salt thereof wherein Rx, Ry, Rx, R5, R6, A, B, L, n and m are as defined in the description. The invention also relates to pharmaceutical compositions of said compounds, the use of said compounds as medicaments and in the production of an anti-angiogenic effect in a warm blooded animal. The invention also relates to processes for the preparation of said compounds.
- -
-
Page/Page column 40
(2008/12/07)
-
- QUINOXALINE DERIVATIVES AS PI3 KINASE INHIBITORS
-
Invented is a method of inhibiting the activity/function of PI3 kinases using quinoxaline derivatives. Also invented is a method of treating 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 by the administration of quinoxaline derivatives.
- -
-
Page/Page column 86
(2009/01/20)
-
- QUINAZOLINE DERIVATIVES AS PI3 KINASE INHIBITORS
-
Invented is a method of inhibiting the activity/function of P13 kinases using quinazoline derivatives. Also invented is a method of treating 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 by the administration of quinazoline derivatives.
- -
-
Page/Page column 83-84
(2009/01/23)
-
