- NEW FYN AND VEGFR2 KINASE INHIBITORS
-
The invention relates to a N-phenylcarbamoyl compound of Formula (I) or a pharmaceutically acceptable salt thereof for use in the inhibition of at least one of tyrosine kinase selected from Fyn and VEGFR2 in the treatment of diseases and disorders involved with one or both kinases. (Formula)
- -
-
Page/Page column 40; 41
(2021/06/22)
-
- Discovery of a Pyrimidinedione Derivative as a Potent and Orally Bioavailable Axl Inhibitor
-
The receptor tyrosine kinase Axl plays important roles in promoting cancer progression, metastasis, and drug resistance and has been identified as a promising target for anticancer therapeutics. We used molecular modeling-assisted structural optimization starting with the low micromolar potency compound 9 to discover compound 13c, a highly potent and orally bioavailable Axl inhibitor. Selectivity profiling showed that 13c could inhibit the well-known oncogenic kinase Met with equal potency to its inhibition of Axl superfamily kinases. Compound 13c significantly inhibited cellular Axl and Met signaling, suppressed Axl- and Met-driven cell proliferation, and restrained Gas6/Axl-mediated cancer cell migration or invasion. Furthermore, 13c exhibited significant antitumor efficacy in Axl-driven and Met-driven tumor xenograft models, causing tumor stasis or regression at well-tolerated doses. All these favorable data make 13c a promising therapeutic candidate for cancer treatment.
- Zhang, Hefeng,Peng, Xia,Dai, Yang,Shao, Jingwei,Ji, Yinchun,Sun, Yiming,Liu, Bo,Cheng, Xu,Ai, Jing,Duan, Wenhu
-
supporting information
p. 3956 - 3975
(2021/04/12)
-
- FUSED [1,2,4]THIADIAZINE DERIVATIVES WHICH ACT AS KAT INHIBITORS OF THE MYST FAMILY
-
A compound of formula (I): which inhibits the activity of one or more KATs of the MYST family, i.e., TIP60, KAT6B, MOZ, HBO1 and MOF.
- -
-
Page/Page column 113
(2019/03/17)
-
- Preparation and application of novel purine analogue JAK (janus kinase) inhibitor
-
The invention provides medicine for preventing, treating and/or relieving autoimmunity diseases such as Psoriasis, rheumatoid arthritis, inflammatory enteritis diseases, sjogren's syndrome, behcet's diseases, multiple sclerosis and systemic lupus erythematosus. The medicine has excellent JAK inhibitory activity. The invention also provides a medically acceptable composition containing the compoundand a method for preparing the compound.
- -
-
Paragraph 0159; 0166; 0167; 0168; 0169
(2018/09/21)
-
- NAPHTHYLAMIDE COMPOUND, PREPARATION METHOD AND USE THEREOF
-
The present invention relates to a naphthylamide compound of the structure as represented by formula (I), medicinal salts, prodrugs and hydrates or solvates thereof, and also relates to a method of preparing the compounds, pharmaceutical compositions comp
- -
-
Paragraph 0041
(2017/01/09)
-
- 2-AMINOPYRAZINE DERIVATIVES AS CSF-1 R KINASE INHIBITORS
-
The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt, N-oxide, hydrate or solvate thereof: wherein:ring A, R1, R2, n, X, V, W, Z, ring B, [Linker] and R areas defined herein. The compounds are useful as inhibitorsof CSF-1R kinase. The compounds can thus be used in medicine.
- -
-
Page/Page column 42; 43
(2014/01/17)
-
- PYRROLOTRIAZINONE DERIVATIVES AS PI3K INHIBITORS
-
New pyrrolotriazinone derivatives having the chemical structure of formula (I), are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Phosphoinositide 3-Kinases (PI3Ks)
- -
-
Page/Page column 129
(2014/05/07)
-
- SUBSTITUTED PYRIDOPYRAZINES AS NOVEL SYK INHIBITORS
-
Provided are pyridopyrazine compounds of formula (1), pharmaceutical compositions thereof and methods of use therefore, wherein R1, R2, R3, R4 and m are as defined in the specification.
- -
-
Paragraph 0281; 0282; 0283
(2014/05/08)
-
- 2,3-DISUBSTITUTED 1 -ACYL-4-AMINO-1,2,3,4-TETRAHYDROQUINOLINE DERIVATIVES AND THEIR USE AS BROMODOMAIN INHIBITORS
-
The present invention relates to novel compounds of formula (I), wherein R1 is C1-4alkyl; R2 is C1-4alkyl, C3-7cycloalkyl, -CH2CF3, -CH2OCH3 or heterocyclyl; R3 is C1-4alkyl, -CH2F, -CH2OH or -CH2O(O)CH3; R4 when present is as defined in claim 1; R5 when present is H, halo, hydroxy or C1-6alkoxy; A is -NH-, -O-, -S-, -SO-, -SO2-, -N(C1-4alkyl)- or -NC(O)(CH3)-; V is phenyl, heteroaromatic or pyridone any of which may be optionally substituted by 1, 2 or 3 substituents; W is CH or N; X is C or N; Y is C or N; and Z is CH or N; subject to the proviso that no more than 2 of W, X, Y and Z are N, pharmaceutical compositions containing such compounds and to their use as bromodomain inhibitors.
- -
-
Page/Page column 208
(2014/09/29)
-
- Synthesis and biological evaluation of 2-amino-5-aryl-3-benzylthiopyridine scaffold based potent c-Met inhibitors
-
A series of 2-amino-N-benzylpyridine-3-carboxnamides, 2-amino-N- benzylpyridine-3-sulfonamides and 2-amino-3-benzylthiopyridines against c-Met were designed by means of bioisosteric replacement and docking analysis. Optimization of the 2-amino-3-benzylthiopyridine scaffold led to the identification of compound (R)-10b displaying c-Met inhibition with an IC 50 up to 7.7 nM. In the cytotoxic evaluation, compound (R)-10b effectively inhibited the proliferation of c-Met addictive human cancer cell lines (IC50 from 0.19 to 0.71 μM) and c-Met activation-mediated cell metastasis. At a dose of 100 mg/Kg, (R)-10b evidently inhibited tumor growth (45%) in NIH-3T3/TPR-Met xenograft model. Of note, (R)-10b could overcome c-Met-activation mediated gefitinib-resistance, which indicated its potential use for drug combination. Taken together, 2-amino-3-benzylthiopyridine scaffold was first disclosed and exhibited promising pharmacological profiles against c-Met, which left room for further exploration.
- Zhang, Dengyou,Zhang, Xiaowei,Ai, Jing,Zhai, Yun,Liang, Zhongjie,Wang, Ying,Chen, Yi,Li, Chunpu,Zhao, Fei,Jiang, Hualiang,Geng, Meiyu,Luo, Cheng,Liu, Hong
-
p. 6804 - 6820
(2013/10/22)
-
- Thienopyridine ureas as dual inhibitors of the VEGF and Aurora kinase families
-
In an effort to identify multi-targeted kinase inhibitors with a novel spectrum of kinase activity, a screen of Abbott proprietary KDR inhibitors against a broad panel of kinases was conducted and revealed a series of thienopyridine ureas with promising activity against the Aurora kinases. Modification of the diphenyl urea and C7 moiety of these compounds provided potent inhibitors with good pharmacokinetic profiles that were efficacious in mouse tumor models after oral dosing. Compound 2 (ABT-348) of this series is currently undergoing Phase I clinical trials in solid and hematological cancer populations.
- Curtin, Michael L.,Frey, Robin R.,Heyman, H. Robin,Soni, Niru B.,Marcotte, Patrick A.,Pease, Lori J.,Glaser, Keith B.,Magoc, Terrance J.,Tapang, Paul,Albert, Daniel H.,Osterling, Donald J.,Olson, Amanda M.,Bouska, Jennifer J.,Guan, Zhiwen,Preusser, Lee C.,Polakowski, James S.,Stewart, Kent D.,Tse, Chris,Davidsen, Steven K.,Michaelides, Michael R.
-
scheme or table
p. 3208 - 3212
(2012/06/18)
-
- Tetrahydroquinoline Derivatives And Their Pharmaceutical Use
-
Tetrahydroquinoline compounds of formula (I) and salts thereof, pharmaceutical compositions containing such compounds and their use in therapy.
- -
-
Page/Page column 48
(2012/08/28)
-
- 5, 7-SUBSTITUTED-IMIDAZO [1, 2-C] PYRIMIDINES AS INHIBITORS OF JAK KINASES
-
Compounds of Formula I: (Formula should be inserted here) and stereoisomers and pharmaceutically acceptable salts and solvates thereof in which R1, R2, R3, R4, R5, R6, R7, X1 and X2 have the meanings given in the specification, are inhibitors of one or more JAK kinases and are useful in the treatment of autoimmune diseases, inflammatory diseases, rejection of transplanted organs, tissues and cells, as well as hematologic disorders and malignancies and their co-morbidities.
- -
-
Page/Page column 82-83
(2011/11/01)
-
- TETRAHYDROQUINOLINE DERIVATIVES AND THEIR PHARMACEUTICAL USE
-
Tetrahydroquinoline compounds of Formula (I) and salts thereof, pharmaceutical compositions containing such compounds and their use in therapy.
- -
-
Page/Page column 107
(2011/06/11)
-
- PYRROLOPYRIDINE AND PYRROLOPYRIMIDINE INHIBITORS OF KINASES
-
The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts, wherein A, B, R1, R2, R3, R4a, R5, and Z are defined in the description. The present invention relates also to methods of making said compounds, and compositions containing said compounds which are useful for inhibiting kinases such as aurora.
- -
-
Page/Page column 45
(2011/11/30)
-
- INDAZOLE INHIBITORS OF KINASE
-
The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts, wherein A1, A2, A3 and L are defined in the description. The present invention relates also to methods of making said compounds, and compositions containing said compounds which are useful for inhibiting kinases such as aurora and KDR.
- -
-
Page/Page column 21
(2011/11/30)
-
- PYRAZOLO [1, 5-A] PYRIMIDINE DERIVATIVES AS MTOR INHIBITORS
-
The present invention provides methods for inhibiting mTOR using pyrazolo[1,5-a]pyrimidine compounds and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with mTOR using such compounds.
- -
-
Page/Page column 359-360
(2010/11/03)
-
- cMET INHIBITORS
-
Compounds of the following formula are provided for use with cMET: wherein the variables are as defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful for making the compounds; and methods of using said compounds.
- -
-
Page/Page column 155
(2010/04/03)
-
- KINASE INHIBITORS WITH IMPROVED CYP SAFETY PROFILE
-
Compounds that inhibit protein kinases such as Aurora-kinases and the VEGFR and PDGFR families of kinases, with an improved safety profile due to low CYP3A4 inhibition, compositions containing the compounds and methods of treating diseases using the compounds are disclosed.
- -
-
Page/Page column 15
(2010/06/19)
-
- KINASE INHIBITOR COMPOUNDS
-
Pyridine and pyridazine derivatives have unexpected drug properties as inhibitors of protein kinases and are useful in treating disorders related to abnormal protein kinase activities such as cancer.
- -
-
Page/Page column 47
(2008/12/07)
-
- FUSED THIAZOLE DERIVATIVES AS KINASE INHIBITORS
-
A series of 5,5-dimethyl-5,6-dihydro-1,3-benzothiazol-7(4H)-one and 7,7-dimethyl-5,6,7,8-tetrahydro-4H-[1,3]thiazolo[5,4-c]azepin-4-one derivatives, and analogues thereof, which are substituted in the 2-position by an optionally substituted benzofused mor
- -
-
Page/Page column 35
(2008/06/13)
-