844443-80-7Relevant articles and documents
Design, synthesis, and biological evaluation of 4-benzoylamino-1H-pyrazole-3-carboxamide derivatives as potent CDK2 inhibitors
Lin, Tingting,Li, Jiacheng,Liu, Liping,Li, Yuanqing,Jiang, Hualiang,Chen, Kaixian,Xu, Pan,Luo, Cheng,Zhou, Bing
, (2021/02/26)
Cyclin-dependent kinases play significant roles in cell cycle progression and are promising targets for cancer therapy. However, most potent CDK inhibitors lack the balance between efficacy and safety because of poor selectivity. Given the roles of CDK2 i
Tartaric acid addition salt of 3,4-disubstituted 1H-pyrazole compound and crystal form thereof
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Paragraph 0106-0109, (2019/05/15)
The invention provides one or more pharmaceutical composition of 4-(2,6-dichloro-benzoyl) amino)-1H-pyrazole-3-formate piperidine-4-yl-acyl tartaric acid addition salt, a crystallization form of the tartaric acid addition salt and use of the tartaric acid
Design and synthesis of 4-(Heterocyclic substituted amino)-1h-pyrazole-3-carboxamide derivatives and their potent activity against acute myeloid leukemia (AML)
Zhi, Yanle,Wang, Zhijie,Yao, Chao,Li, Baoquan,Heng, Hao,Cai, Jiongheng,Xiang, Li,Wang, Yue,Lu, Tao,Lu, Shuai
, (2019/11/21)
Fms-like receptor tyrosine kinase 3 (FLT3) has been emerging as an attractive target for the treatment of acute myeloid leukemia (AML). By modifying the structure of FN-1501, a potent FLT3 inhibitor, 24 novel 1H-pyrazole-3-carboxamide derivatives were designed and synthesized. Compound 8t showed strong activity against FLT3 (IC50: 0.089 nM) and CDK2/4 (IC50: 0.719/0.770 nM), which is more efficient than FN-1501(FLT3, IC50: 2.33 nM; CDK2/4, IC50: 1.02/0.39 nM). Compound 8t also showed excellent inhibitory activity against a variety of FLT3 mutants (IC50 50: 1.22 nM). In addition, compound 8t significantly inhibited the proliferation of most human cell lines of NCI60 (GI50 1 μM for most cell lines). Taken together, these results demonstrated the potential of 8t as a novel compound for further development into a kinase inhibitor applied in cancer therapeutics.
COMBINATIONS OF PYRAZOLE DERIVATIVES FOR THE INHIBITION OF CDKS AND GSK'S
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, (2010/02/17)
A combination comprising (a) a compound of formula (0): or salts or tautomers or N-oxides or solvates thereof; wherein X is R1-A-NR4— or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, SO2, C═O, NR9
PHARMACEUTICAL COMBINATIONS
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Page/Page column 368, (2008/06/13)
The invention provides combinations of an ancillary compound of the formula (0): and a compound of the formula (I'): Also provided are crystalline forms of the constituent compounds, methods for making them and their uses in treating cancers.
MEDICAL USE OF CYCLIN DEPENDENT KINASES INHIBITORS
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Page/Page column 111, (2010/11/29)
The invention provides the use of a compound for the manufacture of a medicament for the treatment of pain, wherein the compound is a compound of the formula (0) : or a salt or tautomers or N-oxides or solvate thereof; wherein X is a group R1-A
Identification of N-(4-piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H- pyrazole-3-carboxamide (AT7519), a novel cyclin dependent kinase inhibitor using fragment-based X-ray crystallography and structure based drug design
Wyatt, Paul G.,Woodhead, Andrew J.,Berdini, Valerio,Boulstridge, John A.,Carr, Maria G.,Cross, David M.,Davis, Deborah J.,Devine, Lindsay A.,Early, Theresa R.,Feltell, Ruth E.,Lewis, E. Jonathan,McMenamin, Rachel L.,Navarro, Eva F.,O'Brien, Michael A.,O'Reilly, Marc,Reule, Matthias,Saxty, Gordon,Seavers, Lisa C. A.,Smith, Donna-Michelle,Squires, Matt S.,Trewartha, Gary,Walker, Margaret T.,Woolford, Alison J.-A.
experimental part, p. 4986 - 4999 (2009/08/16)
The application of fragment-based screening techniques to cyclin dependent kinase 2 (CDK2) identified multiple (>30) efficient, synthetically tractable small molecule hits for further optimization. Structure-based design approaches led to the identification of multiple lead series, which retained the key interactions of the initial binding fragments and additionally explored other areas of the ATP binding site. The majority of this paper details the structure-guided optimization of indazole (6) using information gained from multiple ligand-CDK2 cocrystal structures. Identification of key binding features for this class of compounds resulted in a series of molecules with low nM affinity for CDK2. Optimisation of cellular activity and characterization of pharmacokinetic properties led to the identification of 33 (AT7519), which is currently being evaluated in clinical trials for the treatment of human cancers.
PHARMACEUTICAL COMBINATIONS OF DIAZOLE DERIVATIVES FOR CANCER TREATMENT
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Page/Page column 205, (2008/06/13)
The invention provides a combination comprising (or consisting essentially of) an ancillary compound and a compound of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein: R1 is 2,6-dichlorophenyl; R2a and R
4- (2,6-DICHLORO-BENZOYLAMINO) -1H-PYRAZOLE-3-CARBOXYLIC ACID (1-METHANESULPHONYL-PIPERIDIN-4-YL) -AMIDE FOR THE TREATMENT OF CANCER
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Page/Page column 77-78, (2010/11/29)
The invention provides the compound of formula (I) 4-(2,6-dichloro-benzoylamino)-1H-pyrazole- 3-carboxylic acid (l-methanesulphonyl-piperidin-4-yl)-amide in a substantially crystalline form, therapeutic uses thereof and pharmaceutical compositions contain
PHARMACEUTICAL COMPOUNDS
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Page/Page column 184, (2008/06/13)
The invention provides a combination of a cytotoxic compound or signalling inhibitor and a compound having the formula (0): or salts or tautomers or N-oxides or solvates thereof; wherein X is a group R1-A-NR4- or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, SO2, C=O, NRg(C=O) or 0(C=O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4alkoxy; Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length; R1 is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C1-8hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e.g. fluorine), hydroxy, C1-4 hydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from O, S, NH, SO, SO2; R2 is hydrogen; halogen; C1-4 alkoxy (e.g. methoxy); or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4alkoxy (e.g. methoxy); R3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; and R4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy).
