1013116-83-0Relevant articles and documents
Pyrrolopyrimidine BTK inhibitor as well as preparation method and application thereof
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Paragraph 0095-0097, (2021/11/03)
The invention provides a pyrrolopyrimidine BTK inhibitor as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The compound has the structural general formula shown in a formula (I). In-flight
1,4,6-Trisubstituted imidazo[4,5-c]pyridines as inhibitors of Bruton's tyrosine kinase
Kraj?ovi?ová, Soňa,Jorda, Radek,Vanda, David,Soural, Miroslav,Kry?tof, Vladimír
, (2020/12/21)
Herein, we report an efficient synthetic approach towards trisubstituted imidazo [4,5-c]pyridines designed as inhibitors of Bruton's tyrosine kinase (BTK). Two alternative synthetic routes for the simple preparation of desired compounds with variable substitutions at the N1, C4, C6 positions were introduced with readily available building blocks. Further, the developed synthetic approach was feasible for isomeric compounds bearing imidazo [4,5-b]pyridine scaffolds. In contrast to expectations based on previous studies, the imidazo [4,5-c]pyridine inhibitor exhibited a significantly higher activity against BTK compared to its imidazo [4,5-b]pyridine isomer. An inherent SAR study in the series of imidazo [4,5-c]pyridine compounds revealed a remarkably high tolerance of C6 substitutions for both hydrophobic and hydrophilic substituents. Preliminary cellular experiments indicated selective BTK targeting in Burkitt lymphoma and mantle cell lymphoma cell lines. The inhibitors could thus serve as starting points for further development, eventually leading to BTK inhibitors that could be used after ibrutinib failure.
NOVEL IRREVERSIBLE BRUTON'S TYROSINE KINASE INHIBITOR
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, (2019/01/04)
The present invention provides an inhibitor of Bruton's tyrosine kinase, which is a compound of formula (I), or its pharmaceutically acceptable salt, solvate, ester, acid, metabolite or prodrug. The present invention also provides a pharmaceutical composition comprsing the compound. The present invention also provides a method for inhibiting the activity of tyrosine kinase activity or for treating a disease, disorder, or condition, which would benefit from the inhibition of Bruton's tyrosine kinase(s), by using the Bruton's tyrosine kinase inhibitor, as well as application of the Bruton's tyrosine kinase inhibitor for the same.
Design and synthesis of novel pyrimidine analogs as highly selective, non-covalent BTK inhibitors
Kawahata, Wataru,Asami, Tokiko,Irie, Takayuki,Sawa, Masaaki
, p. 145 - 151 (2017/12/06)
BTK is a promising target for the treatment of multiple diseases such as B cell malignances, asthma, and rheumatoid arthritis. Here, we report the discovery of a series of novel pyrimidine analogs as potent, highly selective, non-covalent inhibitors of BTK. Compound 25d demonstrated higher affinity to an unactivated conformation of BTK that resulted in an excellent kinase selectivity. Compound 25d showed a good oral bioavailability in mice, and significantly inhibits the PCA reaction in mice.
PYRAZOLO[3,4-b]PYRIDINE AND PYRROLO[2,3-b]PYRIDINE INHIBITORS OF BRUTON'S TYROSINE KINASE
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Paragraph 0751; 0762, (2018/07/31)
Disclosed are pyrazolo[3,4-b]pyridine and pyrrolo[2,3-b]pyridine inhibitors of Bruton's tyrosine kinase (Btk). Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are described, alone or in combin
Discovery of N-(3-(5-((3-acrylamido-4-(morpholine-4-carbonyl)phenyl)amino)-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-methylphenyl)-4-(tert-butyl)benzamide (CHMFL-BTK-01) as a highly selective irreversible Bruton's tyrosine kinase (BTK) inhibitor
Liang, Qianmao,Chen, Yongfei,Yu, Kailin,Chen, Cheng,Zhang, Shouxiang,Wang, Aoli,Wang, Wei,Wu, Hong,Liu, Xiaochuan,Wang, Beilei,Wang, Li,Hu, Zhenquan,Wang, Wenchao,Ren, Tao,Zhang, Shanchun,Liu, Qingsong,Yun, Cai-Hong,Liu, Jing
, p. 107 - 125 (2017/03/21)
Currently there are several irreversible BTK inhibitors targeting Cys481 residue under preclinical or clinical development. However, most of these inhibitors also targeted other kinases such as BMX, JAK3, and EGFR that bear the highly similar active cysteine residues. Through a structure-based drug design approach, we discovered a highly potent (IC50: 7?nM) irreversible BTK inhibitor compound 9 (CHMFL-BTK-01), which displayed a high selectivity profile in KINOMEscan (S score (35)?=?0.00) among 468 kinases/mutants at the concentration of 1?μM. Compound 9 completely abolished BMX, JAK3 and EGFR's activity. Both X-ray crystal structure and cysteine-serine mutation mediated rescue experiment confirmed 9's irreversible binding mode. 9 also potently inhibited BTK Y223 auto-phosphorylation (EC50: 30?nM), arrested cell cycle in G0/G1 phase and induced apoptosis in U2932 and Pfeiffer cells. We believe these features would make 9 a good pharmacological tool to study the BTK related pathology.
NOVEL TRIAZINE DERIVATIVE
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Paragraph 0088; 0089, (2015/02/02)
To provide a novel triazine derivative represented by the following formula (I): A triazine derivative represented by the following formula (I) : wherein R1 represents a substituted or unsubstituted aryl group, a substituted or unsubstituted he
Design, synthesis and evaluation of novel 5-phenylpyridin-2(1H)-one derivatives as potent reversible Bruton's tyrosine kinase inhibitors
Zhao, Xinge,Xin, Minhang,Huang, Wei,Ren, Yanliang,Jin, Qiu,Tang, Feng,Jiang, Hailong,Wang, Yazhou,Yang, Jie,Mo, Shifu,Xiang, Hua
, p. 348 - 364 (2015/02/05)
A series of novel reversible Btk inhibitors has been designed based on the structure of the recently reported preclinical drug RN486. The synthesis and SAR of these compounds are described. Among these derivatives, compound 16b was identified to be a potent and orally available reversible agent with satisfactory Btk enzymatic and cellular inhibition in vitro, as well as favorable PK properties and inhibition of arthritis in vivo.
