- Design, synthesis and SAR study of 2-aminopyridine derivatives as potent and selective JAK2 inhibitors
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The abnormal activation of JAK2 kinase is closely related to the occurrence and progression of myeloproliferative neoplasms (MPNs). At present, there is still an obvious unmet medical need for selective JAK2 inhibitors in clinic. In this paper, a class of 2-aminopyridine derivatives as potent and selective JAK2 inhibitors was obtained by combining drug design, synthesis and structure-activity relationship studies based on the previously identified lead Crizotinib. Among them, 21b exhibited high inhibitory activity against JAK2 with an IC50 of 9 9 nmol/L, moreover, it showed 276- and 184-fold selectivity over JAK1 and JAK3, respectively. Besides, 21b had a significant antiproliferative activity against HEL cells, and also inhibited the phosphorylation of JAK2 and its down-stream signaling pathway. These results indicated that 2-aminopyridine compound 21b had the potential to be developed as a selective JAK2 inhibitor for further study.
- Diao, Yanyan,Ge, Huan,Li, Honglin,Liu, Dandan,Liu, Wenjun,Xu, Fangling,Xu, Yufang,Zhao, Zhenjiang,Zhu, Lili
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supporting information
(2022/02/14)
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- Design, synthesis, and structure activity relationship (SAR) studies of novel imidazo[1,2-a] pyridine derivatives as Nek2 inhibitors
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Never in mitosis (NIMA) related kinase 2 (Nek2) is involved in multiple cellular processes such as cell cycle checkpoint regulation, cell division, DNA damage response and cell apoptosis. Nek2 has been reported to be overexpressed in various tumors and correlated with poor prognosis. Herein, a series of imidazo[1,2-a] pyridines Nek2 inhibitors were designed, synthesized, and their biological activities were investigated. Besides, structure activity relationship analysis of these compounds were performed in the MGC-803 cell. The screening results are promising, and compound 28e shows good proliferation inhibitory activity with an IC50 of 38 nM. The results would be helpful to design and develop more effective Nek2 inhibitors for the treatment of gastric cancer.
- Chen, Yunzhong,Du, Yijie,Duan, Yanhong,Gu, Xiaofan,Li, Hongyu,Ma, Mingliang,Ren, Ziwei,Wang, Haili,Wang, Shuting,Xi, Jianbei,Zhang, Xiongwen,Zhu, Tong
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- Imidazo [1, 2 - a] pyridine derivatives and preparation method and application thereof (by machine translation)
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The invention discloses 3 -phenyl imidazo [1, 2 - a] pyridine derivatives represented by a formula (I) or 3 - (thiophene -2 substituted) imidazo [1, 2 - a] pyridine derivatives and a preparation method, and also discloses application. of the 3 -phenyimidazo [1, 2 - a] pyridine derivatives or 3 - (thiophene -2 substituted) imidazo [1, 2 - a] pyridine derivatives as a class of novel structural novel small molecule inhibitors, and the like. (by machine translation)
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Paragraph 0116; 0126
(2019/07/29)
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- HETEROARYL COMPOUNDS AND PHARMACEUTICAL APPLICATIONS THEREOF
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The present invention provides herein is a heteroaryl compound or a stereoisomer, a geometric isomer, a tautomer, a racemate, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, as well as a pharmaceutical composition containing the compound disclosed herein. The present invention also provides herein is use of the compound or the pharmaceutical composition thereof disclosed herein in the manufacture of a medicine for treating autoimmune diseases or proliferative diseases.
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Paragraph 00719
(2016/01/25)
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- Hetaryl-[1,8]naphthyridine derivatives
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Novel hetaryl-[1,8]naphthyridine derivatives of formula (I) wherein R1, R2, W1, W3, W5 and W6 have the meaning according to claim 1, are inhibitors of ATP consuming proteins, and can be employed, inter alia, for the treatment of tumors.
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Paragraph 0306; 0307; 0308
(2013/03/26)
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- PYRIDAZINONE DERIVATIVES
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Compounds of the formula (I), in which R1, R2, R3, W and D have the meanings indicated in Claim 1, are inhibitors of tyrosine kinases, in particular of Met kinase, and can be employed, inter alia, for the treatment of tumours.
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Page/Page column 22
(2011/02/26)
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- DIHYDROPYRAZOLE DERIVATIVES AS TYROSINE KINASE MODULATORS FOR THE TREATMENT OF TUMORS
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Compounds of the formula I, in which R1, R2, R3′, R3, R4 and D have the meanings indicated in Claim 1, are inhibitors of tyrosine kinases, in particular Met kinase, and can be employed, inter alia, for the treatment of tumours.
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Page/Page column 21
(2011/04/18)
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- 3-(3-PYRIMIDIN-2-YLBENZYL)-1,2,4-TRIAZOLO[4,3-B]PYRIDAZINE DERIVATIVES AS MET KINASE INHIBITORS
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Compounds of the formula (I), in which R1, R2, R3, R3′, R4 have the meanings indicated in Claim 1, are inhibitors of tyrosine kinases, in particular of Met kinase, and can be employed, inter alia, for the treatment of tumours.
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Page/Page column 20-21
(2011/05/03)
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- HETARYL-[1,8]NAPHTHYRIDINE DERIVATIVES
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Novel hetaryl-[1,8]naphthyridine derivatives of formula (I) wherein R1, R2, W1, W3, W5 and W6 have the meaning according to claim 1, are inhibitors of ATP consuming proteins, and can be employed, inter alia, for the treatment of tumors.
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Page/Page column 93
(2011/09/14)
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- Pyridazinone derivatives
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Compounds of the formula (I) in which D, R1, R2, R3, R4 have the meanings indicated in Claim 1, are inhibitors of tyrosine kinases, in particular of Met kinase, and can be employed, inter alia, for the treatment
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Page/Page column 24
(2011/11/12)
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- PYRROLOPYRIDINE AND PYRROLOPYRIMIDINE INHIBITORS OF KINASES
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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.
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Page/Page column 40
(2011/11/30)
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- 3 (3-Pyrimidin-2-ylbenzyl)-1,2,4-triazolo[4,3-b]pyridazine derivatives
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Compounds of the formula (I), in which R1, R2, R3, R3′, R4 have the meanings indicated in claim 1, are inhibitors of tyrosine kinases, in particular Met kinase, and can be employed, inter alia, for th
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Page/Page column 23
(2011/10/31)
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- 2-BENZYLPYRIDAZINONE DERIVATIVES AS MET KINASE INHIBITORS
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Compounds of the formula I in which R1, R2, R3, R4′ have the meanings indicated in claim 1, are inhibitors of tyrosine kinases, in particular Met kinase, and can be employed, inter alia, for the treatment of tumours.
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Page/Page column 20-21
(2010/12/26)
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