Syntheses of phenylpyrazolodiazepin-7-ones as conformationally rigid analogs of aminopyrazole amide scaffold and their antiproliferative effects on cancer cells
- Authors
- Kim, Hyangmi; Kim, Minjung; Lee, Junghun; Yu, Hana; Hah, Jung-Mi
- Issue Date
- Nov-2011
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Keywords
- Dihydropyrazolodiazepinone; Antiproliferative activity; Cancer cell line; Kinase inhibitor; Kinase selectivity
- Citation
- BIOORGANIC & MEDICINAL CHEMISTRY, v.19, no.22, pp.6760 - 6767
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOORGANIC & MEDICINAL CHEMISTRY
- Volume
- 19
- Number
- 22
- Start Page
- 6760
- End Page
- 6767
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/36407
- DOI
- 10.1016/j.bmc.2011.09.042
- ISSN
- 0968-0896
- Abstract
- Recently, we have reported the syntheses and antiproliferative activities of N-(5-amino-1-(4-methoxybenzyl)-1H-pyrazol-4-yl amide derivatives on melanoma cells. As a continuous work for antiproliferative agents in melanoma, here we report the synthesis of conformationally rigid analogs, phenyl-6,8-dihydropyrazolo[3,4-b][1,4] diazepin-7(1H)-one derivatives7a-g, 8a-o and their antiproliferative activities against A375P melanoma cell line and U937 hematopoietic cell line. Most compounds showed competitive antiproliferative activities to sorafenib, the reference standard. Among them, N-(3-(1-benzyl-7-oxo-1,6, 7,8-tetrahydropyrazolo[3,4-b][1,4]diazepin-5-yl)phenyl)-4-chloro-3-(trifluoro methyl)benzamide-amino1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-5-(3-(4-chloro-3-(trifluoromethyl) phenyl) ureido)-2-methylbenzamide (7b) exhibited potent activities (GI(50) = 0.43 mu M and 0.06 mu M) on both cell lines. It has been further confirmed to be a potent and selective Raf kinases inhibitor and also mild inhibitor of PI3K alpha. (C) 2011 Elsevier Ltd. All rights reserved.
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