620948-83-6Relevant articles and documents
Discovery and optimization of novel phenyldiazepine and pyridodiazepine based Aurora kinase inhibitors
Tamizharasan, Natarajan,Gajendran, Chandru,Kristam, Rajendra,Sulochana, Suresh P.,Sivanandhan, Dhanalakshmi,Mullangi, Ramesh,Mathivathanan, Logesh,Hallur, Gurulingappa,Suresh, Palaniswamy
, (2020/04/15)
Aurora B plays critical role in the process of chromosome condensation and chromosome orientation during the regulation of mitosis. The overexpression of Aurora B has been observed in several tumor types. As a part of our ongoing effort to develop Aurora B inhibitors, herein, we described the design, synthesis and evaluation of phenyl/pyridine diazepine analogs. The diazepane aniline pyrimidine (4a) was identified as an initial hit (Aurora B IC50 6.9 μM). Molecular modeling guided SAR optimization lead to the identification of 8-fluorobenzodiazepine (6c) with single digit nM potency (Aurora B IC50 8 nM). In the antiproliferation assay 6c showed activity across the cell lines with IC50 of 0.57, 0.42, and 0.69 μM for MCF-7, MDA-MB 231, and SkoV3 respectively. In the in vivo PK profile. 6c has shown higher bioavailability (73%) along with good exposure (AUC of 1360 ng.h/mL).
Design, synthesis, and pharmacological evaluation of fused β-homophenylalanine derivatives as potent DPP-4 inhibitors
Jiang, Tao,Zhou, Yuren,Chen, Zhuxi,Sun, Peng,Zhu, Jianming,Zhang, Qiang,Wang, Zhen,Shao, Qiang,Jiang, Xiangrui,Li, Bo,Chen, Kaixian,Jiang, Hualiang,Wang, Heyao,Zhu, Weiliang,Shen, Jingshan
, p. 602 - 606 (2015/05/27)
Dipeptidyl peptidase-4 (DPP-4) inhibitors are accepted as a favorable class of agents for the treatment of type 2 diabetes. Herein, a series of fused β-homophenylalanine derivatives as novel DPP-4 inhibitors were designed, synthesized, and evaluated for their inhibitory activities against DPP-4. Most of them displayed excellent DPP-4 inhibitory activities and good selectivity. Among them, 9aa, 18a, and 18m also showed good efficacy in an oral glucose tolerance test (OGTT) in ICR mice. Moreover, when dosed 8 h prior to glucose challenge, 18m showed significantly greater potency than sitagliptin. It thus provides potential candidates for the further development into potent drugs targeting DPP-4.
Cycloalkyl[b][1,4]benzodiazepinoindoles are agonists at the human 5-HT 2C receptor
Sabb, Annmarie L.,Vogel, Robert L.,Welmaker, Gregory S.,Sabalski, Joan E.,Coupet, Joseph,Dunlop, John,Rosenzweig-Lipson, Sharon,Harrison, Boyd
, p. 2603 - 2607 (2007/10/03)
Evaluation of selected compounds from our Corporate Compound Library in a human 5-HT2C receptor binding assay led to the discovery of WAY-629, a cyclohexyl[b][1,4]benzodiazepinoindole (Ki 56nM, Emax 90%), which is selectiv
[1,4]Diazepino[6,7,1-ij]quinoline derivatives as antipsychotic and antiobesity agents
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Page/Page column 18, (2008/06/13)
Compounds of Formula I or a pharmaceutically acceptable salt thereof are provided: where R1 through R7 are defined herein. The compounds of Formula I are 5HT2c agonists or partial agonists, and are useful for treating a variety of di
