851886-82-3Relevant academic research and scientific papers
Design and Synthesis of Benzimidazoles As Novel Corticotropin-Releasing Factor 1 Receptor Antagonists
Mochizuki, Michiyo,Kori, Masakuni,Kobayashi, Katsumi,Yano, Takahiko,Sako, Yuu,Tanaka, Maiko,Kanzaki, Naoyuki,Gyorkos, Albert C.,Corrette, Christopher P.,Cho, Suk Young,Pratt, Scott A.,Aso, Kazuyoshi
, p. 2551 - 2566 (2016)
Benzazole derivatives with a flexible aryl group bonded through a one-atom linker as a new scaffold for a corticotropin-releasing factor 1 (CRF1) receptor antagonist were designed, synthesized, and evaluated. We expected that structural diversity could be expanded beyond that of reported CRF1 receptor antagonists. In a structure-activity relationship study, 4-chloro-N2-(4-chloro-2-methoxy-6-methylphenyl)-1-methyl-N7,N7-dipropyl-1H-benzimidazole-2,7-diamine 29g had the most potent binding activity against a human CRF1 receptor and the antagonistic activity (IC50 = 9.5 and 88 nM, respectively) without concerns regarding cytotoxicity at 30 μM. Potent CRF1 receptor-binding activity in brain in an ex vivo test and suppression of stress-induced activation of the hypothalamus-pituitary-adrenocortical (HPA) axis were also observed at 138 μmol/kg of compound 29g after oral administration in mice. Thus, the newly designed benzimidazole 29g showed in vivo CRF1 receptor antagonistic activity and good brain penetration, indicating that it is a promising lead for CRF1 receptor antagonist drug discovery research.
NITROGEN-CONTAINING FUSED HETEROCYCLIC COMPOUNDS
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Page/Page column 135-136, (2010/02/11)
There is provided a CRF receptor antagonist comprising a compound of the formula (I): wherein, ring A is a 5-membered ring represented by the formula (A'): wherein X is a carbon and X is an oxygen, a sulfur or - NR -,or formula (A"): wherein X is a nitrogen and R is an optionally substituted hydrocarbyl, Ris an amino substituted by two optionally substituted hydrocarbyl groups, Ris an phenyl, Y is CR or a nitrogen, Y is CRor a nitrogen and Yis CRor a nitrogen, provided that one or less of Y, Y, and Y is nitrogen, W is a bond, -(CH2)n-, and Z is a bond, -NR -,etc.; or a salt thereof or a prodrug thereof.
