Ogawa H, Yamashita H, Kondo K, Yamamura Y, Miyamoto H, Kan K, Kitano K, Tanaka M, Nakaya K, Nakamura S, Mori T, Tominaga M, Yabuuchi Y
Second Institute of New Drug Research, Otsuka Pharmaceutical Co., Tokushima, Japan.
J Med Chem. 1996 Aug 30;39(18):3547-55. doi: 10.1021/jm960133o.
This paper describes a novel series of nonpeptide vasopressin V2 receptor antagonists. It has been demonstrated that the 1-[4-(benzoylamino)benzoyl]-2,3,4,5-1H-benzazepines and 1-[4-(benzoylamino)benzoyl]-2,3,4,5-1H-1,5-benzodiazepines show a high affinity for V2 (and V1a) receptors. Among the 1-[4-(benzoylamino)benzoyl]-2,3,4,5-1H-benzazepine series, compounds with an alkylamino group on the benzazepine ring have been shown to have oral activity. A lipophilic group at the ortho position on the terminal benzoyl ring is important for both high V2 receptor affinity and oral activity. On the basis of these favorable properties, clinical testing of 31b has begun for use as an oral and iv aquaretic agent.
本文描述了一系列新型非肽类血管加压素V2受体拮抗剂。已证明1-[4-(苯甲酰氨基)苯甲酰基]-2,3,4,5-1H-苯并氮杂卓和1-[4-(苯甲酰氨基)苯甲酰基]-2,3,4,5-1H-1,5-苯并二氮杂卓对V2（和V1a）受体具有高亲和力。在1-[4-(苯甲酰氨基)苯甲酰基]-2,3,4,5-1H-苯并氮杂卓系列中，苯并氮杂卓环上带有烷基氨基的化合物已显示具有口服活性。末端苯甲酰环邻位的亲脂性基团对于高V2受体亲和力和口服活性均很重要。基于这些有利特性，31b已开始作为口服和静脉注射利水剂进行临床试验。
