7-Chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoyl-amino)benzoyl ]-2,3,4,5-tetrahydro-1H-1-benzazepine (OPC-41061): a potent, orally active nonpeptide arginine vasopressin V2 receptor antagonist

K Kondo; H Ogawa; H Yamashita; H Miyamoto; M Tanaka; K Nakaya; K Kitano; Y Yamamura; S Nakamura; T Onogawa; T Mori; M Tominaga

doi:10.1016/s0968-0896(99)00101-7

7-Chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoyl-amino)benzoyl ]-2,3,4,5-tetrahydro-1H-1-benzazepine (OPC-41061): a potent, orally active nonpeptide arginine vasopressin V2 receptor antagonist

Bioorg Med Chem. 1999 Aug;7(8):1743-54. doi: 10.1016/s0968-0896(99)00101-7.

Authors

K Kondo¹, H Ogawa, H Yamashita, H Miyamoto, M Tanaka, K Nakaya, K Kitano, Y Yamamura, S Nakamura, T Onogawa, T Mori, M Tominaga

Affiliation

¹ Second Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Co., Ltd., Japan.

PMID: 10482466
DOI: 10.1016/s0968-0896(99)00101-7

Abstract

We previously reported a series of benzazepine derivatives as orally active nonpeptide arginine vasopressin (AVP) V2 receptor antagonists. After the lead structure OPC-31260 was structurally evaluated and optimized, the introduction of the 7-Cl moiety on the benzazepine and 2-CH3 on the aminobenzoyl moiety enhanced its oral activity. The new AVP-V2 selective antagonist OPC-41061 was determined to be a potent and orally active agent.

MeSH terms

Animals
Antidiuretic Hormone Receptor Antagonists*
Arginine Vasopressin / metabolism
Benzazepines / chemistry
Benzazepines / metabolism
Benzazepines / pharmacology*
Diuretics / pharmacology
Magnetic Resonance Spectroscopy
Male
Molecular Structure
Radioligand Assay
Rats
Rats, Sprague-Dawley
Receptors, Vasopressin / metabolism
Tolvaptan

Substances

Antidiuretic Hormone Receptor Antagonists
Benzazepines
Diuretics
Receptors, Vasopressin
Arginine Vasopressin
Tolvaptan