Chem. Pharm. Bull., 47(2), 226-240, February 1999

Regular Articles

Synthesis of 2-Phenylbenzofuran Derivatives as Testosterone 5a-Reductase Inhibitor

Koki ISHIBASHI,^a Katsuyoshi NAKAJIMA,^a Yuki SUGIOKA,^a Mitsuo SUGIYAMA,^a Takakazu HAMADA,^b Hiroyoshi HORIKOSHI,^b and Takahide N^ISHI*,a

Medicinal Chemistry Research Laboratories^a and Pharmacology and Molecular Biology Research Laboratories,^b Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
Received September 11, 1998; accepted November 20, 1998

A series of 2-phenylbenzofuran derivatives with a carbamoyl, alkylamino, or alkyloxy group at the 5 or 6 position of the benzofuran ring were synthesized and evaluated for rat and human testosterone 5a-reductase inhibitory activities in vitro. Against rat enzyme, the carbamoyl derivatives had more potent inhibitory activities than the alkylamino or alkyloxy derivatives, and the 6-carbamoyl derivatives tended to be more potent than the 5-carbamoyl derivatives. Against human enzyme, the 6-substituted derivatives had more potent inhibitory activities than the 5-substituted derivatives. The 6-carbamoyl and 6-alkylamino derivatives tended to show stronger inhibitory activities against human type 1 enzyme than against type 2 enzyme, but they were not largely selective.

Key words 2-phenylbenzofuran; testosterone 5a-reductase inhibitor; benign prostatic hyperplasia