Synthesis of Tricyclic Compounds as Steroid 5[alpha]-Reductase Inhibitors

A series of 4-phenoxybutyric acid derivatives attached to a tricyclic skelton were prepared and evaluated as 5α-reductase inhibitors. Structure activity relationships for these compounds in terms of rat epididymls (type 2)5α-reductase inhibitory activities reveal that 1) the substitution pattern at...

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Published inChemical & pharmaceutical bulletin Vol. 48; no. 4; p. 552
Main Authors TAKAMI, Hitoshi, NONAKA, Hiromi, KISHIBAYASHI, Nobuyuki, ISHII, Akio, KASE, Hiroshi, KUMAZAWA, Toshiaki
Format Journal Article
LanguageEnglish
Published Tokyo Japan Science and Technology Agency 01.04.2000
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Abstract A series of 4-phenoxybutyric acid derivatives attached to a tricyclic skelton were prepared and evaluated as 5α-reductase inhibitors. Structure activity relationships for these compounds in terms of rat epididymls (type 2)5α-reductase inhibitory activities reveal that 1) the substitution pattern at the 11-position of dibenz[b, e]oxepin influenced potency, 2) higher lipophilicity of the tricylic skeleton improved potency, whereas the existence of a basic nitrogen atom in this skeleton was detrimental to potency, and 3) isobutyl substitution at the 8 position of the azepine skelton was tolerated. Among the tricyclic compounds studied, 4-[3-[5-benzyl-8-(2-methyl)propyl-10, 11-dihydrodibenz[b, f]azepine-2-carboxamido]phenoxy]butyric adid (26) was the most potent inhibitor of rat type 2 5α-reductase at 0.1μM.
AbstractList A series of 4-phenoxybutyric acid derivatives attached to a tricyclic skelton were prepared and evaluated as 5α-reductase inhibitors. Structure activity relationships for these compounds in terms of rat epididymls (type 2)5α-reductase inhibitory activities reveal that 1) the substitution pattern at the 11-position of dibenz[b, e]oxepin influenced potency, 2) higher lipophilicity of the tricylic skeleton improved potency, whereas the existence of a basic nitrogen atom in this skeleton was detrimental to potency, and 3) isobutyl substitution at the 8 position of the azepine skelton was tolerated. Among the tricyclic compounds studied, 4-[3-[5-benzyl-8-(2-methyl)propyl-10, 11-dihydrodibenz[b, f]azepine-2-carboxamido]phenoxy]butyric adid (26) was the most potent inhibitor of rat type 2 5α-reductase at 0.1μM.
Author TAKAMI, Hitoshi
NONAKA, Hiromi
KISHIBAYASHI, Nobuyuki
KASE, Hiroshi
KUMAZAWA, Toshiaki
ISHII, Akio
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