The synthesis of 17beta-[N-(phenyl)methyl/phenyl-amido] substituted 10-azasteroids has been accomplished by either the TiCl4- or TMSOTf-catalysed reaction of carbamates 11 and 12 with Danishefsky's diene. The reaction provided 5alpha-H isomers 3a-5a and 5beta-H isomers 3b-5b depending on the reaction conditions. Both epimers of each compound were tested against human 5alpha-reductase types I and II. Unexpectedly, 5beta-H compounds were found more active than their 5a-H counterparts, the best inhibitors being 3b (IC50=279 and 2000 nM toward isoenzyme I and II, respectively) and 5b (IC50=913 and 247 nM toward isoenzymes I and II, respectively).
Synthesis of 17b-N-Substituted 19-Nor-10-Azasteroids as Inhibitors of Human 5a-Reductase I and II / D. SCARPI; E. OCCHIATO; G. DANZA; M. SERIO; A. GUARNA. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - STAMPA. - 10:(2002), pp. 3455-3461. [10.1016/S0968-0896(02)00254-7]
Synthesis of 17b-N-Substituted 19-Nor-10-Azasteroids as Inhibitors of Human 5a-Reductase I and II
SCARPI, DINA;OCCHIATO, ERNESTO GIOVANNI;DANZA, GIOVANNA;SERIO, MARIO;GUARNA, ANTONIO
2002
Abstract
The synthesis of 17beta-[N-(phenyl)methyl/phenyl-amido] substituted 10-azasteroids has been accomplished by either the TiCl4- or TMSOTf-catalysed reaction of carbamates 11 and 12 with Danishefsky's diene. The reaction provided 5alpha-H isomers 3a-5a and 5beta-H isomers 3b-5b depending on the reaction conditions. Both epimers of each compound were tested against human 5alpha-reductase types I and II. Unexpectedly, 5beta-H compounds were found more active than their 5a-H counterparts, the best inhibitors being 3b (IC50=279 and 2000 nM toward isoenzyme I and II, respectively) and 5b (IC50=913 and 247 nM toward isoenzymes I and II, respectively).File | Dimensione | Formato | |
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