Structure-activity relationships of a new family of steroidal aromatase inhibitor .1. Synthesis and evaluation of a series of analogs related to 19-[(methylthio)methyl]androstenedione (RU54115)

被引：16

作者：

Lesuisse, D ^{[1
]}

Gourvest, JF ^{[1
]}

Benslimane, O ^{[1
]}

Canu, F ^{[1
]}

Delaisi, C ^{[1
]}

Doucet, B ^{[1
]}

Hartmann, C ^{[1
]}

Lefrancois, JM ^{[1
]}

Tric, B ^{[1
]}

Mansuy, D ^{[1
]}

Philibert, D ^{[1
]}

Teutsch, G ^{[1
]}

机构：

[1] UNIV PARIS 05, UNITE ASSOCIEE CNRS, URA 400, F-75270 PARIS 06, FRANCE

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1996年 / 39卷 / 03期

关键词：

D O I：

10.1021/jm950539l

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

During the course of a study aimed at the search for new potent aromatase inhibitors, several new androstenedione analogs were synthesized and evaluated. This study led to the discovery of 19-[(methylthio)methyl]androsta-4,9(11)-diene-3,17-dione (7; RU54115) already described by our laboratory. The object of the present series of papers is to disclose the result of the structure-activity relationship studies that gave rise to this compound. This first part deals mainly with the substitution in the 19-position of the steroid nucleus. Several parameters were varied, the length of the chain and its rigidity and branching, as well as the nature of the heteroatom itself and its substitution. The interaction of these new compounds with human placental aromatase in competition with the substrate androstenedione was studied by difference visible spectroscopy. The in vivo aromatase-inhibiting activities were evaluated by measuring the estradiol lowering after oral administration of the compounds to PMSG-primed female rats.

引用

页码：757 / 772

页数：16

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