Novel lead generation through hypothetical pharmacophore three-dimensional database searching:: Discovery of isoflavonoids as nonsteroidal inhibitors of rat 5α-reductase

被引：36

作者：

Chen, GS

Chang, CS

Kan, WM

Chang, CL

Wang, KC

Chern, JW

机构：

[1] Natl Taiwan Univ, Coll Med, Sch Pharm, Taipei, Taiwan

[2] Natl Cheng Kung Univ, Coll Med, Dept Pharmacol, Tainan 70101, Taiwan

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2001年 / 44卷 / 23期

关键词：

D O I：

10.1021/jm010433s

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A hypothetical pharmacophore of 5 alpha -reductase inhibitors was generated and served as a template in virtual screening. When the pharmacophore was used, eight isoflavone derivatives were characterized as novel potential nonsteroidal inhibitors of rat 5 alpha -reductase. This investigation has demonstrated a practical approach toward the development of lead compounds through a hypothetic pharmacophore via three-dimensional database searching.

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页码：3759 / 3763

页数：5

相关论文

共 23 条

[1]

ANDERSSON S, 1989, J BIOL CHEM, V264, P16249

[2] 4-AZA-3-OXO-5-ALPHA-ANDROST-1-ENE-17-BETA-N-ARYL-CARBOXAMIDES AS DUAL INHIBITORS OF HUMAN TYPE-1 AND TYPE-2 STEROID 5-ALPHA-REDUCTASES - DRAMATIC EFFECT OF N-ARYL SUBSTITUENTS ON TYPE-1 AND TYPE-2 5-ALPHA-REDUCTASE INHIBITORY POTENCY [J].

BAKSHI, RK ;

RASMUSSON, GH ;

PATEL, GF ;

MOSLEY, RT ;

CHANG, B ;

ELLSWORTH, K ;

HARRIS, GS ;

TOLMAN, RL .

JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (17) :3189-3192

[3] MOLECULAR MODELING SOFTWARE AND METHODS FOR MEDICINAL CHEMISTRY .2. [J].

COHEN, NC ;

BLANEY, JM ;

HUMBLET, C ;

GUND, P ;

BARRY, DC .

JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (03) :883-894

[4] INHIBITION OF 5-ALPHA-REDUCTASE IN GENITAL SKIN FIBROBLASTS AND PROSTATE TISSUE BY DIETARY LIGNANS AND ISOFLAVONOIDS [J].

EVANS, BAJ ;

GRIFFITHS, K ;

MORTON, MS .

JOURNAL OF ENDOCRINOLOGY, 1995, 147 (02) :295-302

[5] STRUCTURE-ACTIVITY-RELATIONSHIPS FOR INHIBITION OF TYPE-1 AND TYPE-2 HUMAN 5-ALPHA-REDUCTASE AND HUMAN ADRENAL 3-BETA-HYDROXY-DELTA(5)-STEROID DEHYDROGENASE 3-KETO-DELTA(5)-STEROID ISOMERASE BY 6-AZAANDROST-4-EN-3-ONES - OPTIMIZATION OF THE C17 SUBSTITUENT [J].

FRYE, SV ;

HAFFNER, CD ;

MALONEY, PR ;

HINER, RN ;

DORSEY, GF ;

NOE, RA ;

UNWALLA, RJ ;

BATCHELOR, KW ;

BRAMSON, HN ;

STUART, JD ;

SCHWEIKER, SL ;

VANARNOLD, J ;

BICKETT, DM ;

MOSS, ML ;

TIAN, GC ;

LEE, FW ;

TIPPIN, TK ;

JAMES, MK ;

GRIZZLE, MK ;

LONG, JE ;

CROOM, DK .

JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (14) :2621-2627

[6] 19-nor-10-azasteroids, a new class of steroid 5 alpha-reductase inhibitors .2. X-ray structure, molecular modeling, conformational analysis of 19-nor-10-azasteroids and comparison with 4-azasteroids and 6-azasteroids [J].

Guarna, A ;

Occhiato, EG ;

Machetti, F ;

Marrucci, A ;

Danza, G ;

Serio, M ;

Paoli, P .

JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (21) :3466-3477

[7]

HOLT KG, 1993, PHYS THER PRACT, V2, P1

[8]

Igarashi S, 2000, CHEM PHARM BULL, V48, P382

[9] Identification of novel farnesyl protein transferase inhibitors using three-dimensional database searching methods [J].

Kaminski, JJ ;

Rane, DF ;

Snow, ME ;

Weber, L ;

Rothofsky, ML ;

Anderson, SD ;

Lin, SL .

JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (25) :4103-4112

[10] Pharmacological options in the treatment of benign prostatic hyperplasia [J].

Kenny, B ;

Ballard, S ;

Blagg, J ;

Fox, D .

JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (09) :1293-1315