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.

引用

页码：3759 / 3763

页数：5

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
BAKSHI, RK
RASMUSSON, GH
PATEL, GF
MOSLEY, RT
CHANG, B
ELLSWORTH, K
HARRIS, GS
TOLMAN, RL
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (17) : 3189 - 3192
[3] MOLECULAR MODELING SOFTWARE AND METHODS FOR MEDICINAL CHEMISTRY .2.
COHEN, NC
BLANEY, JM
HUMBLET, C
GUND, P
BARRY, DC
[J]. 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
EVANS, BAJ
GRIFFITHS, K
MORTON, MS
[J]. 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
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
[J]. 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
Guarna, A
Occhiato, EG
Machetti, F
Marrucci, A
Danza, G
Serio, M
Paoli, P
[J]. 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
Kaminski, JJ
Rane, DF
Snow, ME
Weber, L
Rothofsky, ML
Anderson, SD
Lin, SL
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (25) : 4103 - 4112
[10] Pharmacological options in the treatment of benign prostatic hyperplasia
Kenny, B
Ballard, S
Blagg, J
Fox, D
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (09) : 1293 - 1315

← 1 2 3 →