Both 5-Arylidene-2-thioxodihydropyrimidine-4,6(1H,5H)-diones and 3-Thioxo-2,3-dihydro-1H-imidazo[1,5-a]indol-1-ones are light-dependent tumor necrosis Factor-α antagonists

被引：69

作者：

Voss, ME ^{[1
]}

Carter, PH ^{[1
]}

Tebben, AJ ^{[1
]}

Scherle, PA ^{[1
]}

Brown, GD ^{[1
]}

Thompson, LA ^{[1
]}

Xu, MZ ^{[1
]}

Lo, YC ^{[1
]}

Yang, GJ ^{[1
]}

Liu, RQ ^{[1
]}

Strzemienski, P ^{[1
]}

Everlof, JG ^{[1
]}

Trzaskos, JM ^{[1
]}

Decicco, CP ^{[1
]}

机构：

[1] Bristol Myers Squibb Pharmaceut, Expt Stn, Wilmington, DE 19880 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 03期

关键词：

D O I：

10.1016/S0960-894X(02)00941-1

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

Based on the realization that N-alkyl 5-arylidene-2-thioxo-1,3-thiazolidin-4-ones are tumor necrosis factor-a antagonists, we discovered two additional classes of antagonists: 3-thioxo-2,3-dihydro-1H-imidazo[1,5-a]indol-1-ones (via rational design) and 5-arylidene-2-thioxodihydropyrimidine-4,6(1H,5H)-diones (via computer-guided screening). Chemical modification of the lead structures showed that the structure-activity relationship profiles for both of these series were dependent on the electronic properties of the molecules. Subsequent studies showed that they were light-dependent inhibitors. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：533 / 538

页数：6

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