Discovery and characterization of the potent, selective and orally bioavailable MMP inhibitor ABT-770

被引：20

作者：

Curtin, ML ^{[1
]}

Florjancic, AS ^{[1
]}

Heyman, HR ^{[1
]}

Michaelides, MR ^{[1
]}

Garland, RB ^{[1
]}

Holms, JH ^{[1
]}

Steinman, DH ^{[1
]}

Dellaria, JF ^{[1
]}

Gong, J ^{[1
]}

Wada, CK ^{[1
]}

Guo, Y ^{[1
]}

Elmore, IB ^{[1
]}

Tapang, P ^{[1
]}

Albert, DH ^{[1
]}

Magoc, TJ ^{[1
]}

Marcotte, PA ^{[1
]}

Bouska, JJ ^{[1
]}

Goodfellow, CL ^{[1
]}

Bauch, JL ^{[1
]}

Marsch, KC ^{[1
]}

Morgan, DW ^{[1
]}

Davidsen, SK ^{[1
]}

机构：

[1] Abbott Labs, Canc Res Area, Dept 47J, Abbott Pk, IL 60064 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 12期

关键词：

D O I：

10.1016/S0960-894X(01)00032-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Modification of the biphenyl portion of MMP inhibitor 2a gave analogue 2i which is greater than 1000-fold selective against MMP-2 versus MMP-1. The stereospecific synthesis of both enantiomers of 2i was achieved beginning with (S)- or (R)-benzyl glycidyl ether. The (S)-enantiomer, 11 (ABT-770), is orally bioavailable and efficacious in an in vivo model of tumor growth. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：1557 / 1560

页数：4

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