Curtin M L, Florjancic A S, Heyman H R, Michaelides M R, Garland R B, Holms J H, Steinman D H, Dellaria J F, Gong J, Wada C K, Guo Y, Elmore I B, Tapang P, Albert D H, Magoc T J, Marcotte P A, Bouska J J, Goodfellow C L, Bauch J L, Marsh K C, Morgan D W, Davidsen S K
Cancer Research Area, Abbott Laboratories, Dept. 47J, Bldg. AP10, 100 Abbott Park Road, Abbott Park, IL 60064, USA.
Bioorg Med Chem Lett. 2001 Jun 18;11(12):1557-60. doi: 10.1016/s0960-894x(01)00032-4.
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.
对基质金属蛋白酶（MMP）抑制剂2a的联苯部分进行修饰得到类似物2i，其对MMP-2的选择性比对MMP-1高1000倍以上。以（S）-或（R）-苄基缩水甘油醚为起始原料，实现了2i两种对映体的立体定向合成。（S）-对映体11（ABT-770）口服生物利用度良好，在肿瘤生长的体内模型中有效。
