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

  • Bioorg Med Chem Lett. 2001 Jun 18;11(12):1557-60. doi: 10.1016/s0960-894x(01)00032-4.
M L Curtin  1 ,  A S Florjancic ,  H R Heyman ,  M R Michaelides ,  R B Garland ,  J H Holms ,  D H Steinman ,  J F Dellaria ,  J Gong ,  C K Wada ,  Y Guo ,  I B Elmore ,  P Tapang ,  D H Albert ,  T J Magoc ,  P A Marcotte ,  J J Bouska ,  C L Goodfellow ,  J L Bauch ,  K C Marsh ,  D W Morgan ,  S K Davidsen
Affiliations
  • 1. Cancer Research Area, Abbott Laboratories, Dept. 47J, Bldg. AP10, 100 Abbott Park Road, Abbott Park, IL 60064, USA. [email protected]
PMID: 11412980 DOI: 10.1016/s0960-894x(01)00032-4
Abstract

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.

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