1.
Bioorg Med Chem Lett
; 11(12): 1553-6, 2001 Jun 18.
Article
in English
| MEDLINE
| ID: mdl-11412979
ABSTRACT
A novel series of biaryl ether reverse hydroxamate MMP inhibitors has been developed. These compounds are potent MMP-2 inhibitors with limited activity against MMP-1. Select members of this series exhibit excellent pharmacokinetic properties with long elimination half-lives (7 h) and high oral bioavailability (100%).
Subject(s)
Hydroxamic Acids/chemical synthesis , Matrix Metalloproteinase Inhibitors , Administration, Oral , Animals , Antineoplastic Agents/blood , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacokinetics , Biological Availability , Enzyme Inhibitors/blood , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacokinetics , Half-Life , Hydroxamic Acids/chemistry , Inhibitory Concentration 50 , Injections, Intravenous , Macaca fascicularis
2.
Bioorg Med Chem Lett
; 11(12): 1557-60, 2001 Jun 18.
Article
in English
| MEDLINE
| ID: mdl-11412980
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.