Biaryl ether retrohydroxamates as potent, long-lived, orally bioavailable MMP inhibitors

M R Michaelides; J F Dellaria; J Gong; J H Holms; J J Bouska; J Stacey; C K Wada; H R Heyman; M L Curtin; Y Guo; C L Goodfellow; I B Elmore; D H Albert; T J Magoc; P A Marcotte; D W Morgan; S K Davidsen

doi:10.1016/s0960-894x(01)00031-2

Biaryl ether retrohydroxamates as potent, long-lived, orally bioavailable MMP inhibitors

Bioorg Med Chem Lett. 2001 Jun 18;11(12):1553-6. doi: 10.1016/s0960-894x(01)00031-2.

Authors

M R Michaelides¹, J F Dellaria, J Gong, J H Holms, J J Bouska, J Stacey, C K Wada, H R Heyman, M L Curtin, Y Guo, C L Goodfellow, I B Elmore, D H Albert, T J Magoc, P A Marcotte, D W Morgan, S K Davidsen

Affiliation

¹ Cancer Research Area, Abbott Laboratories, Dept. 47J, Bldg. AP10, 100 Abbott Park Road, Abbott Park, IL 60064, USA. [email protected]

PMID: 11412979
DOI: 10.1016/s0960-894x(01)00031-2

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%).

MeSH terms

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 / chemical synthesis*
Hydroxamic Acids / chemistry
Inhibitory Concentration 50
Injections, Intravenous
Macaca fascicularis
Matrix Metalloproteinase Inhibitors*

Substances

Antineoplastic Agents
Enzyme Inhibitors
Hydroxamic Acids
Matrix Metalloproteinase Inhibitors