The development of potent non-peptidic PTP-1B inhibitors
Claude Dufresne1, Patrick Roy, Zhaoyin Wang
1Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe-Claire, Dorval, Canada H9R 4P8. claude_l_dufresne@merck.com
Bioorganic & Medicinal Chemistry Letters
|March 12, 2004
Abstract:
The SAR from our peptide libraries was exploited to design a series of potent deoxybenzoin PTP-1B inhibitors. The introduction of an ortho bromo substituent next to the difluoromethylphosphonate warhead gave up to 20-fold increase in potency compared to the desbromo analogues. In addition, these compounds were orally bioavailable and active in the animal models of non-insulin dependent diabetes mellitus (NIDDM).
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