| Autor: |
Sparks RB; Incyte Corporation, Discovery Chemistry, Experimental Station, Route 141 and Henry Clay Road, Wilmington, DE 19880, USA. rsparks@incyte.com, Polam P, Zhu W, Crawley ML, Takvorian A, McLaughlin E, Wei M, Ala PJ, Gonneville L, Taylor N, Li Y, Wynn R, Burn TC, Liu PC, Combs AP |
| Jazyk: |
angličtina |
| Zdroj: |
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2007 Feb 01; Vol. 17 (3), pp. 736-40. Date of Electronic Publication: 2006 Oct 28. |
| DOI: |
10.1016/j.bmcl.2006.10.079 |
| Abstrakt: |
Benzothiazole benzimidazole (S)-isothiazolidinone ((S)-IZD) derivatives 5 were discovered through a peptidomimetic modification of the tripeptide (S)-IZD protein tyrosine phosphatase 1B (PTP1B) inhibitor 1. These derivatives are potent, competitive, and reversible inhibitors of PTP1B with improved caco-2 permeability. An X-ray co-crystal structure of inhibitor 5/PTP1B at 2.2A resolution demonstrated that the benzothiazole benzimidazole forms bi-dentate H-bonds to Asp48, and the benzothiazole interacts with the surface of the protein in a solvent exposed region towards the C-site. The design, synthesis, and SAR of this novel series of benzothiazole benzimidazole containing (S)-IZD inhibitors of PTP1B are presented herein. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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