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2-(2-Aminothiazol-4-yl)pyrrolidine-based tartrate diamides as potent, selective and orally bioavailable TACE inhibitors.

Authors :
Dai C
Li D
Popovici-Muller J
Zhao L
Girijavallabhan VM
Rosner KE
Lavey BJ
Rizvi R
Shankar BB
Wong MK
Guo Z
Orth P
Strickland CO
Sun J
Niu X
Chen S
Kozlowski JA
Lundell DJ
Piwinski JJ
Shih NY
Siddiqui MA
Source :
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2011 May 15; Vol. 21 (10), pp. 3172-6. Date of Electronic Publication: 2011 Jan 06.
Publication Year :
2011

Abstract

TNF-α converting enzyme (TACE) inhibitors are promising agents to treat inflammatory disorders and cancer. We have investigated novel tartrate diamide TACE inhibitors where the tartrate core binds to zinc in a unique tridentate fashion. Incorporating (R)-2-(2-N-alkylaminothiazol-4-yl)pyrrolidines into the left hand side amide of the tartrate scaffold led to the discovery of potent and selective TACE inhibitors, some of which exhibited good rat oral bioavailability.<br /> (Copyright © 2011. Published by Elsevier Ltd.)

Details

Language :
English
ISSN :
1464-3405
Volume :
21
Issue :
10
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
21458257
Full Text :
https://doi.org/10.1016/j.bmcl.2011.01.002