Potent, exceptionally selective, orally bioavailable inhibitors of TNF-α Converting Enzyme (TACE): Novel 2-substituted-1H-benzo[d]imidazol-1-yl)methyl)benzamide P1′ substituents

Gregory R Ott,Rajan Anand,David D Christ,Naoyuki Asakawa,Krishna Vaddi,Mingxin Qian,Maryanne B Covington,James M Trzaskos,Robert C Newton,Rui-Qin Liu,Zhonghui Lu,James J.-W Duan

doi:10.1016/j.bmcl.2008.01.075

Potent, exceptionally selective, orally bioavailable inhibitors of TNF-α Converting Enzyme (TACE): Novel 2-substituted-1H-benzo[d]imidazol-1-yl)methyl)benzamide P1′ substituents

Gregory R Ott, Rajan Anand + Show 10 more

https://doi.org/10.1016/j.bmcl.2008.01.075

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Journal: Bioorganic & Medicinal Chemistry Letters	Publication Date: Jan 26, 2008
Citations: 41

Affiliation: Bristol-Myers Squibb (United States)

#TNF-alpha Converting Enzyme #ADAM Proteases + Show 8 more

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Abstract

Novel ((2-substituted-1H-benzo[d]imidazol-1-yl)methyl)benzamides were found to be excellent P1' substituents in conjunction with unique constrained beta-amino hydroxamic acid scaffolds for the discovery of potent selective inhibitors of TNF-alpha Converting Enzyme (TACE). Optimized examples proved potent for TACE, exceptionally selective over a wide panel of MMP and ADAM proteases, potent in the suppression of LPS-induced TNF-alpha in human whole blood and orally bioavailable.

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