Design and synthesis of procollagen C-proteinase inhibitors

Eric Turtle; Nicholas Chow; Charles Yang; Sergio Sosa; Udo Bauer; Mitch Brenner; David Solow-Cordero; Wen-Bin Ho

doi:10.1016/j.bmcl.2012.10.067

Design and synthesis of procollagen C-proteinase inhibitors

Bioorg Med Chem Lett. 2012 Dec 15;22(24):7397-401. doi: 10.1016/j.bmcl.2012.10.067. Epub 2012 Oct 24.

Authors

Eric Turtle¹, Nicholas Chow, Charles Yang, Sergio Sosa, Udo Bauer, Mitch Brenner, David Solow-Cordero, Wen-Bin Ho

Affiliation

¹ FibroGen Inc., 409 Illinois St, SF, CA 94158, USA.

PMID: 23134659
DOI: 10.1016/j.bmcl.2012.10.067

Abstract

Non-peptidic inhibitors of procollagen C-proteinase (PCP) were designed from substrate leads. Compounds were optimized for potency and selectivity, with N-substituted aryl sulfonamide hydroxamates having the best combination of these properties. Compounds 89 and 60 have IC(50) values of 10 and 80 nM, respectively, against PCP; excellent selectivity over MMP's 1, 2, and 9; and activity in cell-based collagen deposition assays.

MeSH terms

3T3-L1 Cells
Animals
Bone Morphogenetic Protein 1 / antagonists & inhibitors*
Bone Morphogenetic Protein 1 / metabolism
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Design*
Humans
Mice
Molecular Structure
Protease Inhibitors / chemical synthesis
Protease Inhibitors / chemistry
Protease Inhibitors / pharmacology*
Structure-Activity Relationship

Substances

Protease Inhibitors
BMP1 protein, human
Bone Morphogenetic Protein 1