N-[2-methyl-5-({[(3,4,5-trimethoxybenzoyl)amino]carbonothioyl}amino)phenyl]biphenyl-4-carboxamide

Chemical Formula: C31H29N3O5S

Molecular Weight: 555.6579

OTAVAchemicals Catalogue Number: 7070707159

CAS Registry Number: 1263132-08-6

Purity: 99% (HPLC)

Ref.: A. Solinas et al. Acylthiourea, acylurea, and acylguanidine derivatives with potent hedgehog inhibiting activity. Journal of Medicinal Chemistry (2012), 55(4), 1559-1571

Abstract: The Smoothened (Smo) receptor is the major transducer of the Hedgehog (Hh) signaling pathway. On the basis of the structure of the acylthiourea Smo antagonist (MRT-10), a number of different series of analogous compounds were prepared by ligand- based structural optimization. The acylthioureas, originally identified as actives, were converted into the corresp onding acylureas or acylguanidines. In each series, similar structural trends delivered potent compounds with I C values in the nanomolar range with respect to the inhibition of the Hh signaling pathway in various cell-based assays and of BODIPY-cyclopamine binding to human Smo. The similarity of their biol. activities, in spite of discrete structural differences, may reveal the existence of hydrogen-bonding interactions between the ligands and the receptor pocket. Biol. potency of compounds I(X = S, O) and II (MRT-83) were comparable to those of the clin. candidate GDC-0449. These findings suggest that these original mols. will help delineate Smo and Hh functions and can be developed as potential anticancer agents.

DOI: 10.1021/jm2013369