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Title: Amino derivatives of indole as potent inhibitors of isoprenylcysteine carboxyl methyltransferase
Authors: Go, M.-L. 
Leow, J.L.
Gorla, S.K. 
Schüller, A.P. 
Wang, M. 
Casey, P.J. 
Issue Date: 14-Oct-2010
Citation: Go, M.-L., Leow, J.L., Gorla, S.K., Schüller, A.P., Wang, M., Casey, P.J. (2010-10-14). Amino derivatives of indole as potent inhibitors of isoprenylcysteine carboxyl methyltransferase. Journal of Medicinal Chemistry 53 (19) : 6838-6850. ScholarBank@NUS Repository.
Abstract: The enzyme isoprenylcysteine carboxyl methyltransferase (Icmt) plays an important role in the post-translational modification of proteins that are involved in the regulation of cell growth. The indole acetamide cysmethynil is by far the most potent and widely investigated Icmt inhibitor, but it has modest antiproliferative activity and may have pharmacokinetic limitations due to its lipophilic character. We report here that cysmethynil can be structurally modified to give analogues that are as potent in inhibiting Icmt but with significantly greater antiproliferative activity. Key modifications were the replacement of the acetamide side chain by tertiary amino groups, the n-octyl side chain by isoprenyl and the 5-m-tolyl ring by fluorine. Moreover, these analogues have lower lipophilicities that could lead to improved pharmacokinetic profiles. © 2010 American Chemical Society.
Source Title: Journal of Medicinal Chemistry
ISSN: 00222623
DOI: 10.1021/jm1002843
Appears in Collections:Staff Publications

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