912482-46-3Relevant academic research and scientific papers
Structure-based design and synthesis of potent, ethylenediamine-based, mammalian farnesyltransferase inhibitors as anticancer agents
Fletcher, Steven,Keaney, Erin Pusateri,Cummings, Christopher G.,Blaskovich, Michelle A.,Hast, Michael A.,Glenn, Matthew P.,Chang, Sung-Youn,Bucher, Cynthia J.,Floyd, Ryan J.,Katt, William P.,Gelb, Michael H.,Van Voorhis, Wesley C.,Beese, Lorena S.,Sebti, Said M.,Hamilton, Andrew D.
experimental part, p. 6867 - 6888 (2010/12/18)
A potent class of anticancer, human farnesyltransferase (hFTase) inhibitors has been identified by "piggy-backing" on potent, antimalarial inhibitors of Plasmodium falciparum farnesyltransferase (PfFTase). On the basis of a 4-fold substituted ethylenediam
Structural Basis for Binding and Selectivity of Antimalarial and Anticancer Ethylenediamine Inhibitors to Protein Farnesyltransferase
Hast, Michael A.,Fletcher, Steven,Cummings, Christopher G.,Pusateri, Erin E.,Blaskovich, Michelle A.,Rivas, Kasey,Gelb, Michael H.,Van Voorhis, Wesley C.,Sebti, Said M.,Hamilton, Andrew D.,Beese, Lorena S.
scheme or table, p. 181 - 192 (2010/08/19)
Protein farnesyltransferase (FTase) catalyzes an essential posttranslational lipid modification of more than 60 proteins involved in intracellular signal transduction networks. FTase inhibitors have emerged as a significant target for development of antic
COMPOUNDS AND METHODS FOR THE TREATMENT OF MALARIA AND CANCER
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Page/Page column 44, (2008/06/13)
Formula (I): Where R1 is an optionally substituted C3-C12 hydrocarbyl group (preferably a cyclic alkyl group), an optionally substituted heterocyclic group, an optionally substituted aromatic group or an optionally substituted heteroaromatic group; R is a C(O)yR' group (preferably forming an optionally substituted C2-C5 acyl group), or a S(O)xR' group, where y is 0 or 1 and x is 0, 1 or 2 and R' is H or an optionally substituted C1-C12 alkyl group, or R' is an optionally substituted C5-C12 cycloalkyl group, an optionally substituted heterocyclic group, an optionally substituted aromatic group or an optionally substituted heteroaromatic group; R5, R6, R7, R8, R9 and R10 are each independently selected from H, an optionally substituted C1-C12 hydrocarbyl group, including a C5-C12 cycloalkyl group, an optionally substituted heterocyclic group, an optionally substituted aromatic group or an optionally substituted heteroaromatic group, or R5 and R6, R7 and R8 or R9 and R10 together form a keto (C=O) group; RN is H, an optionally substituted C1-C12 hydrocarbyl group, an optionally substituted heterocyclic group, an optionally substituted aromatic group, or an optionally substituted heteroaromatic group; A is Formula (II): a Formula (III): group, or a Formula (IV) or Formula (V) group, where Z is N, O or S; Ra is H, a C1-C12 optionally substituted hydrocarbyl group or an optionally substituted aromatic group; n is from 0 to 3; and pharmaceutically acceptable salts thereof. Compounds according to the invention are useful in one or more aspects to inhibit farnesyl transferase, or to treat malaria, neoplasia, a hyperproliferative disease state or arthritis, including rheumaroid arthritis or osteoarthritis.
Structurally simple, potent, Plasmodium selective farnesyltransferase inhibitors that arrest the growth of malaria parasites
Glenn, Matthew P.,Chang, Sung-Youn,Hornéy, Carrie,Rivas, Kasey,Yokoyama, Kohei,Pusateri, Erin E.,Fletcher, Steven,Cummings, Christopher G.,Buckner, Frederick S.,Pendyala, Prakash R.,Chakrabarti, Debopam,Sebti, Sa?d M.,Gelb, Michael,Van Voorhis, Wesley C.,Hamilton, Andrew D.
, p. 5710 - 5727 (2007/10/03)
Third world nations require immediate access to inexpensive therapeutics to counter the high mortality inflicted by malaria. Here, we report a new class of antimalarial protein farnesyltransferase (PFT) inhibitors, designed with specific emphasis on simple molecular architecture, to facilitate easy access to therapies based on this recently validated antimalarial target. This novel series of compounds represents the first Plasmodium falciparum selective PFT inhibitors reported (up to 145-fold selectivity), with lead inhibitors displaying excellent in vitro activity (IC50 50 100 nM). Initial studies of absorption, metabolism, and oral bioavailability are reported.
