Carrico, Dora; Ohkanda, Junko; Kendrick, Howard; Yokoyama, Kohei; Blaskovich, Michelle A.; Bucher, Cynthia J.; Buckner, Frederick S.; Van Voorhis, Wesley C.; Chakrabarti, Debopam; Croft, Simon L.; Gelb, Michael H.; Sebti, Said M.; Hamilton, Andrew D. published the artcile< In vitro and in vivo antimalarial activity of peptidomimetic protein farnesyltransferase inhibitors with improved membrane permeability>, Computed Properties of 16426-64-5, the main research area is FRI2148 prodrug preparation antimalarial Plasmodium farnesyltransferase inhibitor.
A series of protein farnesyltransferase inhibitor ester prodrugs of FTI-2148 were synthesized in order to evaluate the effects of ester structure modification on antimalarial activity and for further development of a farnesyltransferase inhibitor with in vivo activity. Evaluation against P. falciparum in red blood cells showed that all the investigated esters exhibited significant antimalarial activity, with the benzyl ester 16 showing the best inhibition (ED50 = 150 nM). Addnl., compound I displayed in vivo activity and was found to suppress parasitemia by 46.1% at a dose of 50 mg kg-1 day-1 against Plasmodium berghei in mice. The enhanced inhibition potency of the esters is consistent with improved cell membrane permeability compared to that of the free acid. The results of this study suggest that protein farnesyltransferase is a valid antimalarial drug target and that the antimalarial activity of these compounds derives from a balance between the hydrophobic character and the size and conformation of the ester moiety.
Bioorganic & Medicinal Chemistry published new progress about Antimalarials. 16426-64-5 belongs to class bromides-buliding-blocks, and the molecular formula is C7H4BrNO4, Computed Properties of 16426-64-5.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary