85103-02-2Relevant articles and documents
Structurally simple inhibitors of lanosterol 14α-demethylase are efficacious in a rodent model of acute Chagas disease
Suryadevara, Praveen Kumar,Olepu, Srinivas,Lockman, Jeffrey W.,Ohkanda, Junko,Karimi, Mandana,Verlinde, Christophe L. M. J.,Kraus, James M.,Schoepe, Jan,Van Voorhis, Wesley C.,Hamilton, Andrew D.,Buckner, Frederick S.,Gelb, Michael H.
supporting information; experimental part, p. 3703 - 3715 (2010/04/24)
We report structure-activity studies of a large number of dialkyl imidazoles as inhibitors of Trypanosoma cruzi lanosterol-14α-demethylase (L14DM). The compounds have a simple structure compared to posaconazole, another L14DM inhibitor that is an anti-Chagas drug candidate. Several compounds display potency for killing T. cruzi amastigotes in vitro with values of EC 50 in the 0.4-10 nM range. Two compounds were selected for efficacy studies in a mouse model of acute Chagas disease. At oral doses of 20-50 mg/kg given after establishment of parasite infection, the compounds reduced parasitemia in the blood to undetectable levels, and analysis of remaining parasites by PCR revealed a lack of parasites in the majority of animals. These dialkyl imidazoles are substantially less expensive to produce than posaconazole and are appropriate for further development toward an anti-Chagas disease clinical candidate.
Synthesis and calcium antagonist activity of new 1,4-dihydropyridines containing nitrobenzylimidazolyl substituent in ginea-pig ileal smooth muscle
Zarghi,Derakhshandeh,Roshanzamir,Jorjani,Rastegar,Varmazyari,Shafiee
, p. 15 - 20 (2007/10/03)
New alkyl ester analogues of nifedipine, in which the ortho-nitrophenyl group of position 4 is replaced by 1-(4-nitrobenzyl)-5-imidazolyl or 2-methylthio-1-(4-nitrobenzyl)-5-imidazolyl substituent, were synthesized and evaluated as calcium-channel antagonists using the electrically induced contraction of guinea-pig ileal longitudinal smooth muscle. Our results demonstrate that all compounds inhibited the contractile response of guinea-pig ileum to electrical stimulation and the IC50 value of the most potent compounds 6a and 6f were significantly lower than that of nifedipine. Therefore, they are more potent than nifedipine.