4-Aminopyridyl-Based CYP51 Inhibitors as Anti-Trypanosoma cruzi Drug Leads with Improved Pharmacokinetic Profile and in Vivo Potency was written by Calvet, Claudia M.;Vieira, Debora F.;Choi, Jun Yong;Kellar, Danielle;Cameron, Michael D.;Siqueira-Neto, Jair Lage;Gut, Jiri;Johnston, Jonathan B.;Lin, Li;Khan, Susan;McKerrow, James H.;Roush, William R.;Podust, Larissa M.. And the article was included in Journal of Medicinal Chemistry in 2014.Category: bromides-buliding-blocks This article mentions the following:
CYP51 is a P 450 enzyme involved in the biosynthesis of the sterol components of eukaryotic cell membranes. CYP51 inhibitors have been developed to treat infections caused by fungi, and more recently the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease. To specifically optimize drug candidates for T. cruzi CYP51 (TcCYP51), we explored the structure-activity relation (SAR) of a N-indolyl-oxopyridinyl-4-aminopropanyl-based scaffold originally identified in a target-based screen. This scaffold evolved via medicinal chem. to yield orally bioavailable leads with potent anti-T. cruzi activity in vivo. Using an animal model of infection with a transgenic T. cruzi Y luc strain expressing firefly luciferase, we prioritized the biaryl and N-arylpiperazine analogs by oral bioavailability and potency. The drug-target complexes for both scaffold variants were characterized by x-ray structure anal. Optimization of both binding mode and pharmacokinetic properties of these compounds led to potent inhibitors against exptl. T. cruzi infection. In the experiment, the researchers used many compounds, for example, Methyl 4-bromo-2-fluorobenzoate (cas: 179232-29-2Category: bromides-buliding-blocks).
Methyl 4-bromo-2-fluorobenzoate (cas: 179232-29-2) belongs to organobromine compounds. Bromo compounds are employed in a variety of metal-catalyzed coupling reactions. They are also ideal candidates for the synthesis of Grignard reagents that have wide-applicability in organic synthesis. alpha-Bromoesters are employed in the Reformatsky reaction for the synthesis of beta-hydroxyesters. In the pharmaceutical industry organo bromine derivatives are used as sedatives, vasodilators, antiseptic agents, and anticancer agents.Category: bromides-buliding-blocks
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary