Binding Mode and Potency of N-Indolyloxopyridinyl-4-aminopropanyl-Based Inhibitors Targeting Trypanosoma cruzi CYP51 was written by Vieira, Debora F.;Choi, Jun Yong;Calvet, Claudia M.;Siqueira-Neto, Jair Lage;Johnston, Jonathan B.;Kellar, Danielle;Gut, Jiri;Cameron, Michael D.;McKerrow, James H.;Roush, William R.;Podust, Larissa M.. And the article was included in Journal of Medicinal Chemistry in 2014.Computed Properties of C8H6BrFO2 This article mentions the following:
Chagas disease is a chronic infection in humans caused by Trypanosoma cruzi and manifested in progressive cardiomyopathy and/or gastrointestinal dysfunction. Limited therapeutic options to prevent and treat Chagas disease put 8 million people infected with T. cruzi worldwide at risk. CYP51, involved in the biosynthesis of the membrane sterol component in eukaryotes, is a promising drug target in T. cruzi. We report the structure-activity relationships (SAR) of an N-arylpiperazine series of N-indolyloxopyridinyl-4-aminopropanyl-based inhibitors designed to probe the impact of substituents in the terminal N-Ph ring on binding mode, selectivity and potency. Depending on the substituents at C-4, two distinct ring binding modes, buried and solvent-exposed, have been observed by X-ray structure anal. (resolution of 1.95-2.48 Å). The 5-chloro-substituted analogs 9 and 10 with no substituent at C-4 demonstrated improved selectivity and potency, suppressing ≥99.8% parasitemia in mice when administered orally at 25 mg/kg, b.i.d., for 4 days. In the experiment, the researchers used many compounds, for example, Methyl 4-bromo-2-fluorobenzoate (cas: 179232-29-2Computed Properties of C8H6BrFO2).
Methyl 4-bromo-2-fluorobenzoate (cas: 179232-29-2) belongs to organobromine compounds. Many of the organo bromine compounds are relatively nonpolar. Bromine is more electronegative than carbon (2.8 vs 2.5) and hence the carbon in a carbonbromine bond is electrophilic in nature. Many of the alkyl bromine derivatives are excellent alkylating agents since bromides are good leaving groups. Tribromides, like tetrabutylammonium tribromide, are used as a solid source of bromine. N-bromosuccimide (NBS) is used for the selective bromination of allylic bonds.Computed Properties of C8H6BrFO2
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary