Hameed P, Shahul; Chinnapattu, Murugan; Shanbag, Gajanan; Manjrekar, Praveena; Koushik, Krishna; Raichurkar, Anandkumar; Patil, Vikas; Jatheendranath, Sandesh; Rudrapatna, Suresh S.; Barde, Shubhada P.; Rautela, Nikhil; Awasthy, Disha; Morayya, Sapna; Narayan, Chandan; Kavanagh, Stefan; Saralaya, Ramanatha; Bharath, Sowmya; Viswanath, Pavithra; Mukherjee, Kakoli; Bandodkar, Balachandra; Srivastava, Abhishek; Panduga, Vijender; Reddy, Jitender; Prabhakar, K. R.; Sinha, Achyut; Jimenez-Diaz, Maria Belen; Martinez, Maria Santos; Angulo-Barturen, Inigo; Ferrer, Santiago; Sanz, Laura Maria; Gamo, Francisco Javier; Duffy, Sandra; Avery, Vicky M.; Magistrado, Pamela A.; Lukens, Amanda K.; Wirth, Dyann F.; Waterson, David; Balasubramanian, V.; Iyer, Pravin S.; Narayanan, Shridhar; Hosagrahara, Vinayak; Sambandamurthy, Vasan K.; Ramachandran, Sreekanth published the artcile< Aminoazabenzimidazoles, a Novel Class of Orally Active Antimalarial Agents>, Category: pyridine-derivatives, the main research area is aminoazabenzimidazole preparation SAR antimalarial Plasmodium.
Whole-cell high-throughput screening of the AstraZeneca compound library against the asexual blood stage of Plasmodium falciparum (Pf) led to the identification of amino imidazoles, a robust starting point for initiating a hit-to-lead medicinal chem. effort. Structure-activity relation studies followed by pharmacokinetics optimization resulted in the identification of (I) as an attractive lead with good oral bioavailability. Compound I was efficacious (ED90 of 28.6 mg·kg-1) in the humanized P. falciparum mouse model of malaria (Pf/SCID model). Representative compounds displayed a moderate to fast killing profile that is comparable to that of chloroquine. This series demonstrates no cross-resistance against a panel of Pf strains with mutations to known antimalarial drugs, thereby suggesting a novel mechanism of action for this chem. class.
Journal of Medicinal Chemistry published new progress about Antimalarials. 21901-29-1 belongs to class pyridine-derivatives, and the molecular formula is C6H7N3O2, Category: pyridine-derivatives.