Floyd, David M.; Stein, Philip; Wang, Zheng; Liu, Jian; Castro, Steve; Clark, Julie A.; Connelly, Michele; Zhu, Fangyi; Holbrook, Gloria; Matheny, Amy; Sigal, Martina S.; Min, Jaeki; Dhinakaran, Rajkumar; Krishnan, Senthil; Bashyum, Sridevi; Knapp, Spencer; Guy, R. Kiplin published the artcile< Hit-to-Lead Studies for the Antimalarial Tetrahydroisoquinolone Carboxanilides>, Synthetic Route of 1003-32-3, the main research area is tetrahydroisoquinolone carboxanilide preparation antimalarial structure activity.
Phenotypic whole-cell screening in erythrocytic co-cultures of Plasmodium falciparum identified a series of dihydroisoquinolones that possessed potent anti-malarial activity against multiple resistant strains of P. falciparum in vitro and show no cytotoxicity to mammalian cells. Systematic structure-activity studies revealed relationships between potency and modifications at N-2, C-3 and C-4. Careful structure-property relationship studies, coupled with studies of metabolism, addressed the poor aqueous solubility and metabolic vulnerability, as well as potential toxicol. effects, inherent in the more potent primary screening hits such as (I). Analogs (II) and (+)-SJ733 (13i), with structural modifications at each site, were shown to possess excellent anti-malarial activity in vivo. The (+)-(3S,4S) enantiomer of 13i and similar analogs were identified as the more potent. Based on these studies, the authors have selected (+)-13i for further study as a preclin. candidate.
Journal of Medicinal Chemistry published new progress about Antimalarials. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Synthetic Route of 1003-32-3.
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica