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Facile Synthesis and Preliminary Structure-Activity Analysis of New Sulfonamides Against Trypanosoma brucei.

ABSTRACT: The high throughput screening of a library of over 87,000 drug-like compounds against the African sleeping sickness parasite resulted in the discovery of hits with a wide range of molecular diversity. We report here the medicinal chemistry development of one such hit, a tetrahydroisoquinoline disulfonamide, with the synthesis and testing of 26 derivatives against the trypanosome subspecies. Activities in the 2-4 ?M range were revealed with a selectivity index suitable for further development.

SUBMITTER: Rashad AA

PROVIDER: S-EPMC4027789 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Facile Synthesis and Preliminary Structure-Activity Analysis of New Sulfonamides Against Trypanosoma brucei.

Rashad Adel A AA Jones Amy J AJ Avery Vicky M VM Baell Jonathan J Keller Paul A PA

ACS medicinal chemistry letters 20140310 5

The high throughput screening of a library of over 87,000 drug-like compounds against the African sleeping sickness parasite resulted in the discovery of hits with a wide range of molecular diversity. We report here the medicinal chemistry development of one such hit, a tetrahydroisoquinoline disulfonamide, with the synthesis and testing of 26 derivatives against the trypanosome subspecies. Activities in the 2-4 μM range were revealed with a selectivity index suitable for further development. ...[more]

PMID: 24900868

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