The Synthesis of New Antimalarial Drugs.
Abstract
The purpose of the work was to prepare compounds belonging to three chemical classes for evaluation as antimalarial drugs. Alpha-(Di-n-butylaminomethyl)-2-phenyl-3',4',6,8-tetrachloro-1, 2,3,4-tetrahydro-4-quinolinemethanol and its N-acetyl and N-ethyl derivatives were prepared to test the hypothesis that reduction of the pyridine ring in WR 30090 would eliminate an undesirable phototoxic side-effect. Phototoxicity and antimalarial activity were decreased in equivalent fashion. A synthesis of a pyrrocolinemethanol, alpha-(di-n-butylaminomethyl)-7,9-dichloro-5-pyrrolo(1,2-a)quinolinemethanol, was undertaken in order to determine the effect of replacing the 2-aryl group of a conventional 2-aryl-4-quinolinemethanol antimalarial by a cyclic structure. The synthesis has proceeded to 7,9-dichloro-5-methylpyrrolo-(1,2-a)quinoline. Fluorenemethanols having aminoalcohol sidechains at the 1- and 4-position, and related compounds having 9-hydroxy or 9-keto groups, were prepared. None had antimalarial activity. However, when chlorine atoms were introduced at the 2,7-positions high antimalarial activity resulted. (Author)
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 1971
- Accession Number
- AD0732879
Entities
People
- Edward R. Atkinson
- Felix E. Granchelli
Organizations
- Arthur D. Little