Accession Number : AD0732879

Title :   The Synthesis of New Antimalarial Drugs.

Descriptive Note : Annual rept. no. 1,

Corporate Author : LITTLE (ARTHUR D) INC CAMBRIDGE MASS

Personal Author(s) : Atkinson,Edward R. ; Granchelli,Felix E.

Report Date : NOV 1971

Pagination or Media Count : 85

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)

Descriptors :   (*ANTIMALARIALS, SYNTHESIS(CHEMISTRY)), (*QUINOLINES, ANTIMALARIALS), (*FLUORENES, ANTIMALARIALS), HALOGENATED HYDROCARBONS, CHLORINE COMPOUNDS, AMINES, ALCOHOLS, TOXICITY, BROMINE COMPOUNDS, KETONES, FLUORINE COMPOUNDS

Subject Categories : Pharmacology
      Organic Chemistry

Distribution Statement : APPROVED FOR PUBLIC RELEASE