Accession Number : AD0694404

Title :   THE SYNTHESIS OF NEW ANTIMALARIAL DRUGS. 4- AND 5-QUINOLINEMETHANOLS.

Descriptive Note : Annual rept. no. 3 (Final),

Corporate Author : LITTLE (ARTHUR D) INC CAMBRIDGE MASS

Personal Author(s) : Atkinson,Edward R. ; Puttick,Anthony J.

Report Date : AUG 1969

Pagination or Media Count : 120

Abstract : The purpose of the work was to prepare analogs and derivatives of potent quinolinemethanol antimalarial drugs that had been prepared originally during the World War II antimalarial program. Most of the work was confined to the 2-phenyl-4-quinolinemethanol series; two target compounds in the 5-quinolinemethanol series were also prepared. In three formal reports, of which this is the last, 95 compounds have been described, most of which are novel. Of these, 35 target compounds and 43 intermediates were submitted for appropriate pharmacological evaluation. The inclusion of a free phenolic function at the 3'- and 4'-positions of 2-phenyl-4-quinolinemethanol drugs caused a complete loss of both phototoxicity and antimalarial activity. The reduction of the pyridine ring in a highly phototixic 2-phenyl-4-quinolinemethanol appeared to decrease the antimalarial activity without also causing a satisfactory decrease in phototoxicity. The inclusion of iodine atoms at the 3'-, 4'-- and 7-positions of a 2-phenyl-4-quinolinemethanol drug allowed the antimalarial activity to remain high. When at the 3'- and 4'-positions a significant decrease in phototoxicity occurred. A 2-phenyl-5-quinolinemethanol drug was a potent antimalarial but was also highly phototoxic. When the 2-phenyl group was omitted, anti-malarial activity was lost. Most of the structural modifications studied were based on our understanding of the mechanism of drug-induced phototoxicity, which is discussed at length. (Author)

Descriptors :   (*ANTIMALARIALS, *QUINOLINES), (*MOLECULAR STRUCTURE, ANTIMALARIALS), (*PHOTOCHEMICAL REACTIONS, ANTIMALARIALS), SYNTHESIS(CHEMISTRY), IODINE COMPOUNDS, HALOGENATED HYDROCARBONS, CHLORINE COMPOUNDS, TOXICITY, MOLECULAR ENERGY LEVELS, BOROHYDRIDES

Subject Categories : Pharmacology
      Organic Chemistry
      Radiation and Nuclear Chemistry

Distribution Statement : APPROVED FOR PUBLIC RELEASE