The Synthesis of New Antimalarial Drugs Derivatives of Benzothiopyrans, Derivatives of Menoctone.
Abstract
The purpose of the work performed was to prepare analogs and derivatives of the compounds N,N-dimethyl-N'-(6-chloro-2-phenyl-4H-1-benzothiopyran-4- ylidene)-1,3-propanediamine hydrochloride (WR 95214) and to prepare derivatives of the naphthoquinone antimalarial menoctone (3-(8-cyclohexyloctyl) -2-hydroxy-1,4-naphthoquinone) that might retain the antimalarial potency of menoctone but achieve an enhanced distribution and metabolism in vivo. The compound 3-(8-cyclohexyloctyl)-1-4-dimethoxy-2-naphthol was of particular interest. In the report the synthesis of 43 target benzothiopyrans and 23 intermediates is described. Of the 43 target compounds evaluated as antimalarials 9 were active, 10 were curative, and 24 were inactive in a mouse screen at dose levels of 160-640 mg/kg. A few general conclusions were reached relevant to structure-activity relationships in this series. A 4-step synthesis of 3-(8-cyclohexyloctyl)-1,4-dimethoxy-2-naphthol from menoctone was developed and samples of 3 intermediates and the target compound were submitted for evaluation. In addition, a water-soluble derivative of menoctone was prepared by esterification of the phenolic group with 4-diethylaminobutyric acid hydrochloride. (Author)
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1971
- Accession Number
- AD0728829
Entities
People
- Avinash C. Mehta
- Edward R. Atkinson
- Klaus K. Weinhardt
- Raj K. Razdan
- Robert J. Bruni
Organizations
- Arthur D. Little