Synthesis and antimalarial activity of novel medium-sized 1,2,4,5-tetraoxacycloalkanes

H S Kim; Y Nagai; K Ono; K Begum; Y Wataya; Y Hamada; K Tsuchiya; A Masuyama; M Nojima; K J McCullough

doi:10.1021/jm010026g

Synthesis and antimalarial activity of novel medium-sized 1,2,4,5-tetraoxacycloalkanes

J Med Chem. 2001 Jul 5;44(14):2357-61. doi: 10.1021/jm010026g.

Authors

H S Kim¹, Y Nagai, K Ono, K Begum, Y Wataya, Y Hamada, K Tsuchiya, A Masuyama, M Nojima, K J McCullough

Affiliation

¹ Faculty of Pharmaceutical Sciences, Okayama University, Tsushima, Okayama 700-8530, Japan.

PMID: 11428929
DOI: 10.1021/jm010026g

Abstract

CsOH- or Ag(2)O-mediated cycloalkylation of (alkylidene)bisperoxides 3 and 1,n-dihaloalkanes (n = 3-8) provided the corresponding medium-sized 1,2,4,5-tetraoxacycloalkanes 4-8 in moderate yields. Subsequent evaluation of the antimalarial activity of the cyclic peroxides 4-8 in vitro and in vivo revealed that 1,2,6,7-tetraoxaspiro[7.11]nonadecane 4a has considerable potential as a new, inexpensive, and potent antimalarial drug.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antimalarials / chemical synthesis*
Antimalarials / chemistry
Antimalarials / pharmacology
Cesium
Cyclization
Drug Evaluation, Preclinical
Heterocyclic Compounds, 2-Ring / chemical synthesis*
Heterocyclic Compounds, 2-Ring / chemistry
Heterocyclic Compounds, 2-Ring / pharmacology
Hydroxides
Malaria / drug therapy
Malaria / parasitology
Mice
Oxides
Plasmodium berghei
Plasmodium falciparum / drug effects
Silver Compounds
Spiro Compounds / chemical synthesis*
Spiro Compounds / chemistry
Spiro Compounds / pharmacology
Structure-Activity Relationship

Substances

1,2,6,7-tetraoxaspiro(7.11)nonadecane
Antimalarials
Heterocyclic Compounds, 2-Ring
Hydroxides
Oxides
Silver Compounds
Spiro Compounds
Cesium
disilver oxide