Two analogues of fenarimol show curative activity in an experimental model of Chagas disease.

Abstract:

:Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is an increasing threat to global health. Available medicines were introduced over 40 years ago, have undesirable side effects, and give equivocal results of cure in the chronic stage of the disease. We report the development of two compounds, 6 and (S)-7, with PCR-confirmed curative activity in a mouse model of established T. cruzi infection after once daily oral dosing for 20 days at 20 mg/kg 6 and 10 mg/kg (S)-7. Compounds 6 and (S)-7 have potent in vitro activity, are noncytotoxic, show no adverse effects in vivo following repeat dosing, are prepared by a short synthetic route, and have druglike properties suitable for preclinical development.

journal_name

J Med Chem

authors

Keenan M,Chaplin JH,Alexander PW,Abbott MJ,Best WM,Khong A,Botero A,Perez C,Cornwall S,Thompson RA,White KL,Shackleford DM,Koltun M,Chiu FC,Morizzi J,Ryan E,Campbell M,von Geldern TW,Scandale I,Chatelain E,Charman

doi

10.1021/jm401610c

subject

Has Abstract

pub_date

2013-12-27 00:00:00

pages

10158-70

issue

24

eissn

0022-2623

issn

1520-4804

journal_volume

56

pub_type

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