2. Academic Validation
  3. Synthesis and antitrypanosomal evaluation of derivatives of N-benzyl-1,2-dihydroquinolin-6-ols: Effect of core substitutions and salt formation

Synthesis and antitrypanosomal evaluation of derivatives of N-benzyl-1,2-dihydroquinolin-6-ols: Effect of core substitutions and salt formation

  • Bioorg Med Chem. 2011 Jan 1;19(1):513-23. doi: 10.1016/j.bmc.2010.11.003.
Carolyn S Reid 1,  Donald A Patrick,  Shanshan He,  Jean Fotie,  Kokku Premalatha,  Richard R Tidwell,  Michael Zhuo Wang,  Qiang Liu,  Pavel Gershkovich,  Kishor M Wasan,  Tanja Wenzler,  Reto Brun,  Karl A Werbovetz
Affiliations

Affiliation

  • 1 Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, Columbus, OH 43210, USA.
PMID: 21112788 DOI: 10.1016/j.bmc.2010.11.003
Abstract

Analogs of the trypanocidal lead compound 1-benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-yl acetate were prepared to extend the structure-activity relationship in this series of molecules, improve the in vivo antitrypanosomal activity of the lead, and determine whether ester prodrugs are needed to overcome the instability of the dihydroquinolin-6-ols. Two of the most active compounds identified in this study were 1-benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-ol hydrochloride and 1-(2-methoxy)benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-ol hydrochloride. These stable solids possessed low nanomolar IC(50) values against Trypanosoma brucei rhodesiense STIB900 in vitro and provided cures in an early treatment acute mouse model of African trypanosomiasis when given IP at 50mg/kg/day for four consecutive days.

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