T3p-promoted synthesis of a series of 2-aryl-3-phenyl-2,3-dihydro-4h-pyrido[3,2-e][1,3]thiazin-4-ones and their activity against the kinetoplastid parasite trypanosoma brucei

Document Type

Article

Publication Date

10-1-2021

Abstract

A series of fourteen 2-aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones was prepared at room temperature by T3P-mediated cyclization of N-phenyl-C-aryl imines with thion-icotinic acid, two difficult substrates. The reactions were operationally simple, did not require specialized equipment or anhydrous solvents, could be performed as either two or three component reactions, and gave moderate–good yields as high as 63%. This provides ready access to N-phenyl compounds in this family, which have been generally difficult to prepare. As part of the study, the first crystal structure of neutral thionicotinic acid is also reported, and showed the molecule to be in the form of the thione tautomer. Additionally, the synthesized compounds were tested against T. brucei, the causative agent of Human African Sleeping Sickness. Screening at 50 µM concentration showed that five of the compounds strongly inhibited growth and killed parasites.

Identifier

85117223866 (Scopus)

Publication Title

Molecules

External Full Text Location

https://doi.org/10.3390/molecules26206099

e-ISSN

14203049

PubMed ID

34684680

Issue

20

Volume

26

Grant

1S10RR023439-01

Fund Ref

National Institutes of Health

This document is currently not available here.

Share

COinS