Publication
Title
Late‐stage diversification of pyrazoles as antileishmanial agents
Author
Abstract
N ‐Pyrazolylcarboxamides and N ‐pyrazolylureas represent promising lead compounds for the development of novel antileishmanial drugs. Herein, we report the late‐stage diversification of 3‐bromopyrazoles 10 A / B and 14 A by Pd‐catalyzed Sonogashira and Suzuki‐Miyaura cross coupling reactions. The electron‐withdrawing properties of the cyano moiety in 4‐position of the pyrazole ring limited the acylation of the primary amino moiety in 5‐position. A large set of pyrazoles bearing diverse aryl and alkynyl substituents in 3‐position was prepared and the antileishmanial and antitrypanosomal activity was recorded. The urea 38 lacking the electron withdrawing cyano moiety in 4‐position and containing the large 4‐benzylpiperidinoo moiety exhibited a modest antileishmanial ( IC 50 =19 μM) and antitrypanosomal activity ( IC 50 =7.9 μM)). However, its considerable toxicity against the PMM and MRC‐5 cells indicates low selectivity, i. e . a small gap between the desired antiparasitic activity and undesired cytotoxicity of <2‐ to 4‐fold.
Language
English
Source (journal)
ChemMedChem. - Place of publication unknown
Publication
Place of publication unknown : 2024
ISSN
1860-7179 [print]
1860-7187 [online]
DOI
10.1002/CMDC.202400028
Volume/pages
19 :8 (2024) , p. 1-21
Article Reference
e202400028
ISI
001163448800001
Pubmed ID
38289147
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 27.02.2024
Last edited 23.04.2024
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