Late-Stage Diversification of Pyrazoles as Antileishmanial Agents.
ChemMedChem
; 19(8): e202400028, 2024 Apr 16.
Article
en En
| MEDLINE
| ID: mdl-38289147
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 (IC50=19â
µM) and antitrypanosomal activity (IC50=7.9â
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.
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1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antiprotozoarios
Idioma:
En
Revista:
ChemMedChem
Asunto de la revista:
FARMACOLOGIA
/
QUIMICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Alemania