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A Two‐Step Multicomponent Synthetic Approach and Anti‐inflammatory Evaluation of N ‐Substituted 2‐Oxopyrazines
Author(s) -
HernándezVázquez Eduardo,
ChávezRiveros Alejandra,
NietoCamacho Antonio,
Miranda Luis D.
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201800634
Subject(s) - acetamide , trifluoromethyl , chemistry , in vivo , inflammation , myeloperoxidase , stereochemistry , pharmacology , organic chemistry , medicine , biology , alkyl , microbiology and biotechnology
Inflammation is widely reported as a main factor for the development of chronic diseases such as cancer, diabetes, and even metabolic syndrome. Thus, the search for novel anti‐inflammatory compounds is required. Herein we describe the synthesis of a collection of peptidic pyrazinones by a convenient approach involving a multicomponent isocyanide‐based reaction followed by a tandem deprotection/oxidative cyclization step. This series of compounds were tested for their potential anti‐inflammatory capacity in an in vivo murine model, and four compounds were identified to inhibit tetradecanoylphorbol acetate (TPA)‐induced edema by more than 75 %. The two most active compounds, N ‐benzyl‐2‐(4‐hydroxy‐3,5‐dimethoxyphenyl)‐2‐[2‐oxopyrazin‐1(2 H )‐yl]acetamide ( 10 o ) and N ‐cyclohexyl‐2‐[2‐oxopyrazin‐1(2 H )‐yl]‐2‐[4‐(trifluoromethyl)phenyl]acetamide ( 10 x ), with methyl and trifluoromethyl groups, were also able to decrease myeloperoxidase activity and leukocyte infiltration. Moreover, 10 x decreased the thickness of TPA‐treated mouse ears, as observed in histological analysis of the tissues.