Premium
New Substituted 1‐Aryl‐4,4,6‐Trimethyl‐3,4‐Dihydropyrimidine‐2‐(1 H )Thiones; A Metal‐Free and Solvent‐Free Synthesis, Characterization, and Lymphoid Tyrosine Phosphatase Inhibition Studies
Author(s) -
Khurshid Asma,
Saeed Aamer
Publication year - 2017
Publication title -
journal of the chinese chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.329
H-Index - 45
eISSN - 2192-6549
pISSN - 0009-4536
DOI - 10.1002/jccs.201600805
Subject(s) - chemistry , substituent , aryl , potassium thiocyanate , solvent , ring (chemistry) , medicinal chemistry , stereochemistry , catalysis , organic chemistry , alkyl
A series of fourteen 3,4‐dihydropyrimidine‐2‐thiones ( 3a–n ) were synthesized by a green protocol, and their structures were characterized by spectroanalytical data. The compounds were obtained in high yields by efficient annulation of mesityl oxide (4‐methylpent‐3‐en‐2‐one) with anilines in the presence of potassium thiocyanate. The reaction is essentially metal‐catalyst‐ and solvent‐free, as mesityl oxide itself is the solvent as well as the reactant. The compounds were tested for their ability to inhibit the lymphoid tyrosine phosphatase PTPN22, and 5 of the 14 compounds exhibited IC 50 values in the mid‐micromolar range, with the most potent hit being the compound 3d , having a methoxy substituent at the 2‐position of the phenyl ring with an IC 50 = 18 ± 1 μM, and second most potent compound ( 3c ) with an IC 50 value of 45 ± 3 μM, having methyl substituents at both 2‐ and 4‐position of the phenyl ring.