@article{article_188380, title={Synthesis, QSAR and docking studies of 5HT2A receptor antagonising thiazolo[3,2-a]pyrimidines as antipsychotic agents}, journal={Marmara Pharmaceutical Journal}, volume={18}, pages={109–119}, year={2014}, DOI={10.12991/mpj.2014187237}, author={Sawant, Ramesh and Ramdın, Supriya and Wadekar, Jyoti}, keywords={Molecular docking, QSAR, Schizophrenia, Thiazolo[3,2-a]pyrimidine, 5HT2A receptor antagonist.}, abstract={<p align="LEFT">A series of twenty two compounds containing thiazolo[3,2-a] </p> <p align="LEFT">pyrimidine carboxamide nucleus was synthesized by using </p> <p align="LEFT">microwave. Substituted acetoacetanilide was condensed with </p> <p align="LEFT">thiourea and substituted benzaldehydes in the presence of </p> <em> </em> <p align="LEFT"> <span style="font-family: TimesNewRomanPS-ItalicMT; font-size: xx-small;"> <span style="font-family: TimesNewRomanPS-ItalicMT; font-size: xx-small;"> <em>p </em> </span> </span> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;"> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;">-toluenesulfonic acid as catalyst in ethanol to get 2-thioxo- </span> </span> </p> <p align="LEFT">1,2,3,4-tetrahydropyrimidine carboxamide. In the second step, </p> <p align="LEFT">1,2,3,4-tetrahydropyrimidine carboxamides were treated with </p> <p align="LEFT">chloroacetic acid, anhydrous sodium acetate and glacial acetic </p> <p align="LEFT">acid to yield the title compounds. The reaction progress and </p> <p align="LEFT">purity of the synthesized compounds were monitored by TLC </p> <p align="LEFT">using silica gel G and by determining their melting points. </p> <p align="LEFT">Structures of title compounds were confirmed by elemental </p> <p align="LEFT"> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;"> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;">analysis, IR, </span> </span> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;"> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;">1 </span> </span> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;"> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;">H NMR and mass spectral data. The </span> </span> </p> <p align="LEFT">antipsychotic activity for title compounds was performed using </p> <em> </em> <p align="LEFT"> <span style="font-family: TimesNewRomanPS-ItalicMT; font-size: xx-small;"> <span style="font-family: TimesNewRomanPS-ItalicMT; font-size: xx-small;"> <em>albino </em> </span> </span> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;"> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;">mice by rotarod and tail suspension method. </span> </span> </p> <p align="LEFT">Compounds have shown antipsychotic activity comparable </p> <p align="LEFT">with the standard risperidone. The 2D, 3D QSAR and </p> <p align="LEFT">molecular docking studies were performed using VLife MDS </p> <p align="LEFT">3.5 software. The molecular modelling studies reveals that </p> <p align="LEFT">more potent antipsychotics from this series can be generated </p> <p align="LEFT"> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;"> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;">by substituting electronegative group at </span> </span> <em> <span style="font-family: TimesNewRomanPS-ItalicMT; font-size: xx-small;"> <span style="font-family: TimesNewRomanPS-ItalicMT; font-size: xx-small;">para </span> </span> </em> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;"> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;">and </span> </span> <em> <span style="font-family: TimesNewRomanPS-ItalicMT; font-size: xx-small;"> <span style="font-family: TimesNewRomanPS-ItalicMT; font-size: xx-small;">meta </span> </span> </em> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;"> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;">position </span> </span> </p> <p align="LEFT"> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;"> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;">of </span> </span> <em> <span style="font-family: TimesNewRomanPS-ItalicMT; font-size: xx-small;"> <span style="font-family: TimesNewRomanPS-ItalicMT; font-size: xx-small;">N </span> </span> </em> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;"> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;">-phenyl ring and less bulky group at 5-phenyl ring of </span> </span> </p> <p align="LEFT">thiazolo[3,2-a]pyrimidine-6-carboxamide nucleus. </p> <strong> </strong> <p align="LEFT"> <span style="font-family: TimesNewRomanPS-BoldMT; font-size: xx-small;"> <span style="font-family: TimesNewRomanPS-BoldMT; font-size: xx-small;"> <strong>Keywords: </strong> </span> </span> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;"> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;">Molecular docking, QSAR, Schizophrenia, </span> </span> </p> <p> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;"> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;">Thiazolo[3,2-a]pyrimidine, 5HT </span> </span> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;"> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;">2A </span> </span> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;"> <span style="font-family: TimesNewRomanPSMT; font-size: xx-small;">}, number={3}, publisher={Marmara University}