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Microwave Assisted Synthesis of Pyrimidines in Ionic Liquid and Their Potency as Non‐Classical Malarial Antifolates
Author(s) -
Bhatt Jaimin D.,
Chudasama Chaitanya J.,
Patel Kanuprasad D.
Publication year - 2016
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201600148
Subject(s) - chemistry , bioavailability , pyrazole , dihydrofolate reductase , potency , plasmodium falciparum , ionic liquid , in silico , combinatorial chemistry , pyrimidine , stereochemistry , enzyme , in vitro , biochemistry , pharmacology , biology , malaria , gene , immunology , catalysis
Synthesis of pyrazole‐linked triazolo‐pyrimidine hybrids was achieved by employing Biginelli‐type reaction methodology in an ionic liquid (triethylammonium acetate) under microwave irradiation. This method proved to be highly efficient and the ionic liquid employed was found recyclable for up to five consecutive cycles. The synthesized molecules were further screened for their antimalarial efficacy screening out the active scaffolds J15 , J18 , J21 , J24 , J27 , and J30 . The active molecules were evaluated in an enzyme inhibition study against the active Plasmodium falciparum dihydrofolate reductase ( Pf ‐DHFR), computationally as well as in vitro , demonstrating their potency as DHFR inhibitors. The active entities were also investigated for their oral bioavailability by predicting ADME properties in silico , indicating good bioavailability.