Design, synthesis & evaluation of condensed 2H-4-arylaminopyrimidines as novel antifungal agents

  • Eur J Med Chem. 2014 Apr 22:77:166-75. doi: 10.1016/j.ejmech.2014.02.066.
Kishor S Jain  1 ,  Vijay M Khedkar  2 ,  Nikhilesh Arya  3 ,  Prasad V Rane  4 ,  Pratip K Chaskar  5 ,  Evans C Coutinho  2
Affiliations
  • 1. Department of Pharmaceutical Chemistry, Sinhgad Institute of Pharmaceutical Sciences, Lonavala, Pune, 410401 Maharashtra, India. Electronic address: [email protected].
  • 2. Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Kalina, Mumbai, 400098 Maharashtra, India.
  • 3. Department of Pharmaceutical Chemistry, Sinhgad Institute of Pharmaceutical Sciences, Lonavala, Pune, 410401 Maharashtra, India.
  • 4. Department of Pharmaceutical Chemistry, RJSPM's College of Pharmacy, Moshi-Alandi Road, Pune, 412105 Maharashtra, India.
  • 5. Department of Pharmaceutical Chemistry, Vivekanand Education Society's College of Pharmacy, Chembur, Mumbai, 400074 Maharashtra, India.
PMID: 24631896 DOI: 10.1016/j.ejmech.2014.02.066
Abstract

A small, focussed library of condensed 2H-4-arylaminopyrimidines, with 3-diversity points, based on an initial design by molecular docking study of this scaffold at the active site of the Fungal enzyme of Cytochrome P450 family, lanosterol 14α-demethylase (CYP51) was synthesized through a one-pot green chemical synthetic protocol. The screening of the synthesised compounds for Antifungal activity against Candida albicans, Aspergillus fumigatus &Aspergillus niger revealed activity in many of the compounds as comparable to that of fluconazole. Based on the Antifungal activity and physicochemical property data of these derivatives, a meaningful SAR has been proposed.

Keywords
Antifungal activity; Condensed pyrimidines; Docking; Lanosterol 14-α-demethylase; MWI; SAR.
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