Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Pharmacophore Hypothesis for Atypical Antipsychotics

  • Sekhar, Kondapalli Venkata Gowri Chandra (Department of Chemistry, BITS Pilani Hyderabad Campus, Jawahar Nagar, Shamirpet Mandal, Ranga Reddy District) ;
  • Vyas, Devambhatla Ravi Kumar (Department of Chemistry, BITS Pilani Hyderabad Campus, Jawahar Nagar, Shamirpet Mandal, Ranga Reddy District) ;
  • Nagesh, Hunsur Nagendra (Department of Chemistry, BITS Pilani Hyderabad Campus, Jawahar Nagar, Shamirpet Mandal, Ranga Reddy District) ;
  • Rao, Vajja Sambasiva (Department of Chemistry, BITS Pilani Hyderabad Campus, Jawahar Nagar, Shamirpet Mandal, Ranga Reddy District)
  • Received : 2011.11.21
  • Accepted : 2012.06.04
  • Published : 2012.09.20
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Abstract

A three-dimensional pharmacophore hypothesis was developed for atypical antipsychotics in order to map common structural features of highly active compounds by using HipHop in CATALYST program. The pharmacophore hypotheses were generated using 12 compounds as training set and validated using 11 compounds as test set. The most predictive hypothesis (Hypo1) comprises five features viz. two hydrophobic regions, two hydrogen bond acceptor lipid and one aromatic ring. In the absence of information like crystallized structure of 5-$HT_{2A}$ receptor and binding mode of antipsychotics with 5-$HT_{2A}$ receptor, this hypothesis will serve as a potentially valuable tool in the design of novel atypical antipsychotics acting primarily at 5-$HT_{2A}$ and $D_2$ receptors.

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