3D-QSAR Studies on Thiazolidin-4-one S1P1 Receptor Agonists by CoMFA and CoMSIA

نویسندگان

  • Chuiwen Qian
  • Junxia Zheng
  • Gaokeng Xiao
  • Jialiang Guo
  • Zhaoqi Yang
  • Li Huang
  • Wei Chao
  • Longyi Rao
  • Pinghua Sun
چکیده

Selective S1P(1) receptor agonists have therapeutic potential to treat a variety of immune-mediated diseases. A series of 2-imino-thiazolidin-4-one derivatives displaying potent S1P(1) receptor agonistic activity were selected to establish 3D-QSAR models using CoMFA and CoMSIA methods. Internal and external cross-validation techniques were investigated as well as some measures including region focusing, progressive scrambling, bootstraping and leave-group-out. The satisfactory CoMFA model predicted a q(2) value of 0.751 and an r(2) value of 0.973, indicating that electrostatic and steric properties play a significant role in potency. The best CoMSIA model, based on a combination of steric, electrostatic, hydrophobic and H-bond donor descriptors, predicted a q(2) value of 0.739 and an r(2) value of 0.923. The models were graphically interpreted using contour plots which gave more insight into the structural requirements for increasing the activity of a compound, providing a solid basis for future rational design of more active S1P(1) receptor agonists.

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عنوان ژورنال:

دوره 12  شماره 

صفحات  -

تاریخ انتشار 2011