title: Three-dimensional pharmacophore screening for fentanyl derivatives.
abstract: Fentanyl is a highly selective μ-opioid receptor agonist with high analgesic activity. Three-dimensional pharmacophore models were built from a set of 50 fentanyl derivatives. These were employed to elucidate ligand-receptor interactions using information derived only from the ligand structure to identify new potential lead compounds. The present studies demonstrated that three hydrophobic regions, one positive ionizable region and two hydrogen bond acceptor region sites located on the molecule seem to be essential for analgesic activity. The results of the comparative molecular field analysis model suggested that both steric and electrostatic interactions play important roles. The contributions from steric and electrostatic fields for the model were 0.621 and 0.379, respectively. The pharmacophore model provides crucial information about how well the common features of a subject molecule overlap with the hypothesis model, which is very valuable for designing and optimizing new active structures.
authors: College of Life Science, Capital Normal University, Beijing 100048, China.
authors: Ming
authors: M
authors: Liu
authors: Department of Chemistry, Capital Normal University, Beijing 100048, China.
authors: Zhiguo
authors: Z
authors: Sun
authors: College of Life Science, Capital Normal University, Beijing 100048, China ; Department of Chemistry, Capital Normal University, Beijing 100048, China.
authors: Wenxiang
authors: W
authors: Hu
keywords: analgesic; comparative molecular field analysis; fentanyl; genetic algorithm with linear assignment of hypermolecular alignment of datasets; pharmacophore
references: Org Lett. 2009 Sep 3;11(17):3922-5
references: 19708703
references: Arzneimittelforschung. 2005;55(5):265-70
references: 15960425
references: J Med Chem. 2005 Jun 30;48(13):4389-99
references: 15974591
references: J Comput Aided Mol Des. 2002 Aug-Sep;16(8-9):653-81
references: 12602956
references: J Comput Aided Mol Des. 2000 Mar;14(3):215-32
references: 10756477
references: Blood. 2000 Nov 15;96(10):3343-56
references: 11071626
references: J Asian Nat Prod Res. 2008 May-Jun;10(5-6):439-45
references: 18464084
references: J Comput Aided Mol Des. 2001 Jul;15(7):587-612
references: 11688943
references: Annu Rev Biochem. 2004;73:953-90
references: 15189164
references: Biochem J. 1993 Nov 1;295 ( Pt 3):625-8
references: 8240267
references: J Chem Inf Comput Sci. 2002 Sep-Oct;42(5):1230-40
references: 12377013
references: J Comput Aided Mol Des. 2003 Jan;17(1):13-38
references: 12926853
references: J Nanosci Nanotechnol. 2010 Oct;10(10):6298-304
references: 21137722
references: Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):3-26
references: 11259830
references: J Comput Aided Mol Des. 2007 Apr;21(4):145-53
references: 17203365
references: Nature. 1997 Sep 11;389(6647):203-6
references: 9296501
references: J Org Chem. 2009 Aug 21;74(16):6111-9
references: 19610637
references: J Med Chem. 2005 Sep 22;48(19):6066-83
references: 16162008
references: Drug Discov Ther. 2008 Feb;2(1):52-7
references: 22504455
references: J Med Chem. 2003 Sep 11;46(19):4063-9
references: 12954059