Pharmacophore identification for sigma-1 (sigma1) receptor binding: application of the "deconstruction-reconstruction-elaboration" approach.
At least two different types of sigma (sigma1 and sigma2) receptors have been identified. A structural feature common to high-affinity (Ki <10 nM) sigma1 ligands is: C-N(R)-X-Ph; both C and Ph are associated with regions of bulk tolerance. Numerous other ligands bind, but typically do so with lower affinity.
Glennon
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Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia 23298-0540, USA. glennon@hsc.vcu.edu
D000588:Amines / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D008024:Ligands; D010879:Piperazines / Q000138:chemical synthesis / Q000494:pharmacology*; D010880:Piperidines / Q000138:chemical synthesis / Q000494:pharmacology*; D011485:Protein Binding; D011955:Receptors, Drug / Q000378:metabolism*; D017480:Receptors, sigma / Q000378:metabolism*
D000588:Amines; D008024:Ligands; D010879:Piperazines; D010880:Piperidines; D011955:Receptors, Drug; D017480:Receptors, sigma