Korean J Physiol Pharmacol.  2009 Feb;13(1):55-59. 10.4196/kjpp.2009.13.1.55.

Quantitative Structure Activity Relationship between Diazabicyclo[4.2.0]octanes Derivatives and Nicotinic Acetylcholine Receptor Agonists

• Kim EA
• Jung KC
• Sohn UD
• Im C

• KMID: 2285372
• DOI: http://doi.org/10.4196/kjpp.2009.13.1.55

Abstract

Three dimensional quantitative structure activity relationship between diazabicyclo[4.2.0]octanes and nicotinic acetylcholine receptor (h alpha4beta2 and h alpha3beta4) agonists was studied using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). From 11 CoMFA and CoMSIA models, CoMSIA with steric and electrostatic fields gave the best predictive models (q2=0.926 and 0.945, r2(ncv)=0.983 and 0.988). This study can be used to develop potent h alpha4beta2 receptor agonists with low activity on h alpha3beta4 subtype.

Keyword

Diazabicyclo[4.2.0]octanes; CoMFA; CoMSIA; Nicotinic acetylcholine receptors (nAChRs)

MeSH Terms

Quantitative Structure-Activity Relationship
Receptors, Nicotinic
Receptors, Nicotinic

Figure

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  Fig. 1. The superimposed structures of aligned training set.

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  Fig. 2. CoMSIA contour map of steric field for the hα4β2 subtype.

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  Fig. 3. CoMSIA contour map of electrostatic field for the hα4β2 subtype.

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  Fig. 4. CoMSIA contour map of steric field for the hα3β4 subtype.

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  Fig. 5. CoMSIA contour map of electrostatic field for the hα3β4 subtype.

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