Nicotinic pharmacophore

Fig. 12.12 Four molecules used to derive the nicotinic pharmacophore by distance geometry and the pharmacophore obtained.

Sheridan R P, R Ndakantan, J S Dixon and R Venkataraghavan 1986. The Ensemble Approach to Distanc Geometry Application to the Nicotinic Pharmacophore. Journal of Medicinal Chemistry 29 899-906. 

RP Sheridan, R Nilakatan, JS Dixson, R Venkataraghavan. The ensemble approach to distance geometry Application to the nicotinic pharmacophore. J Med Chem 29 899-906, 1986. 

Recent EHT calculations on the neostigmine molecule have led to a conformation prediction locating the onium group about 4.5 A from the carbonyl oxygen (81) in support of the postulated nicotinic pharmacophore (17). 

Figure 14.14. Example of pharmacophoric element selection for molecular modeling of nicotine. Pharmacophoric elements A and B are nitrogens and element C is on the nAChR receptor with which element B would optimally connect. Carbon, green nitrogen, light blue hydrogen attached to the basic nitrogen, white putative nAChR binding site, dark blue.

The Ensemble Approach to Distance Geometry Application to the Nicotinic Pharmacophore. 

For example, in 1970 a useful nicotinic pharmacophore model was already described by Beers and Reich and subsequently improved by Sheridan et al. [103]. Starting from different models a distance from the onium group to a point on the van der Waals surface of the H-bond acceptor of 5.9 A was common to several ligands. Up to now three binding models of neonicotinoids have been proposed (cf Fig. 29.1.2) [104]. 

Figure 3. Example results for 3-D database search using nicotinic pharmacophore...

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