Conformational restriction serotonin

Zefirova ON, Baranova TYu, Lyssenko KA et al (2012) Synthesis and biological testing of conformationally restricted serotonin analogues with bridgehead moieties. Mendeleev Commun 22(2) 75-77... 

The conformationally restricted 17/-2-benzazepine derivative 353, which is a dual inhibitor of acetylcholinesterase (ICso=14nM) and the serotonin transporter (IC5o = 6nM), is a potential agent for the treatment of Alzheimer s disease <2003BMC4389>. 

Conformational restriction was introduced into the side chain of a nonclassical serotonin bioisostere (28), a selective 5-HT and 5-HT receptor agonist) by its incorporation into a fused six-membered ring (29) (23). 

The conformational restrictions imposed on the indole-3-ethylamine moiety permitted retention of affinity for the 5-HT receptor but it diminished affinity for the 5-HT receptor by a factor of 1000. In two functional assays, (29) exhibited potency equal to or marginally greater than that of serotonin. Com-... 

Ghosh, A., Wang, W., Freeman, J.P., Althaus, J.S., von Voigtlander, P.F. et al. (1991) Stereocontrolled syntheses of some conformationally restricted analogs of serotonin. Tetrahedron Lett. 47 8653-8662. 

Conformationally restricted analogs of other low molecular mass agonists have been synthesized or discovered in attempts to characterize the bioactive conformation of the ligand., This field is vast and selected examples of constrained agonist analogs of dopamine (23.10) versus (23.11), GABA (23.12) versus (23.13)-(23.14),2 glutamic acid (23.15) versus (23.16) and (23.17), histamine (23.18) versus (23.19) and (23.20), serotonin (23.21) versus (23.22) that have been discovered by application of this approach are shown in Fig. 23.2. 

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