| Title : Design, synthesis, and activity of a series of arylpyrid-3-ylmethanones as type I positive allosteric modulators of alpha7 nicotinic acetylcholine receptors - Hogenkamp_2013_J.Med.Chem_56_8352 |
| Author(s) : Hogenkamp DJ , Ford-Hutchinson TA , Li WY , Whittemore ER , Yoshimura RF , Tran MB , Johnstone TB , Bascom GD , Rollins H , Lu L , Gee KW |
| Ref : Journal of Medicinal Chemistry , 56 :8352 , 2013 |
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Abstract :
A series of novel arylpyrid-3-ylmethanones (7a-aa) were designed as modulators of alpha7 nicotinic acetylcholine receptors (nAChRs). The methanones were found to be type I positive allosteric modulators (PAMs) of human alpha7 nAChRs expressed in Xenopus ooctyes. Structure-activity relationship (SAR) studies resulted in the identification of compound 7v as a potent and efficacious type I PAM with maximum modulation of a nicotine EC5 response of 1200% and EC50 = 0.18 muM. Compound 7z was active in reversing the effect of scopolamine in the novel object recognition (NOR) paradigm with a minimum effective ip dose of 1.0 mg/kg (2.7 mumol/kg). This effect was blocked by the selective alpha7 nAChR antagonist methyllycaconitine (MLA). These compounds are potent type I positive allosteric modulators of alpha7 nAChRs that may have therapeutic value in restoring impaired sensory gating and cognitive deficits in schizophrenia and Alzheimer's disease. |
| PubMedSearch : Hogenkamp_2013_J.Med.Chem_56_8352 |
| PubMedID: 24098954 |
Hogenkamp DJ, Ford-Hutchinson TA, Li WY, Whittemore ER, Yoshimura RF, Tran MB, Johnstone TB, Bascom GD, Rollins H, Lu L, Gee KW (2013)
Design, synthesis, and activity of a series of arylpyrid-3-ylmethanones as type I positive allosteric modulators of alpha7 nicotinic acetylcholine receptors
Journal of Medicinal Chemistry
56 :8352
Hogenkamp DJ, Ford-Hutchinson TA, Li WY, Whittemore ER, Yoshimura RF, Tran MB, Johnstone TB, Bascom GD, Rollins H, Lu L, Gee KW (2013)
Journal of Medicinal Chemistry
56 :8352