PF-04995274   Click here for help

GtoPdb Ligand ID: 9059

Synonyms: compound 2d [PMID: 22974325] | PF 04995274 | PF04995274
Compound class: Synthetic organic
Comment: PF-04995274 is a serotonin 5-HT4 receptor partial agonist, developed as a potential pro-cognitive agent for the treatment of Alzheimer's disease (AD) [1].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 4
Hydrogen bond donors 1
Rotatable bonds 7
Topological polar surface area 86.42
Molecular weight 432.23
XLogP 2.21
No. Lipinski's rules broken 0
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Canonical SMILES OC1(CCOCC1)CN1CCC(CC1)COc1noc2c1c(ccc2)OC1COCC1
Isomeric SMILES OC1(CCOCC1)CN1CCC(CC1)COc1noc2c1c(ccc2)O[C@H]1COCC1
InChI InChI=1S/C23H32N2O6/c26-23(7-12-27-13-8-23)16-25-9-4-17(5-10-25)14-29-22-21-19(30-18-6-11-28-15-18)2-1-3-20(21)31-24-22/h1-3,17-18,26H,4-16H2/t18-/m1/s1
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Summary of Clinical Use Click here for help
Development of PF-04995274 in Alzheimer's disease (AD) was discontinued at Phase 1.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
A decrease of soluble amyloid precursor protein alpha (sAPPα) in cerebrospinal fluid has been associated with cognitive decline in aged rats and in AD patients. In vitro and in vivo studies suggested that 5-HT4 receptor agonists reverse this effect, thereby potentially slowing cognitive decline in AD. In healthy human subjects administered a single dose of F-04995274, no significant difference in sAPPα was observed between treatment and placebo groups [2].