P7C3

P7C3 (pool 7, compound 3) is a drug related to latrepirdine (dimebon) which has neuroprotective and proneurogenic effects and may be potentially useful for the treatment of Alzheimer's disease and similar neurodegenerative disorders. The pharmacological effects of P7C3 in vitro resemble those of endogenous proneurogenic peptides such as fibroblast growth factor 1 (FGF-1), and the proneurogenic activity of P7C3 was around thirty times that of latrepirdine when they were compared in mice. P7C3 was chosen for further animal studies on the basis of favorable pharmacokinetic factors, such as its high oral bioavailability and long duration of action, but several other related compounds showed similar activity such as the more potent fluorinated analogue P7C3A20 which is up to ten times stronger again, and the methoxy analogue P7C3-OMe, for which it was determined that the (R) enantiomer is the active form.[1]

P7C3A20 and (R)-P7C3-OMe
P7C3
Identifiers
IUPAC name
  • 1-anilino-3-(3,6-dibromocarbazol-9-yl)propan-2-ol
CAS Number
PubChem CID
ChemSpider
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC21H18Br2N2O
Molar mass474.196 g·mol−1
3D model (JSmol)
SMILES
  • c4ccccc4NCC(O)Cn2c1ccc(Br)cc1c(c3)c2ccc3Br
InChI
  • InChI=1S/C21H18Br2N2O/c22-14-6-8-20-18(10-14)19-11-15(23)7-9-21(19)25(20)13-17(26)12-24-16-4-2-1-3-5-16/h1-11,17,24,26H,12-13H2 N
  • Key:FZHHRERIIVOATI-UHFFFAOYSA-N N
 NY (what is this?)  (verify)

The mechanism of action of the P7C3 series of compounds involves activation of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme responsible for the transformation of nicotinamide into nicotinamide adenine dinucleotide (NAD).[2] By activating NAMPT, the P7C3 compounds result in an increase in intracellular levels of NAD.[2]

References
  1. Pieper AA, Xie S, Capota E, Estill SJ, Zhong J, Long JM, Becker GL, Huntington P, Goldman SE, Shen CH, Capota M, Britt JK, Kotti T, Ure K, Brat DJ, Williams NS, MacMillan KS, Naidoo J, Melito L, Hsieh J, De Brabander J, Ready JM, McKnight SL (July 2010). "Discovery of a proneurogenic, neuroprotective chemical". Cell. 142 (1): 39–51. doi:10.1016/j.cell.2010.06.018. PMC 2930815. PMID 20603013.
  2. Wang G, Han T, Nijhawan D, Theodoropoulos P, Naidoo J, Yadavalli S, Mirzaei H, Pieper AA, Ready JM, McKnight SL (2014). "P7C3 neuroprotective chemicals function by activating the rate-limiting enzyme in NAD salvage". Cell. 158 (6): 1324–34. doi:10.1016/j.cell.2014.07.040. PMC 4163014. PMID 25215490.


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