PF-04457845

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PF-04457845
PF-04457845 structure.png
Systematic (IUPAC) name
N-pyridazin-3-yl-4-[(3-[5-(trifluoromethyl)pyridin-2-yl]oxyphenyl)methylidene]piperidine-1-carboxamide
Clinical data
Legal status Investigational New Drug
Identifiers
ATC code None
PubChem CID 24771824
ChemSpider 26390839
ChEMBL CHEMBL1651534
Chemical data
Formula C23H20F3N5O2 
Mol. mass 455.432 g/mol

PF-04457845 is a potent and exquisitely selective inhibitor of the enzyme fatty acid amide hydrolase (FAAH), with an IC50 of 7.2nM, and both analgesic and antiinflammatory effects in animal studies comparable to naproxen. It has been well tolerated in human trials even at high dose ranges with no evidence for cognitive dysfunction, and has completed Phase II clinical trials for the treatment of osteoarthritis.[1][2][3][4]

See also[edit]

References[edit]

  1. ^ Johnson, D. S.; Stiff, C.; Lazerwith, S. E.; Kesten, S. R.; Fay, L. K.; Morris, M.; Beidler, D.; Liimatta, M. B.; Smith, S. E.; Dudley, D. T.; Sadagopan, N.; Bhattachar, S. N.; Kesten, S. J.; Nomanbhoy, T. K.; Cravatt, B. F.; Ahn, K. (2011). "Discovery of PF-04457845: A Highly Potent, Orally Bioavailable, and Selective Urea FAAH Inhibitor". ACS Medicinal Chemistry Letters 2 (2): 91–96. doi:10.1021/ml100190t. PMC 3109749. PMID 21666860.  edit
  2. ^ Ahn K, Smith SE, Liimatta MB, Beidler D, Sadagopan N, Dudley DT, Young T, Wren P, Zhang Y, Swaney S, Van Becelaere K, Blankman JL, Nomura DK, Bhattachar SN, Stiff C, Nomanbhoy TK, Weerapana E, Johnson DS, Cravatt BF. Mechanistic and pharmacological characterization of PF-04457845: a highly potent and selective fatty acid amide hydrolase inhibitor that reduces inflammatory and noninflammatory pain. Journal of Pharmacology and Experimental Therapeutics. 2011 Jul;338(1):114-24. PMID 21505060
  3. ^ Li, G. L.; Winter, H.; Arends, R.; Jay, G. W.; Le, V.; Young, T.; Huggins, J. P. (2012). "Assessment of the pharmacology and tolerability of PF-04457845, an irreversible inhibitor of fatty acid amide hydrolase-1, in healthy subjects". British Journal of Clinical Pharmacology 73 (5): 706–716. doi:10.1111/j.1365-2125.2011.04137.x. PMID 22044402.  edit
  4. ^ A Study To Investigate Whether PF-04457845 Is Effective In Treating Pain, Is Safe And Tolerable In Patients With Osteoarthritis Of The Knee