Chemistry:PF-4840154

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Short description: Pyrimidine derivative chemical
PF-4840154
PF-4840154.svg
Names
Preferred IUPAC name
N-Benzyl-4-[(2-methylpropyl)amino]-2-{4-[(oxan-3-yl)methyl]piperazin-1-yl}pyrimidine-5-carboxamide
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
Properties
C26H38N6O2
Molar mass 466.630 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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PF-4840154 is a pyrimidine derivative discovered by Pfizer at its Sandwich, Kent research center. The compound is a potent, selective activator of both the human (EC50 = 23 nM) and rat (EC50 = 97 nM) TRPA1 channels.[1] This compound elicits nociception in a mouse model through TRPA1 activation. PF-4840154 is used as a reference agonist of the TRPA1 channel for in-vitro high-throughput screening purposes, and is superior to allyl isothiocyanate for this use.[2] The TRPA1 channel is considered an attractive pain target based on the fact that TRPA1 knockout mice showed near complete attenuation of pain behaviors in some pre-clinical development models.[3][4]

See also

References

  1. Samanta, Amrita; Kiselar, Janna; Pumroy, Ruth A.; Han, Seungil; Moiseenkova-Bell, Vera Y. (2018-04-27). "Structural insights into the molecular mechanism of mouse TRPA1 activation and inhibition". Journal of General Physiology (Rockefeller University Press) 150 (5): 751–762. doi:10.1085/jgp.201711876. ISSN 0022-1295. PMID 29703838. 
  2. "Design and pharmacological evaluation of PF-4840154, a non-electrophilic reference agonist of the TrpA1 channel". Bioorg. Med. Chem. Lett. 21 (16): 4857–4859. July 2011. doi:10.1016/j.bmcl.2011.06.035. PMID 21741838. 
  3. "TRPA1 mediates formalin-induced pain". Proc. Natl. Acad. Sci. U.S.A. 104 (33): 13525–30. August 2007. doi:10.1073/pnas.0705924104. PMID 17686976. 
  4. "Increasingly irritable and close to tears: TRPA1 in inflammatory pain". Cell 124 (6): 1123–5. March 2006. doi:10.1016/j.cell.2006.03.006. PMID 16564004.