PF-4840154

PF-4840154
Names
IUPAC name
4-Isobutylamino-2-[4-(tetrahydro-pyran-3-ylmethyl)-piperazin-1-yl]-pyrimidine-5-carboxylic acid benzylamide
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
Properties
C26H38N6O2
Molar mass 466.63 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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Infobox references

PF-4840154 is 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. 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.[1] 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.[2][3]

References

  1. Ryckmans T, Aubdool AA, Bodkin JV, Cox P, Brain SD, Dupont T, Fairman E, Hashizume Y, Ishii N, Kato T, Kitching L, Newman J, Omoto K, Rawson D, Strover J (July 2011). "Design and pharmacological evaluation of PF-4840154, a non-electrophilic reference agonist of the TrpA1 channel". Bioorganic. Med. Chem. Lett. (21): 4857–4859. doi:10.1016/j.bmcl.2011.06.035. PMID 21741838.
  2. McNamara CR, Mandel-Brehm J, Bautista DM, Siemens J, Deranian KL, Zhao M, Hayward NJ, Chong JA, Julius D, Moran MM, Fanger CM (August 2007). "TRPA1 mediates formalin-induced pain". Proc. Natl. Acad. Sci. U.S.A. 104 (33): 13525–30. doi:10.1073/pnas.0705924104. PMC 1941642. PMID 17686976.
  3. McMahon SB, Wood JN (March 2006). "Increasingly irritable and close to tears: TRPA1 in inflammatory pain". Cell. 124 (6): 1123–5. doi:10.1016/j.cell.2006.03.006. PMID 16564004.
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