:PF-4840154

{{short description|Pyrimidine derivative chemical}}

{{Chembox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 442500296

| ImageFile = PF-4840154.svg

| ImageSize = 200px

| ImageAlt =

| PIN = N-Benzyl-4-[(2-methylpropyl)amino]-2-{4-[(oxan-3-yl)methyl]piperazin-1-yl}pyrimidine-5-carboxamide

| OtherNames =

|Section1={{Chembox Identifiers

| IUPHAR_ligand = 6309

| CASNo = 1332708-14-1

| PubChem = 53380803

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 1818218

| SMILES = O=C(NCC1=CC=CC=C1)C(C=N2)=C(NCC(C)C)N=C2N(CC3)CCN3CC4CCCOC4

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 26610754

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 1S/C26H38N6O2/c1-20(2)15-27-24-23(25(33)28-16-21-7-4-3-5-8-21)17-29-26(30-24)32-12-10-31(11-13-32)18-22-9-6-14-34-19-22/h3-5,7-8,17,20,22H,6,9-16,18-19H2,1-2H3,(H,28,33)(H,27,29,30)

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = PPANZCQXFYBGHN-UHFFFAOYSA-N}}

|Section2={{Chembox Properties

| C=26 | H=38 | N=6 | O=2

| Appearance =

| Density =

| MeltingPt =

| BoilingPt =

| Solubility = }}

|Section3={{Chembox Hazards

| MainHazards =

| FlashPt =

| AutoignitionPt = }}

}}

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.{{cite journal | last1=Samanta | first1=Amrita | last2=Kiselar | first2=Janna | last3=Pumroy | first3=Ruth A. | last4=Han | first4=Seungil | last5=Moiseenkova-Bell | first5=Vera Y. | title=Structural insights into the molecular mechanism of mouse TRPA1 activation and inhibition | journal=Journal of General Physiology | publisher=Rockefeller University Press | volume=150 | issue=5 | date=2018-04-27 | issn=0022-1295 | doi=10.1085/jgp.201711876 | pages=751–762| pmid=29703838 | pmc=5940248 }} 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.{{cite journal |vauthors=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 | title = Design and pharmacological evaluation of PF-4840154, a non-electrophilic reference agonist of the TrpA1 channel | journal = Bioorg. Med. Chem. Lett. | issue = 16 | pages = 4857–4859 |date=July 2011| volume = 21 | pmid = 21741838 | doi = 10.1016/j.bmcl.2011.06.035 }} 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.{{cite journal |vauthors=McNamara CR, Mandel-Brehm J, Bautista DM, Siemens J, Deranian KL, Zhao M, Hayward NJ, Chong JA, Julius D, Moran MM, Fanger CM | title = TRPA1 mediates formalin-induced pain | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 104 | issue = 33 | pages = 13525–30 |date=August 2007 | pmid = 17686976 | pmc = 1941642 | doi = 10.1073/pnas.0705924104 | doi-access = free | bibcode = 2007PNAS..10413525M }}{{cite journal |vauthors=McMahon SB, Wood JN | title = Increasingly irritable and close to tears: TRPA1 in inflammatory pain | journal = Cell | volume = 124 | issue = 6 | pages = 1123–5 |date=March 2006 | pmid = 16564004 | doi = 10.1016/j.cell.2006.03.006 | doi-access = free }}