PF-4455242

PF-4455242
Clinical data

Routes of administration	Oral
ATC code	None
Identifiers
IUPAC name 2-Methyl-N-{[2’-(1-pyrrolidinylsulfonyl)-4-biphenylyl]methyl}-1-propanamine
CAS Number	1202647-54-8
PubChem CID	44599828
ChemSpider	26610764
UNII	Y3530Z78QD
CompTox Dashboard (EPA)	DTXSID30152783
Chemical and physical data
Formula	C₂₁H₂₈N₂O₂S
Molar mass	372.53 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CC(C)CNCC1=CC=C(C=C1)C2=CC=CC=C2S(=O)(=O)N3CCCC3
InChI InChI=1S/C21H28N2O2S/c1-17(2)15-22-16-18-9-11-19(12-10-18)20-7-3-4-8-21(20)26(24,25)23-13-5-6-14-23/h3-4,7-12,17,22H,5-6,13-16H2,1-2H3 Key:OWVIKBRKPCTDEP-UHFFFAOYSA-N

PF-4455242 is a selective, short-acting (non-"inactivating") antagonist of the κ-opioid receptor.^[1]^[2] Discovered by Pfizer in 2009, it was pursued in a phase I clinical trial for the treatment of bipolar disorder,^[3] and was also investigated as a treatment for depression and substance abuse.^[4] However, development was stopped in September 2010 due to toxicology findings in animals that had been exposed to the drug for three months.^[3]

References

^ Verhoest PR, Basak AS, Parikh V, Hayward M, Kauffman GW, Paradis V, et al. (August 2011). "Design and discovery of a selective small molecule κ opioid antagonist (2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242)". Journal of Medicinal Chemistry. 54 (16): 5868–5877. doi:10.1021/jm2006035. PMID 21744827.
^ Melief EJ, Miyatake M, Carroll FI, Béguin C, Carlezon WA, Cohen BM, et al. (November 2011). "Duration of action of a broad range of selective κ-opioid receptor antagonists is positively correlated with c-Jun N-terminal kinase-1 activation". Molecular Pharmacology. 80 (5): 920–929. doi:10.1124/mol.111.074195. PMC 3198912. PMID 21832171.
^ ^a ^b Chaki S, Kanuma K (2012). "Neuropeptide Receptors: Novel Therapeutic Targets for Depression and Anxiety Disorders". In Rankovic Z, Hargreaves R, Bingham M (eds.). Drug Discovery for Psychiatric Disorders. Royal Society of Chemistry. pp. 314–317. ISBN 978-1-84973-365-6.
^ Goli V, Pryde D, Omoto K (2013). "Oral Opioids". In Allerton C, Fox D (eds.). Pain Therapeutics: Current and Future Treatment Paradigms. Royal Society of Chemistry. p. 50. ISBN 978-1-84973-645-9.