WAY-100135

WAY-100135 is a serotonergic drug of the phenylpiperazine family which is used in scientific research.[1] It acts as potent 5-HT_1A receptor antagonist,[2] and was originally believed to be highly selective, but further studies have demonstrated that it also acts as a partial agonist of the 5-HT_1D receptor (pK_i = 7.58; virtually the same affinity for 5-HT_1A), and to a much lesser extent, of the 5-HT_1B receptor (pK_i = 5.82).[3] These findings may have prompted the development of the related compound WAY-100635, another purportedly selective and even more potent 5-HT_1A antagonist, which was synthesized shortly thereafter.[4] However, WAY-100635 turned out to be non-selective as well, having been shown to act additionally as a potent D₄ receptor agonist later on.[5]

WAY-100135

Clinical data
ATC code	None
Identifiers
IUPAC name (S)-N-tert-Butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide
CAS Number	133025-23-7^Y
PubChem CID	115111
IUPHAR/BPS	79
ChemSpider	103008^N
ChEMBL	ChEMBL38288^N
CompTox Dashboard (EPA)	DTXSID80927903
Chemical and physical data
Formula	C24H33N3O2
Molar mass	395.547 g·mol^−1
3D model (JSmol)	Interactive image
SMILES c2ccccc2C(C(=O)NC(C)(C)C)CN(CC3)CCN3c1ccccc1OC
InChI InChI=1S/C24H33N3O2/c1-24(2,3)25-23(28)20(19-10-6-5-7-11-19)18-26-14-16-27(17-15-26)21-12-8-9-13-22(21)29-4/h5-13,20H,14-18H2,1-4H3,(H,25,28)^N Key:UMTDAKAAYOXIKU-UHFFFAOYSA-N^N
^NY (what is this?)  (verify)

See also

• WAY-100635

References

1. Fletcher A, Bill DJ, Bill SJ, et al. (June 1993). "WAY100135: a novel, selective antagonist at presynaptic and postsynaptic 5-HT1A receptors". European Journal of Pharmacology. 237 (2–3): 283–91. doi:10.1016/0014-2999(93)90280-u. PMID 8365456.
2. Cliffe IA, Brightwell CI, Fletcher A, et al. (May 1993). "(S)-N-tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide [(S)-WAY-100135]: a selective antagonist at presynaptic and postsynaptic 5-HT1A receptors". Journal of Medicinal Chemistry. 36 (10): 1509–10. doi:10.1021/jm00062a028. PMID 8496920.
3. Davidson C, Ho M, Price GW, Jones BJ, Stamford JA (June 1997). "(+)-WAY 100135, a partial agonist, at native and recombinant 5-HT1B/1D receptors". British Journal of Pharmacology. 121 (4): 737–42. doi:10.1038/sj.bjp.0701197. PMC 1564750. PMID 9208142.
4. Fornal CA, Metzler CW, Gallegos RA, Veasey SC, McCreary AC, Jacobs BL (August 1996). "WAY-100635, a potent and selective 5-hydroxytryptamine1A antagonist, increases serotonergic neuronal activity in behaving cats: comparison with (S)-WAY-100135". The Journal of Pharmacology and Experimental Therapeutics. 278 (2): 752–62. PMID 8768728.
5. Chemel BR, Roth BL, Armbruster B, Watts VJ, Nichols DE (October 2006). "WAY-100635 is a potent dopamine D4 receptor agonist". Psychopharmacology. 188 (2): 244–51. doi:10.1007/s00213-006-0490-4. PMID 16915381.