Substance P receptor antagonists

Hill, R (2000) NKl (substance P) receptor antagonists—why are they not analgesic in humans Trends Pharmacol. Sci. 21 244 246. 

Herpfer I and Lieb K (2003). Substance P and substance P receptor antagonists in the pathogenesis and treatment of affective disorders. World Journal of Biological Psychiatry, 4, 56-63. 

S. W. Huskey, D. Luffer-Atals, B. J. Dean, E. M. McGowan, W. P. Feeney, S. H. Lee Chiu, Substance P Receptor Antagonist I Conversion of Phosphoramidate Prodrug after i.v. Administration to Rats and Dogs , Drug Metab. Dispos. 1999, 27, 1367- 1373. 

Caesar, M., Seabrook, G. R., Kemp, J. A. Block of voltage-dependent sodium currents by the substance P receptor antagonist CP96.345 in neurones cultured from rat cortex, Br. J. Pharmacol. 1993, 109, 918-924. 

Af-acylation of L-tryptophan benzyl esters, followed by replacement of the 3,5-dimethyl groups by their trifluor-omethyl analogs, achieved an almost 1,000-fold increase in potency in a series of substance P receptor antagonists (Figure 20.32). ... 

Merchant, K.)., Lewis, R.T., MacLeod, A.M. (1994) Synthesis of homochiral ketones derived from L-tryptophan Potent substance P receptor antagonists. Tetrahedron Lett. 35, 4205 208. 

Obach RS. Metabolism of ezlopitant, a nonpeptidic substance P receptor antagonist, in liver microsomes enzyme kinetics, cytochrome P450 isoform identity, and in vitro-in vivo correlation. Drug Metab Dispos 2000 28 1069 1076. 

Prakash C, O Donnell J, Khojesteh C. Excretion, pharmacokinetics and metabolism of the substance P receptor antagonist, CJ-11,974, in humans Identification of polar metabolites by LC/MS/MS and chemical derivatization Drug Metab Dispos 2007b 35 1071-1080. 

A recent publication described a short enantioselective synthesis of (+)-L-733,060, a selective and potent nonpeptide neurokinin substance P receptor antagonist. The key chirality-inducing step involved a Shi epoxidation of homoallylic carboxylate 89. Subsequent intramolecular reductive cyclization of azidolactone constructed the piperidine ring. 

Prabhakar NR, Cao H, Lowe JAD, Snider RM. Selective inhibition of tbe carotid body sensory response to h poxia by tbe substance P receptor antagonist CP-96,345. Proc Natl Acad Sci USA 1993 90 10041-10045. 

Thornton E, Vink R (2012) Treatment with a substance P receptor antagonist is neuropro-tective in the intrastiiatal 6-hydroxydopamine model of early Parkinson s disease. PLoS One 7 e34138... 

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