Neurokinin-3 receptor antagonists

Ichinose, M., Nakajima, N., Takahashi, T., Yamauchi, H., Inoue, H., Takishima, T. Protection against bradykinin-induced bronchoconstriction in asthmatic patients by neurokinin receptor antagonist, Lancet 1992, 340, 1248-1251. 

Longmore, J., Hill, R. G., Hargreaves, R. J. Neurokinin-receptor antagonists pharmacological tools and therapeutic drugs, Can. J. Physiol. Pharmacol. 1997, 75, 612-621. 

Dableh LJ, Yashpal K, Rochford J, Henry JL. Antidepressant-like effects of neurokinin receptor antagonists in the forced swim test 86. in the rat. Eur. J. Pharmacol., 2005 507 99-105. 

OH Chan, HL Schmid, B-S Kuo, DS Wright, W Howson, BH Stewart. Absorption of Cam-2445, an NK1 neurokinin receptor antagonist in vivo, in situ and in vitro evaluations. J Pharm Sd 85 253—257,1996. 

Chan OH, Schmid HL, Kuo B, Wright DS, Howson W, and Stewart BH. Absorption of Cam-2445, an NKl Neurokinin Receptor Antagonist in vivo, in situ, and in vitro evaluations./P/iarm Sci 1996 85 253-257. 

SCHEME 34.41. Asymmetric secondary alcohol oxidation kinetic resolution step in the synthesis of human neurokinin receptor antagonist h-NKl 156. 

A third example of drug synthesis consists in the preparation of the human neurokinin receptor antagonist h-NKl 156. An chiral intermediate toward its synthesis is prepared by kinetic resolution of a 2-aryl-cyclopentenol derivative 157 in chloroform with the usual Pd(II) with (—)-sparteine 132 obtaining very high selectivity up to 82.7, which is a really impressive result, with conversion of 50.8% and ee of 94.7% of the product 158 (Scheme 34.41). 

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