New quinoline NK3 receptor antagonists with CNS activity

Bioorganic & Medicinal Chemistry Letters
Paul W SmithLee A Dawson

Abstract

Lead optimisation starting from the previously reported selective quinoline NK(3) receptor antagonists talnetant 2 (SB-223412) and 3 (SB-222200) led to the identification of 3-aminoquinoline NK(3) antagonist 10 (GSK172981) with excellent CNS penetration. Investigation of a structurally related series of sulfonamides with reduced lipophilicity led to the discovery of 20 (GSK256471). Both 10 and 20 are high affinity, potent NK(3) receptor antagonists which despite having different degrees of CNS penetration produced excellent NK(3) receptor occupancy in an ex vivo binding study in gerbil cortex.

References

Oct 30, 2004·Receptors & Channels·Robert AmesMichael Romanos
Dec 13, 2005·Nature Reviews. Drug Discovery·Will SpoorenHerbert Meltzer
Aug 31, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Lee A DawsonJim Hagan
Nov 1, 2007·Nature Reviews. Drug Discovery·Paul D Leeson, Brian Springthorpe
Jan 29, 2008·Recent Patents on CNS Drug Discovery·Paul W Smith, Lee A Dawson
Jan 23, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jeanette WatsonKevin D Read

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Citations

Jul 3, 2013·Nature Reviews. Endocrinology·Robert P Millar, Claire L Newton
Mar 23, 2011·Expert Opinion on Therapeutic Patents·Pari MalherbeHassen Ratni
Aug 21, 2013·Saudi Pharmaceutical Journal : SPJ : the Official Publication of the Saudi Pharmaceutical Society·Akranth MarellaMohammad Mumtaz Alam
Apr 22, 2015·Chemical Communications : Chem Comm·Ryosuke Takechi, Takahiro Nishimura
Sep 29, 2018·Minerva ginecologica·Claire L NewtonRobert P Millar
Jan 15, 2021·Bioorganic & Medicinal Chemistry·Basavarajaiah Suliphuldevara MatadaNagesh Gunavanthrao Yernale
Nov 5, 2010·Journal of Medicinal Chemistry·Werner J GeldenhuysMark A Simmons
Dec 17, 2014·Journal of Medicinal Chemistry·Zoran Rankovic
Apr 23, 2020·The Journal of Organic Chemistry·Md Shafaat Al Mehedi, Jetze J Tepe

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