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Bioorg Med Chem Lett. 2016 Dec 15;26(24):5855-5859. doi: 10.1016/j.bmcl.2016.11.022. Epub 2016 Nov 10.

The discovery of quinoline based single-ligand human H1 and H3 receptor antagonists.

Author information

1
Medicinal Chemistry, GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, United Kingdom. Electronic address: pan.a.procopiou@gsk.com.
2
Medicinal Chemistry, GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, United Kingdom.
3
R&D Platform Technology and Science, GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, United Kingdom.
4
Respiratory Biology, GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, United Kingdom.

Abstract

A novel series of potent quinoline-based human H1 and H3 bivalent histamine receptor antagonists, suitable for intranasal administration for the potential treatment of allergic rhinitis associated nasal congestion, were identified. Compound 18b had slightly lower H1 potency (pA2 8.8 vs 9.7 for the clinical goldstandard azelastine), and H3 potency (pKi 9.1vs 6.8 for azelastine), better selectivity over α1A, α1B and hERG, similar duration of action, making 18b a good back-up compound to our previous candidate, but with a more desirable profile.

KEYWORDS:

Allergic rhinitis; H(1)H(3) histamine receptor antagonist; Nasal congestion; Quinoline; Single ligand

PMID:
27866818
DOI:
10.1016/j.bmcl.2016.11.022
[Indexed for MEDLINE]

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