Browse views: by Year, by Function, by GLF, by Subfunction, by Conference, by Journal

The discovery of LML134, a histamine H3 receptor inverse agonist for the clinical treatment of excessive sleep disorders

Troxler, Thomas J. and Feuerbach, Dominik and Zhang, Xuechun and Yang, Charles and Lagu, Bharat and Perrone, Mark and Wang, Tie-Lin and Briner, Karin and bock, Mark and Auberson, Yves (2019) The discovery of LML134, a histamine H3 receptor inverse agonist for the clinical treatment of excessive sleep disorders. ChemMedChem. ISSN 18607187

Abstract

Histamine 3 receptor (H3R) inverse agonists that have been in clinical trials for treatment of excessive sleep disorders, have been plagued with insomnia as a mechanism based side effect. We focussed on identifying compounds that achieve high receptor occupancy within a short time, followed by fast disengagement from the receptor, a target profile that could provide the therapeutic benefits without the undesired insomnia side effect. The article describes the optimization work that led to the discovery of 1-(1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)piperidin-4-yl 4-cyclobutylpiperazine-1-carboxylate (18b, LML134).

Item Type: Article
Keywords: carbamate H3 receptor Histamine medicinal chemistry neurotransmitters
Date Deposited: 28 May 2019 00:45
Last Modified: 28 May 2019 00:45
URI: https://oak.novartis.com/id/eprint/38280

Search

Email Alerts

Register with OAK to receive email alerts for saved searches.