Troxler, Thomas J., Feuerbach, Dominik, Zhang, Xuechun, Yang, Charles, Lagu, Bharat, Perrone, Mark, Wang, Tie-Lin, Briner, Karin, 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