1429414-20-9Relevant academic research and scientific papers
The Discovery of LML134, a Histamine H3 Receptor Inverse Agonist for the Clinical Treatment of Excessive Sleep Disorders
Troxler, Thomas,Feuerbach, Dominik,Zhang, Xuechun,Yang, Charles R.,Lagu, Bharat,Perrone, Mark,Wang, Tie-Lin,Briner, Karin,Bock, Mark G.,Auberson, Yves P.
, p. 1238 - 1247 (2019)
Histamine H3 receptor (H3R) inverse agonists that have been in clinical trials for the treatment of excessive sleep disorders, have been plagued with insomnia as a mechanism-based side effect. We focused on the identification of compounds that achieve high receptor occupancy within a short time, followed by rapid disengagement from the receptor, a target profile that could provide therapeutic benefits without the undesired side effect of insomnia. This 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 (18 b, LML134).
