2,3-Dihydrobenzo-dioxine piperidine derivatives as potent and selective α2c antagonists

Shouming Wang; Anssi Haikarainen; Antti Pohjakallio; Julius Sipilä; Janne Kaskinoro; Satu Juhila; Niina Jalava; Mikko Koskinen; Marja Vesajoki; Esa Kumpulainen; Jarmo Pystynen; Tuula Koskelainen; Patrik Holm; David Din Belle

doi:10.1016/j.bmcl.2022.128783

2,3-Dihydrobenzo-dioxine piperidine derivatives as potent and selective α2c antagonists

Bioorg Med Chem Lett. 2022 Aug 1:69:128783. doi: 10.1016/j.bmcl.2022.128783. Epub 2022 May 13.

Affiliations

¹ Department of Medicinal Chemistry, Orion Corporation Orion Pharma, Orionintie 1, PL 65, FI-02101, Finland. Electronic address: shouming.wang@orionpharma.com.
² Department of Medicinal Chemistry, Orion Corporation Orion Pharma, Orionintie 1, PL 65, FI-02101, Finland.
³ Department of DMPK & Safety Science, Orion Corporation Orion Pharma, Orionintie 1, PL 65, FI-02101, Finland.
⁴ Department of CNS Research, Orion Corporation Orion Pharma, Tengströminkatu 8, 20360, Turku, Finland.
⁵ Department of Biology, Orion Corporation Orion Pharma, Tengströminkatu 8, 20360 Turku, Finland.

PMID: 35569686
DOI: 10.1016/j.bmcl.2022.128783

Abstract

In this manuscript, we report a series of benzodioxine methyl piperidine derivatives as highly potent and selective α2C antagonists by ligand design to improve the pharmacokinetics of a previous candidate molecule.

Keywords: Benzodioxine; Piperidine; α2 adrenoceptors; α2c Antagonist.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Dioxins*
Piperidines / pharmacology
Receptors, Adrenergic, alpha-2*

Substances

Dioxins
Piperidines
Receptors, Adrenergic, alpha-2