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Heteroaryl derivatives of suvorexant as OX1R selective PET ligand candidates: Cu-mediated ¹⁸F-fluorination of boroxines, in vitro and initial in vivo evaluation.

ABSTRACT:

Background

The orexin receptor (OXR) plays a role in drug addiction and is aberrantly expressed in colorectal tumors. Subtype-selective OXR PET ligands suitable for in vivo use have not yet been reported. This work reports the development of ¹⁸F-labeled OXR PET ligand candidates derived from the OXR antagonist suvorexant and the OX1R-selective antagonist JH112.

Results

Computational analysis predicted that fluorine substitution (1e) and introduction of the fluorobenzothiazole scaffold (1f) would be suitable for maintaining high OX1R affinity. After multi-step synthesis of 1a-1f, in vitro OXR binding studies confirmed the molecular dynamics calculations and revealed single-digit nanomolar OX1R affinities for 1a-f, ranging from 0.69 to 2.5 nM. The benzothiazole 1f s

SUBMITTER: Bolik KV

PROVIDER: S-EPMC11374953 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature

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Dataset Information

Heteroaryl derivatives of suvorexant as OX1R selective PET ligand candidates: Cu-mediated ¹⁸F-fluorination of boroxines, in vitro and initial in vivo evaluation.

Background

Results

OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Heteroaryl derivatives of suvorexant as OX1R selective PET ligand candidates: Cu-mediated 18F-fluorination of boroxines, in vitro and initial in vivo evaluation.

Background

Results

OmicsDI is part of the ELIXIR infrastructure

Tweets

Heteroaryl derivatives of suvorexant as OX1R selective PET ligand candidates: Cu-mediated ¹⁸F-fluorination of boroxines, in vitro and initial in vivo evaluation.