Optimization of benzimidazole series as opioid receptor-like 1 (ORL1) antagonists: SAR study directed toward improvement of selectivity over hERG activity

Optimization of benzimidazole series as opioid receptor-like 1 (ORL1) antagonists: SAR study directed toward improvement of selectivity over hERG activity

Optimization of benzimidazole series as ORL1 antagonists is reported. Compound 7h exhibited potent ORL1 activity with high selectivity over binding affinity for hERG. A structure–activity relationship (SAR) study on the benzimidazole series of opioid receptor-like 1 (ORL1) antagonists related to 1 i...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2009-06, Vol.19 (11), p.3100-3103
Hauptverfasser: Kobayashi, Kensuke, Kato, Tetsuya, Yamamoto, Izumi, Shimizu, Atsushi, Mizutani, Sayaka, Asai, Masanori, Kawamoto, Hiroshi, Ito, Satoru, Yoshizumi, Takashi, Hirayama, Mioko, Ozaki, Satoshi, Ohta, Hisashi, Okamoto, Osamu
Format: Artikel
Sprache:eng
Schlagworte:
Benzimidazole
Benzimidazoles - chemical synthesis
Benzimidazoles - chemistry
Benzimidazoles - pharmacology
Biological and medical sciences
Cyclohexanes - chemical synthesis
Cyclohexanes - pharmacology
ERG1 Potassium Channel
Ether-A-Go-Go Potassium Channels - metabolism
hERG channel
Medical sciences
Narcotic Antagonists
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Nociceptin/orphanin FQ
ORL1 antagonist
Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems
Pharmacology. Drug treatments
Receptors, Opioid - metabolism
Structure-Activity Relationship
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Zusammenfassung:Optimization of benzimidazole series as ORL1 antagonists is reported. Compound 7h exhibited potent ORL1 activity with high selectivity over binding affinity for hERG. A structure–activity relationship (SAR) study on the benzimidazole series of opioid receptor-like 1 (ORL1) antagonists related to 1 is described. Optimization of 1 by introduction of a hydrophilic substituent into the thioether part resulted in identification of potent ORL1 antagonists with high selectivity over binding affinity for hERG and other opioid receptors.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2009.04.022