Introducing nitrogen atoms to amidoalkylindoles: potent and selective cannabinoid type 2 receptor agonists with improved aqueous solubility
| Autor: | Zhi-Long Wang, Jun-Jie Shi, Jie Tang, Xin Xie, Hendra Gunosewoyo, Ji Yueyang, Li-Fang Yu, Jiao-Jiao Li, Fang-Ning Pei, Fan Yang |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Pharmacology
Indole test Benzimidazole Indazole Cannabinoid receptor 010405 organic chemistry medicine.medical_treatment Organic Chemistry Pharmaceutical Science 01 natural sciences Biochemistry Partial agonist Combinatorial chemistry 0104 chemical sciences 010404 medicinal & biomolecular chemistry chemistry.chemical_compound Chemistry chemistry Drug Discovery medicine Cannabinoid receptor type 2 Molecular Medicine lipids (amino acids peptides and proteins) Cannabinoid Receptor |
| Zdroj: | Medchemcomm |
| Popis: | Previously we identified a series of amidoalkylindoles as potent and selective CB(2) partial agonists. In the present study, we report our continuous effort to improve the aqueous solubility by introducing N atoms to the amidoalkylindole framework. Synthesis, characterization, and pharmacology evaluations were described. Bioisosteric replacements of the indole nucleus with an indazole, azaindole and benzimidazole were explored. Benzimidazole 43 (EC(50,CB(1)) = NA, EC(50,CB(2)) = 0.067 μM) and azaindole 24 (EC(50,CB(1)) = NA, EC(50,CB(2)) = 0.048 μM) were found to be potent and selective CB(2) receptor partial agonists, both with improved aqueous solubility. |
| Databáze: | OpenAIRE |
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