Introducing nitrogen atoms to amidoalkylindoles: potent and selective cannabinoid type 2 receptor agonists with improved aqueous solubility

Yue Yang Ji; Zhi Long Wang; Fang Ning Pei; Jun Jie Shi; Jiao Jiao Li; Hendra Gunosewoyo; Fan Yang; Jie Tang; Xin Xie; Li Fang Yu

doi:10.1039/c9md00411d

Introducing nitrogen atoms to amidoalkylindoles: potent and selective cannabinoid type 2 receptor agonists with improved aqueous solubility

Yue Yang Ji
, Zhi Long Wang
, Fang Ning Pei
, Jun Jie Shi
, Jiao Jiao Li
, Hendra Gunosewoyo
, Fan Yang
, Jie Tang
, Xin Xie^*
, Li Fang Yu^*

^*Corresponding author for this work

School of Chemistry and Molecular Engineering

East China Normal University
CAS - Shanghai Institute of Materia Medica
Curtin University

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Previously we identified a series of amidoalkylindoles as potent and selective CB₂ 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,CB₁ = NA, EC_50,CB₂ = 0.067 μM) and azaindole 24 (EC_50,CB₁ = NA, EC_50,CB₂ = 0.048 μM) were found to be potent and selective CB₂ receptor partial agonists, both with improved aqueous solubility.

Original language	English
Pages (from-to)	2131-2139
Number of pages	9
Journal	MedChemComm
Volume	10
Issue number	12
DOIs	https://doi.org/10.1039/c9md00411d
State	Published - Dec 2019

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title = "Introducing nitrogen atoms to amidoalkylindoles: potent and selective cannabinoid type 2 receptor agonists with improved aqueous solubility",

abstract = "Previously we identified a series of amidoalkylindoles as potent and selective CB2 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 (EC50,CB1 = NA, EC50,CB2 = 0.067 μM) and azaindole 24 (EC50,CB1 = NA, EC50,CB2 = 0.048 μM) were found to be potent and selective CB2 receptor partial agonists, both with improved aqueous solubility.",

author = "Ji, \{Yue Yang\} and Wang, \{Zhi Long\} and Pei, \{Fang Ning\} and Shi, \{Jun Jie\} and Li, \{Jiao Jiao\} and Hendra Gunosewoyo and Fan Yang and Jie Tang and Xin Xie and Yu, \{Li Fang\}",

note = "Publisher Copyright: This journal is {\textcopyright} The Royal Society of Chemistry, 2019",

year = "2019",

month = dec,

doi = "10.1039/c9md00411d",

language = "英语",

volume = "10",

pages = "2131--2139",

journal = "MedChemComm",

issn = "2040-2503",

publisher = "Royal Society of Chemistry",

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TY - JOUR

T1 - Introducing nitrogen atoms to amidoalkylindoles

T2 - potent and selective cannabinoid type 2 receptor agonists with improved aqueous solubility

AU - Ji, Yue Yang

AU - Wang, Zhi Long

AU - Pei, Fang Ning

AU - Shi, Jun Jie

AU - Li, Jiao Jiao

AU - Gunosewoyo, Hendra

AU - Yang, Fan

AU - Tang, Jie

AU - Xie, Xin

AU - Yu, Li Fang

PY - 2019/12

Y1 - 2019/12

N2 - Previously we identified a series of amidoalkylindoles as potent and selective CB2 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 (EC50,CB1 = NA, EC50,CB2 = 0.067 μM) and azaindole 24 (EC50,CB1 = NA, EC50,CB2 = 0.048 μM) were found to be potent and selective CB2 receptor partial agonists, both with improved aqueous solubility.

AB - Previously we identified a series of amidoalkylindoles as potent and selective CB2 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 (EC50,CB1 = NA, EC50,CB2 = 0.067 μM) and azaindole 24 (EC50,CB1 = NA, EC50,CB2 = 0.048 μM) were found to be potent and selective CB2 receptor partial agonists, both with improved aqueous solubility.

UR - https://www.scopus.com/pages/publications/105037020022

U2 - 10.1039/c9md00411d

DO - 10.1039/c9md00411d

M3 - 文章

AN - SCOPUS:105037020022

SN - 2040-2503

VL - 10

SP - 2131

EP - 2139

JO - MedChemComm

JF - MedChemComm

IS - 12

ER -

Introducing nitrogen atoms to amidoalkylindoles: potent and selective cannabinoid type 2 receptor agonists with improved aqueous solubility

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