Design，Synthesis and in vitro Hypoglycemic Activity Study of N-aroyl Substituted Indoline- 3-Acetic Acid Derivatives
- VernacularTitle:N-芳酰基取代的二氢吲哚-3-乙酸类衍生物的设计、合成与体外降糖活性研究
- Author:
Jiquan ZHANG
1
,
2
;
Tingting WU
1
;
Caiyu MA
1
;
Xiao MA
1
;
Jianta WANG
1
;
Lei TANG
2
Author Information
1. College of Pharmaceutical Sciences，Guizhou Medical University，Guiyang 550025，China
2. Guizhou Medical University/Guizhou Provincial Engineering Technolog y Research Center for Chemical Drug R&D，Guiyang 550004，China
- Publication Type:Journal Article
- Keywords:
Indoline-3-acetic acid derivative;
Hypoglycemic activity;
Synthesis;
Structure-activity relationship
- From:
China Pharmacy
2019;30(3):318-322
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE： To design and synthesize N-aroyl substituted indoline-3-acetic acid derivatives and evaluate their in vitro hypoglycemic activity. METHODS： Using indoline derivative 2-[5-（benzyloxy）-1-（4-chlorobenzoyl）-2-methyl-1H-inclol-3-yl]acetic acid （GY3） as leading compound， 4-（benzyloxy）phenyl hydrazine hydrochloride and methyl 4-oxopentanoate as raw material， 8 kinds of N-aroyl （3-hydroxybenzoyl， 3-cyanobenzoyl， 4-nitrobenzoyl， 4-methylsulfonylbenzoyl， 4-acetamidobenzoyl， 3-acetylaminobenzoyl， isoniacyl and pyridine-2-formyl） substituted indoline-3-acetic acid derivatives were synthesized via 4 steps reactions： Fischer indole cyclization， reduction， amidation and hydrolyzation. The human hepatoma HepG2 cell lines were used to investigate the glucose consumption activity of the target compounds. RESULTS： Totally 8 various N-aroyl substituted indoline-3-acetic acids were synthesized and their structures were confirmed by mass spectrum（MS）， nuclear magnetic resonance 1H-NMR and 13C spectrum. Under the condition of 1.0 μmol/L， the percentage of glucose- promoting consumption of the synthesized compounds on HepG2 cells was 5.4％-9.1％. 2-[（2R， 3S）-5-benzyloxy-2-methyl-1-（4-methylsulfonyl benzoyl）-2，3-dihydro-indole-3-yl] acetic acid showed the best hypoglycemic activity. The percentage of glucose- promoting consumption was （9.1±1.81）％， which was close to that of positive control metformin [（10.58±1.68）％]， but less potent than that of leading compound GY3[（12.15±0.78）％]. CONCLUSIONS： Different electron-withdrawing substituents are introduced into N-aroyl aromatic rings of dihydroindole compounds， such as cyano， nitro， methyl sulfonyl； hypoglycemic activity decreases in varying degrees and is weaker than halogen substituents.
