17825-44-4Relevant articles and documents
Discovery, stereospecific characterization and peripheral modification of 1-(pyrrolidin-1-ylmethyl)-2-[(6-chloro-3-oxo-indan)-formyl]-1,2,3,4-tetrahydroisoquinolines as novel selective κ opioid receptor agonists
Gan, Zong-Jie,Wang, Yu-Hua,Xu, Yun-Gen,Guo, Ting,Wang, Jun,Song, Qiao,Xu, Xue-Jun,Hu, Shi-Yuan,Wang, Yu-Jun,Wang, De-Chuan,Sun, De-Zhu,Zhang, Di,Xi, Tao,Li, Hao-Dong,Zhang, Hai-Bo,Hang, Tai-Jun,Lu, Hong-Guo,Liu, Jing-Gen
, p. 5656 - 5673 (2015/05/27)
A novel series of 1-(pyrrolidin-1-ylmethyl)-2-[(3-oxo-indan)-formyl]-1,2,3,4-tetrahydroisoquinoline derivatives maj-3a-maj-3u were synthesized and evaluated in vitro for their binding affinity at κ-opioid receptors. Maj-3c displayed the highest affinity for κ-opioid receptors (Ki = 0.033 nM) among all the compounds evaluated. Furthermore, all four stereoisomers of compound 3c were prepared, and (1S,18S)-3c was identified as the most potent (Ki = 0.0059 nM) κ-opioid receptor agonist among the four stereoisomers. Maj-3c produced significant antinociception (ED50 = 0.000406 mg kg-1) compared to U-50,488H and original BRL 52580 in the acetic acid writhing assay, but its strong sedative effect (ED50 = 0.000568 mg kg-1) observed in the mouse rotation test reduced its druggability. To minimize the central nervous system side effects, a series of hydroxyl-containing analogs of maj-3c were synthesized, and maj-11a was found to be a potent κ-opioid receptor agonist (Ki = 35.13 nM). More importantly, the dose for the sedative effect (ED50 = 9.29 mg kg-1) of maj-11a was significantly higher than its analgesic dose (ED50 = 0.392 mg kg-1), which made it a promising peripheral analgesic candidate compound with weak sedative side effects.
TETRAHYDRO ISOQUINOLINE DERIVATIVES, PREPARATION METHODS AND MEDICINAL USES THEREOF
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Page/Page column 11, (2009/04/23)
A kind of tetrahydro isoquinoline derivatives (I), their preparation methods, medicine compositions and medicinal uses thereof, especially their uses as κ-opioid receptor excitant in pain relieving, which belongs to the medicine chemistry. The substituents R1, R2, R3, R4 of general formula (I) are defined as the description.
Studies on indan acids as potential oral hypoglycemic agents
Lahiri Ch.,Gupta
, p. 1041 - 1043 (2007/10/06)
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