ePrints@IIScePrints@IISc Home | About | Browse | Latest Additions | Advanced Search | Contact | Help

Opioid Receptor Modulators with a Cinnamyl Group

Ravilla, Lokesh and Naidu, N. Venkata Subba and Dogra, Shalini and Umrao, Deepmala and Yadav, Prem N and Biswas, Ansuman and Michael, Daliah and Sekar, Kanagaraj and Nagarajan, Kuppuswamy (2017) Opioid Receptor Modulators with a Cinnamyl Group. In: JOURNAL OF MEDICINAL CHEMISTRY, 60 (15). pp. 6733-6750.

[img] PDF
Jou_Med_Che_60-15_6733_2017.pdf - Published Version
Restricted to Registered users only

Download (3MB) | Request a copy
Official URL: http://doi.org/10.1021/acs.jmedchem.7b00643


To obtain selective and potent opioid receptor ligands, we synthesized dehydro derivatives of alvimopan and found compound (28f), a selective but modest affinity MOR antagonist weaker than alvimopan (1). We replaced the arylpiperidine unit by an arylpiperazine to obtain the 1-(alpha-carboxycinnamyl)-4-arylpiperazines like 13h, which to our surprise had no MOR or DOR activity but was a KOR agonist with moderate affinity. In contrast, literature examples of arylpiperazines 4 and 5 were reported to be pan opioid receptor antagonists, while 6 was a MOR agonist. Two compounds (131 and 11b) showed analgesic response in tail flick test which was blocked by pretreatment with norbinaltorphimine (norBNI). Among 10 1-(alpha-carboxycinnamyl)-4-arylpiperidines, compound 28g and five others were specific MOR antagonists. Interestingly, compound 26b of this series was found to be more potent than naloxone but weaker than 1. Docking studies have explained differential activities of the above piperazines and piperidines.

Item Type: Journal Article
Additional Information: Copy right for this article belongs to the AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
Department/Centre: Division of Interdisciplinary Sciences > Supercomputer Education & Research Centre
Division of Physical & Mathematical Sciences > Physics
Date Deposited: 01 Sep 2017 07:03
Last Modified: 01 Sep 2017 07:03
URI: http://eprints.iisc.ac.in/id/eprint/57699

Actions (login required)

View Item View Item