Synthesis and stereochemistry of 7-phenyl-2-propionanilidobenzo[a]quinolizidine derivatives. Structural probes of fentanyl analgesics
- 1 January 1981
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 24 (1) , 79-88
- https://doi.org/10.1021/jm00133a017
Abstract
The 4 diastereomers of N-(1,3,4,6,7,11b-hexahydro-7-phenyl-2H-benzo[a]quinolizin-2-yl)-N-phenylpropanamide (7c, 7d, 9c and 9d), which are conformationally restricted analogs of fentanyl, were synthesized and separately tested for analgesic activity and affinity for the opiate receptor of rat brain. Stereochemical assignments for 7c, 7d, 9c and 9d were deduced from NMR spectral analyses. Conformational analysis revealed that the 2.alpha. isomers (7d and 9d) exist in solution as mixtures of cis- and trans-fused conformers with .apprx. 90 and 45% cis form, respectively. Other compounds related to these propionanilides were prepared, stereochemically characterized and tested. Weak analgesic activity was observed for 7d and both 7d and 9d bound to the opiate receptor with an I50 [median inhibition concentration] of .apprx. 1100 and 1500 nM, respectively (.apprx. 0.5% of fentanyl and 2% of morphine). The analgesic activity of 7d was abolished by the opiate antagonist naloxone.This publication has 9 references indexed in Scilit:
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