Bridged aminotetralins as novel potent analgesic substances

Abstract

Anal. (C15H22C1N0) C, , N [sample dried at 120°(0.5 mm) prior to analysis]. pKa Measurement The p values were determined potentiometrically as described by Albert and Serjeant19 by titration of of the HC1 salts (0.25 mmol) in 50% EtOH-H20 (47.5 ml) against 0.05 N KOH at 25°.

Opioids: 3.4 Opioids with Clinical Relevance

“…Synthesis (Freed and Potoski (American Home), 1971;Freed, 1973;Kleemann et al, 1999,): Dezocine is prepared through the following sequence: The condensation of 1-methyl-7-methoxy-2-tetralone with 1,5-dibromopentane by means of NaH or potassium tertbutylate affords 1-(5-bromopentyl)-1-methyl-7-methoxy-2-tetralone; this product is cyclized with NaH to give 5-methyl-3methoxy-5, 6,7,8,9,10,11,12-octahydro-5,11-methanobenzocyclodecen-13-one i. The ketone i, by reaction with hydroxylamine hydrochloride in pyridine, is converted into its oxime ii, which is reduced with H2 over Raney Ni to a mixture of isomeric amines which were separated by crystallization of the HCI salts giving 5-ot-methyl-3methoxy-5, 6,7,8,9,11a,12-octahydro-5,11-methanobenzocyclodecen-13p-amine, which is finally cleaved with concentrated HBr.…”

Synthesis of two Conformationally Restricted Piperazine Scaffolds for Combinatorial Chemistry

“…Various cyclic 2-phenylalkylamines possessing a phenolic hydroxy group in meta- or para-position, such as the partial µ-opioid agonists dezocine (8, Dalgan  ), [11,12] metazocine (9), [13] profadol (10) [14] and meptazinol (11, Meptid  , Nestan  ; [15] 4114 ure 3), exhibit analgesic activity through a morphine-like mechanism. [1,16] Since scaffold 7 shares this structural feature with the drugs described, its derivatives might possess an affinity to opioid receptors.…”

Double-blind placebo-controlled comparison of dezocine and morphine for post-operative pain relief

“…In standard animal analgesic tests, dezocine was found to be 7 to 18 times as potent as morphine with a therapeutic index of greater than 1000.1"2 In addition, it demonstrated slightly less antagonistic activity than nalorphine. 1 In tests for dependence liability, dezocine did not suppress abstinence in withdrawn morphinedependent monkeys, nor did it produce dependence when administered chronically in monkeys. 2 In the dog, dezocine was found to possess less potential for producing bronchoconstriction, respiratory de- pression, hypotension, and histamine-release than either morphine or pentazocine.…”