Benzomorphans. Optically Active and <i>trans</i> Isomers

Tullar, B. F.; Harris, L. S.; Perry, Robert L.; Pierson, Anne K.; Soria, Albert E.; Wetterau, W. F.; Albertson, Noel F.

doi:10.1021/jm00315a022

Cited by 45 publications

(14 citation statements)

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“…Likewise, nalorphine acted like a competitive antagonist against morphine. The " pA2" value of 4 2 was close to Results for the rat tail-flick test were taken from Archer et al (1964), Tullar et al (1967), and Pearl et al (1968). All drugs were injected subcutaneously.…”

Section: Discussionsupporting

confidence: 52%

“…In the present study, the lower the effective dose of the antagonist, the greater the difference in the antagonist potency of the optical isomers. This seems to hold not only for the antagonist potency of benzomorphans (Archer et al, 1964;Tullar et al, 1967) but also for several agonist-like effects of the benzomorphans (Pearl et al, 1968).…”

Section: Discussionmentioning

confidence: 99%

“…Optical and geometric isomers in the benzomorphan series are designated in the results section. Geometric isomerism in this series arises from the disposition of the angular alkyl groups at C-5 and C-9 (Tullar et al, 1967). At C-S the alkyl group is fixed by the rigid geometry of the fused tricyclic system.…”

Section: Methodsmentioning

confidence: 99%

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Effects of opiates and opiate antagonists on the Straub tail reaction in mice

Aceto

McKean

Pearl

1969

British J Pharmacology

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. Subcutaneous injections of opiates produced the Straub tail reaction in mice. The potencies of the opiates in mice were consistent with previous estimates of the analgesic potencies in animals and in man. . The potencies of sixteen antagonists in counteracting the reaction were consistent with those previously obtained with the rat tail‐flick test. . The (–) isomers of four benzomorphan derivatives were much more potent in counteracting the reaction than their (+) isomers and about twice as potent as their racemates. The activity of the isomers seemed to follow Pfeiffer's rule: the lower the effective dose of a drug, the greater the difference in the pharmacological effects of the optical isomers. One of the trans isomers acted like an opiate, while its cis isomer acted like an antagonist. . Naloxone and nalorphine fulfilled conventional criteria for competitive antagonism, whereas atropine and the (–) and the (+) isomers of pentazocine and of cyclazocine did not do so. . The Straub tail test seems to be useful for studying structure‐activity relations among opiates and opiate antagonists.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

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Effects of opiates and opiate antagonists on the Straub tail reaction in mice

Aceto

McKean

Pearl

1969

British J Pharmacology

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“…59 It is worth noting that (À)-pentazocine is biologically more active compared with its enantiomer. 60 Pentazocine is known to possess sedative activity. Commercially, it is available as Talwin (Hospira, Inc., Lake Forest, IL; pentazocine hydrochloride) and Talacen (Sanofi-Aventis, Bridgewater, NJ; combination of pentazocine hydrochloride and acetaminophen).…”

Section: Asymmetric and Diastereoselective Hydroamination In Total Symentioning

confidence: 99%

Asymmetric Hydroamination and Reductive Amination in Total Synthesis

Ghorai

Tiwari

Bhattacharyya

2013

Stereoselective Synthesis of Drugs and Natural Products

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Asymmetric hydroamination (AHA) and asymmetric reductive amination (ARA) are one of the most popular strategies for enantioselective synthesis of chiral amines, which are very important from a synthetic and a biological point of view. The addition of the NH bond across an unsaturated CC bond is known as hydroamination. AHA is ideal for industrial processes as it is a 100% atom‐economic reaction and involves readily available substrates. For broadening its scope for a variety of substrates, many metal‐based as well as metal‐free catalytic systems have been developed for asymmetric hydroamination. Along with the synthesis of functionalized chiral amines, AHA has served as a key strategy in the synthesis of the core of various natural products like codeine, pseudodistomin, swainsonine and of drugs like pentazocine. Reductive amination is a widely used efficient synthetic protocol to install an amine group in place of a carbonyl group in an organic compound. The reaction proceeds through the formation of imine and subsequent one‐pot reduction of it to give the product amine. Use of a metal‐chiral ligand combination, chiral Brønsted acid or chiral organocatalyst, or chiral auxiliary in the reaction can give rise to chiral amine products that are often valuable synthetic intermediates en route to many drugs and natural products. Application of these protocols in the total synthesis of drugs and natural products will be discussed along with some experimental procedures.

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“…Where the absolute stereochemistry is known or implied, the same configuration is found at the a-carbon of the tyramine unit (13-19), exemplified by a number of morphinan and 6,7-benzomorphan analgesic agonists and/or antagonists: 11, (-)-3-hydroxy-Nmethylisomorphinan (20), (-)-butorphan01 (21), levorphanol, levallorphan, (-)-etorphine, (-bnalorphine, and (-)-cyclazocine (22); as a series, these compounds have other portions of their structures, remote from the tyramine segment, grossly altered. Among morphine-like structures, one enantiomer is commonly much more active than its counterpart (11,12:1.…”

mentioning

confidence: 92%