Benzomorphan derivatives

Many benzomorphan derivatives with morphine-like potencies or better have a low physical dependence capacity (PDC) in monkeys especially potent members, however, such as phenazocine and the /3-isomers (Table 5.2, Nos. 8 and 16) have high to intermediate PDC properties [5, 63, 68]. Unusual results have been reported. for the enantiomorphs of a-(X) (R = Me, R = = Et) the... 

Benzomorphan derivatives pentazocine hydrochloride pentazocine lactate... 

Grauert, M., Bechtel, W. D., Ensinger, H. A., Merz, H., Carter, A. J. Synthesis and structure-activity relationships of 6,7-benzomorphan derivatives as antagonists of the NMDA receptor-channel complex, J. Med. Chem. 1997, 40, 2922-2930... 

The fact that N-arginyl-Met-enkephalin(/3-lipotropin 60-65) has an activity comparable with that of the parent by in vitro tests,<173) prompted the examination of benzomorphan derivatives in which the piperidino nitrogen was linked to a variety of amino acids (Gly, Met, Leu, Arg). The Arg derivative 20 was close in potency to Met-enkephalin in a binding assay against [3H]naloxone (as was the nor-base) and all others had very low activities.074 Peptidase action, liberating the active drug from Arg derivatives of both the enkephalin and benzomorphan, may explain these results, although there is contrary evidence in the case of peptide. 

Table 7.10 Opioid Receptor Affinities and Opioid Activity in the GPI and MVD of Benzomorphan Derivatives and TRK-820 ...

Novel Rearrangement Reaction for Converting a 6,14-Endoethanomorphinan Derivative to a Benzomorphan Derivative [97]... 

Pasquinucci L, Iadanza M, Marrazzo A, Prezzavento O, Ronsisvalle S, Scoto GM, Parenti C, De Luca L, Ronsisvalle G (2007) New benzomorphan derivatives of MPCB as MOP and KOP receptor ligands. Pharmazie 62 813-824... 

Ten years ago, when this project began in the Parke-Davis Laboratories there were a number of chemical structures reported in the literature as possessing high affinity for the kappa opioid receptor. Some of these are shown below (fig. 1). They include the endogenous peptide, dynorphin, the benzomorphan derivative EKC, the benzodiazepine tifluadom, and the 1,2 aminoamide U-50488. 

The 8-keto benzomorphan derivative lb was prepared from ( - )5,9-a-dimethyl-2 -hydroxy-6,7-benzomorphan... 

Neumeyer, J.L., Bidlack, J.M., Zong, R., Bakthavachalam, V., Gao, P., Cohen, D.J., Negus, S.S., Mello, N.K., 1999. Synthesis and opioid receptor affinity of morphinan and benzomorphan derivatives. Mixed kappa agonists and mu agonists/antagonists as potential pharma-cotherapeutics for cocaine dependence. J. Med. Chem. (in press). 

Mass spectral, o.r.d., and c.d. studies have been carried out on unnatural b/c /rans-fused morphine derivatives. Characteristic dilferences between m.s. fragmentation patterns of C-14 epimeric derivatives were observed which should have diagnostic value. Mass spectral investigations were also used in structural and stereochemical assignments of benzomorphan derivatives. The C n.m.r. spectrum of codeine has been analysed. A method for selective... 

Scheme 8.26 Synthesis of benzomorphan derivatives, as described by Khartulyari and Maier [58].

Narcotic medicines contain substances causing addiction. Many opioid preparations show strong analgetic action, which can alleviate even the strongest pain. Therefore, they are used in acute, post-traumatic conditions post-traumatic shock, as prevention and in cancer. Based on chemical criteria, these drugs are divided into morphine and its products, morphinan derivatives, benzomorphan derivatives, piperidine derivatives and diphenylpropylamine derivatives. 

A variety of reactive anileridine or benzomorphan derivatives have been prepared as potential non-equilibrium inactivators of the analgetic receptor. Certain long-term activity of some of these compounds... 

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