Morphine analogues

According to Eddy, as quoted by Small, the analgesic action of neopine, n omorphine, 6-acetylneomorphine or 3 6-diacetylneomorphine (p. 218) is definitely less than that of morphine and its corresponding analogues. The first two are about half as toxic as codeine and morphine respectively, and the second pair are more toxic than their morphine analogues. None of the four shows the Straub reaction and the convulsant action is less marked. 

The principles expounded in Chapter T 39 apply to di-hydropyridlnes, e,g., (23), wanted in their own right in this case for the synthesis of morphine analogues. The 1,5-dlcarbonyl compound needed for (23) is (24), available by a Michael reaction. 

Hyotylainen, T., Siren, H., and Riekkola, M.L., Determination of morphine analogues, caffeine and amphetamine in biological fluids by capillary electrophoresis with the marker technique, J, Chromatogr., 735,439,1996... 

TABLE 1. SYNTHETIC MORPHINE ANALOGUES Name Molecular formula Structure... 

Moreover, 0.5-pm diameter MIP beads have been prepared for chronoamperometric determination of morphine [204]. These beads were synthesized by thermo-radical precipitation polymerization of the MAA functional monomer, TRIM cross-linker, AIBN initiator and morphine template in the ACN solution. Then the beads were immobilized in a film of the PEDOT conducting polymer, electropolymerized onto the ITO electrode. The morphine detection with the use of the resulting chemosensor was much more sensitive to morphine (41.63 pA cm 2 mM for the morphine concentration range of 0.1-2 mM) than to morphine analogues. LOD for morphine was 0.3 mM. 

A fair number of carbo-ammonium dicationic species and related systems have been reported. These distonic superelectrophiles have been directly observed and shown to be useful in synthetic methodologies. For example, the acid-catalyzed Grewe-cyclization is a well-known reaction used in the preparation of morphine analogues.37 The conversion involves formation of the distonic superelectrophile (102) from an appropriate... 

The pyranopyridine ring system is also present in numerous alkaloids, two examples are ajmalicine (145) <92JCS(P1)517> and camptothecin (146) <92JA10971>. The trans 8 -aryloctahydropyrano[4,3-cjpyridine (88) and related compounds have been prepared as morphine analogues <89JCS(Pi)ii77>. 

Morphine The Prototype Opioid Ligand 262 11.4.1 Initial Studies of Morphine Analogues 263... 

This work allowed the synthesis Finall7, the weak base bicarbonate (HCO, ) is enough to remove a proton from the cation forme- and trial of morphine analogues as,. 

This compound, the morphine analogue of dihydro- -codeinone is obtained in unsatisfactory yield by the demethylation of the latter [7]. 

O-desmethylthebainone-A [xi], the morphine analogue of thebainone-A, results from the catalytic rearrangement of morphine in the presence of palladized charcoal at 80° C. [2] it is doubtless identical with the ketone obtained by the hydrolysis of /3-ethylthiomorphide [14-15], Although it cannot be methylated to thebainone-A, on reduction it yields O-desmethyldihydrothebainone [xn], which gives dihydrothe-bajnone on treatment with diazomethane [2]. 

Fiirst S, Hosztafi S (2008) The chemical and pharmacological importance of morphine analogues. Acta Physiol Hung 95 3—44... 

The first and easiest morphine analogues which can be made are those involving peripheral modifications of the molecule (that is, changes which do not affect the basic skeleton of the molecule). In this approach, we are looking at the different functional groups and discovering whether they are needed or not. 

We now move on to consider the development of morphine analogues. As mentioned in Chapter 7, there are several strategies used in drug development. 

We shall consider the following strategies in the development of morphine analogues. 

Fig. 12.35 Morphine analogue containing a phenethyl substituent on the nitrogen. 2 Feinberg, A.P., Creese, I., and Snyder, S.H. (1976). Proc. Natl. Acad. Sci. USA, 73, 4215.

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