N-Propyl-apomorphine

Thus the analogue N-propyl-apomorphine is a more powerful dopaminergic agonist than the apomorphine itself. The creation of bulkiness is obviously not limited to cationic head groups and lipophilic groups can be attached to any other part of the molecule (Fig. 12.18). ... 

Figure 5 Orthogonal views of the CoMFA steric contours top, positive bottom, negative) for D2 dopamine agonists superimposed on N-propyl-apomorphine, a potent agonist. The contours describe the coefficients discovered by PLS and their location in space. This CoMFA model was based on 26 compounds with four significant latent variables. Only steric fields were statistically significant. Reprinted with permission from Ref. 169. Copyright 1996, Academic Press.

The synthesis of three l,2,10,ll-tetrasubstituted./V-(n-propyl)noraporphines, using either the Bischler-Napieralski-Pschorr sequence or a Reissert alkylation-Pschorr cyclization, has been achieved.29 Patents have been taken out on the morphine-apomorphine rearrangement that is induced by phosphoric acid and which leads to N- alkylated norapomorphines.30 Other patents concern the vanadium-trichloride-induced cyclization of tetrahydrobenzylisoquinolines that are hydroxylated at C-7, to furnish a series of 1-hydroxylated aporphines such as thaliphorphine. 31,32... 

The antiparkinsonism activity of a series of N- (n-propyl)norapomorphine diesters has been tabulated.43 The stability of apomorphine in solutions contain-... 

A method for the preparation of (—)-apomorphine (50) and (-)-N-(n-propyl)norapomorphine (51) from thebaine (49) has been described. The sequence has also been extended to the transformation of (+)-bulbocapnine (52) into (+)-apomorphine.55... 

The synthesis of a number of radiolabelled apomorphine derivatives has been described.59-62 A full paper has appeared on the preparation of (—)-2,10,11-trihydroxy-/V-(n-propyl)noraporphine, a dopaminergic compound with anticonvulsant activity.63 The potential dopamine-inhibiting properties of (—)-N-(2-chloroethyl)norapomorphine and related compounds have been assessed. A-Chloroethylation in the aporphine series can abolish dopamine agonist action, and can confer a long-lasting dopamine antagonist potential.64... 

When the courses of the curves after s.c. administration of compounds 11, 80, and 12, respectively, are compared it can be seen that the duration of action of the N- -propyl analogues is longer than that of R-(-)-apomorphine. 

Various substituted and unsubstituted methylenedioxyl derivatives of apomorphine and V-n-propyl-norapomorphine have been studied by Baldessarini et and one of... 

Various substituted and unsubstituted methylenedioxyl derivatives of apomorphine and V-n-propy 1-norapomorphine have been studied by Baldessarini et and one of these, 10,11-methylenedioxy-V-n-propyl-norapomorphine, was found to be both a long-acting and an orally efficient prodrug (Figure 36.29a). The oral activity of the compound can be ascribed to the protection of the catechol system from first-pass effects by the methylenedioxyl group. The conversion to the free catechol is possible, thanks to the hepatic microsomal enzymes (see Chapters 33 and 34 on drug metabohsm). 

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