Guanethidine derivatives

The azocane derivative guanethidine (5.99), an antihypertensive agent, is largely converted to the ot-amino acid metabolite without formation of a lactam metabolite [191], a reactivity that is difficult to explain. 

Synthetic guanidine derivatives have been used successfully in the treatment of a variety of diseases, but the major success has undoubtedly been their exploitation as antihypertensive drugs. Guanethidine has still not been displaced. 

Table 3.7. THE ACTIVITY OF BICYCLIC DERIVATIVES OF GUANETHIDINE RGHjGHjNHGIiNHINHj...

The available information on the relationship between structure and potency in preventing guanethidine-mduced ptosis in mice is summarized semi-quantitatively in Table 3.23. The most active compounds are aralkylguanidines Table 3.23. ANTAGONISM BY GUANIDINE DERIVATIVES OF... 

Ephedra has negative interactions with cardiac heart glycosides, halothene, guanethidine, MAO inhibitors, and secale alkaloid derivatives or oxytocin. 

Among the guanethidine analogs it again should be emphasized that there would not appear to be any a priori rationalization for proceeding directly to the optimum compound other than by chance, and a considerable number of molecular modifications needed to be prepared in order to permit selection of the most interesting derivative. 

Base-catalysed attack of nitromethane on the imidate (102) gave the derivative (103) which was hydrogenated to the diamine (104). Finally, treatment with 5 -methylisothiourea gave guanazodine (105) (Scheme 5.25.) [113], The actions are similar to those of guanethidine, but this drug is less potent [114]. 

Guanethidine Analogs - In a series of 25 derivatives of benzyl-guanidine, the most active compounds were p-trifluoromethyl-... 

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