Guanidines structure-activity relationship

We first tried to optimize the environment around the charged guanidine using 5a (R5 = OH) as a reference compound for structure-activity relationship (SAR) determination. 

The more usual methods which have been employed for testing guanidine derivatives as potential antihypertensive drugs depend on detecting some form of interference with the sympathetic nervous system. This.subject has also been reviewed recently in considerable detail [202], and only those methods which have been, or could be, widely applied to elucidating structure-activity relationships are described here. 

In the histaminic H2 receptor antagonist series, the classical urea-thiourea-guanidine progression was successfully completed by the use of the V-nitro and V-cyanoguanidines and, later on, by l,l-diamino-2-nitroethylene groups (Fig. 13.19). Cyano amidines and carbamoyl amidines were also used, and structure-activity relationship patterns were rationalized in terms of dipole moment orientation of related bioisosteric groups. ... 

Unusual biological activity has been associated with a number of natural products having guanidino functionality, e.g. in tetrodotoxin (the poison of the puffer fish). With the purpose of investigating structure-activity relationships, a number of bicyclic guanidines have been synthesized (Scheme 11). 

Guanethidine-like Compounds - Structure activity relationships for a series of branched alkyl guanidines were reported, t-Octylguanldine was found to show fewer side effects and less toxicity clinically than guanethidine, but its h otensive effect was not as good or consistent as the latter. 

Yamamoto, T., Hori, M., Watanabe, 1., Tsutsui, H., Harada, K., Ikeda, S. el al. (1998). Synthesis and quantitative structure-activity relationships of N-(3-Oxo-3,4-dihydro-2H-benzo[l,4]oxazine-6-carbonyl) guanidines as Na/H exchange inhibitors. Chem Pharm Bull, 46, pp. 1716-1723. 

Catalytic enantio- and diastereoselective nitroaldol reactions were explored by using designed guanidine-thiourea brfunctional organocatalysts like 15 (Figure 4.4) under mUd and operationally simple biphasic conditions. These catalytic asymmetric reactions have a broad substrate generality with respect to the variety of aldehydes and nitroalkanes [43]. On the basis of studies of structure and catalytic activity relationships, a plausible guanidine-thiourea cooperative mechanism and a transition state of the catalytic reactions are proposed. 

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... 

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