Biguanide Subject

A discussion of metal complexes of biguanides has recently formed part of m extensive review (532) on co-ordination compounds, so that this subject need not be considered here in detail. As in the past, Indian laboratories continue to be the main source of publications on this aspect of biguanide chemistry (38, 193, 195, 281, 282, 300, 435, 527, 528, 529, 533, 586, 649, 650). 

In view of the manifold interest and obvious medical value of biguanides it is not surprising that a large proportion of the available information is embodied in patent specifications, many of them of fundamental scientific interest. Although investigations on biguanides have been diverse, much remains to be done. It is hoped that the present account will go some way towards stimulating further interest in the chemistry of these reactive and versatile compounds, and that some of the inconsistencies and omissions in the literature will become the subject of further studies. 

A knowledge of the site of protonation in biguanides is of particular interest, because of the importance of such cations as reactive entities, and their possible function in physiologically active biguanides. The problem has attracted a great deal of attention (see Section VI) and has been the subject of critical discussion (20(5, 227, 602). A recent study... 

The numerous highly coloured metal complexes obtainable from biguanides and elements of the transition series have posed yet another interesting structural problem. The accumulated evidence suggests that the structures agreeing most satisfactorily with the observations are of type (I o M = divalent metal). This aspect of the subject has been discussed fully by Ray [532). 

The acid hydrolysis of biguanides under a variety of conditions 5uelds chiefly amidinoureas the subject has been reviewed by Ray (531). The reaction proceeds slowly under very mild conditions at room temperature thus, Paludrine, when stored in 2N hydrochloric add slowly deposits N-p-chlorophenyl-N -isopropylamidinourea hydrochloride (140). That this product was not the isomeric N-isopropyl-N -p-chlorophenyl-amidinourea was verified by its rmequivocal s3uithesis from isopropyl-guanidine and p-chlorophenyl isocyanate (140) ... 

The alkylation of acyl (usually lauroyl or stearoyl) biguanides, generally by means of dimethyl sulphate at 100—110°, has been the subject of numerous patents 53, 54, 234, 241—245, 248—251, 275, 277). However, the structure of the final products was not specified except in one case (275) where the position of the methyl-group remained again undefined ("methyl 2-stearoyl-5-phenylbiguanide ). 

When carbodiimides are subjected to anionic polymerisation, the oligomers are formed with repeating type 4 biguanide units (Figure 5). The polymer chain has restrictions in its conformational degreees of freedom and adopts an helical conformation.7 If the N-substituents of the carbodiimide are chiral, there is intensive induction to yield one of the two diasteroisomeric chiral helices, as shown by optical studies. 

This review will concentrate on new agents or new data on older agents reported in the past 5 years, and is confined to compounds with reported hypoglycaemic activity in man and/or animal models of IDDM or NIDDM. The patent literature has been recently reviewed [6] and will not be covered here. Established agents (sulphonylureas, biguanides) have been the subject of recent reviews and the reader is referred to those [4, 7-12]. 

Epoxy resins may be cured in the manner of polyadditions, i. e., homogeneously catalyzed by multifunctional amines and isocyanates, or cyclic anhydride, dicyan-diamide, or biguanide derivatives. On the other hand epoxy resins are also subject to homopolymerization. The catalysts represent Lewis bases, preferably tertiary amines, imidazoles, or ureas (the latter exclusively for the dicyandiamide curing)... 

There have been various reports that metformin increases fibrinolysis, reduces thrombus formation (Weichert and Breddin, 1988) and reduces platelet adhesiveness and aggregation (Holmes et al., 1984). This, however, was mostly felt to be secondary to improved glycaemic control, because similar effects have been reported with sulphonylureas (Vague et al., 1987). In healthy subjects, biguanides should therefore not be used to increase fibrinolytic activity. 

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