Amidines medicinal

Fusion of an additional heterocyclic ring onto that already present in the benzodiazepines has led to some medicinal agents with considerable activity. Treatment of an intermediate like 15 with phosphorus pentasulfide affords the corresponding thio-amide (37). Condensation of this intermediate with acetyl hydra-zide affords triazolam )37). The same agent can be prepared by reaction of the amidine, 38, ° with acetylhydrazide. ... 

Amidines such as the ones presented here appear to have a number of advantages, displaying good water solubility, and not producing formaldehyde during breakdown. Varying the dialkylamino group can modulate the lipo-philicity and the rate of nonenzymatic hydrolysis, and the stability of amidines under the acidic conditions that prevail in the stomach is compatible with oral administration. Future studies will certainly reveal the potential medicinal value of amidines. 

The basic groups met in medicinal chemistry are the amines, the amidines, the guanidines and practically all nitrogen-containing heterocycles. Basic gronps are polar and one... 

There seems to be no major limitation regarding the selection of aldehydes and isonitriles. For 2-aminoazenes, both heteroaromatic amidines and heteroaromatic guanidines participated in this novel 3CR. Flowever, aliphatic amidines were found to be inactive. Many variants have since been reported by different research groups, both academic and industrial, due to the medicinal importance of this family of heterocycles [68]. 

Some of the medicines that contain amidines and/or guanidines have been reviewed, too [9]. 

In this chapter, natural products and medicines bearing guanidine and amidine functions are discussed. The topics covered include the amidine and guanidine natural products for which isolation, total synthesis and/or structural revision have recently been reported, as well as medicines, with the focus on activity, stability and mode-of-action. 

In this section, medicinal amidine and guanidine derivatives are detailed. Amidines and guanidines also play important roles in medicinal chemistry in terms of the control of the basicity, high coordination ability and nitric oxide source. 

This summary of the physiologically active amidine and guanidine compounds clearly establishes the biological versatility of these related chemical groups. Many of the compounds have given temporarry excitement to their discoverers and then been dropped - the commonest experience in medicinal chemistry. However, there are important, clinically used, medicines in all the major categories of therapeutic action discussed in the review. 

On the other hand, nitriles are widely used as intermediates in the synthesis of many types of heterocycles [7] and other compounds of interest in medicinal chemistry, for example, 3,4-dihydroisoquinolines [8], imidazoles [9], indoles [10], lactim ethers [11], napthyridines [12], pyridones [13], pyridopyrimidi-nes [14], pyrimidines [15], quinazolines [16], quinazolones [17], quinolines [18], sydnones [19], 1,2,4,5-tetrazines [20], tetrazoles [21,22], 1,2,4-triazoles [20], N-substituted amides [23], amidines [24] and basic esters [25]. 

New anthelmintic agents which are already in use in veterinary medicine have been found in two cyclic amidine derivatives, pyrantel tartrate (Banminth, Strongid) (269) and morantel tartrate (Banminth II) (270). For references concerning their evaluation in sheep, cattle, pigs, horses, dogs, and man see Ref. 260. These compounds are most probably prepared by condensation of the appropriate thiophen aldehyde with 1,4,5,6-tetra-hydro-l,2-dimethylpyrimidine. Extensive investigations on structure-... 

Spear, N., and Tian, G. (2007) Application of fragment-based lead generation to the discovery of novel, cyclic amidine beta-secretase inhibitors with nanomolar potency, cellular activity, and high ligand efficiency. Journal of Medicinal Chemistry,... 

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