Guanidines functionalities

The guanidine function, when attached to an appropriate lipophilic function, often yields compounds that exhibit antihypertensive activity by means of their peripheral sympathetic blocking effects. Attachment of an aromatic ring via a phenolic ether seems to fulfill these structural requirements. Alkylation of 2,6-dichlorophenol with bromochloroethane leads to the intermediate, 58. Alkylation of hydrazine with that halide gives 59. Reaction of the hydrazine with S-methylthiourea affords the guanidine, guanoclor (60). ... 

As we have had occasion to note more than a few times previously, the guanidine function forms the basis of a family of hypotensive agents active by reason of their activity as blockers of the peripheral sympathetic system. Condensation of tetra-hydroisoquinoline with the S-methyl ether of thiourea affords the antihypertensive drug debrisoquin (135). ... 

VII. RESINS AND LINKERS FOR GENERATION OF SULFONAMIDE, UREA, AND GUANIDINE FUNCTIONS... 

Guanethidine (77) was the first of a series of antihypertensive agents which act by interfering with adrenergic transmission. It was subsequently found that simple substitution of the guanidine function onto a nucleus with appropriate lipophilicity almost invariably affords such sympathetic inhibitors. 

The structures of drugs that have proven clinically useful for treatment of hypertension tend to fall into discrete classes according to their mode of action. It is thus usually a safe assumption that a drug containing a guanidine function will show the... 

Guanidine functionality has been found in a high number of pharmacologically active natural compounds and some of them contain the pyrrolo[l,2-f]pyrimidin-l(277)-imine fragment. Consequently different synthetic approaches... 

T lohnson, RC Sheppard. A new t-butyl-based acid-labile protecting group for the guanidine function of Na-11 uorcnyI mcthyoxycarbonyl -argi n i nc. (Btb) J Chem Soc Chem Commun 1605, 1990. 

The guanidine function in compounds such as guanethidine is essentially completely protonated at physiological pH, and adrenergic neurone blockade is presumably caused by interactions of the cationic species at hypothetical... 

Scheme 6.164 Strecker reaction for examination of the catalytic efficiency of guanidine-functionalized diketopiperazine 177.

A quaternary ammonium hydroxide ion exchange resin 6 was shown to sequester phenols, hydroxypyrazoles, and other weakly acidic heterocycles.25 The sequestered nucleophiles could also be used as polymer-supported reactants. Similarly, the guanidine-functionalized resin 7 was also shown to be a useful capture agent for weakly acidic nucleophiles, including phenols and cyclic iV-acyl sulfonamides.26... 

The novel structure of cylindrospermopsin, with a guanidine embedded in a tricyclic system, six chiral centers, and polar sulfate, uracil and guanidine functional groups, makes its synthesis challenging. Its potent toxicity makes the synthesis of cylindrospermopsin an important problem that has been the subject of intense interest.1,7 8... 

Li, C., Lewis, M.R., Gilbert, A.B., et al. (1999) Antimicrobial activities of amine- and guanidine- functionalized cholic acid derivatives. Antimicrob. Agents Chemother. 43,1347-1349. 

Resins carrying the guanidine function have been patented as catalyst[128] for the preparation of organic disulfides and polysulfides11291 and the preparation of sulfonated olefins.[130]... 

Le Perchec, P., Abusio, M., Arretz, E. Resins having a primary amine or guanidine function and their preparation. 1996, WO 9721740. 

The guanidine function of these structures was suggested by a positive Sakaguchi test and confirmed by the formation of the 4,6-dimethylpyrimi-dine derivatives. The combination of chemical degradation reactions with MS and H-NMR studies led to the proposed structures 164-166 (117). Additional proof of the structures was obtained by synthesis of the three compounds (122). 

Marine rather than terrestrial organisms produce a large variety of structurally intriguing metabolites endowed with guanidine functions [1], The most well known probably are saxitoxin (1), an extremely potent Na" channel blocker, and tetro-dotoxin (2), the powerful poison of the puffer fish family (Scheme 1). 

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