Guanidines substituted

ET-IR spectroscopy was employed to investigate the structures of the 1 1 complexes between Li" and the guanidine-substituted azo compounds pyiidine-2-azo-p-phenyltetramethylguanidine and 4,4 -bis(tetramethylguanidine)azoben-zene. Both Li" complexes exist as dimers in acetonitrile solution.The structural chemistry of potassium N,N -di(tolyl)formamidinate complexes has been investigated in detail. These compounds were prepared by deprotonation of the parent Af,N -di(tolyl)formamidines with potassium hydride (Scheme 13). The resulting adducts with either THE or DME display one-dimensional polymeric solid-state structures that exhibit /r-fj fj -coordinated formamidinates. 

Amidinate- and guanidinate-substituted boron halides are normally prepared using the two standard synthetic routes, i.e., salt-metathesis between suitable... 

An equally efficient preparation of a new carbocyclic influenza sialidase inhibitor, namely the guanidine substituted cyclohexene derivative 265, has been recently reported by Bianco and co-workers [65], choosing (-)-quinic acid 159 as a starting precursor (Scheme 42). Moving... 

Bone, R. Lu, T. Illig, C.R. Soil, R.M. Spurlino, J.C. Structural analysis of thrombin complexed with potent inhibitors incorporating a phenyl group as a peptide mimetic and aminopyridines as guanidine substitutes. J. Med. Chem. 1998, 41 (12), 2068-2075. 

Guanidines. Substituted thioureas are converted to guanidines by reaction with primary amines under the influence of the chloropyridinium salt in the presence of EijN. 

There are several results here which are markedly different from cimetidine, implying that famotidine and cimetidine are not interacting in the same way with the H2 receptor. Further evidence for this is the fact that guanidine substitution at the equivalent position of cimetidine analogues leads to very low activity. 

Can it be replaced by some vague bioisosteric equivalent snch as a guanidino group (Af-methyl piperazine was used as guanidine substitute in the design of thrombine inhibitors) ... 

Can it be replaced by homopiperazine (b), by piperidine (c and d), by ring-opened diamines (e)7 Can it be substituted (g and h) or bridged (i)7 Can it be replaced by some vague bioisosteric equivalent such as a guanidino group (Af-methyl piperazine was used as a guanidine substitute in the design of thrombine inhibitors) ... 

The use of guanidine for cyclization gives amino substituted derivatives (e.g. 212) (52CB1012), and in this case o-aminonitriles may be used to furnish diamines (e.g. 8UOC1394). An unusual reaction involving nitriles occurred during the preparation of nicotinonitrile from the amide and ammonium sulfamate, when a 60% yield of the dimeric by-product (213) was formed via the nitrile (69BSB289). Similar products have been obtained from... 

Amidines and related systems such as guanidines react with a-halogenoketones to form imidazoles. a-Hydroxyketones also take part in this reaction to form imidazoles, and a variety of substituents can be introduced into the imidazole nucleus by these procedures. Reaction of the a-halogenoketone (73) with an alkyl- or aryl-substituted carboxamidine (76) readily gave the imidazole (77) (01CB637, 48JCS1960). Variation of the reaction components that successfully take part in this reaction process is described in Chapter 4.08. 

Diaziridinimines were made analogously. Tri-t-butylguanidine (281) with r-butyl hypochlorite gave (176) in 80% yield. (281) itself is a sufficiently strong base to deprotonate its Af-chloro derivative (69AG(E)448). This procedure also works with methyl- or phenyl-substituted guanidines. 

The Goodyear vulcanization process takes hours or even days to be produced. Accelerators can be added to reduce the vulcanization time. Accelerators are derived from aniline and other amines, and the most efficient are the mercaptoben-zothiazoles, guanidines, dithiocarbamates, and thiurams (Fig. 32). Sulphenamides can also be used as accelerators for rubber vulcanization. A major change in the sulphur vulcanization was the substitution of lead oxide by zinc oxide. Zinc oxide is an activator of the accelerator system, and the amount generally added in rubber formulations is 3 to 5 phr. Fatty acids (mainly stearic acid) are also added to avoid low curing rates. Today, the cross-linking of any unsaturated rubber can be accomplished in minutes by heating rubber with sulphur, zinc oxide, a fatty acid and the appropriate accelerator. 

Thereafter, molecules have been synthesised with a bicyclic ring, such as a quinoleine or an indole, inserted. Many of these compounds like zoniporide and BMS-284640 are selective NHE1 inhibitors, but some inhibit also other isoforms. Most recently, an additional group of compounds with 4-substituted (benzo[b]thiophene-2-carbonyl) guanidines has been synthesised and these are potent NHE1 inhibitors. A structurally distinct compound, S-3226, was found to be the first selective NHE3 inhibitor. 

When cyanogen bromide was used instead of CS2, the corresponding guanidines 169 were obtained under analogous conditions [108]. Moreover, differently substituted guanidines 171 could be obtained in very good yields when the isothiourea 168 was alkylated with Mel under microwave irradiation and the product treated with a primary amine. An intramolecular version of this reaction was also described for the preparation of structure 172 present in several important natural products (Scheme 61). 

Moreau and co-workers have also prepared (ll ,2K)-l,2-diaminocyclo-hexane amino-urea and thiourea derivatives [43]. Diphenylethylenediamine-substituted monothioureas are more stable than the cyclohexyldiamine counterpart, but they can also rearrange to guanidine derivatives, especially at high temperature or in the presence of metal [43]. Under the same conditions, thioureas also rearrange to guanidines in the presence of amines. Selective formation of substituted guanidines from thiourea derivatives of diaminocy-clohexane or diphenylethylenediamine were also reported in a recent paper from Ishikawa [44]. 

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