Thioamides biological activities

The chemistry of thiazoles is interesting in view of their propensity for biological activity. Eor that reason thiazoloquinolines have also been a widely studied group of compounds. A preferred route to thiazoles exploits a-halogeno ketones in a reaction with thioamides to give the fused 2-substituted thiazole derivatives. 

Several reports are available on the biological activities of thioamide derivatives. The thioamide derivatives have shown significant activities, such as antituberculosis drug, anti-influenza virus activity, antitumor activity, anthelmintic activity, opioid receptor binding property, etc.94 101... 

L. Lakiewicz D. B. Sherman A. E. Spatola, Subtle Amide Bond Surrogates The Effect of Backbone Thioamides on the Physical Properties, Conformation, and Biological Activities of Peptides. In Peptides J. E. Rivier, R. G. Marshall, Eds. ESCOM Leiden, 1990 p 976. 

Replacement of the amide by a thioamide bond in peptides represents a minimal modification that may be of interest as it increases resistance against enzymatic degradation. 483,484 Such modification has been reported to both increase14 5 486 and decrease biological activities, and the effect is not readily predictable. 487-489 ... 

Addition of a carbanion [39] or an enolate [40, 41] to methyl isothiocyanate provided an entry to a new class of biologically active thioamides, bearing sulfinyl and pyridyl groups, introduced by Rhone-Poulenc-Rorer as cellular potassium channel openers... 

Biologically active molecules containing amide bonds suffer usually of pharmacokinetic liability. In order to increase their stability, bioisosteric transformation of the carboxamide have been performed and yielded a lot of successful examples especially in the area of petidomimetic. The isosteric replacements for peptidic bonds have been summarized by Spatola and by Fauchere. " The most used and well-established modihcations are iV-methylation, configuration change (o-conhguration at Ca), formation of a retroamide or an a-azapeptide, use of aminoisobutyric or dehydroamino acids, replacement of the amidic bond by an ester [depsipeptide], ketomethylene, hydroxyethyl-ene or thioamide functional group, carba replacement of the amidic carbonyl, and use of an olefinic double bond (Figure 15.33). 

The thiazole ring system is a useful structural motif found in numerous biologically active molecules. Addition of thioamide or thiourea to the aqueous solution of phenacyl bromide-j3-CD complex gave the corresponding thiazole or aminothiazole, respectively (>82%), without the formation of by-products or rearranged products (Figure 4.16). The role of CD appears to be to activate and solubilize the phenacyl bromide, and drive the reaction to completion in decreased reaction times. Without CD, the reaction took place but the yields were poor (20%). Selenazoles were also prepared from a-bromoketones and selenourea in the presence of )3-CD at 50 °C under atmospheric pressure. ... 

Nitrogen nucleophiles used to diplace the 3 -acetoxy group include substituted pyridines, quinolines, pyrimidines, triazoles, pyrazoles, azide, and even aniline and methylaniline if the pH is controlled at 7.5. Sulfur nucleophiles include aLkylthiols, thiosulfate, thio and dithio acids, carbamates and carbonates, thioureas, thioamides, and most importandy, from a biological viewpoint, heterocycHc thiols. The yields of the displacement reactions vary widely. Two general approaches for improving 3 -acetoxy displacement have been reported. One approach involves initial, or in situ conversion of the acetoxy moiety to a more facile leaving group. The other approach utilizes Lewis or Brmnsted acid activation (87). 

Thioamides and their use in the preparation of the heterocyclic compounds are widely reported in the literature. Also they attract considerable interests in peptide chemistry. Molecular and crystal structures of some thioamide derivatives have been confirmed by X-ray diffraction data.8 10 Lawesson s reagent or phosphorus pentasulfide (P4S10) is actively used for the synthesis of thio-carbonyl compounds. Their preparation methods, reactions, applications in the synthesis of heterocycles and biological effects are mainly described in this section. 

Reports regarding selenoamides and selenoureas are less than the corresponding thioamides, thioureas, amides and ureas because of instability of compounds including selenium atom and their difficulty in the preparation. Recently, preparation methods to overcome some difficulties have been developed. Their reactions, preparation, application to heterocycles or biological assay systems have been actively investigated. 

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