Thiadiazole chemical structures

The thiadiazole chemical class in Figure 25.11a is a recently reported lead for InhA with desired antibacterial activity [22]. We utilized the cocrystal structure of InhA with this ligand for our docking exercise. The virtual hit shown in Figure 25.11b adopts a similar shape as the reference ligand, but with very different pharmacophoric features. The virtual hit depicted in Figure 25.11c revealed a novel binding mode. The primary alcohol picks up... 

Chemical Name 4-amino-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide Common Name Sulfamethylthiadiazole Structural Formula A ... 

Carbon-13 NMR is often a more useful tool than H NMR for the elucidation of heterocyclic structures in which there are few or no ring protons. For symmetrically substituted 1,2,3-thiadiazoles, the carbon adjacent to the nitrogen atom is expected to have a lower field chemical shift than the carbon atom adjacent to the sulfur atom, as exemplified in CHEC-II(1996) <1996CHEC-II(4)289>. Several examples that follow this rule are illustrated in Table 5. There is now a more extensive body of data available and it is possible to more accurately predict the chemical shift of ring carbons. In the case of monosubstituted 1,2,3-thiadiazoles, the substituted carbon usually has a lower field chemical shift than the unsubstituted carbon. 

While it may be intellectually unsatisfying, the electronic structure of 1,2,5-thiadiazole cannot be depicted in a single drawing. The physical and chemical data as they relate to the position and nature of the double bonds can best be represented by a series of canonical forms (Scheme 1) <84CHEC-I(6)513>. 

Heteropentalenes with a nonclassical ring structure have been observed to partake in interesting dipolar cycloaddition reactions <75ACR139,77T3203). It is believed that by increasing the number of heteroatoms in the ring the resultant chemical reactivity decreases as a consequence of increased stability of the system. This hypothesis was reinforced when no evidence was found for cycloaddition of dipolarophiles to 6-methyl-4-phenylpyrazolo[3,4-c][l,2,5]thiadiazole (24a) <8UOC4065>. 

C NMR data can be quite diagnostic for heterocyclic structures. With reasonable certainty one can usually expect the carbon atom adjacent to the nitrogen atom in a 1,2,3-thiadiazole to have a lower field chemical shift than the carbon atom adjacent to the sulfur. Several examples are illustrated in Table 6. 

Although 3,4-dichloro-l,2,5-thiadiazole-l,1-dioxide (76) is related structurally to 3,4-dichlorothiophene-1,1-dioxide their chemical properties are quite different. The thiophene compound is a reactive diene and readily dimerizes via an auto Diels-Alder reaction. Furthermore, its chlorine atoms are unreactive toward weak nucleophilic reagents like water and alcohol. The thiadiazole compound, on the other hand, shows no tendency to dimerize and is highly reactive toward water and alcohol. 

Thiadiazoles are of theoretical interest because as a class they are in a formal sense iso-7r-electronic with thiophene, thiazoles, and five-membered cyclic mono- and diazines. At the same time they are related by physical and chemical similarity to those six-membered cyclic diazines which contain an ethylenic grouping in place of the sulfur atom. 1,2,5-Thiadiazole is thus related to thiophene, isothiazole, imidazole, and pyrazine. It is therefore not surprising that the thiadiazoles have been assigned to the broad class of aromatic structures. 

The chemical reactions described in this Section are classified, as far as possible, according to the functions of the 1,2,4-thiadiazole structure, but some overlap has occurred when related results are summarized more effectively and briefly in one place. For the same reason some reactions have already been dealt with in the context of the syntheses. 

Monocyclic and Bicyclic aromatic heterocycles such as imidazoles, thiazoles, thiadiazoles, oxazoles, oxadiazoles quinazolines, indoles, benzimidazoles, purines pyrido[43-d]pyri-midines, thiazolo[5,4-d]pyrimidines, thiazolo[4,5-d]pyrimidines, oxazolo[5,4-d]pyrimi-dines and thieno[2,3-d]pyrimidines are renowned pharmacophores in drug discovery. These special structures are well explained and exemplified in chemical compound libraries. In this chapter, several types of thiazole based heterocyclic scaffolds such as mono-cyclic or bicyclic systems synthesis and their biological activities studies are presented, which are not frequently present in books and reviews. We mention the first importance of synthetic route of various thiazole based compounds and their applications in medicinal chemistry in this chapter. 

Pesin and his group have continued their investigation of benzo-2,1,3-thiadiazoles and have provided a summary of their recent work. In their opinion, the quinoid structure of benzo-2,1,3-thiadiazole and its selenium analogue is excluded by the sum of their physical and chemical properties, especially i.r. spectra. However, their preferred heteroaromatic structure... 

Chemical Properties.—Alkylation. Methylation of 2-amino-5-benzoyl-l,3,4-thiadiazole and its derivatives has been systematically examined. The direction of methylation, which occurs at the N-3 atom of the ring and the exocyclic amino-group, is influenced by the structure of the substrate, the nature of the reagent (Mel, Me2S04, or CH2N2), and the reaction conditions. 2-(Substituted amino)-l,3,4-thiadiazoline-5-thiones (104) are 5-methylated to (105) by one equivalent of methyl iodide, in the presence or absence of alkali. Further methylation occurs at N-3 or N-4, but may lead to mixtures, the composition of which depends on the ratio of the reactants and on the degree of substitution of the 2-amino-group in (105). At 190 C, (105 R = R = Me) isomerizes to (106) ... 

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