“…It is to be noted that for 5a , the efficiency of the reaction benefits by this latter protocol increasing the overall yield from 25% (obtained employing the step-by-step procedure) to 79% (Table 1). Moreover, the implemented strategy broadens the substitution patterns at the amino-N1 and at C4 of the heterocycle skeleton with electron-withdrawing groups ( 5a – e ) and tolerates the aromatic (amino-N1) and aliphatic (C4) groups, as for 5j [15,17,18] (Table 1).…”
Section: Resultsmentioning
confidence: 99%
“…To date, the most widespread method used for the synthesis of N -substituted 1-amino-1 H -imidazol-2(3 H )-thiones can be referred to the Schantl’s protocol, which consists of reacting α-haloketones with potassium thiocyanate and monosubstituted arylhydrazines in weak acidic medium (Scheme 1) [13,14,15,16,17,18,19]. This multistep reaction is considered to proceed via the formation of conjugated azoalkenes, derived from α-thiocyanatohydrazones D (Scheme 2) and dipolarophile isothiocyanic acid intermediate that in turn undergo a [3+2] cycloaddition reaction providing substituted 1-arylamino-1 H -imidazole-2(3 H )-thione I scaffolds [20,21].…”
A multicomponent reaction (MCR) strategy, alternative to the known cycloaddition reaction, towards variously substituted 1-amino-1H-imidazole-2(3H)-thione derivatives has been successfully developed. The novel approach involves α-halohydrazones whose azidation process followed by tandem Staudinger/aza-Wittig reaction with CS2 in a sequential MCR regioselectively leads to the target compounds avoiding the formation of the regioisomer iminothiazoline heterocycle. The approach can be applied to a range of differently substituted α-halohydrazones bearing also electron-withdrawing groups confirming the wide scope and the substituent tolerance of the process for the synthesis of the target compounds. Interestingly, the concurrent presence of reactive functionalities in the scaffolds so obtained ensures post-modifications in view of N-bridgeheaded heterobicyclic structures.
“…It is to be noted that for 5a , the efficiency of the reaction benefits by this latter protocol increasing the overall yield from 25% (obtained employing the step-by-step procedure) to 79% (Table 1). Moreover, the implemented strategy broadens the substitution patterns at the amino-N1 and at C4 of the heterocycle skeleton with electron-withdrawing groups ( 5a – e ) and tolerates the aromatic (amino-N1) and aliphatic (C4) groups, as for 5j [15,17,18] (Table 1).…”
Section: Resultsmentioning
confidence: 99%
“…To date, the most widespread method used for the synthesis of N -substituted 1-amino-1 H -imidazol-2(3 H )-thiones can be referred to the Schantl’s protocol, which consists of reacting α-haloketones with potassium thiocyanate and monosubstituted arylhydrazines in weak acidic medium (Scheme 1) [13,14,15,16,17,18,19]. This multistep reaction is considered to proceed via the formation of conjugated azoalkenes, derived from α-thiocyanatohydrazones D (Scheme 2) and dipolarophile isothiocyanic acid intermediate that in turn undergo a [3+2] cycloaddition reaction providing substituted 1-arylamino-1 H -imidazole-2(3 H )-thione I scaffolds [20,21].…”
A multicomponent reaction (MCR) strategy, alternative to the known cycloaddition reaction, towards variously substituted 1-amino-1H-imidazole-2(3H)-thione derivatives has been successfully developed. The novel approach involves α-halohydrazones whose azidation process followed by tandem Staudinger/aza-Wittig reaction with CS2 in a sequential MCR regioselectively leads to the target compounds avoiding the formation of the regioisomer iminothiazoline heterocycle. The approach can be applied to a range of differently substituted α-halohydrazones bearing also electron-withdrawing groups confirming the wide scope and the substituent tolerance of the process for the synthesis of the target compounds. Interestingly, the concurrent presence of reactive functionalities in the scaffolds so obtained ensures post-modifications in view of N-bridgeheaded heterobicyclic structures.
“…Yurttas et al [ 35 ] developed 2-((1-((4-substituted phenyl) amino)-4,5-dimethyl-1H-imidazol-2-yl)thio)-N-(6-substitutedbenzo[d]thiazol-2-yl)acetamide by using (Scheme 14 ) and evaluated for antitumor potential by MTT assay against two different cancer cell lines such as C6 (rat glioma) and HepG2 (human liver) using cisplatin as a reference drug. Among the synthesized derivatives compound 20g shows good cytotoxic potential.…”
Section: Main Textmentioning
confidence: 99%
“…Among the synthesized derivatives compound 20g shows good cytotoxic potential. The conclusion of antitumor potential was presented in (Table 14 , Yurttas et al [ 35 ]). Scheme 14 Synthesis of 2-((1-((4-substitutedphenyl)amino)-4,5-dimethyl-1 H- imidazol-2-yl)thio)- N -(6-substitutedbenzo[ d ]thiazol-2-yl)acetamide …”
Imidazole is a five-membered heterocyclic moiety that possesses three carbon, two nitrogen, four hydrogen atoms, and two double bonds. It is also known as 1, 3-diazole. It contains two nitrogen atoms, in which one nitrogen bear a hydrogen atom, and the other is called pyrrole type nitrogen. The imidazole name was reported by Arthur Rudolf Hantzsch (1857–1935) in 1887. 1, 3-diazole is an amphoteric in nature i.e. it shows both acidic and basic properties. It is a white or colorless solid that is highly soluble in water and other polar solvents. Due to the presence of a positive charge on either of two nitrogen atom, it shows two equivalent tautomeric forms. Imidazole was first named glyoxaline because the first synthesis has been made by glyoxal and ammonia. It is the basic core of some natural products such as histidine, purine, histamine and DNA based structures, etc. Among the different heterocyclic compounds, imidazole is better known due to its broad range of chemical and biological properties. Imidazole has become an important synthon in the development of new drugs. The derivatives of 1, 3-diazole show different biological activities such as antibacterial, antimycobacterial, anti-inflammatory, antitumor, antidiabetic, anti-allergic, antipyretic, antiviral, antioxidant, anti-amoebic, antihelmintic, antifungal and ulcerogenic activities, etc. as reported in the literature. There are different examples of commercially available drugs in the market which contains 1, 3-diazole ring such as clemizole (antihistaminic agent), etonitazene (analgesic), enviroxime (antiviral), astemizole (antihistaminic agent), omeprazole, pantoprazole (antiulcer), thiabendazole (antihelmintic), nocodazole (antinematodal), metronidazole, nitroso-imidazole (bactericidal), megazol (trypanocidal), azathioprine (anti rheumatoid arthritis), dacarbazine (Hodgkin's disease), tinidazole, ornidazole (antiprotozoal and antibacterial), etc. This present review summarized some pharmacological activities and various kinds of synthetic routes for imidazole and their derived products.
“…Being a group of highly diversified structures, nitrogen rich heterocycles and their fused systems are widely incorporated into the structure of various pharmacologically active agents and synthetic drugs [6]. Among these bioactive heterocycles, imidazole derivatives [7], particularly substituted thioimidazoles are known in medicinal chemistry as antiobesity [8], antitubercular [9], antidiabetic [10], anticancer [11][12][13], antimicrobial [14,15], and antioxidant agents [16]. 1,2,3-triazoles have also marked their position as a significant pharmacophore from nitrogen rich heterocyclic compounds with spectacular therapeutic potential [17,18].…”
A library of novel imidazole-1,2,3-triazole hybrids were designed and synthesized based on the hybrid pharmacophore approach. Therefore, copper(I)catalyzed click reaction of thiopropargylated-imidazole 2 with several organoazides yielded two sets of imidazole-1,2,3-triazole hybrids carrying different un/functionalized alkyl/aryl side chains 4a–k and 6a–e. After full spectroscopic characterization using different spectral techniques (IR, 1H, 13C NMR) and elemental analyses, the resulted adducts were screened for their anticancer activity against four cancer cell lines (Caco-2, HCT-116, HeLa, and MCF-7) by the MTT assay and showed significant activity. In-silico molecular docking study was also investigated on one of the prominent cancer target receptors, i.e., glycogen synthase kinase-3β (GSK-3β), revealing a good binding interaction with our potent compound, 4k and was in agreement with the in vitro cytotoxic results. In addition, the ADMET profile was assessed for these novel derivatives to get an insight on their pharmacokinetic/dynamic attributes. Finally, this research design and synthesis offered click chemistry products with interesting biological motifs mainly 1,2,3 triazoles linked to phenyl imidazole as promising candidates for further investigation as anticancer drugs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
