6125-31-1

Upstream product

• 2103-99-3 4-(4-chlorophenyl)-2-thiazolamine 
• 79-04-9 chloroacetyl chloride 
• 536-38-9 4-chlorobenzoylmethyl bromide 
• 99-91-2 para-chloroacetophenone 
• 937-20-2 p-chlorophenacyl chloride 

Downstream Products

• 6202-62-6 N,N'-bis-[4-(4-chloro-phenyl)-thiazol-2-yl]-2,2'-piperazine-1,4-diyl-bis-acetamide 
• 6121-89-7 N-benzyl-N-phenyl-glycine 4-(4-chloro-phenyl)-thiazol-2-ylamide 
• 6122-05-0 2-benzoimidazol-1-yl-N-[4-(4-chloro-phenyl)-thiazol-2-yl]-acetamide 
• 6122-23-2 N-[4-(4-chloro-phenyl)-thiazol-2-yl]-2-(2-methyl-benzoimidazol-1-yl)-acetamide 
• 6664-66-0 N-ethyl-N-phenyl-glycine 4-(4-chloro-phenyl)-thiazol-2-ylamide 
• 100956-98-7 N,N-diethyl-glycine 4-(4-chloro-phenyl)-thiazol-2-ylamide 
• 131942-98-8 N-[4-(4-Chloro-phenyl)-thiazol-2-yl]-2-(4-phenyl-5-p-tolyloxymethyl-4H-[1,2,4]triazol-3-ylsulfanyl)-acetamide 
• 135747-43-2 2-[4-(4-Chloro-phenyl)-3-cyano-5,6,7,8-tetrahydro-quinolin-2-ylsulfanyl]-N-[4-(4-chloro-phenyl)-thiazol-2-yl]-acetamide 
• 135747-49-8 3-Amino-4-(4-chloro-phenyl)-5,6,7,8-tetrahydro-thieno[2,3-b]quinoline-2-carboxylic acid [4-(4-chloro-phenyl)-thiazol-2-yl]-amide 
• 135747-55-6 5-(4-Chloro-phenyl)-2-[4-(4-chloro-phenyl)-thiazol-2-yl]-6,7,8,9-tetrahydro-2H-11-thia-2,3,4,10-tetraaza-benzo[b]fluoren-1-one 
• 878440-42-7 C₁₆H₁₉ClN₄OS 
• 879616-03-2 N-(4-(4-chlorophenyl)thiazol-2-yl)-2-(4-phenylpiperazin-1-yl)acetamide 
• 52471-10-0 2-[4-(4-chloro-phenyl)-thiazol-2-ylamino]-thiazol-4-one 

Relevant academic research and scientific papers

Novel thienopyrimidine-aminothiazole hybrids: Design, synthesis, antimicrobial screening, anticancer activity, effects on cell cycle profile, caspase-3 mediated apoptosis and VEGFR-2 inhibition

A series of novel hybrid compounds of hexahydrobenzo[4,5]thieno[2,3-d]pyrimidine with aminothiazole scaffolds were synthesized. The synthesized compounds were evaluated for their cytotoxic activity against the NCI-60 human tumor cell line panel. Compounds 7c, 7d and 7e exhibited significant antiproliferative activities at 10?5 M dose. Compound 7c exhibited excellent cytotoxic activity against CNS cancer cell lines including SNB-75 and SF-295 as well as renal cancer cell line CAKI-1 when compared with sorafenib as standard anticancer drug. In addition, compound 7d showed almost comparable anticancer activity to sorafenib against SNB-75 cell line and displayed moderate activity against SF-295 and CAKI-1 cell lines in comparison to sorafenib. Compound 7c inhibited the vascular endothelial growth factor receptor 2 (VEGFR-2) with IC50 of 62.48 ± 3.7 nM and decreased both total VEGFR-2 and phosphorylated VEGFR-2 in treated SNB-75 cells suggesting its ability to down regulate cell proliferation, growth, and survival. The flow cytometric analysis showed that 7c displayed its cytotoxic activity through the reduction of the cellular proliferation and induction of cell cycle arrest at the G2/M phase. Compound 7c clearly boosted the level of the apoptotic caspase-3. All the synthesized compounds were also screened for their antibacterial and antifungal activity against four pathogenic strains of both Gram-positive and Gram-negative as well as Candida albicans. Only compound 7d exhibited antifungal activity against Candida albicans compared to nystatin as the standard antifungal compound.

Design, synthesis and molecular docking of pyrazolo [3,4d] thiazole hybrids as potential anti-HIV-1 NNRT inhibitors

A series of pyrazolo[3.4,d]thiazole hybrids 6 were synthesized from 5-arylidene-2-imino-3-(4-arylthiazol-2-yl)-thiazolidin-4-ones 5. The 5-arylidene-2-imino-3-(4-arylthiazol-2-yl)-thiazolidin-4-ones 5 were synthesized from 2-amino-4-arylthiazoles 1 and 2-chloro-acetamido-4-arylthiazoles 2 via the formation of 2-imino-3-(4-substituted-arylthiazol-2-yl)-thiazolidin-4-ones 3 using substituted aldehydes 4. The 5-acrylidene derivative 5 on cyclisation with phenyl hydrazine give the pyrazolo [3, 4, d] thiazole derivatives 6. The obtained pyrazolo [3.4, d]thiazole derivatives were studied as anti-HIV-1 NNRT inhibitors. It was found that these compounds might have potent RT inhibition activity.

Synthesis and biological screening of diethyl [N-(thiazol-2-yl)carbamoyl]methylphosphonates

A three-step synthesis, involving condensation of bromomethyl aryl ketones with urea to afford 2- aminothiazoles, their chloroacetylation and subsequent solvent-free Arbuzov phosphonation has afforded a series of novel diethyl [N-(thiazol-2-yl)carbamoyl]methylphosphonates 3a-3f in good overall yields; the 4- carboxythiazole analogue 3g was obtained by selective hydrolysis of the corresponding ethyl ester 3f. The phosphonate esters exhibited significant anti-cancer activity (nM - low μM IC50 values) against SH-SY5Y cells and, in one case, 7.6 μM MIC90 anti-TB activity against the virulent M. tuberculosis H37Rv strain; the chloroacetamido precursors all exhibited some antimalarial (PfLDH) activity, three with IC50 values in the range 1.0 - 8.9 μM.

Synthesis, biological evaluation, and docking studies of novel 5,6-diaryl-1,2,4-triazine thiazole derivatives as a new class of α-glucosidase inhibitors

A novel 5,6-diaryl-1,2,4-triazine thiazole derivatives (7a-7q) were synthesized and characterized by 1H NMR and 13C NMR and evaluated for their α-glucosidase inhibitory activity. All tested compounds displayed good α-glucosidase inhibitory activity with IC50 values ranging between 2.85 ± 0.13 and 14.19 ± 0.23 μM when compared to the standard drug acarbose (IC50 = 817.38 ± 6.27 μM). Compound 7i (IC50 = 2.85 ± 0.13 μM) exhibited the highest activity among this series of compounds. Molecular docking studies were carried out in order to investigate the binding mode of this class of compounds to α-glucosidase. This study showed that these 5,6-diaryl-1,2,4-triazine thiazole derivatives are a new class of α-glucosidase inhibitors.

Design and discovery of novel thiazole derivatives as potential MMP inhibitors to protect against acute lung injury in sepsis rats: Via attenuation of inflammation and apoptotic oxidative stress

Acute lung injury (ALI) is considered to be an inflammatory syndrome of the airway system that is initiated by failure of the respiratory system. In this study, we evaluated the possible benefits of some novel thiazole derivatives against ALI. These derivatives were synthesised and evaluated for the inhibition of MMP-8 and MMP-2. Most of the tested compounds had better inhibitory activity for MMP-8 than for MMP-2, with compound 26 being the most potent analogue among the tested series. Thus, compound 26 was further investigated to determine its beneficial effects in an ALI model of rats with sepsis. In vivo results suggested that compound 26 significantly reduced the protein concentration together with a decline in enhanced leukocytes compared with those in ALI induced by cecal ligation and puncture. The effect of compound 26 on myeloperoxidase activity was also quantified, which was found to be significantly reduced at the maximum tested dose of 20 mg kg-1. The protective effect of compound 26 against ALI was also established to occur via the significant modulation of various biomarkers; for example, the malondialdehyde level was found to be reduced, while there were increased levels of superoxide dismutase and glutathione. Thus, it is proposed that compound 26 exerts a protective effect against ALI via modulation of the antioxidant status. Furthermore, the compounds tested caused significant attenuation of the levels of tumour necrosis factor-α, interleukin-1β, and interleukin-6, and protected the lung through the modulation of systemic inflammatory mediators in septic rats. In conclusion, we identified a novel series of thiazoles, which potentially exert protective effects against ALI via the inhibition of numerous pathways.

Synthesis, antibacterial, antifungal, and antioxidant evaluation of some new thiazole clubbed oxadiazole derivatives

A series of thiazole incorporated oxadiazole derivatives (6a-6f) was synthesized by reacting 2-chloro-N-(4-(4-substituted phenyl) thiazol-2-yl) acetamide with 5-pyridine-1,3,4-oxadiazole-2-thione using multistep solution phase chemistry. The synthesized compounds were structurally characterized on the basis of elemental analysis and using various spectral data. All the compounds were evaluated for their in vitro antibacterial, antifungal, and antioxidant activity. Some of the new compounds exhibited good antimicrobial and antioxidant activity and are suitable candidates for further scientific explorations.

Design and Synthesis of 3-Substituted-thiazolyl-2-iminothiazolidin-4-ones as a New Class of Anticonvulsants

A new series of 3-substituted-thiazolyl-2-iminothiazolidin-4-ones were synthesized by nucleophilic substitution of p-substituted-thiazol-2-yl-chloroacetamides with potassium thiocyanide by cyclization. The starting material p-substituted-thiazol-2-yl-chloroacetamides were synthesized from p-substituted-thiazol-2-yl-amines with chloroacetyl chloride, which in turn was prepared from one pot reaction of substituted aryl acetophenone and amino group of thiourea. The title compounds were investigated for their anticonvulsant activity. Among the tested compounds, compound 3-(4-(4-fluorophenyl)thiazol-2-yl)-2-iminothiazolidin-4-one (16) emerged as the most active compound of the series, and it is moderately more potent than the reference standard diazepam.

1-Piperazinylphthalazines as potential VEGFR-2 inhibitors and anticancer agents: Synthesis and in vitro biological evaluation

In our endeavor towards the development of effective VEGFR-2 inhibitors, three novel series of phthalazine derivatives based on 1-piperazinyl-4-arylphthalazine scaffold were synthesized. All the newly prepared phthalazines 16a-k, 18a-e and 21a-g were evaluated in vitro for their inhibitory activity against VEGFR-2. In particular, compounds 16k and 21d potently inhibited VEGFR-2 at sub-micromolar IC50 values 0.35 ± 0.03 and 0.40 ± 0.04 μM, respectively. Moreover, seventeen selected compounds 16c-e, 16g, 16h, 16j, 16k, 18c-e and 21a-g were evaluated for their in vitro anticancer activity according to US-NCI protocol, where compounds 16k and 21d proved to be the most potent anticancer agents. While, compound 16k exhibited potent broad spectrum anticancer activity with full panel GI50 (MG-MID) value of 3.62 μM, compound 21d showed high selectivity toward leukemia and prostate cancer subpanels [subpanel GI50 (MG-MID) 3.51 and 5.15 μM, respectively]. Molecular docking of compounds16k and 21d into VEGFR-2 active site was performed to explore their potential binding mode.

Novel 3-nitrotriazole-based amides and carbinols as bifunctional antichagasic agents

3-Nitro-1H-1,2,4-triazole-based amides with a linear, rigid core and 3-nitrotriazole-based fluconazole analogues were synthesized as dual functioning antitrypanosomal agents. Such compounds are excellent substrates for type I nitroreductase (NTR) located in the mitochondrion of trypanosomatids and, at the same time, act as inhibitors of the sterol 14α-demethylase (T. cruzi CYP51) enzyme. Because combination treatments against parasites are often superior to monotherapy, we believe that this emerging class of bifunctional compounds may introduce a new generation of antitrypanosomal drugs. In the present work, the synthesis and in vitro and in vivo evaluation of such compounds is discussed.

Synthesis and biological evaluation of novel 2-heteroarylimino-1,3-thiazolidin-4-ones as potential anti-tumor agents

A series of 35 heteroarylimino-1,3-thiazolidinones with three sites of functionalization were synthesized and their antiproliferative properties were studied. The in vitro screening by MTT assay was performed against five cancer cell lines (human colon cancer cell lines HT29, HCT116 and SW620 and breast cancer cell lines MCF7 and MDA-MB-231). It was observed that N3-substituted thiazolidinones had moderate activities whereas 5-benzylidene thiazolidinones showed promising activities. To investigate the mechanism of action, detailed biological studies of six selected compounds (those presenting the lower mitotic index) were carried out on the human colon cancer HT29 cell line. Cell cycle assay revealed that those compounds induced cell accumulation in G2/M and in subG0/G1 phases of cell cycle. Moreover, dissipation of mitochondria membrane potential was observed as well as redox changes in treated cells.