69818-65-1

Upstream product

• 50458-37-2 N,N-diethylbenzamidine 
• 2131-55-7 4-Chlorophenyl isothiocyanate 
• 106-47-8 4-chloro-aniline 

Downstream Products

• 1095593-26-2 C₂₄H₂₄Cl₂N₄ 
• 952613-93-3 3-(4-acetyl-phenyl)-2-[2-(4-chloro-phenylamino)-4-phenylthiazol-5-yl]-3H-quinazolin-4-one 
• 952612-59-8 2-[2-(4-chloro-phenylamino)-4-phenyl-thiazol-5-yl]-3-phenyl-3H-quinazolin-4-one 
• 952613-46-6 3-(2-chloro-phenyl)-2-[2-(4-chloro-phenylamino)-4-phenyl-thiazol-5-yl]-3H-quinazolin-4-one 
• 1418139-53-3 N-(4-chlorophenyl)-5-phenyl-1,2,4-oxadiazol-3-amine 
• 69818-58-2 (4-chloro-phenyl)-(5-nitro-4-phenyl-thiazol-2-yl)-amine 

Relevant academic research and scientific papers

Design, computational studies, synthesis and biological evaluation of thiazole-based molecules as anticancer agents

Background: Abolition of cancer warrants effective treatment modalities directed towards specific pathways dysregulated in tumor proliferation and survival. The antiapoptotic Bcl-2 proteins are significantly altered in several tumor types which position them as striking targets for therapeutic intervention. Here we designed, computationally evaluated, synthesized, and biologically tested structurally optimized thiazole-based small molecules as anticancer agents. Methods: The virtually designed 200 molecules were subjected to rigorous docking and in silico ADME-Toxicity studies. Out of this, 23 skeletally diverse thiazole-based molecules which passed pan assay interference compounds (PAINS) filter and were synthetically feasible were synthesized in 3 steps using cheap and readily available reagents. The molecules were in vitro evaluated against Bcl-2-Jurkat, A-431 cancerous cell lines and ARPE-19 cell lines. Molecular Dynamics (MD) simulation studies were performed to analyse conformational changes induced by ligand 32 in Bcl-2. Flow cytometry analysis of compound 32 treated Bcl-2 cells was done to check apoptosis. Results: The molecules exhibited appreciable interactions with Bcl-2 and were having acceptable drug like properties as tested in silico. The multi step synthesis yielded 23 skeletally diverse thiazole-based molecules in up to 80% yield. The molecules simultaneously inhibited Bcl-2 Jurkat cells in vitro without causing detectable toxicity to normal cells (ARPE-19 cells). Among them molecules 32, 50, 53, 57 and 59 showed considerable activities against Bcl-2 Jurkat and A-431cell lines at concentrations ranging from 32–46 μM and 34–52 μM, respectively. The standard doxorubicin exhibited IC50 in Bcl-2 Jurkat and A-431cell lines at 45.87 μM and 42.37 μM, respectively. The molecule 32, almost equipotent in both the cell lines was subjected to molecular dynamics (MD) simulation with Bcl-2 protein (4IEH). It was shown that 32 interacted with protein majorly via hydrophobic interactions and few H-bonding interactions. Fluorescence-activated cell sorting (FACS) analysis established that molecule is dragging cancerous cells towards apoptosis. Discussion and conclusion: The chemical intuition was checked by computation coupled with biological results confirmed that thiazole-based hits have the potential to be developed downstream into potent and safer leads against antiapoptotic Bcl-2 cells.

Thiazolyl-thiadiazines as Beta Site Amyloid Precursor Protein Cleaving Enzyme-1 (BACE-1) Inhibitors and Anti-inflammatory Agents: Multitarget-Directed Ligands for the Efficient Management of Alzheimer's Disease

Alzheimer's disease (AD) is associated with multiple neuropathological events including β-site amyloid precursor protein cleaving enzyme-1 (BACE-1) inhibition and neuronal inflammation, ensuing degeneracy, and death to neuronal cells. Targeting such a complex disease via a single target directed treatment was found to be inefficacious. Hence, with an intention to incorporate multiple therapeutic effects within a single molecule, multitarget-directed ligands (MTDLs) have been evolved. Herein, for the first time, we report the discovery of novel thiazolyl-thiadiazines that can serve as MTDLs as evident from the in vitro and in vivo studies. These MTDLs exhibited BACE-1 inhibition down to micromolar range, and results from the in vivo studies demonstrated efficient anti-inflammatory activity with inherent gastrointestinal safety. Moreover, compound 6d unveiled noteworthy antioxidant, antiamyloid, neuroprotective, and antiamnesic properties. Overall, results of the present study manifest the potential outcome of thiazolyl-thiadiazines for AD treatment.

(3+2) annulation of amidinothioureas with binucleophile: Synthesis and antimicrobial activity of 3-phenylamino-5-aryl/alkyl-1,2, 4-oxadiazole derivatives

Herein, we report an efficient method for preparation of 3-phenylamino-5-aryl/alkyl-1,2,4-oxadiazole by (3+2) annulation of amidinothioureas with binucleophilic hydroxylamine hydrochloride in the presence of mercury (II) chloride. Desired 3-phenylamino-5-aryl/alkyl-1,2,4-oxadiazole was prepared in good to moderate yields. On the basis of the literature precedence, the mechanism for the formation of 3-phenylamino- 5-aryl/alkyl-1,2,4-oxadiazole is proposed. The synthesized compounds were tested for their antimicrobial activity and showed promising inhibition of Gram-positive bacteria (Staphylococcus aureus) and fungi (Candida albicans).

Mercury(II) chloride-mediated desulphurization of amidinothioureas: Synthesis and antimicrobial activity of 3-amino-1,2,4-triazole derivatives

The synthesis of 3-amino-1,2,4-triazole via mercury(II) chloride-mediated cyclization of amidinothiourea is described. This procedure offers a general and efficient route to synthesize the title compound by 3 + 2 annulation reaction. On the basis of the l

A diversified assembly of 1,2,4-oxadiazol-3-amines: Metallic thiophile catalyzed chemoselective one-pot reaction of aryl isothiocyanates, amidines/guanidines, and hydroxylamine

An efficient one-pot synthesis of 1,2,4-oxadiazol-3-amines from simple starting materials, isothiocyanates, amidines/guanidines, and hydroxylamine, is described. The reaction is facilitated by metallic-thiophile-assisted desulfurization of in situ formed amidino- or guanidinothiourea to give chemoselectively N-hydroxyguanidine intermediates that give exclusively various 1,2,4-oxadiazol-3-amines in good to excellent yields. The reaction mechanistic pathway may proceed through an intramolecular 5-exo-trig cyclization.

Design, synthesis and characterization of novel 2-(2,4-disubstituted-thiazole-5-yl)-3-aryl-3H-quinazoline-4-one derivatives as inhibitors of NF-κB and AP-1 mediated transcription activation and as potential anti-inflammatory agents

A series of 2-(2,4-disubstituted-thiazole-5-yl)-3-aryl-3H-quinazoline-4-one derivatives were designed and synthesized. Synthesized molecules were further evaluated for their inhibitory activity towards transcription factors NF-κB and AP-1 mediated transcr