116344-13-9

Upstream product

• 116344-09-3 2-dimethylaminomethylene-4-methyl-3-oxo-pentanoic acid ethyl ester 
• 100-63-0 phenylhydrazine 
• 84794-38-7 5-(1-hydroxy-2-methylpropylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione 
• 7152-15-0 ethyl 4-methyl-3-oxo-pentanoate 
• 4637-24-5 N,N-dimethyl-formamide dimethyl acetal 

Downstream Products

• 3191-88-6 5-isopropyl-1-phenyl-1H-pyrazole 
• 153863-68-4 4-Bromomethyl-5-isopropyl-1-phenyl-1H-pyrazole 
• 153863-39-9 (5-Isopropyl-1-phenyl-1H-pyrazol-4-yl)-methanol 
• 116344-18-4 5-Isopropyl-1-phenyl-1H-pyrazole-4-carboxylic acid 

Relevant academic research and scientific papers

Pyrazole-4-Carboxamide (YW2065): A Therapeutic Candidate for Colorectal Cancer via Dual Activities of Wnt/β-Catenin Signaling Inhibition and AMP-Activated Protein Kinase (AMPK) Activation

Dysregulation of the Wnt/β-catenin signaling pathway has been widely recognized as a pathogenic mechanism for colorectal cancer (CRC). Although numerous Wnt inhibitors have been developed, they commonly suffer from toxicity and unintended effects. Moreover, concerns have been raised in targeting this pathway because of its critical roles in maintaining stem cells and regenerating tissues and organs. On the basis of the anthelmintic drug pyrvinium and previous lead FX1128, we have developed a compound YW2065 (1c) which demonstrated excellent anti-CRC effects in vitro and in vivo. YW2065 achieves its inhibitory activity for Wnt signaling by stabilizing Axin-1, a scaffolding protein that regulates proteasome degradation of β-catenin. Simultaneously, YW2065 also led to the activation of the tumor suppressor AMPK, providing an additional anticancer mechanism. In addition, YW2065 showed favorable pharmacokinetic properties without obvious toxicity. The anti-CRC effect of YW2065 was highlighted by its promising efficacy in a mice xenograft model.

Catalyst-free one-pot synthesis of 1,4,5-trisubstituted pyrazoles in 2,2,2-trifluoroethanol

A simple, efficient and three component one-pot synthesis of 1,4,5-trisubstituted pyrazoles by condensation of β-dicarbonyls, N,N-dimethylformamide dimethyl acetal (DMFDMA) and hydrazine derivatives in 2,2,2-trifluoroethanol without using any catalyst and activation, is described.

Microwave-assisted solution-phase synthesis of 1,4,5-trisubstituted pyrazoles

A small parallel library of 1,4,5-trisubstituted pyrazoles was prepared in solution using a three-step procedure starting from Meldrum acid. The Meldrum acid was acylated with different acyl chlorides and the products opened with different alcohols and amines to give substituted β-keto esters and β-keto amines. Further reaction with N,N-dimethylformamide dimethylacetal and the final cyclisation were effectively carried out under microwave irradiation. Scavenger resins were employed exclusively in the first step, whereas use of microwaves allowed complete conversion of the starting materials in the other two steps. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.