41167-60-6

Upstream product

• 553-90-2 Dimethyl oxalate 
• 403-42-9 1-(4-fluorophenyl)ethanone 
• 33560-65-5 oxalic acid tert-butyl ester methyl ester 
• 124-41-4 sodium methylate 
• 95-92-1 oxalic acid diethyl ester 
• 67-56-1 methanol 

Downstream Products

• 235789-31-8 methyl 5-(4-fluorophenyl)-1-phenylpyrazole-3-carboxylate 
• 235789-37-4 methyl 5-(4-fluorophenyl)-1-(3-methylphenyl)pyrazole-3-carboxylate 
• 461681-73-2 (Z)-2-Amino-4-(4-fluoro-phenyl)-4-oxo-but-2-enoic acid methyl ester 
• 1046152-05-9 methyl 5-(4-fluorophenyl)-1-(4-methanesulfonylphenyl)-1H-pyrazole-3-carboxylate 
• 1261280-08-3 C₅H₁₃N₃*C₁₈H₁₀FNO₅ 
• 1391501-07-7 C₂₃H₁₉BrFN₃O₃ 
• 1391501-09-9 C₂₃H₁₉BrIN₃O₃ 
• 900325-79-3 2-hydroxy-4-oxo-4-(4-fluorophenyl)-2-butenoic acid N-(4-(acetylaminosulfonyl)phenyl)amide 

Relevant academic research and scientific papers

Discovery of Novel Central Nervous System Penetrant Metabotropic Glutamate Receptor Subtype 2 (mGlu2) Negative Allosteric Modulators (NAMs) Based on Functionalized Pyrazolo[1,5- a]pyrimidine-5-carboxamide and Thieno[3,2- b]pyridine-5-carboxamide Cores

A scaffold hopping exercise from a monocyclic mGlu2 NAM with poor rodent PK led to two novel heterobicyclic series of mGlu2 NAMs based on either a functionalized pyrazolo[1,5-a]pyrimidine-5-carboxamide core or a thieno[3,2-b]pyridine-5-carboxamide core. These novel analogues possess enhanced rodent PK, while also maintaining good mGlu2 NAM potency, selectivity (versus mGlu3 and the remaining six mGlu receptors), and high CNS penetration. Interestingly, SAR was divergent between the new 5,6-heterobicyclic systems.

Design and biological evaluation of novel hybrids of 1, 5-diarylpyrazole and Chrysin for selective COX-2 inhibition

The overexpress of COX-2 was clearly associated with carcinogenesis and COX-2 as a possible target has long been exploited for cancer therapy. In this work, we described the design and synthesis of a series of diarylpyrazole derivatives integrating with c

Synthesis of novel hybrids of pyrazole and coumarin as dual inhibitors of COX-2 and 5-LOX

In our previous study, we designed a series of pyrazole derivatives as novel COX-2 inhibitors. In order to obtain novel dual inhibitors of COX-2 and 5-LOX, herein we designed and synthesized 20 compounds by hybridizing pyrazole with substituted coumarin w

Design, synthesis and evaluation of benzenesulfonamide-substituted 1,5-diarylpyrazoles containing phenylacetohydrazide derivatives as COX-1/COX-2 agents against solid tumors

Novel benzenesulfonamide-substituted 1,5-diarylpyrazoles containing phenylacetohydrazide derivatives have been designed, synthesized and evaluated for their biological activities as selective COX-2 inhibitors with anticancer potential. In vitro the bioass

Coumarin sulfonamides derivatives as potent and selective COX-2 inhibitors with efficacy in suppressing cancer proliferation and metastasis

Cyclooxygenase-2 is frequently overexpression in malignant tumors and the product PGE2promotes cancer cell progression and metastasis. We designed novel series of coumarin sulfonamides derivatives to improve biological activities of COX-2 inhib

Discovery, synthesis, and biological evaluation of orally active pyrrolidone derivatives as novel inhibitors of p53-MDM2 protein-protein interaction

The p53-MDM2 interaction has been proved to be a valuable target to develop effective antitumor agents. Novel p53-MDM2 inhibitors bearing pyrrolidone scaffolds were successfully identified by structure-based design. The nanomolar inhibitor 5 possessed good p53-MDM2 inhibitory activity (Ki = 780 nM) due to its hydrophobic and hydrogen bonding interactions with MDM2. Further hit optimization led to the discovery of a number of highly potent pyrrolidone derivatives with improved p53-MDM2 inhibitory activity and in vitro antiproliferative potency. Compounds 41 (Ki = 260.0 nM) and 60a (Ki = 150.0 nM) showed good and selective activity against tumor cells with deleted p53. In addition, these two compounds also effectively inhibited the tumor growth in the A549 xenograft model. Interestingly, compound 41 was proved to be a potent MDM2/MDMX dual inhibitor. The novel pyrrolidone p53-MDM2 inhibitors represent promising lead structures for the development of novel antitumor agents.

Diazen-1-ium-1,2-diolated nitric oxide donor ester prodrugs of 1-(4-methanesulfonylphenyl)-5-aryl-1H-pyrazol-3-carboxylic acids: Synthesis, nitric oxide release studies and anti-inflammatory activities

A new group of hybrid nitric oxide-releasing anti-inflammatory drugs (NONO-coxibs) wherein an O2-acetoxymethyl-1-(N-ethyl-N-methylamino)diazen-1-ium-1,2-diolate (11a-c) NO-donor moiety is attached directly to the carboxylic acid group of 1-(4-methanesulfonylphenyl)-5-aryl-1H-pyrazol-3-carboxylic acids were synthesized. The diazen-1-ium-1,2-diolate compounds 11a-c all released a low amount of NO upon incubation with phosphate buffer (PBS) at pH 7.4 (7.7-9.3% range). In comparison, the percentage of NO released was significantly higher (67.5-73.6% of the theoretical maximal release of two molecules of NO/molecule of the parent hybrid ester prodrug) when the diazen-1-ium-1,2-diolate ester prodrugs were incubated in the presence of rat serum. These incubation studies suggest that both NO and the anti-inflammatory 1-(4-methanesulfonylphenyl)-5-(4-H, 4-F or 4-Me-phenyl)-1H-pyrazol-3-carboxylic acid (9a-c) would be released from the parent NONO-coxib upon in vivo cleavage by non-specific serum esterases. The 1-(4-methanesulfonylphenyl)-5-(4-H, 4-F or 4-Me-phenyl)-1H-pyrazol-3-carboxylic acids (9a-c) exhibited AI activities (ID50 = 85.2-104.4 mg/kg po range) between that exhibited by the reference drugs aspirin (ID50 = 128.7 mg/kg po) and celecoxib (ID50 = 10.8 mg/kg po). Hybrid ester anti-inflammatory/NO-donor prodrugs (NONO-coxibs) offers a potential drug design concept targeted toward the development of anti-inflammatory drugs that are devoid of adverse ulcerogenic and/or cardiovascular effects.

Novel dimeric aryldiketo containing inhibitors of HIV-1 integrase: Effects of the phenyl substituent and the linker orientation

Aryl diketoacids (ADK) and their bioisosteres are among the most promising HIV-1 integrase (IN) inhibitors. Previously, we designed a series of ADK dimers as a new class of IN inhibitors that were hypothesized to target two divalent metal ions on the active site of IN. Herein we present a further structure-activity relationship (SAR) study with respect to the substituent effect of the ADK and the dimerization with conformationally constrained linkers such as piperazine, 4-amino-piperidine, piperidin-4-ol, and trans-cyclohexan-1,4-diamine. The substituents on the phenyl ring as well as the spatial orientation of the two diketo units were observed to play important roles in the IN inhibitory potency. The hydrophobic group was an optimal substitution at the 3-position of the aryl ring. The piperazine and 4-amino-piperidine linkers brought about the most potent analogs among the hydrophobic group or halogen substituted ADK dimers. The docking studies suggested that the bulky hydrophobic substitution at 3-phenyl ring and the linker of 4-amino-piperidine were beneficial for adopting an active conformation to achieve strong interactions with the active site Mg2+ and the key residue E152 within the catalytic core domain. This study is a significant extension of our previous report on the dimeric ADK-containing IN inhibitors, providing a new promising template for further lead optimization.

Improved preparation and structural investigation of 4-aryl-4-oxo-2- hydroxy-2-butenoic acids and methyl esters

A simple and efficient oxalylation of aryl methyl ketones was accomplished with dimethyl oxalate in the presence of sodium methoxide. The unpreviously reported sodium ketoenolate esters were isolated and gently hydrolyzed into the ketoenol esters in good yields. Alternatively the sodium ketoenolate esters hydrolysis could also be conducted to directly afford the ketoenol acids, which represent one of the most promising class of HIV-1 integrase inhibitors. Advantages over previously reported procedures were better yields and simplicity of the purification protocol.

Highly efficient preparation of aryl β-diketo acids with tert-butyl methyl oxalate

An improved and efficient oxalylation of aryl methyl ketones was accomplished with tert-butyl methyl oxalate. This is the key step in constructing the pharmacophore of aryl β-diketo acids, which represent a promising new class of HIV-1 integrase inhibitors. Structurally diverse aryl β-diketo acids, including bisdiketo acids, can be prepared rapidly in impressive yields under mild conditions with this method. Advantages over conventional methods with dimethyl (or diethyl) oxalate were observed in both yield and reaction time.