99134-77-7

Upstream product

• 99-92-3 p-aminobenzophenone 
• 1885-14-9 phenyl chloroformate 
• 1170292-50-8 phenyl (2,4,6-trinitrophenyl) carbonate 

Downstream Products

• 86781-35-3 1,1-dibutyl-3-(4-acetylphenyl)urea 
• 476360-60-8 4-[(phenoxycarbonyl)amino]phenacyl bromide 

Relevant academic research and scientific papers

Discovery and Mechanism of Action of Small Molecule Inhibitors of Ceramidases**

Sphingolipid metabolism is tightly controlled by enzymes to regulate essential processes in human physiology. The central metabolite is ceramide, a pro-apoptotic lipid catabolized by ceramidase enzymes to produce pro-proliferative sphingosine-1-phosphate. Alkaline ceramidases are transmembrane enzymes that recently attracted attention for drug development in fatty liver diseases. However, due to their hydrophobic nature, no specific small molecule inhibitors have been reported. We present the discovery and mechanism of action of the first drug-like inhibitors of alkaline ceramidase 3 (ACER3). In particular, we chemically engineered novel fluorescent ceramide substrates enabling screening of large compound libraries and characterized enzyme:inhibitor interactions using mass spectrometry and MD simulations. In addition to revealing a new paradigm for inhibition of lipid metabolising enzymes with non-lipidic small molecules, our data lay the ground for targeting ACER3 in drug discovery efforts.

Ligand-based optimization to identify novel 2-aminobenzo[d]thiazole derivatives as potent sEH inhibitors with anti-inflammatory effects

Inhibition of the soluble epoxide hydrolase (sEH) is a promising new therapeutic approach in the treatment of inflammation. Driven by the in-house database product lead 1, a hybridization strategy was utilized for the design of a series of novel benzo [d]thiazol derivatives. To our delight, D016, a byproduct of compound 9, was obtained with an extraordinarily low IC50 value of 0.1 nM but poor physical and chemical properties. After removal of a non-essential urea moiety or replacement of the urea group by an amide group, compounds 15a, 17p, and 18d were identified as promising sEH inhibitors, and their molecular binding modes to sEH were constructed. Furthermore, compounds 15a and 18d exhibited more effective in vivo anti-inflammatory effect than t-AUCB in carrageenan-induced mouse paw edema. Compound 15a also showed moderate metabolic stability with a half-time of 34.7 min. Although 18d was unstable in rat liver microsomes, it might be a “prodrug”. In conclusion, this study could provide valuable insights into discovery of new sEH inhibitors, and compounds 15a and 18d were worthy of further development as potential drug candidates to treat inflammation.

Benzothiazole derivatives and their uses

The present invention relates to benzothiazole derivatives and their uses, specifically to compounds shown in formula I or stereoisomers thereof and pharmaceutically acceptable salts, solvates or prodrugs thereof, methods of preparation thereof, and pharmaceutical compositions containing the compounds, wherein the substituentsR1,R2,R8 , X, Y, Z, Q have the meaning given in the instruction manual. The present invention further relates to the application of compounds of formula I in the preparation of drugs for the treatment and / or prevention of sEH-mediated diseases, in particular in the preparation of drugs for the treatment of inflammatory diseases, cardiovascular and cerebrovascular diseases, diabetes mellitus, diabetic complications, diabetes-related diseases, fibrotic diseases, neurological and psychiatric diseases, pain, ulcerative diseases and the like.

Discovery of 4-piperazinyl-2-aminopyrimidine derivatives as dual inhibitors of JAK2 and FLT3

Hybridization strategy is an effective strategy to obtain multi-target inhibitors in drug design. In this study, we assembled the pharmacophores of momelotinib and tandutinib to get a series of 4-piperazinyl-2-aminopyrimidine derivatives. All compounds were tested for the inhibition of JAK2 and FLT3 enzymes, of which, compounds with potent enzyme activities were assayed for antiproliferative activities against three cancer cell lines (HEL, MV4-11, and HL60). The structure-activity relationship studies were conducted through variations in two regions, the “A” phenyl ring and “B” phenyl ring. Compound 14j showed the most balanced in vitro inhibitory activity against JAK2 and FLT3 (JAK2 IC50 = 27 nM, FLT3 IC50 = 30 nM), and it also showed potent inhibition against the above tested cell lines. In the cellular context, 14j strongly induced apoptosis by arresting cell cycle in the G1/S phase, and was selected as a promising JAK2/FLT3 dual inhibitor.

Concerted aminolysis of diaryl carbonates: Kinetic sensitivity on the basicity of the nucleophile, nonleaving group, and nucleofuge

The kinetics of the reactions of 4-methylphenyl, phenyl, and 4-chlorophenyl 2,4,6-trinitrophenyl carbonates (1, 2, and 3, respectively) with a series of anilines and secondary alicyclic (SA) amines has been carried out spectrophotometrically in 44 wt% ethanol-water, at 25.0°C, ionic strength 0.2 M. The BrAnsted plots (statistically corrected) for the reactions of carbonates 1-3 with anilines and SA amines were linear with slopes (βN) in the range of 0.69-0.78 and 0.45-0.48, respectively, attributed to a concerted mechanism. The negative values found for the sensitivity of log kN to the basicity of the nonleaving (βnlg) and leaving (βlg) groups are discussed. Anilines are more reactive than isobasic SA amines, probably because of the greater steric hindrance offered by the latter.

Novel orally active NPY Y5 receptor antagonists: Synthesis and structure-activity relationship of spiroindoline class compounds

Spiroindoline urea derivatives, designed to act as NPY Y5 receptor antagonists, were synthesized and their structure-activity relationships were investigated. Of these derivatives, compound 3a showed good Y5 binding affinity with favorable pharmacokinetic

Synthesis and biological activity of strongly fluorescent tricyclic analogues of acyclovir and ganciclovir

In search of strongly fluorescent tricyclic analogues of acyclovir (ACV, 1) and ganciclovir (GCV, 2), derivatives of the 3,9-dihydro-9-oxo-5H-imidazo[1,2-α]purine system, several 6-[4- (acyloxy)-phenyl], 6-[4-(acylamino)phenyl], and 6-[4-(phenoxycarbonyloxy)phenyl]-substituted TACV and TGCV analogues were synthesized and evaluated for their activity against herpes simplex virus types 1 and 2 in cell culture. All TACV and TGCV analogues showed strong fluorescence (quantum yield of 30-65% vs 2-aminopurine 100%). The 6-[4-(phenoxycarbonyloxy)phenyl]-substituted compounds 11 and 19 displayed the best combination of the fluorescence and antiviral potency.

Practical synthesis of urea derivatives

STR1 A very mild and efficient approach for the synthesis of ureas is described. Phenyl carbamates were used as intermediates for the preparation of N,N'- substituted ureas. The carbamates were treated with an approximate stoichiometric amount of amine in dimethyl sulfoxide at ambient temperature, generating the ureas in high yield. The reaction was simple, safe, fast, inexpensive, and amenable to large scale production of the product.

A practical synthesis of ureas from phenyl carbamates

Using DMSO as solvent, a mild and efficient procedure for the synthesis of unsymmetrical N,N'-disubstituted ureas from phenyl carbamates is described. The carbamates are treated with a stoichiometric amount of amine at ambient temperature, generating the