3848-41-7

Upstream product

• 5070-13-3 bis-(p-nitrophenyl) carbonate 
• 106-47-8 4-chloro-aniline 
• 7693-46-1 4-Nitrophenyl chloroformate 
• 100-02-7 4-nitro-phenol 
• 104-12-1 p-chlorphenylisocyanate 

Downstream Products

• 1219-99-4 N,N'-bis(4-chlorophenyl)urea 
• 92277-80-0 1-(4-Chloro-phenyl)-3-(4-methyl-benzyl)-urea 
• 52039-87-9 4-(4-chlorophenyl)urazole 
• 103492-33-7 ethyl 2-((4-chlorophenyl)carbamoyl)hydrazinecarboxylate 
• 104-12-1 p-chlorphenylisocyanate 
• 725685-95-0 ethyl 3-{3-tert-butyl-5-[3-(4-chlorophenyl)ureido]-1H-pyrazol-1-yl}benzoate 

Relevant academic research and scientific papers

Kinetics and mechanism of the aminolysis of p-nitrophenyl N-phenylcarbamates

Kinetic studies of the reactions of p-nitrophenyl N-phenylcarbamates with benzylamines were carried out in acetonitrile at 25·0°C. Second-order (k2) and third-order (k3) rate constants were observed for all the Y-substituted carbamates except for Y=m Cl. The relatively large magnitude of ρx (for X-substituted benzylamines) and ρY together with a positive cross-interaction constant ρxy supports a stepwise mechanism involving rate-limiting breakdown of the zwitterionic tetrahedral intermediate T±. Kinetic isotope effect studies with deuterated benzylamine (XC6H4CH2ND2) indicate that in the base-catalyzed path, k3, rate-limiting deprotonation occurs at the amino group of benzylamine within the T± intermediate. The low ΔH≠ and ΔS≠ values for the k3 process are in accord with the proposed mechanism.

Discovery of Cytochrome P450 4F11 Activated Inhibitors of Stearoyl Coenzyme A Desaturase

Stearoyl-CoA desaturase (SCD) catalyzes the first step in the conversion of saturated fatty acids to unsaturated fatty acids. Unsaturated fatty acids are required for membrane integrity and for cell proliferation. For these reasons, inhibitors of SCD represent potential treatments for cancer. However, systemically active SCD inhibitors result in skin toxicity, which presents an obstacle to their development. We recently described a series of oxalic acid diamides that are converted into active SCD inhibitors within a subset of cancers by CYP4F11-mediated metabolism. Herein, we describe the optimization of the oxalic acid diamides and related N-acyl ureas and an analysis of the structure-activity relationships related to metabolic activation and SCD inhibition.

METHODS AND COMPOSITIONS FOR SELECTIVE AND TARGETED CANCER THERAPY

Provided herein are methods and compositions for selective and targeted cancer therapy, in particular certain benzothiophenes, benzothiazoles, oxalamides, N-acyl ureas and chromones, and their use in selectively treating certain adenocarcinomas. In some embodiments, the selective toxicity of the compounds may be mediated through SCD1 and/or CYP450 such as CYP4F11.

Novel and efficient synthesis of 4-substituted-1,2,4-triazolidine-3,5- diones from anilines

A simple and efficient three-step synthetic procedure for the preparation of 4-substituted phenyl derivatives of 1,2,4-triazolidindiones (urazoles), starting from anilines, has been developed. In this method, aniline derivatives were reacted with 4-nitrophenyl chloroformate to provide corresponding carbamate derivatives. In the second step, semicarbazide derivatives were prepared from these carbamates by reaction with ethyl carbazate. The cyclization reaction of corresponding semicarbazides furnished 1,2,4-triazolidindiones in high yields. Copyright Taylor & Francis Group, LLC.

Nucleophilic substitution reactions of phenyl chloroformates

Methanolysis and aminolysis of phenyl chloroformates in acetonitrile have been investigated.The rates are slow due to initial-state stabilization by strong resonance electron donation from the phenoxy group.In both reactions the large positive values of ρY = 0.8-1.6 and low ΔH(excit.) and ΔS(excit.) values show that the transition state is strongly associative with little bond breaking.This mechanism is supported by the relatively large solvent isotope effect, kMeOH/kMeOD = ca. 2.3-2.5, and by the relatively strong inverse secondary kinetic isotope effect, kH/kD =/ca. 0.74-0.94, involving deuteriated aniline nuclephiles, in addition to a negative value of ρXY.The dependence on aniline basicity, βx(βnuc) =/ca. 0.8, and the ρX values of -2.3 are similar to those corresponding values for the reactions of benzoyl chlorides which have been predicted to react by an associative SN2 mechanism.These observations are consistent with a concerted displacement mechanism for the methanolysis and aminolysis of phenyl chloroformates.