130818-98-3

Upstream product

• 130818-97-2 3-(1-benzylpiperidin-4-yl)oxazolidin-2-one 
• 87120-72-7 1-(tert-butoxycarbonyl)-4-aminopiperidine 
• 1148003-95-5 tert-butyl 4-(2-ketooxazolidin-3-yl)piperidin-1-carboxylate 

Downstream Products

• 841203-37-0 3-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidin-4-yl)oxazolidin-2-one 
• 841203-34-7 3-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidin-4-yl)oxazolidin-2-one 

Relevant academic research and scientific papers

Synthetic method of 3-(piperidin-4-yl)oxazolidine-2-one and salt thereof

The invention relates to a synthetic method of 3-(piperidin-4-yl)oxazolidine-2-one and a salt thereof. The synthetic method is characterized by comprising the following steps: carrying out a substitution reaction on 4-amino-1-tert-butyloxycarbonyl piperidine and 2-chloroethyl chloroformate as raw materials to obtain tert-butyl-4-(((2-chloroethoxy)acyl)amido)piperidine-1-carbonate; then, carrying out a ring closing reaction to obtain tert-butyloxycarbonyl-4-(2-ketooxazolidine-3-yl) piperidine-1-carbonate; then removing tert-butyloxycarbonyl to obtain the 3-(piperidin-4-yl)oxazolidine-2-one salt; and then further performing dissociation to obtain the 3-(piperidin-4-yl)oxazolidine-2-one. Compared with the prior art, the synthetic method has the following advantages that the raw materials areeasy to obtain, safe and low in toxicity, requirements of the reactions on equipment are not high, the reactions are simple, the operability is strong, the process is safe and reliable, the total costis low, the aftertreatment is simple and convenient, the reaction product yield is high, and the method is suitable for industrial production.

Identification of a potent, selective, and orally active leukotriene A 4 hydrolase inhibitor with anti-inflammatory activity

LTA4H is a ubiquitously distributed 69 kDa zinc-containing cytosolic enzyme with both hydrolase and aminopeptidase activity. As a hydrolase, LTA4H stereospecifically catalyzes the transformation of the unstable epoxide LTA4 to the diol LTB4, a potent chemoattractant and activator of neutrophils and a chemoattractant of eosinophils, macrophages, mast cells, and T cells. Inhibiting the formation of LTB4 is expected to be beneficial in the treatment of inflammatory diseases such as inflammatory bowel disease (IBD), asthma, and atherosclerosis. We developed a pharmacophore model using a known inhibitor manually docked into the active site of LTA4H to identify a subset of compounds for screening. From this work we identified a series of benzoxazole, benzthiazole, and benzimidazole inhibitors. SAR studies resulted in the identification of several potent inhibitors with an appropriate cross-reactivity profile and excellent PK/PD properties. Our efforts focused on further profiling JNJ 27265732, which showed encouraging efficacy in a disease model relevant to IBD.

BENZIMIDAZOLE, BENZTHIAZOLE AND BENZOXAZOLE DERIVATIVES AND THEIR USE AS LTA4H MODULATORS

Leukotriene A4 hydrolase (LTA4H) inhibitors of formula I, compositions containing them, and their use for the inhibition of LTA4H enzyme activity and the treatment, prevention or inhibition of inflammation and/or conditions associated with inflammation, wherein X is selected from the group consisting of NR5, O, and S, with R5 being one of the H and CH3; Y is selected from the group consisting of CH2 and O; R4 is selected from the group consisting of H, OCH3, Cl, F, Br, I, OH, NH2, CN, CF3.