1228590-91-7

Basic information

• Product Name: N-[6-(3-amino-4-fluorophenoxy)-7-cyano-1,3-benzothiazol-2-yl]cyclopropanecarboxamide
• Synonyms: N-[6-(3-amino-4-fluorophenoxy)-7-cyano-1,3-benzothiazol-2-yl]cyclopropanecarboxamide
• CAS NO: 1228590-91-7
• Molecular Weight: 368.391
• Mol File: 1228590-91-7.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: N-[6-(3-amino-4-fluorophenoxy)-7-cyano-1,3-benzothiazol-2-yl]cyclopropanecarboxamide(CAS DataBase Reference)
• NIST Chemistry Reference: N-[6-(3-amino-4-fluorophenoxy)-7-cyano-1,3-benzothiazol-2-yl]cyclopropanecarboxamide(1228590-91-7)
• EPA Substance Registry System: N-[6-(3-amino-4-fluorophenoxy)-7-cyano-1,3-benzothiazol-2-yl]cyclopropanecarboxamide(1228590-91-7)

Safety Data

• Hazardous Substances Data: 1228590-91-7(Hazardous Substances Data)

Upstream product

• 1228590-90-6 N-(7-cyano-6-{4-fluoro-3-[(trifluoroacetyl)amino]phenoxy}-1,3-benzothiazol-2-yl)cyclopropanecarboxamide 
• 62257-16-3 5-hydroxy-2-fluoroaniline 
• 17417-09-3 2-fluoro-5-nitrobenzonitrile 
• 1228590-89-3 N-(5-((2-amino-7-cyanobenzo[d]thiazol-6-yl)oxy)-2-fluorophenyl)-2,2,2-trifluoroacetamide 
• 1228590-88-2 N-[5-(4-amino-2-cyanophenoxy)-2-fluorophenyl]-2,2,2-trifluoroacetamide 
• 1228590-87-1 N-[5-(2-cyano-4-nitrophenoxy)-2-fluorophenyl]-2,2,2-trifluoroacetamide 
• 1228590-86-0 2-(3-amino-4-fluorophenoxy)-5-nitrobenzonitrile 

Downstream Products

• 1228590-92-8 3-(1-cyanocyclopropyl)-N-[5-({7-cyano-2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazol-6-yl}oxy)-2-fluorophenyl]benzamide 
• 1228590-85-9 2-chloro-3-(1-cyanocyclopropyl)-N-[5-({7-cyano-2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazol-6-yl}oxy)-2-fluorophenyl]benzamide 
• 1228590-94-0 2-chloro-N-[5-({7-cyano-2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazol-6-yl}oxy)-2-fluorophenyl]-3-(1-cyano-1-methylethyl)benzamide 
• 1448850-83-6 N-{7-cyano-6-[4-fluoro-3-({[3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-1,3-benzothiazol-2-yl}-cyclopropanecarboxamide 
• 1228591-30-7 N?(7-cyano-6-(4-fluoro-3-(2-(3-(trifluoromethyl)phenyl)acetamido)phenoxy)benzo[d]thiazol-2-yl)cyclopropanecarboxamide 
• 1228590-93-9 N-{7-cyano-6-[4-fluoro-3-({[4-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy ]-1,3-benzothiazol-2-yl}cyclopropanecarboxamide 

Relevant articles and documents

N-(7-Cyano-6-(4-fluoro-3-(2-(3-(trifluoromethyl)phenyl)acetamido)phenoxy)benzo[ d]thiazol-2-yl)cyclopropanecarboxamide (TAK-632) Analogues as Novel Necroptosis Inhibitors by Targeting Receptor-Interacting Protein Kinase 3 (RIPK3): Synthesis, Structure-Activity Relationships, and in Vivo Efficacy

Necroptosis, a form of programmed cell death, plays a critical role in various diseases, including inflammatory, infectious, and degenerative diseases. We previously identified N-(7-cyano-6-(4-fluoro-3-(2-(3-(trifluoromethyl)phenyl)acetamido)phenoxy)benzo[d]thiazol-2-yl)cyclopropanecarboxamide (TAK-632) (6) as a potent inhibitor of necroptosis by targeting both receptor-interacting protein kinase 1 (RIPK1) and 3 (RIPK3) kinases. Herein, we performed three rounds of structural optimizations of TAK-632 and elucidated structure-activity relationships to generate more potent inhibitors by targeting RIPK3. The analogues with carbamide groups exhibited great antinecroptotic activities, and compound 42 showed >60-fold selectivity for RIPK3 than RIPK1. It blocked necrosome formation by specifically inhibiting the phosphorylation of RIPK3 in necroptotic cells. In a tumor necrosis factor-induced systemic inflammatory response syndrome model, it significantly protected mice from hypothermia and death at a dose of 5 mg/kg, which was much more effective than TAK-632. Moreover, it showed favorable and druglike pharmacokinetic properties in rats with an oral bioavailability of 25.2%. Thus, these RIPK3-targeting small molecules represent promising lead structures for further development.

BENZOTHIAZOLE DERIVATIVES AS ANTICANCER AGENTS

Provided is a fused heterocycle derivative showing a strong Raf inhibitory activity. A compound represented by the formula (I) wherein each symbol is as defined in the present specification, or a salt thereof.