877665-34-4

Basic information

• Product Name: Cyclohexanecarboxylic acid, 4-[[(2S,5S)-1-[[7-fluoro-2-[(5-fluoro-2-methylphenyl)amino]-6-benzoxazol yl]acetyl]-5-(2-isoxazolidinylmethyl)-2-pyrrolidinyl]methoxy]-, trans-
• CAS NO: 877665-34-4
• Molecular Formula: C32H38F2N4O6
• Molecular Weight: 612.674
• Mol File: 877665-34-4.mol
• Article Data: 1

Chemical Properties

• CAS DataBase Reference: Cyclohexanecarboxylic acid, 4-[[(2S,5S)-1-[[7-fluoro-2-[(5-fluoro-2-methylphenyl)amino]-6-benzoxazol yl]acetyl]-5-(2-isoxazolidinylmethyl)-2-pyrrolidinyl]methoxy]-, trans-(CAS DataBase Reference)
• NIST Chemistry Reference: Cyclohexanecarboxylic acid, 4-[[(2S,5S)-1-[[7-fluoro-2-[(5-fluoro-2-methylphenyl)amino]-6-benzoxazol yl]acetyl]-5-(2-isoxazolidinylmethyl)-2-pyrrolidinyl]methoxy]-, trans-(877665-34-4)
• EPA Substance Registry System: Cyclohexanecarboxylic acid, 4-[[(2S,5S)-1-[[7-fluoro-2-[(5-fluoro-2-methylphenyl)amino]-6-benzoxazol yl]acetyl]-5-(2-isoxazolidinylmethyl)-2-pyrrolidinyl]methoxy]-, trans-(877665-34-4)

Safety Data

• Hazardous Substances Data: 877665-34-4(Hazardous Substances Data)

Upstream product

• 877665-36-6 ethyl trans-4-[1-[[7-fluoro-2-(5-fluoro-2-methylphenylamino)-6-benzoxazolyl]acetyl]-(5S)-(1-isoxazolidinylmethyl)-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylate 
• 877665-35-5 ethyl trans-4-[1-tert-butoxycarbonyl-(5S)-(1-isoxazolidinylmethyl)-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylate 
• 877664-92-1 ehyl trans-4-[1-tert-butoxycarbonyl-(5S)-formyl-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylate 
• 1416961-17-5 ethyl 4-[(5S)-benzyloxymethyl-1-tert-butoxycarbonyl-(2S)-pyrrolidinylmethoxy]benzoate 
• 138528-06-0 (2S,5S)-5-benzyloxymethyl-1-tert-butoxycarbonyl-2-hydroxymethylpyrrolidine 

Relevant articles and documents

A novel, potent, and orally active VLA-4 antagonist with good aqueous solubility: Trans-4-[1-[[2-(5-Fluoro-2-methylphenylamino)-7-fluoro-6- benzoxazolyl]acetyl]-(5S)-[methoxy(methyl)amino]methyl-(2S)-pyrrolidinylmethoxy] cyclohexanecarboxylic acid

We have carried out the optimization of substituents at the C-3 or the C-5 position on the pyrrolidine ring of VLA-4 antagonist 3 with 2-(phenylamino)-7- fluorobenzoxazolyl moiety for the purpose of improving in vivo efficacy while maintaining good aqueous solubility. As a result, we successfully increased in vitro activity in the presence of 3% human serum albumin and achieved an exquisite lipophilic and hydrophilic balance of compounds suitable for oral administrative regimen. The modification resulted in the identification of zwitterionic compound 7n with (5S)-[methoxy(methyl)amino]methylpyrrolidine, which significantly alleviated bronchial hyper-responsiveness to acetylcholine chloride at 12.5 mg/kg, p.o. in a murine asthma model and showed favorable aqueous solubility (JP1, 89 μg/mL; JP2, 462 μg/mL). Furthermore, this compound showed good oral bioavailability (F = 54%) in monkeys.