372988-91-5

Basic information

• Product Name: 2-Pentenoic acid, 5-(3,4-dichlorophenyl)-4-[[(1,1-dimethylethoxy)carbonyl]methylamino]-, (2E)-
• CAS NO: 372988-91-5
• Molecular Formula: C17H21Cl2NO4
• Molecular Weight: 374.264
• Mol File: 372988-91-5.mol
• Article Data: 2

Chemical Properties

• CAS DataBase Reference: 2-Pentenoic acid, 5-(3,4-dichlorophenyl)-4-[[(1,1-dimethylethoxy)carbonyl]methylamino]-, (2E)-(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Pentenoic acid, 5-(3,4-dichlorophenyl)-4-[[(1,1-dimethylethoxy)carbonyl]methylamino]-, (2E)-(372988-91-5)
• EPA Substance Registry System: 2-Pentenoic acid, 5-(3,4-dichlorophenyl)-4-[[(1,1-dimethylethoxy)carbonyl]methylamino]-, (2E)-(372988-91-5)

Safety Data

• Hazardous Substances Data: 372988-91-5(Hazardous Substances Data)

Upstream product

• 66130-90-3 diethyl <<(trimethylsilyl)oxy>carbonyl>methanephosphonate 
• 372988-90-4 [1-(3,4-dichlorobenzyl)-2-oxoethyl]methylcarbamic acid tert-butyl ester 
• 18880-04-1 3,4-dichlorobenzyl bromide 
• 42492-57-9 methyl 2-((tert-butoxycarbonyl)(methyl)amino)acetate 
• 372988-89-1 2-(tert-butoxycarbonylmethylamino)-3-(3,4-dichlorophenyl)propionic acid methyl ester 

Downstream Products

• 583028-46-0 [(E)-(R)-1-(3,4-dichlorobenzyl)-3-((R)-2-oxoazepan-3-ylcarbamoyl)allyl]methylcarbamic acid tert-butyl ester 
• 372988-92-6 [(E)-1-(3,4-dichlorobenzyl)-3-((S)-2-oxoazepan-3-ylcarbamoyl)allyl]methylcarbamic acid tert-butyl ester 
• 398507-81-8 DNK 333 
• 372988-88-0 (E)-5-(3,4-dichlorophenyl)-4-methylaminopent-2-enoic acid (S)-(2-oxoazepan-3-yl)amide 
• 583028-47-1 (E)-(R)-5-(3,4-dichlorophenyl)-4-methylaminopent-2-enoic acid (R)-(2-oxoazepan-3-yl)amide 

Relevant articles and documents

Stereoselective preparation of N-[(R,R)-(E)-1-(3,4-dichlorobenzyl)-3-(2-oxoazepan-3-yl)carbamoyl]allyl- N-methyl-3,5-bis(trifluoromethyl)benzamide, a potent and orally active dual neurokinin NK1/NK2 receptor antagonist

In a program aimed at the development of neurokinin antagonists, N-[(R,R)-(E)-1-(3,4-dichloro-benzyl)-3-(2-oxoazepan-3-yl)carbamoyl]allyl- N-methyl-3,5-bis(trifluoromethyl)benzamide (1, DNK333) has been discovered as a potent and balanced neurokinin (tachykinin) NK1/NK2 receptor antagonist. Enantiomerically pure (>99.5% ee) 1 can be prepared in 6 + 1 synthetic steps starting from commercially available optically active BOC-D-3,4-dichlorophenylalanine in an overall yield of ca. 25-30%. 1 showed potent affinities to cloned human NK1 (pKi = 8.38) and NK2 (pKi = 8.02) receptors. When 1 was compared to the other possible three diastereoisomers, it could be demonstrated that only the R,R-isomer (1) exhibits potent and balanced affinity for the cloned human NK1 and NK2 receptors. 1 exhibited favorable pharmacokinetic properties in guinea pigs following oral administration and demonstrated in vivo activity in pharmacological models of substance P- and neurokinin A (NKA)-induced bronchoconstriction in guinea pigs after intravenous and in squirrel monkeys after oral application.