180046-99-5

Basic information

• Product Name: 1-[[(2-NITROPHENYL)AMINO]CARBONYL]-L-PROLYL-N-METHYL-3-(2-NAPHTHALENYL)-N-(PHENYLMETHYL)-L-ALANINAMIDE
• Synonyms: 1-[[(2-NITROPHENYL)AMINO]CARBONYL]-L-PROLYL-N-METHYL-3-(2-NAPHTHALENYL)-N-(PHENYLMETHYL)-L-ALANINAMIDE;SDZ NKT 343
• CAS NO: 180046-99-5
• Molecular Formula: C₃₃H₃₃N₅O₅
• Molecular Weight: 579.64562
• Product Categories: Highly selective human tachykinin NK1 receptor antagonist .
• Mol File: 180046-99-5.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 892.8°Cat760mmHg
• Flash Point: 493.8°C
• Appearance: /
• Density: 1.327g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.676
• Storage Temp.: Store at +4°C
• PKA: 11.66±0.70(Predicted)
• CAS DataBase Reference: 1-[[(2-NITROPHENYL)AMINO]CARBONYL]-L-PROLYL-N-METHYL-3-(2-NAPHTHALENYL)-N-(PHENYLMETHYL)-L-ALANINAMIDE(CAS DataBase Reference)
• NIST Chemistry Reference: 1-[[(2-NITROPHENYL)AMINO]CARBONYL]-L-PROLYL-N-METHYL-3-(2-NAPHTHALENYL)-N-(PHENYLMETHYL)-L-ALANINAMIDE(180046-99-5)
• EPA Substance Registry System: 1-[[(2-NITROPHENYL)AMINO]CARBONYL]-L-PROLYL-N-METHYL-3-(2-NAPHTHALENYL)-N-(PHENYLMETHYL)-L-ALANINAMIDE(180046-99-5)

Safety Data

• Hazardous Substances Data: 180046-99-5(Hazardous Substances Data)

Usage

Uses

SDZ NKT 343 is a potent human NK1 tachykinin receptor antagonist.

Biological Activity

Highly selective human tachykinin NK 1 receptor antagonist (IC 50 values are 0.62 and 451 nM for human and rat receptors respectively) that displays > 130-fold selectivity over human NK 2 and NK 3 receptors. Potently antagonizes SP-induced Ca 2+ efflux in vitro and inhibits mechanical hyperalgesia in vivo .

InChI:InChI=1/C33H33N5O5/c1-36(22-23-10-3-2-4-11-23)32(40)28(21-24-17-18-25-12-5-6-13-26(25)20-24)34-31(39)30-16-9-19-37(30)33(41)35-27-14-7-8-15-29(27)38(42)43/h2-8,10-15,17-18,20,28,30H,9,16,19,21-22H2,1H3,(H,34,39)(H,35,41)/t28-,30-/m0/s1

Upstream product

• 3320-86-3 2-nitrophenyl isocyanate 
• 171856-36-3 (S)-3-(2-naphthyl)alanyl-N-benzyl-N-methylamide 
• 543-27-1 isobutyl chloroformate 
• 147-85-3 L-proline 

Downstream Products

• 212700-46-4 (S)-Pyrrolidine-1,2-dicarboxylic acid 1-[(2-amino-phenyl)-amide] 2-{[(S)-1-(benzyl-methyl-carbamoyl)-2-naphthalen-2-yl-ethyl]-amide} 

Relevant articles and documents

Process development of (2-nitrophenylcarbamoyl)-(S)-prolyl-(S)-3-(2-naphthyl)alanyl-n-benzyl-n- methylamide (SDZ NKT343)

(2-Nitrophenylcarbamoyl)-(S)-prolyl-(S)-3-(2-naphthyl)alanyl-N-benzyl-N- methylamide (1; SDZ NKT343) is a human NK-1 tachykinin receptor antagonist. The development of a robust process for a multikilogram scale, chromatography-free preparation of this compound is described. The new four-step synthesis was based on a convergent approach, which utilized a peptide coupling of 1-[(2-nitrophenylamino)carbonyl]-L-proline (11) with free base of (S)-3-(2-naphthyl)alanyI-N-benzyl-N-methylamide hydrochloride (4) as the key step in the presence of 1,3-dicyclohexylcarbodiimide and 1-hydroxybenzotriazole as coupling agents. A scale-up of the well-known mixed anhydride coupling method, using isobutyl chloroformate, to produce 4 was found to be problematic due to coupling of the amine at the undesired carbonyl group of the mixed anhydride. This problem was overcome. The drug substance, initially an amorphous powder, was obtained with the desired purity without any chromatography. A process for crystallization of 1 was also developed.