138449-07-7

Basic information

• Product Name: FK 888
• Synonyms: N2-[(4R)-4-hydroxyl-1-(1-methyl-1H-indol-3-yl)carbonyl-L-prolyl]-N-methyl-N-phenylmethyl-3-(2-naphthyl)-L-alaninamide hydrate;FK 888;L-Alaninamide, (4R)-4-hydroxy-1-((1-methyl-1H-indol-3-yl)carbonyl)-L-prolyl-N-methyl-3-(2-naphthalenyl)-N-(phenylmethyl)-;L-Alaninamide, trans-4-hydroxy-1-((1-methyl-1H-indol-3-yl)carbonyl)-L-prolyl-N-methyl-3-(2-naphthalenyl)-N-(phenylmethyl)-;N(2)-(4-Hydroxy-1-(1-methyl-1H-indol-3-yl)carbonyl-L-prolyl)-N-methyl-N-phenylmethyl-3-(2-naphthyl)-L-alaninamide;(4R)-4-Hydroxy-1-[(1-methyl-1H-indol-3-yl)carbonyl]-L-prolyl-N-methyl-3-(2-naphthalenyl)-N-(phenylmethyl)-L-alaninamide;(4R)-4-Hydroxy-1-[(1-methyl-1H-indol-3-yl)carbonyl]-L-prolyl-N-methyl-3-(2-naphthalenyl)-N-(phenylmethyl)-L-alaninamide hydrate;FK888 hydrate
• CAS NO: 138449-07-7
• Molecular Formula: C₃₆H₃₆N₄O₄
• Molecular Weight: 588.704
• Mol File: 138449-07-7.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 901.9°Cat760mmHg
• Flash Point: 499.2°C
• Appearance: white to tan/
• Density: 1.26g/cm³
• Vapor Pressure: 5.08E-35mmHg at 25°C
• Refractive Index: 1.658
• Storage Temp.: Store at -20°C
• Solubility: DMSO: ≥13mg/mL
• PKA: 13.01±0.40(Predicted)
• CAS DataBase Reference: FK 888(CAS DataBase Reference)
• NIST Chemistry Reference: FK 888(138449-07-7)
• EPA Substance Registry System: FK 888(138449-07-7)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 138449-07-7(Hazardous Substances Data)

Usage

Uses

FK 888 is a neurokinin NK1 receptor antagonist, which is active both in vivo and in vitro.

Biological Activity

Selective, high affinity tachykinin NK 1 receptor antagonist (K i = 0.69 nM) that displays 320-fold selectivity for human over rat NK 1 receptors. Inhibits substance P-induced contraction of isolated guinea pig trachea (IC 50 = 32 nM) and inhibits substance P-induced airway constriction in vivo following i.v. and oral administration.

InChI:InChI=1/C36H36N4O4/c1-38-23-30(29-14-8-9-15-32(29)38)35(43)40-22-28(41)20-33(40)34(42)37-31(36(44)39(2)21-24-10-4-3-5-11-24)19-25-16-17-26-12-6-7-13-27(26)18-25/h3-18,23,28,31,33,41H,19-22H2,1-2H3,(H,37,42)/t28-,31+,33+/m1/s1

Upstream product

• 32387-21-6 1-methyl-3-indolecarboxylic acid 
• 138449-25-9 Boc-(2S,4R)-Hyp-L-Nap-NMeBzl 
• 138449-24-8 BOC-(S)-3-(2-naphthyl)alanyl-N-benzyl-N-methylamide 
• 103-67-3 benzyl-methyl-amine 
• 56583-58-5 N-tert-butoxycarbonyl-3-(2-naphthyl)-L-alanine 
• 13726-69-7 (2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid 

Relevant articles and documents

Studies of Neurokinin Antagonists. 4. Synthesis and Structure-Activity Relationships of Novel Dipeptide Substance P Antagonists: N2--L-prolyl>-N-methyl-N-(phenylmethyl)-3-(2-naphthyl)-L-alaninamide and Its Related Compounds

As an extension of our studies on discovering a novel substance P (SP) antagonist, we modified the previously reported dipeptide, N2-2-(1H-indol-3-ylcarbonyl)-L-lysyl>-N-methyl-N-(phenylmethyl)-L-phenylalaninamide (2b).The lysine part in 2b was first optimized to a (2S,4R)-hydroxyproline derivative (3h), which is 2-fold more potent than 2b in SP binding assay using guinea pig lung membranes.Next we modified the 1H-indol-3-ylcarbonyl part in 3h.Introduction of a methyl group at the indole nitrogen enhanced the oral activity, while retaining the binding activity.Finally, we modified the phenylalanine part to culminate in the most potent compound 7k (FK888), which is a potent SP antagonist with NK1 selectivity as well as oral activity.