943540-75-8

Basic information

• Product Name: J&J Ex-61
• Synonyms: J&J Ex-61;Quinoline, 6-[difluoro[6-(1-methyl-1H-pyrazol-4-yl)-1,2,4-triazolo[4,3-b]pyridazin-3-yl]methyl]-;6-[Difluoro[6-(1-methyl-1H-pyrazol-4-yl)-1,2,4-triazolo[4,3-b]pyridazin-3-yl]methyl]quinoline;JNJ-38877605;JNJ-33877605;6-[Difluoro[6-(1-methyl-1H-pyrazol-4-yl)-1,2,4-triazolo[4,3-b]pyridazin-3-yl]methyl]quinoline JNJ 38877605;JNJ 38877605 6-[Difluoro[6-(1-methyl-1H-pyrazol-4-yl)-1,2,4-triazolo[4,3-b]pyridazin-3-yl]methyl]quinoline;6-(Difluoro(6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]-triazolo[4,3-b]pyridazin-3-yl)methyl)quinolin
• CAS NO: 943540-75-8
• Molecular Formula: C19H13F2N7
• Molecular Weight: 377.357
• Product Categories: Inhibitors
• Mol File: 943540-75-8.mol
• Article Data: 2

Chemical Properties

• Appearance: /
• Density: 1.50
• Refractive Index: 1.733
• Solubility: insoluble in H2O; ≥18.85 mg/mL in DMSO; ≥3.25 mg/mL in EtOH with ultrasonic
• CAS DataBase Reference: J&J Ex-61(CAS DataBase Reference)
• NIST Chemistry Reference: J&J Ex-61(943540-75-8)
• EPA Substance Registry System: J&J Ex-61(943540-75-8)

Safety Data

• Hazardous Substances Data: 943540-75-8(Hazardous Substances Data)

Usage

Uses

JNJ-38877605 is a potent inhibitor of c-Met catalytic activity. Selective over other tyrosine and serine-threonine kinases (600-fold selectivity). Ability to block constitutive or HGF-stimulated phosphorylation of c-Met demonstrated in vitro. JNJ 38877605 reduces radiation-induced invasion, apoptosis and proliferation of cancer cells in vitro.

Biological Activity

jnj-38877605 is a small-molecule atp-competitive inhibitor of the catalytic activity of c-met.extensive evidence that c-met signaling is involved in the progression and spread of several cancers and an enhanced understanding of its role in disease have generated considerable interest in c-met and hgf asmajor targets in anti-cancer drug development.

in vitro

jnj-38877605 showed ~600-fold selectivity for c-met compared with a panel of ~250 diverse tyrosine and serine-threonine kinases and was found to potently inhibit hgf-stimulated and constitutively activated c-met phosphorylation in vitro [1].

in vivo

jnj-38877605 showed excellent oral bioavailability approaching 100% in all examined species. in addition, jnj-38877605 in a single dose was observed toinhibit met phosphorylation in tumor xenografts for up to16 h. inhibition of met phosphorylation was associated withdose-dependent tumor growth inhibition using a range of oral dosing regimens [2].

references

[1] pererat, l avrijssent, janssens b, et al. jnj-38877605: a selective met kinase inhibitor inducingregression of met-driven tumor models. presented at the 99th aacr annual meeting; 2008 apr 12 -16;

InChI:InChI=1/C19H13F2N7/c1-27-11-13(10-23-27)16-6-7-17-24-25-18(28(17)26-16)19(20,21)14-4-5-15-12(9-14)3-2-8-22-15/h2-11H,1H3

Upstream product

• 1093204-35-3 sodium 2,2-difluoro-2-(quinolin-6-yl)acetate 
• 1093204-33-1 tert-butyl 2-[6-(1-methyl-1H-pyrazol-4-yl)pyridazin-3-yl]hydrazinecarboxylate 
• 1093204-29-5 ethyl 2-oxo-2-(6-quinolyl)acetate 
• 943541-40-0 ethyl 2,2-difluoro-2-(quinolin-6-yl)acetate 
• 943541-20-6 3-chloro-6-(1-methyl-1H-pyrazol-4-yl)pyridazine 
• 13327-31-6 6-iodoquinoline 
• 5332-25-2 6-bromoquinoline 
• 943541-39-7 2,2-difluoro-2-(quinolin-6-yl)acetic acid hydrazide 

Relevant articles and documents

POLYMORPHIC AND HYDRATE FORMS, SALTS AND PROCESS FOR PREPARING 6-{DIFLUORO[6-(1-METHYL-1H-PYRAZOL-4-YL)[1,2,4]TRIAZOLO[4,3-B]PYRIDAZIN-3-YL]METHYL}QUINOLINE

The invention relates to novel polymorphic and hydrate forms and salts of 6-{difluoro[6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4,3-b]pyridazin-3-yl]methyl}quinoline, to methods for their preparation, to pharmaceutical compositions comprising at least one of said polymorphic or hydrate forms or salts, and to the therapeutic and/or prophylactic use of such compositions. The invention also provides new manners for preparing said compound.