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877399-52-5 molecular structure
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3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]pyridin-2-amine

ChemBase ID: 6303
Molecular Formular: C21H22Cl2FN5O
Molecular Mass: 450.3366832
Monoisotopic Mass: 449.11854393
SMILES and InChIs

SMILES:
Clc1ccc(F)c(c1[C@@H](C)Oc1cc(cnc1N)c1cnn(c1)C1CCNCC1)Cl
Canonical SMILES:
Nc1ncc(cc1O[C@@H](c1c(Cl)ccc(c1Cl)F)C)c1cnn(c1)C1CCNCC1
InChI:
InChI=1S/C21H22Cl2FN5O/c1-12(19-16(22)2-3-17(24)20(19)23)30-18-8-13(9-27-21(18)25)14-10-28-29(11-14)15-4-6-26-7-5-15/h2-3,8-12,15,26H,4-7H2,1H3,(H2,25,27)/t12-/m1/s1
InChIKey:
KTEIFNKAUNYNJU-GFCCVEGCSA-N

Cite this record

CBID:6303 http://www.chembase.cn/molecule-6303.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]pyridin-2-amine
IUPAC Traditional name
crizotinib
Synonyms
3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)pyridin-2-amine
(R)-3-(1-(2,6-Dichloro-3-fluorophenyl)ethoxy)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-amine
PF-02341066
Crizotinib
PF-2341066
(R)-3-[1-(2,6-Dichloro-3-fluoro-phenyl)-ethoxy]-5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-pyridin-2-ylamine
PF 2341066
PF02341066
Xalkori
Crizotinib
CAS Number
877399-52-5
MDL Number
MFCD12407409
PubChem SID
160969694
PubChem CID
11626560

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem ALOGPS 2.1
H Acceptors H Donor
LogD (pH = 5.5) -0.118933685  LogD (pH = 7.4) 0.9544419 
Log P 3.5741167  Molar Refractivity 128.4316 cm3
Polarizability 45.653618 Å3 Polar Surface Area 77.99 Å2
Rotatable Bonds Lipinski's Rule of Five true 
Log P 3.82  LOG S -4.87 
Solubility (Water) 6.11e-03 g/l 

PROPERTIES

PROPERTIES

Physical Property Safety Information Pharmacology Properties Product Information Bioassay(PubChem)
Solubility
DMSO expand Show data source
Apperance
white to tan powder expand Show data source
Storage Condition
-20°C expand Show data source
Storage Warning
IRRITANT expand Show data source
MSDS Link
Download expand Show data source
Download expand Show data source
TSCA Listed
false expand Show data source
Storage Temperature
room temp expand Show data source
Target
ALK expand Show data source
c-Met expand Show data source
Purity
≥98% (HPLC) expand Show data source
95% expand Show data source
Salt Data
Free Base expand Show data source
Empirical Formula (Hill Notation)
C21H22Cl2FN5O expand Show data source

DETAILS

DETAILS

DrugBank DrugBank Selleck Chemicals Selleck Chemicals Sigma Aldrich Sigma Aldrich
DrugBank - DB08700 external link
Drug information: experimental
Selleck Chemicals - S1068 external link
Research Area
Description Cancer
Protocol
Kinase Assay [1]
Biochemical kinase assays c-Met catalytic activity is quantitated using a continuous-coupled spectrophotometric assay in which the time-dependent production of ADP by c-Met is determined by analysis of the rate of consumption of NADH. NADH consumption is measured by a decrease in absorbance at 340 nm by spectrophotometry at designated time points. To determine Ki values, PF-2341066 is introduced into test wells at various concentrations in the presence of assay reagents and incubated for 10 minutes at 37 °C. The assay is initiated by the addition of the c-Met enzyme.
Cell Assay [1]
Cell Lines GTL-16 gastric carcinoma cells and T47D breast carcinoma cells
Concentrations 0-256 nM
Incubation Time 1 hour
Methods Cells including GTL-16 gastric carcinoma cells and T47D breast carcinoma cells are seeded in 96-well plates in media supplemented with 10% fetal bovine serum (FBS) and transferred to serum-free media [with 0.04% bovine serum albumin (BSA)] after 24 hours. In experiments investigating ligand-dependent RTK phosphorylation, corresponding growth factors are added for up to 20 minutes. After incubation of cells with PF-2341066 for 1 hour and/or appropriate ligands for the designated times, cells are washed once with HBSS supplemented with 1 mM Na3VO4, and protein lysates are generated from cells. Subsequently, phosphorylation of selected protein kinases is assessed by a sandwich ELISA method using specific capture antibodies used to coat 96-well plates and a detection antibody specific for phosphorylated tyrosine residues. Antibody-coated plates are (a) incubated in the presence of protein lysates at 4 °C overnight; (b) washed seven times in 1% Tween 20 in PBS; (c) incubated in a horseradish peroxidase–conjugated anti–total-phosphotyrosine (PY-20) antibody (1:500) for 30 min; (d) washed seven times again; (e) incubated in 3,3,5,5-tetramethyl benzidine peroxidase substrate to initiate a colorimetric reaction that is stopped by adding 0.09 N H2SO4; and (f) measured for absorbance in 450 nm using a spectrophotometer.
Animal Study [1]
Animal Models Female or male nu/nu mice bearing NCI-H441,or DLD-1, or MDA-MB-231
Formulation
Doses 12.5 mg/kg/day, 25 mg/kg/day, and 50 mg/kg/day
Administration Administered via p.o.
References
[1] Zou HY, et al. Cancer Res. 2007, 67(9), 4408-4417.
[2] Christensen JG, et al. Mol Cancer Ther. 2007, 6(12 Pt 1), 3314-3322.
[3] Sampson ER, et al. J Bone Miner Res. 2011, 26(6), 1283-1294.
[4] Cullinane C, et al. J Nucl Med. 2011, 52(8), 1261-1267.
[5] Gong HC, et al. Int J Proteomics. 2011, 2011, 215496.
Sigma Aldrich - PZ0191 external link
Legal Information
Sold for research purposes under agreement from Pfizer Inc.
Biochem/physiol Actions
Crizotinib (PF-02341066) is an ATP-competitive inhibitor of the receptor tyrosine kinases (RTKs) c-Met (hepatocyte growth factor receptor) and anaplastic lymphoma kinase (ALK). It is a highly specific inhibitor of c-Met and ALK among > 120 different RTKs surveyed. Crizotinib was recently approved for treatment of a subtype of nonsmall-cell lung cancer (NSCLC) with ALK fusion mutations.

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