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602306-29-6 molecular structure
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N-(4-methanesulfonylphenyl)-4-[2-methyl-1-(propan-2-yl)-1H-imidazol-5-yl]pyrimidin-2-amine

ChemBase ID: 73096
Molecular Formular: C18H21N5O2S
Molecular Mass: 371.45664
Monoisotopic Mass: 371.14159594
SMILES and InChIs

SMILES:
c1c(ccc(c1)Nc1nccc(n1)c1cnc(n1C(C)C)C)S(=O)(=O)C
Canonical SMILES:
CC(n1c(C)ncc1c1ccnc(n1)Nc1ccc(cc1)S(=O)(=O)C)C
InChI:
InChI=1S/C18H21N5O2S/c1-12(2)23-13(3)20-11-17(23)16-9-10-19-18(22-16)21-14-5-7-15(8-6-14)26(4,24)25/h5-12H,1-4H3,(H,19,21,22)
InChIKey:
WJRRGYBTGDJBFX-UHFFFAOYSA-N

Cite this record

CBID:73096 http://www.chembase.cn/molecule-73096.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
N-(4-methanesulfonylphenyl)-4-[2-methyl-1-(propan-2-yl)-1H-imidazol-5-yl]pyrimidin-2-amine
IUPAC Traditional name
4-(3-isopropyl-2-methylimidazol-4-yl)-N-(4-methanesulfonylphenyl)pyrimidin-2-amine
Synonyms
AZD 5438
AZD5438
4-(2-methyl-1-isopropyl-1h-imidazol-5-yl)-n-(4-(methylsulfonyl)phenyl)-2-pyrimidinamine
CAS Number
602306-29-6
PubChem SID
162038016
PubChem CID
16747683

DATA SOURCES

DATA SOURCES

All Sources Commercial Sources Non-commercial Sources
Data Source Data ID
PubChem 16747683 external link

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem
Acid pKa 11.680515  H Acceptors
H Donor LogD (pH = 5.5) 1.3089852 
LogD (pH = 7.4) 1.936156  Log P 1.9634863 
Molar Refractivity 101.2594 cm3 Polarizability 40.21276 Å3
Polar Surface Area 89.77 Å2 Rotatable Bonds
Lipinski's Rule of Five true 

PROPERTIES

PROPERTIES

Safety Information Pharmacology Properties Product Information Bioassay(PubChem)
Storage Condition
-20°C expand Show data source
Target
CDK expand Show data source
Purity
97% expand Show data source
Salt Data
Free Base expand Show data source

DETAILS

DETAILS

Selleck Chemicals Selleck Chemicals
Selleck Chemicals - S2621 external link
Research Area
Description Cancer
Biological Activity
Description AZD5438 is a potent inhibitor of CDK1, CDK2 and CDK9 with IC50 of 16 nM, 6 nM, and 20 nM, respectively.
Targets CDK1 CDK2 CDK9
IC50 16 nM [1] 6 nM [1] 20 nM [1]
In Vitro AZD5438 exhibits the potent inhibitory effect on activity of cyclin-dependent kinases including cyclin E-cdk2, cyclin A-cdk2, cyclin B1-cdk1, cyclin D3-cdk6, and cyclin T-cdk9 with IC50 of 6 nM, 45 nM, 16 nM, 21 nM, and 20 nM, respectively. Besides, AZD5438 also inhibits the kinase activity of p25-cdk5 and glycogen synthase kinase 3β with IC50 of 14 nM and 17 nM, respectively. [1] AZD5438 induces cell cycle arrest by inhibiting phosphorylation of cdk-dependent substrates, and exhibits the broad antiproliferative activity against a range of tumor cell lines including lung, colorectal, breast, prostate, and hematologic tumors with IC50 ranging from 0.2 μM (MCF-7) to 1.7 μM (ARH-77). [1]
In Vivo In vivo, oral treatment of AZD5438 leads to statistically significant inhibition against the growth of human tumor xenografts derived from a wide range of different cancer types including breast, colon, lung, prostate, and ovarian with maximum TGI ranging from 38% to 153%. [1] In the SW620 xenograft model, AZD5438 causes the inhibition of several cell cycle proteins such as, phH3, phosphonucleolin, PP1a, and several phospho-pRb epitopes in a dose-dependent manner. [1]
Clinical Trials Study on AZD5438 has been completed in Phase I clinical trials in patients with Advanced Solid Malignancies.
Features AZD5438 is a potent inhibitor of cyclin-dependent kinase (cdk) 1, 2, and 9.
Protocol
Cell Assay [1]
Cell Lines MCF-7, HCT-116, A549, and IM-9
Concentrations 0 to 10 μM
Incubation Time 48 hours or 72 hours
Methods AZD5438 is tested against solid tumor cell lines. Briefly, cells are incubated for 48 hours with AZD5438 at a range of concentrations. At the end of incubation, the cells are pulsed with 5-bromo-2′-deoxyuridine (BrdUrd) and the amount of DNA synthesis is measured. The IC50 for inhibition of proliferation is specifically determined independently of cell death. Multiple myeloma cell lines are seeded into 96-well plates in RPMI 1640 supplemented with 10% FCS and glutamine and dosed with AZD5438 for 72 hours. Cell growth is measured using AlamarBlue and GI50 values are calculated with reference to pretreatment control values.
Animal Study [1]
Animal Models MCF-7, HCT-116, A549, and IM-9 cells are injected s.c. into the Swiss nude mice and nude rats.
Formulation AZD5438 is dissolved in hydroxy-propyl-methyl-cellulose.
Doses ≤100 mg/kg
Administration Administered via p.o.
References
[1] Byth KF, et al. Mol Cancer Ther. 2009, 8(7), 1856-1866.

REFERENCES

REFERENCES

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PATENTS

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