670220-88-9

Basic information

• Product Name: Crenolanib
• Synonyms: Crenolanib;[1-[2-[5-(3-Methyloxetan-3-ylMethoxy)benziMidazol-1-yl]quinolin-8-yl]piperidin-4-yl]aMine;1-[2-[5-[(3-Methyl-3-oxetanyl)Methoxy]-1H-benziMidazol-1-yl]-8-quinolinyl]-4-piperidinaMine;ARO 002;CP 868596;Crenolanib (CP-868569);Crenolanib (CP-868596);CP868569/Crenolanib
• CAS NO: 670220-88-9
• Molecular Formula: C₂₆H₂₉N₅O₂
• Molecular Weight: 443.54076
• Product Categories: Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Tyrosine Kinase Inhibitors;Inhibitors
• Mol File: 670220-88-9.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 676.6±65.0 °C(Predicted)
• Appearance: /
• Density: 1.36
• Storage Temp.: -20°
• Solubility: Soluble in DMSO (up to 15 mg/ml) or in Ethanol (up to 10 mg/ml).
• PKA: 9.84±0.20(Predicted)
• Stability: Stable for 1 year as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 1 month.
• CAS DataBase Reference: Crenolanib(CAS DataBase Reference)
• NIST Chemistry Reference: Crenolanib(670220-88-9)
• EPA Substance Registry System: Crenolanib(670220-88-9)

Safety Data

• Hazardous Substances Data: 670220-88-9(Hazardous Substances Data)

Usage

Description

Crenolanib (670220-88-9) is a potent inhibitor of PDGFR (Kd?for α = 2.1 nM; β = 3.2 nM) and FLT3 (Kd?= 0.74 nM).1?Crenolanib is a type I inhibitor binding only to the active kinase conformation. It showed potent activity against imatinib-resistant PDGFRα mutations D842I, D842V, D842Y, DI842-843M, and deletion I8432?as well as FLT3/ITD and FLT3/D835 mutants3. Crenolanib acted synergistically with FLT3-CAR T-cells in a FLT3-ITD+?AML murine xenograft model.4

Uses

Different sources of media describe the Uses of 670220-88-9 differently. You can refer to the following data:
1. Crenolanib (CP-868569) is a highly selective and potent PDGFR-α inhibitor with IC50 of 0.9 and 1.8 nM against PDGFRα and PDGFRβ, respectively.
2. Crenolanib (CP-868569) is a tyrosine kinase inhibitor that acts by specifically inhibiting the receptor tyrosine kinases PDGFRα and PDGFRβ. Crenolanib (CP-868569) inhibits the activity of PDGFRα D842V kinase and prevented the phosphorylation of wild type PDGFRα. Crenolanib (CP-868569) possesses potential antineoplastic activity. Crenolanib is believed to suppress PDGFR-related signal transduction pathways leading to the inhibition of tumor angiogenesis and tumor cell proliferation.
3. Crenolanib is an orally bioavailable, selective inhibitor of type III tyrosine kinases with nanomolar potencies against platelet-derived growth factor receptor α (PDGFRα) and PDGFRβ and Fms-related tyrosine kinase 3 (FLT3; IC50s = 11, 3.2, and 4 nM, respectively). It also inhibits medically-relevant mutant forms of these kinases, including the D842V-containing form of PDGFR and D835Y and internal tandem duplication mutations of FLT3, at nanomolar concentrations. Crenolanib is more than 100-fold selective for these kinases over other tyrosine and serine/threonine kinases. It is effective when used in cells and in vivo.[Cayman Chemical]

References

1) Lewis?et al.?(2009)?Phase I study of the safety, tolerability, and pharmacokinetics of oral CP-868,596, a highly specific platelet-derived growth factor receptor tyrosine kinase inhibitor in patients with advanced cancers; J. Clin. Oncol.?27?5262 2) Smith?et al.?(2014)?Crenolanib is a selective type I pan-FLT3 inhibitor; Proc. Natl. Acad. Sci. USA?111?5319 3) Heinrich?et al.?(2012)?Crenolanib Inhibits Drug-Resistant PDGFRA D842V Mutation Associated with Imatinib-Resistant Gastrointestinal Stromal Tumors; Clin. Cancer Res.?18?4375 4) Jetani?et al.?(2018)?CAR T-cells targeting FLT3 have potent activity against FLT-ITD+ AML and act synergistically with the FLT3-inhibitor crenolanib; Leukemia?32?1168

Upstream product

• 31568-91-9 2-chloroquinolin-8-ol 
• 41292-65-3 5-hydroxy-1H-benzimidazole 
• 89-63-4 4-Chloro-2-nitroaniline 
• 3143-02-0 3-hydroxymethyl-3-methyloxethane 
• 816463-40-8 tert-butyl N-[1-(2-{5-[(3-methyloxetan-3-yl)methoxy]-1H-1,3-benzodiazol-1-yl}quinolin-8-yl)piperidin-4-yl]carbamate 

Downstream Products

• 670220-93-6 crenolanib besylate 

Relevant articles and documents

Preparation method of anticancer drug

The invention relates to a preparation method of an anticancer drug. The anticancer drug is Crenolanib. The preparation method comprises the following steps: taking 2-chlo-8-hydroxyquinoline as a rawmaterial, reacting with trifluoromethanesulfonyl chloride, condensing, dehydrating, performing dehydrochlorination, and performing deprotection to obtain the anticancer drug. Compared with an existingCrenolanib production technology, the preparation method has the characteristics that processes are simple and easy, the purity is high, the yield is high, the processes are short, materials are easyto obtain and low in price, the cost is low, the operation is safe and the like; the industrial production can be conveniently carried out; and technical foundation is supplied for massive productionof the drug and structure-like drugs.

Preparation method of drug for treating leukemia

The invention relates to a preparation method of a drug for treating leukemia. The preparation method comprises 1, preparation of 2-chloro-8-trifluoromethylsulfonyl quinoline, 2, preparation of 2-chloro-8-(piperidin-4-yl)quinolin-carbamic acid tert-butyl ester, 3, preparation of 5-(3-methyl-oxetan-3-methoxy)benzimidazole, 4, preparation of (1-{2-[5-(3-methyl-oxetan-3-yl-methoxy)-benzimidazole-1-yl]-quinolin-8-yl}-piperidin-4-yl-carbamic acid tert-butyl ester, and 5, preparation of (1-{2-[5-(3-methyl-oxetan-3-yl-methoxy)-benzimidazole-1-yl]-quinolin-8-yl}-4-aminopiperidine.