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, also known as CP-868569, is a highly selective and potent inhibitor of platelet-derived growth factor receptor (PDGFR) alpha and beta, as well as Fms-related tyrosine kinase 3 (FLT3). It is a type I inhibitor that binds only to the active kinase conformation, showing nanomolar potencies against these targets. Crenolanib is an orally bioavailable drug with more than 100-fold selectivity for these kinases over other tyrosine and serine/threonine kinases.

Uses

Used in Oncology:
Crenolanib is used as an antineoplastic agent for the treatment of various cancers. It acts by specifically inhibiting the receptor tyrosine kinases PDGFRα and PDGFRβ, as well as FLT3, which are often implicated in tumor angiogenesis and tumor cell proliferation. Crenolanib is believed to suppress PDGFR-related signal transduction pathways, leading to the inhibition of these processes and potentially reducing tumor growth and progression.
Used in Targeted Cancer Therapy:
Crenolanib is used as a targeted cancer therapy agent for the treatment of imatinib-resistant PDGFRα mutations, such as D842I, D842V, D842Y, DI842-843M, and deletion I8432, as well as FLT3/ITD and FLT3/D835 mutants. Its high selectivity and potency make it a promising candidate for the treatment of cancers driven by these mutations.
Used in Combination Therapy:
Crenolanib is used in combination therapy with other treatments, such as FLT3-CAR T-cells, to enhance the therapeutic effects against certain cancers. In a FLT3-ITD+ AML murine xenograft model, Crenolanib has been shown to act synergistically with FLT3-CAR T-cells, potentially improving treatment outcomes for patients with these types of cancers.

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

• 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 
• 3143-02-0 3-hydroxymethyl-3-methyloxethane 
• 89-63-4 4-Chloro-2-nitroaniline 
• 41292-65-3 5-hydroxy-1H-benzimidazole 
• 31568-91-9 2-chloroquinolin-8-ol 

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.

Synthesis method of drug for treating leukemia

The invention relates to a synthesis method of a drug for treating leukemia. The synthesis method comprises that 1, a compound 3-methyl-3-oxetanemethanol and sodium metal undergo a reaction to produce 3-sodium methoxide-3-methyl-3-oxetane, 2, 4-amino-3-nitrochlorobenzene is added into the product obtained by the step 1 so that reddish-orange solids (A1) are obtained, a compound 8-benzyloxyquinolin-2-chlorine and A1 undergo a reaction to produce orange solids A2, 3, the compounds A2, 13g of palladium/carbon and formic acid undergo a reaction, formamidine acetate is added into the reaction product, and the mixture is subjected to reflux and drying so that white-like (or yellow) solids A3 are obtained, and 4, the compounds A3 and benzenesulfonyl chloride undergo a reaction, the product is dried to form maize-yellow solids A4, BINAP, A4, tert-butyl piperidin-4-yl-carbamate and potassium carbonate undergo a reaction, the reaction product is dried to form A5, and the A5 is refined through the step 5 so that a pure product is obtained. In the steps 1 and 2, a one-pot method is used.