915769-50-5

Basic information

• Product Name: Dovitinib
• Synonyms: dovitinib;4-Amino-5-fluoro-3-[6-(4-methyl-1-piperazinyl)-1H-benzimidazol-2-yl]-2(1H)-quinolinone 2-hydroxypropanoate hydrate (1:1:1);Unii-69vky8p7ea;Dovitinib lactate;Dovitinib lactate(TKI258);Propanoic acid, 2-hydroxy-, coMpd. with 4-aMino-5-fluoro-3-[6-(4-Methyl-1-piperazinyl)-1H-benziMidazol-2-yl]-2(1H)-quinolinone, hydrate (1:1:1);Propanoic acid, 2-hydroxy-, coMpd. with 4-aMino-5-fluoro-3-[6-(4-Methyl-1-piperazinyl)-1H-benziMidazol-2-yl]-2(1H)-quinolinone, hydrate;Dovitinib(C3H6O3：H20)=1：1：1
• CAS NO: 915769-50-5
• Molecular Formula: C₃H₆O₃*C₂₁H₂₁FN₆O*H₂O
• Molecular Weight: 500.5226632
• EINECS: 1308068-626-2
• Product Categories: Anti-cancer&immunity;Inhibitors
• Mol File: 915769-50-5.mol
• Article Data: 1

Chemical Properties

• Appearance: /
• Solubility: insoluble in EtOH; ≥10.62 mg/mL in DMSO; ≥168.2 mg/mL in H2O
• CAS DataBase Reference: Dovitinib(CAS DataBase Reference)
• NIST Chemistry Reference: Dovitinib(915769-50-5)
• EPA Substance Registry System: Dovitinib(915769-50-5)

Safety Data

• Hazardous Substances Data: 915769-50-5(Hazardous Substances Data)

Usage

Anticancer drugs

Dovitinib is an orally active small molecule multi-targeted tyrosine kinase inhibitor which can act directly on the tumor cells and provide nutritional support for blood vessels and stromal tumor cells, it has inhibition effect on a variety of growth factors such as VEGFR1-3, FGFR1-3, PDGFRB, e-KIT, Ret, TraA and csf-1. At present, Dovitinib is in clinical trail phase III ,clinical studies show that it has significant therapeutic effect on breast cancer, urinary tract carcinoma, prostate cancer, multiple myeloma, melanoma. With the development of clinical researches, cancer treatment is expected to expand its scope. Dovitinib performs its anti-tumor effects by anti-angiogenic activity and anti-proliferative survival activity . The drug is used for inoperable/local treatment of advanced hepatocellular carcinoma patients,it requires the lesion diameter greater than 1cm , blood, liver function is good, physical condition is good ,patients do not receive any systemic therapy (allow surgery 4 weeks outside and radiotherapy and intervention ). Preparation: use 5-chloro-2-nitroaniline and N-methyl piperazine as raw materials,after substitution,and reduction, form a ring with β-ethoxy-β-imino-propionate hydrochloride .Finally,after cyclization with 2-amino-6-fluorobenzonitrileto, generate Dovitinib , a total yield of 44.1%. The above information is edited by the lookchem of Tian Ye.

Uses

4-Amino-5-fluoro-3-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one 2-hydroxypropanoate hydrate is a useful research chemical compound.

Biological Activity

fibroblast growth factor receptor 1 (fgfr1) and fgfr2 amplifications are observed in approximately 10% of breast cancers and are related to poor outcomes. dovitinib (tki258) is an oral tyrosine kinase inhibitor (tki) against fgfr1–3, vegfr1–3, and platelet-derived growth factor receptor (pdgfr).

in vitro

dovitinib decreased the concentrations of pfrs2 and perk/mapk in a dose-dependent manner in fgfr1 amplified and fgfr2 amplified cell lines. the ic50 for cell growth inhibition was 190 and 180 nmol/l in mda-mb-134 and sum52, respectively. conversely, ic50 values were more than 2,000 nmol/l in the 11 breast cancer cell lines that had neither fgfr1 nor fgfr2 amplification [1].

in vivo

in vivo model (hbcx-2 breast cancer primary xenograft, with 8 fgfr1 gene copies), dovitinib prevented tumor growth at the 30 mg/kg dose and caused tumor regression at the 50 mg/kg dose. similarly, dovitinib caused tumor regression in hbcx-3 xenografts when administered at a dose of 40 mg/kg daily until day 35 [1].

IC 50

~10 nmol/l for fgfr1–3

references

[1] andré f, bachelot t, campone m, dalenc f, perez-garcia jm, hurvitz sa, turner n, rugo h, smith jw, deudon s, shi m, zhang y, kay a, porta dg, yovine a, baselga j. targeting fgfr with dovitinib (tki258): preclinical and clinical data in breast cancer. clin cancer res. 2013 jul 1;19(13):3693-702.

InChI:InChI=1/C21H21FN6O.C3H6O3.H2O/c1-27-7-9-28(10-8-27)12-5-6-14-16(11-12)25-20(24-14)18-19(23)17-13(22)3-2-4-15(17)26-21(18)29;1-2(4)3(5)6;/h2-6,11H,7-10H2,1H3,(H,24,25)(H3,23,26,29);2,4H,1H3,(H,5,6);1H2

Synthetic route

4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one DL-lactic acid salt → 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]quinolin-2(1H)-one mono 2-hydroxypropanoate hydrate (915769-50-5)

Conditions	Yield
With water In ethanol at 20℃; for 42h; Purification / work up;
at 120℃; for 5h; Neat (no solvent);
With water In butanone at 20℃; for 21h; Purification / work up;
With water In acetonitrile at 50℃; for 24h; Purification / work up;

Upstream product

• 692737-80-7 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one DL-lactic acid salt 

Relevant articles and documents

CRYSTALLINE AND OTHER FORMS OF 4-AMINO-5-FLUORO-3-[6-(4-METHYLPIPERAZIN-1-YL)-1H-BENZIMIDAZOL-2-YL]-1H-QUINOLIN-2-ONE LACTIC ACID SALTS

The present invention relates to non-hydrate crystalline forms of 4-amino- 5-fluoro-3 -[6-(4-methylpiperazin- 1 -yl)- 1 H-benzimidazol-2-yl] - 1 H-quinolin-2-one lactic acid salts, solid pharmaceutical formulations containing the same and methods of use. The present invention also relates to crystalline hydrates of 4-arnino-5-fiuoro-3-[6-(4- methylpiperazin-l-yl)-lH-benzimidazol-2-yl]-lH-quinolin-2-one lactic acid salts, pharmaceutical formulations containing the same and methods of use related thereto. The present invention further relates to crystalline solvates of 4-amino-5-fluoro-3-[6-(4- methylpiperazin-l-yl)-lH-benzimidazol-2-yl]-lH-quinolin-2-one lactic acid salts.