928326-83-4 Usage
Description
BIBF 1120 is a triple kinase inhibitor blocking vascular endothelial growth factor receptor, PDGF receptor, and FGF receptor, which has a potential to inhibit tumor growth and pulmonary fibrosis.
Anticancer Research
BIBF 1120 is a potent inhibitor of VEGFR as well as PDGF and fibroblast growth factor receptor. In a randomized phase II placebo-controlled trial, patients who had just completed chemotherapy for relapsed ovarian cancer, with evidence of response, but at high risk of further early recurrence were treated with BIBF 1120. The study drug was taken continuously (28-day cycles) for 9 cycles (36 weeks) or until disease progression or patient withdrawal. The 36-week PFS 26-week rates were 16.3% and 5.0% in the BIBF 1120 and placebo groups, respectively (HR 0.65; 95% Cl, 0.42 to 1.02; P = .06). Toxicity was also well tolerated.This has prompted a phase III trial (NCTO1O15118) where BIBF 1120 will be combined with carboplatin/paclitaxel as front-line chemotherapy in ovarian cancer.
Side effects
Most of the adverse effects associated with BTBF-1120 were tolerable. They include diarrhea, nausea, vomiting, abdominal pain, and reversible increase in liver enzymes.
Clinical claims and research
BIBF 1120 is a triple tyrosine kinase inhibitor with efficacy on fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), and on platelet-derived growth factor (PDGF).The activation of these pathways has been implicated in the pathogenesis of experimental fibrosis. In a 12-month phase II trial (the TOMORROW trial) patients who received 150 mg of BIBF 1120 twice daily had a trend toward reduction in the decline of FVC.In addition, there was an improved QOL and a reduction in acute exacerbations of IPF. These results led to a phase III trial. This was designed as two identical phase III studies called INPULSIS-1 and INPULSIS-2. The INPULSIS trials tested the effect on IPF disease progression over 52 weeks using 150 mg of twice daily nintedanib (formerly BIBF 1200) versus placebo. The inclusion criteria included patients diagnosed with idiopathic pulmonary fibrosis based on established criteria.In addition, the participants’ HRCT scans and biopsies, if available, were reviewed by a central radiologist or pathologist to confirm the diagnosis. Enrolled subjects had a FVC which was >50% of the predicted value and a DlCO from 30–79% of predicted values. Published data from the two trials indicated that patients who received nintedanib demonstrated a statistically significant reduction in the rate of decline in lung function compared with the placebo group. In the INPULSIS-2 trial, there was a significant reduction in the time to first acute exacerbation of IPF. This was not replicated in the INPULSIS-1 trial data. The most common side effect for the medication was diarrhea. On the basis of this study, nintedanib is pending evaluation for approval for use in the United States.
Check Digit Verification of cas no
The CAS Registry Mumber 928326-83-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 9,2,8,3,2 and 6 respectively; the second part has 2 digits, 8 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 928326-83:
(8*9)+(7*2)+(6*8)+(5*3)+(4*2)+(3*6)+(2*8)+(1*3)=194
194 % 10 = 4
So 928326-83-4 is a valid CAS Registry Number.
InChI:InChI=1/C31H33N5O4/c1-34-15-17-36(18-16-34)20-27(37)35(2)24-12-10-23(11-13-24)32-29(21-7-5-4-6-8-21)28-25-14-9-22(31(39)40-3)19-26(25)33-30(28)38/h4-14,19,32H,15-18,20H2,1-3H3,(H,33,38)/b29-28-
928326-83-4Relevant articles and documents
AN IMPROVED HIGHLY EFFICIENT PROCESS FOR THE PREPRATION OF NINTEDANIB AND PHARMACEUTICALLY ACCEPTABLE SALT THEREOF
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Page/Page column 10; 17-18, (2022/02/15)
The present invention relates to an improved highly efficient and economic process for large-scale production of Nintedanib and pharmaceutically acceptable salt thereof. The present invention also relates to a single step process that form highly pure Nintedanib through novel intermediates. In this process, Nintedanib base [I] is prepared in a single step, in-situ process wherein the process is performed by formation of two novel intermediates namely, methyl-1-(bromoacetyl)-2-oxo-2,3-dihydro-1H-indole-6-carboxylate and methyl-(3Z)-1-(bromoacetyl)-3-[methoxy(phenyl)methylidene]-2-oxo-2,3-dihydro-1H-indole-6-carboxylate. This process avoids use of expensive and hazardous reagent and solvent such as methyl cyclohexane. Further, there is no isolation and analysis of any intermediate after every step completion that made the process easy to perform without much hurdles. Along with the ease of performance, present invention process also gives high-purity final product with high yield. This makes the process highly cost-effective and time-efficient.
Synthesis of the Kinase Inhibitors Nintedanib, Hesperadin, and Their Analogues Using the Eschenmoser Coupling Reaction
Marek, Luká?,Váňa, Ji?í,Svoboda, Jan,Hanusek, Ji?í
, p. 10621 - 10629 (2021/07/31)
A novel synthetic approach involving an Eschenmoser coupling reaction of substituted 3-bromooxindoles (H, 6-Cl, 6-COOMe, 5-NO2) with two substituted thiobenzanilides in dimethylformamide or acetonitrile was used for the synthesis of eight kinase inhibitor
Preparation method of nintedanib key intermediate
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Paragraph 0040-0045, (2021/09/08)
The invention provides a preparation method of a nintedanib key intermediate, and belongs to the technical field of synthesis of medical intermediates. The first preparation method comprises the following steps: carrying out a nitro reduction reaction on a compound IV by taking an alcohol reagent or tetrahydrofuran as a solvent, taking hydrazine hydrate as a reducing agent and taking palladium carbon (Pd/C) as a catalyst until the nitro reduction reaction is complete, performing filtering to remove the catalyst under the protection of nitrogen, performing desolventizing to remove the solvent, performing dissolving by using dichloromethane, performing filtering to remove impurities, and performing desolventizing to obtain a compound I; the second method comprises the following steps: carrying out a nitro reduction reaction on a compound IV by taking hydrazine hydrate as a reducing agent and anhydrous ferric trichloride and activated carbon as catalysts until the nitro reduction reaction is complete, performing performing filtering to remove the catalyst, performing desolventizing to remove the solvent, dissolving dichloromethane, drying anhydrous sodium sulfate, performing filtering, and performing desolventizing to obtain a compound I. The preparation method provided by the invention is high in yield, strong in operability and high in safety, belongs to an environment-friendly process, and is suitable for industrial large-scale production.
