An improved process for the synthesis of nintedanib esylate

Arava, Veera Reddy; Gogireddy, Surendrareddy

doi:10.1080/00397911.2017.1297459

Cited by 8 publications

(4 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fig. 3 shows the flowchart of the introduced synthetic route 2 [8]. The second route makes some optimizations to the first.…”

Section: Synthetic Routementioning

confidence: 99%

Synthesis and efficacy analysis of multi-target TKI drug nintedanib

2023

Second International Conference on Biological Engineering and Medical Science (ICBioMed 2022)

View full text Add to dashboard Cite

In the medical field, nintedanib (BIBF1120) belongs to a very potent small molecular buccal tyrosine kinase inhibitor (TKI), which plays an important role in the treatment of different diseases. For example, it can be used to treat idiopathic pulmonary fibrosis (IPF), lung cancer, and other interstitial lung diseases (ILD). Tripeptidase 1 (TPP1) was discovered to be a direct target for nintedanib using affinity-based protein profiling (AfBPP) technology, which might be a novel tyrosine kinase inhibition and nintedanib vary. After thorough clinical testing, the drug can be used to treat patients with a range of solid tumors and the crippling lung condition IPF. Although this drug is effective in treatment, it is very expensive. Therefore, it is necessary to study the synthesis route of nintedanib to reduce its price and make more patients able to buy the drug. Different synthetic routes for the nintedanib have been developed and greatly increased the yield of the nintedanib. As a result, the three ways that nintedanib is synthesized are analyzed in this article. The first is created via decarboxylated cyclization and acidic hydrogenation. The third employs the synthetic Eschen Moser coupling reaction path, whereas the second refines the first route. After comparing the three approaches, it can derive the best synthetic route of a drug and use it for the synthesis of the target drug. And the therapeutic effect of the target drug on the disease should not be further analyzed.

show abstract

“…Fig. 3 shows the flowchart of the introduced synthetic route 2 [8]. The second route makes some optimizations to the first.…”

Section: Synthetic Routementioning

confidence: 99%

Synthesis and efficacy analysis of multi-target TKI drug nintedanib

2023

Second International Conference on Biological Engineering and Medical Science (ICBioMed 2022)

View full text Add to dashboard Cite

show abstract

“…Another report by the same company revealed the multi‐gram scale preparation of 1 via almost similar procedure using the common amine derivative 11 [8] . One recent paper from different group reported the synthesis of nintedanib through the formation of oxindole via alternative synthetic route [9] …”

Section: Introductionmentioning

confidence: 99%

“…[8] One recent paper from different group reported the synthesis of nintedanib through the formation of oxindole via alternative synthetic route. [9] Nong and Xu et al also reported the synthesis of 1 by a slight modification of the synthetic route. [10] However, a comprehensive scrutiny of these reports discloses that all of these synthetic modifications always lead via the same synthons or their synthetic equivalents.…”

Section: Introductionmentioning

confidence: 99%

An Efficient Approach Towards the Synthesis of Nintedanib

2023

View full text Add to dashboard Cite

Nintedanib, a potent, oral, small‐molecule tyrosine kinase inhibitor, is known as a triple angiokinase inhibitor, inhibiting three major signaling pathways in angiogenesis. Here, we report full details of the alternative path toward the synthesis of nintedanib via novel intermediates. A key feature of our approach is the stereoselective intramolecular cyclization strategy that enables the concise conversion of β‐keto amide into a 3‐acyloxindole derivative, which is an important scaffold for nintedanib synthesis. Subsequent condensation of oxindole scaffold with synthesized amine derivative led to the drug nintedanib with good yields.

show abstract

“…The original synthetic route leading to Nintedanib (Scheme ) was described by Boehringer Ingelheim researchers in a few patents and journal article between 2004 and 2009. To enhance reaction yields of particular steps or avoid specific problems connected with industrial processing, this synthetic approach was later modified ( e.g ., change of the solvent, catalyzing base, leaving group Y, removing of the acetyl group protecting the oxindole nitrogen, or even changing the sequence of the reaction steps) by other authors . However, all of these synthetic alterations always lead to the same synthons or their synthetic equivalents.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of the Kinase Inhibitors Nintedanib, Hesperadin, and Their Analogues Using the Eschenmoser Coupling Reaction

et al. 2021

View full text Add to dashboard Cite

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 inhibitors including Nintedanib and Hesperadin in yields exceeding 76%. Starting compounds for the synthesis are also easily available in good yields. 3-Bromooxindoles were prepared either from corresponding isatins using a three-step synthesis in an average overall yield of 65% or by direct bromination of oxindoles (yield of 65–86%). Starting N-(4-piperidin-1-ylmethyl-phenyl)-thiobenzamide was prepared by thionation of the corresponding benzanilide in an 86% yield and N-methyl-N-(4-thiobenzoylaminophenyl)-2-(4-methylpiperazin-1-yl)acetamide was prepared by thioacylation of the corresponding aniline with methyl dithiobenzoate in an 86% yield.

show abstract

An improved process for the synthesis of nintedanib esylate

Cited by 8 publications

References 10 publications

Synthesis and efficacy analysis of multi-target TKI drug nintedanib

Synthesis and efficacy analysis of multi-target TKI drug nintedanib

An Efficient Approach Towards the Synthesis of Nintedanib

Synthesis of the Kinase Inhibitors Nintedanib, Hesperadin, and Their Analogues Using the Eschenmoser Coupling Reaction

Contact Info

Product

Resources

About