1168152-06-4

Usage

Uses

Used in Pharmaceutical Industry:
(E)-1-acetyl-3-(ethoxy-phenyl-methylene)-2-oxo-2,3-dihydro-1H-indole-6-carboxylic acid methyl ester is used as an impurity in Intedanib (I666650), a drug that targets multiple receptor kinases involved in angiogenesis and cell proliferation. Its presence in the drug may have implications for the drug's safety, efficacy, and quality control during manufacturing processes.

Upstream product

• 108-24-7 acetic anhydride 
• 14192-26-8 2-oxo-2,3-dihydro-1H-indole-6-carboxylic acid methyl ester 
• 1663-61-2 triethoxymethylbenzene 
• 676326-36-6 1-acetyl-2-oxo-2,3-dihydro-1H-indole-6-carboxylic acid methyl ester 

Downstream Products

• 466694-79-1 methyl 3-(Z)-[1-(4-carbamoyl-phenylamino)-1-phenyl-methylidene]-2-indolinone-6-carboxylate 
• 656247-17-5 nintedanib 
• 656247-18-6 methyl (3Z)-3-[({4-[N-methyl-2-(4-methylpiperazin-1-yl)acetamido]phenyl}amino)(phenyl)methylidene]-2-oxo-2,3-dihydro-1H-indole-6-carboxylate ethanesulfonate salt 
• 466694-80-4 methyl 3-(Z)-[1-(4-propylcarbamoyl-phenylamino)-1-phenyl-methylidene]-2-indolinone-6-carboxylate 

Relevant academic research and scientific papers

Preparation method of high-purity nintedanib ethanesulfonate

The invention discloses a preparation method of high-purity nintedanib ethanesulfonate, which comprises the following steps: 1, carrying out one-pot reaction on toluene, SM01, triethyl orthobenzoate,acetic anhydride and DMAP, and carrying out suction filtration to obtain a high-purity intermediate INT02; 2, reacting INT02 and SM02 in a specific solvent system and then separating to obtain an intermediate INT03; 3, enabling INT03, methanol and KOH to react to obtain INT04; 4, reacting INT04, methyl alcohol and ethanesulfonic acid, adding methyl tert-butyl ether and isopropyl ether to obtain nintedanib ethanesulfonate.

INDOLINONES COMPOUNDS AND THEIR USE IN THE TREATMENT OF FIBROTIC DISEASES

The present invention relates inter alia to a compound of formula (I) Wherein R1, R2, R3 and Z are as defined in the specification and to compositions comprising the same and to the use of the compounds and to compositions of the compounds in treatment, for example in the treatment of fibrotic diseases or interstitial lung diseases, in particular idiopathic pulmonary fibrosis.

Substituted indolinone derivative and application thereof

The invention relates to a substituted indolinone derivative represented as the general formula (I) and used as a tyrosine kinase inhibitor, and medicinal acceptable salts or isomers thereof, wherein the R1, R2, R3, R4, R5, R6, R7, n and the ring A are defined as the specifications. The invention also relates to a preparation method of the compound, and an application of the compound in preparation of medicines for prevention or therapy of fibrosis diseases and excess hyperplasia diseases.

Design, synthesis, and evaluation of indolinones as triple angiokinase inhibitors and the discovery of a highly specific 6-methoxycarbonyl-substituted indolinone (BIBF 1120)

Inhibition of tumor angiogenesis through blockade of the vascular endothelial growth factor (VEGF) signaling pathway is a newtreatment modality in oncology. Preclinical findings suggest that blockade of additional pro-angiogenic kinases, such as fibroblast and platelet-derived growth factor receptors (FGFR and PDGFR), may improve the efficacy of pharmacological cancer treatment. Indolinones substituted in position 6 were identified as selective inhibitors of VEGF-, PDGF-, and FGF-receptor kinases. In particular, 6-methoxycarbonyl-substituted indolinones showed a highly favorable selectivity profile. Optimization identified potent inhibitors of VEGF-related endothelial cell proliferation with additional efficacy on pericyctes and smooth muscle cells. In contrast, no direct inhibition of tumor cell proliferation was observed. Compounds 2 (BIBF 1000) and 3 (BIBF 1120) are orally available and display encouraging efficacy in in vivo tumor models while being well tolerated. The triple angiokinase inhibitor 3 is currently in phase III clinical trials for the treatment of nonsmall cell lung cancer.