- [1,3]DIAZINO[5,4-d]PYRIMIDINES AS HER2 INHIBITORS
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The present invention relates to new [1,3]diazino[5,4-d]pyrimidines and derivatives of Formula (I), wherein the groups R1, R2, R3 and R4 have the meanings given in the claims and specification, their use as inhibitors of HER2 and its mutants, pharmaceutical compositions which contain such compounds and their use as medicaments, especially as agents for treatment and/or prevention of oncological diseases.
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Page/Page column 50; 51
(2021/10/30)
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- Preparation method of Tucatinib intermediate
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The invention discloses a preparation method of a tucatinib intermediate, which comprises the following steps: firstly, reacting 4-chloropyrido-2-amine with N,N-dimethylformamide dimethyl acetal, and then adding hydroxylamine hydrochloride for reaction to
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Paragraph 0015; 0029; 0035-0036; 0046-0051; 0052; ...
(2021/06/06)
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- ALKYNYL QUINAZOLINE COMPOUNDS
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The present disclosure relates to compounds of Formula (I'): and pharmaceutically acceptable salts and stereoisomers thereof. The present disclosure also relates to methods of preparation these compounds, compositions comprising these compounds, and methods of using them in the prevention or treatment of abnormal cell growth in mammals, especially humans.
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Paragraph 0858; 0861
(2021/02/19)
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- PYRROLO[2,1-F][1,2,4]TRIAZINE DERIVATIVES SERVING AS SELECTIVE HER2 INHIBITORS AND APPLICATION THEREOF
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The present invention relates to a group of pyrrolo[2, 1-f][1,2,4]triazine derivatives serving as selective HER2 inhibitors and an application thereof in the preparation of a drug that serves as an HER2 inhibitor. Specifically, the present invention relates to a compound represented by formula (I), an isomer thereof or a pharmaceutically acceptable salt thereof.
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- [1,3]DIAZINO[5,4-D]PYRIMIDINES AS HER2 INHIBITORS
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The present invention relates to new [1,3]diazino[5,4-d]pyrimidines and derivatives of Formula (I) wherein the groups R1, R2, R3 and R4 have the meanings given in the claims and specification, their use as inhibitors of HER2 and its mutants, pharmaceutical compositions which contain such compounds and their use as medicaments, especially as agents for treatment and/or prevention of oncological diseases.
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- Synthesis method of Tucatinib and intermediate product thereof
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The invention discloses a synthesis method of Tucatinib, and the method comprises the following step: carrying out substitution reaction on halate of a compound shown in a formula VI or free alkali thereof serving as a raw material and a compound shown in a formula VII under an alkaline condition to obtain a compound shown in a formula VIII. The raw materials used in the whole synthesis route areeasy to obtain, expensive catalysts are not needed, and the method is suitable for large-scale production and beneficial to industrial production of the Tucatinib.
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- Preclinical activity of HER2-selective tyrosine kinase inhibitor tucatinib as a single agent or in combination with trastuzumab or docetaxel in solid tumor models
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HER2 is a transmembrane tyrosine kinase receptor that mediates cell growth, differentiation, and survival. HER2 is overexpressed in approximately 20% of breast cancers and in subsets of gastric, colorectal, and esophageal cancers. Both antibody and smallm
- De Vries, Peter,Forero-Torres, Andres,Kulukian, Anita,Lee, Patrice,Peterson, Scott,Rosler, Robert,Taylor, Janelle,Watson, Daniel
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p. 976 - 987
(2020/08/06)
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- NITROGENOUS HETEROCYCLIC COMPOUND, PREPARATION METHOD, INTERMEDIATE, COMPOSITION, AND APPLICATION
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A nitrogenous heterocyclic compound, a preparation method, an intermediate, a composition, and an application. The present invention provides a nitrogenous heterocyclic compound as represented by formula I, pharmaceutically acceptable salts thereof, enantiomers thereof, diastereoisomers thereof, tautomers thereof, solvates thereof, metabolites thereof, or prodrugs thereof. The compound has high inhibitory activity against ErbB2 tyrosine kinase, has good inhibitory activity against human breast cancer cells BT-474, human gastric cancer cells NCI-N87 and the like with high expression of ErbB2, and in addition has relatively weak inhibitory activity against EGFR kinase, that is, the compound is an EGFR/ErbB2 double target inhibitor that attenuates EGFR kinase inhibitory activity or a small-molecule inhibitor having selectivity for an ErbB2 target. (I)
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- New Synthetic Route to Tucatinib
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A new and improved synthetic route to tucatinib is described that involves three key intermediates. The first of these, 4-([1,2,4]triazolo[1,5- a ]pyridin-7-yloxy)-3-methylaniline, was prepared on a 100 g scale in 33percent yield over five steps and 99percent purity. Next, N 4 -(4-([1,2,4]triazolo[1,5- a ]pyridin-7-yloxy)-3-methylphenyl)quinazoline-4,6-diamine was isolated in 67percent yield over three steps and >99percent purity. Then, 4,4-dimethyl-2-(methylthio)-4,5-dihydrooxazole trifluoromethanesulfonate was prepared under mild conditions in 67percent yield over two steps. Finally, tucatinib was obtained in 17percent yield over nine steps and in >99percent purity (HPLC). Purification methods used to isolate the product and the intermediates involved in the route are also reported.
- Bu, Lehao,Chen, Wenxin,Liu, Yaowei,Mao, Yongjun,Yin, Lingfeng,Zhang, Long
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p. 2660 - 2664
(2019/06/19)
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- CYANO QUINOLINE AMIDE COMPOUNDS AS HER2 INHIBITORS AND METHODS OF USE
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The application relates to a compound having Formula I which modulates the activity of HER2 and/or a mutant thereof, a pharmaceutical composition comprising the compound, and a method of treating or preventing a disease in which HER2 and/or a mutant thereof plays a role.
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- ERBB RECEPTOR INHIBITORS
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Disclosed are compounds inhibiting ErbBs (e. g. HER2), pharmaceutically acceptable salts, hydrates, solvates or stereoisomers thereof and pharmaceutical compositions comprising the compounds. The compound and the pharmaceutical composition can effectively treat diseases associated ErbBs (especially HER2), including cancer.
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- Irbinitinib intermediates for preparation of (by machine translation)
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The invention belongs to the organic synthesis and bulk drug preparation technology field, in particular to the treatment of breast cancer drug Irbinitinib preparation method and intermediate, comprising the steps of: 2 - methyl - 4 - nitro-phenol (formul
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