1421373-98-9

Usage

Uses

Used in Pharmaceutical Industry:
AZ-5104 is used as an impurity in the production of Osimertinib (A808075) for the treatment of nonsmall-cell lung cancer (NSCLC). Its presence in the synthesis process may affect the drug's efficacy and safety, making it essential to monitor and control its levels during manufacturing.
Used in Research and Development:
AZ-5104 can be used as a research compound to study the synthesis process of Osimertinib and understand the factors that contribute to its formation. This knowledge can help in optimizing the production process and minimizing the presence of impurities, ultimately improving the quality and effectiveness of the final drug product.
Used in Quality Control and Analysis:
AZ-5104 can be utilized as a reference material for quality control and analytical purposes in the pharmaceutical industry. By comparing the properties and characteristics of AZ-5104 with those of the synthesized drug, researchers and quality control professionals can ensure the purity and consistency of the final product, ensuring patient safety and compliance with regulatory standards.
Used in Drug Development and Formulation:
AZ-5104 may have potential applications in the development of new drugs or formulations, particularly in the field of cancer treatment. By studying the properties and interactions of AZ-5104, researchers can gain insights into the mechanisms of action of EGFR inhibitors and potentially develop new therapeutic strategies for the treatment of nonsmall-cell lung cancer and other related conditions.

Biological Activity

az5104, is the demethylated metabolite of azd-9291,is a potent egfr inhibitor. ic50 <1 nm, 6 nm, 1 nm, 25 nm, for egfr (l858r/t790m), egfr (l858r), egfr (l861q), and egfr (wildtype), respectively.egfr (epidermal growth factor receptor) is a receptor tyrosine kinase on the cell surface. the receptor activation leads to dimerization and tyrosine autophosphorylation. it induces downstream cellular responses such as modification in gene expression, cell proliferation and cytoskeletal rearrangement etc.compare to azd9291, az5104 has somewhat more potency in mutant egfr cell lines ex19del (2 nmol/l in pc-9), t790m (2 nmol/l in h1975), and wild-type egfr (33 nmol/l in lovo) cell lines. in a phenotypic assay, az5104 showed a greater potency across cell lines in a phenotypic assay.3 hours after oral dosing in the mouse, the circulating active metabolites in plasma is 33% for az5104. in both c/l858r and c/l+t mice, 5 mg/kg/day dose of az5104, also show efficacy in shrinking tumors.

references

1. cross da, ashton se, ghiorghiu s et al. azd9291, an irreversible egfr tki, overcomes t790m-mediated resistance to egfr inhibitors in lung cancer. cancer discov. 2014 sep;4(9):1046-61.

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Relevant academic research and scientific papers

Alkynyl-containing AZD9291 derivative, preparation method and application thereof

The invention relates to an alkynyl-containing AZD9291 derivative, a preparation method and application thereof. The structural general formula (I) of the alkynyl-containing AZD9291 derivative is shown as the specification. Compared with the prior art, an AZD9291 analogue is synthesized and alkynyl is introduced, so that not only is the property of the AZD9291 analogue retained, but also the property of alkynyl is improved, the in-vitro antitumor activity is enhanced, and a good inhibition effect is achieved on a variety of tumor cells, and the alkynyl-containing AZD9291 derivative is an idealmedicine for treating diseases caused by EGFR mutation.

2 - (2,Anilino) pyrimidine compound and application thereof (by machine translation)

The invention relates to certain 2 - (2,anilino) pyrimidine compounds represented by the following formula I and application thereof. These compounds or salts thereof show a higher inhibition of EGFR than wild-type EGFR in the form of an activated or drug resistant mutant. Since the toxicity associated with the wild-type EGFR inhibition is reduced, it is expected that such a compound or salt thereof has excellent pharmacodynamic properties, higher metabolic stability, better blood-brain barrier permeability, and more suitable for use as a therapeutic agent, particularly for the treatment of cancer. , These compounds or salts thereof can be used to prepare EGFR-mediated diseases, in particular non-small cell lung cancer, for the treatment of certain mutated forms. (by machine translation)

Discovery of a potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistance mutations that spares the wild type form of the receptor

Epidermal growth factor receptor (EGFR) inhibitors have been used clinically in the treatment of non-small-cell lung cancer (NSCLC) patients harboring sensitizing (or activating) mutations for a number of years. Despite encouraging clinical efficacy with these agents, in many patients resistance develops leading to disease progression. In most cases, this resistance is in the form of the T790M mutation. In addition, EGFR wild type receptor inhibition inherent with these agents can lead to dose limiting toxicities of rash and diarrhea. We describe herein the evolution of an early, mutant selective lead to the clinical candidate AZD9291, an irreversible inhibitor of both EGFR sensitizing (EGFRm+) and T790M resistance mutations with selectivity over the wild type form of the receptor. Following observations of significant tumor inhibition in preclinical models, the clinical candidate was administered clinically to patients with T790M positive EGFR-TKI resistant NSCLC and early efficacy has been observed, accompanied by an encouraging safety profile.

2 - (2, 4, 5 - SUBSTITUTED -ANILINO) PYRIMIDINE DERIVATIVES AS EGFR MODULATORS USEFUL FOR TREATING CANCER

The present invention relates to certain 2-(2,4,5-substituted-anilino) pyrimidine compounds and pharmaceutically acceptable salts thereof which may be useful in the treatment or prevention of a disease or medical condition mediated through certain mutated forms of epidermal growth factor receptor (for example the L858R activating mutant, the Exonl9 deletion activating mutant and the T790M resistance mutant). Such compounds and salts thereof may be useful in the treatment or prevention of a number of different cancers. The invention also relates to pharmaceutical compositions comprising said compounds and salts thereof, especially useful polymorphic forms of these compounds and salts, intermediates useful in the manufacture of said compounds and to methods of treatment of diseases mediated by various different forms of EGFR using said compounds and salts thereof.