EOS Med Chem produce Afatinib in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.
Afatinib Intermediates, EOS Med Chem have 8; Afatinib Impurity we have 10, all from GMP, FDA plant.
Now Afatinib DMF document is preparing.
Until 2016, Aug, Afatinib more than produced 25kg API, 120kg Intermediates
Afatinib API and intermediates 848133-35-7 ≥98.0% trans-4-Dimethylaminocrotonic acid hydrochloride
Afatinib API and intermediates 13991-36-1 ≥98.0% 4-Bromocrotonic Acid
Afatinib API and intermediates 162012-69-3 ≥98.0% 7-Fluoro-6-nitro-4-hydroxyquinazoline
Afatinib API and intermediates 162012-67-1 ≥98.0% 4-Quinazolinamine, N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitro-
Afatinib API and intermediates 179552-73-9 ≥98.0% 7-Chloro-N-(3-chloro-4-fluorophenyl)-6-nitro-4-quinazolinamine
Name: Afatinib free base
CAS#: 439081-18-2 (free base)
Chemical Formula: C24H25ClFN5O3
Exact Mass: 485.163
Molecular Weight: 485.94
Elemental Analysis: C, 59.32; H, 5.19; Cl, 7.30; F, 3.91; N, 14.41; O, 9.88
Description: Afatinib, also know as BIBW 2992, is an orally bioavailable dual receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. EGFR/HER2 tyrosine kinase inhibitor BIBW 2992 irreversibly binds to and inhibits human epidermal growth factor receptors 1 and 2 (EGFR-1; HER2), which may result in the inhibition of tumor growth and angiogenesis. EGFR/HER2 are RTKs that belong to the EGFR superfamily; both play major roles in tumor cell proliferation and tumor vascularization and are overexpressed in many cancer cell types. Afatinib is approved in much of the world (including the United States, Canada, the United Kingdom and Australia) for the treatment of metastatic non-small cell lung carcinoma (NSCLC), developed by Boehringer Ingelheim. It acts as an angiokinase inhibitor.
Synonym: BIBW-2992; BIBW 2992; BIBW2992. Afatinib free base; trade name: Gilotrif, Tomtovok and Tovok.
IUPAC/Chemical Name: (S,E)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide.
SMILES Code: O=C(NC1=CC2=C(NC3=CC=C(F)C(Cl)=C3)N=CN=C2C=C1O[C@@H]4COCC4)/C=C/CN(C)C
Related:
439081-18-2(Afatinib free base);
850140-73-7 (Afatinib dimaleate)
As of July 2012, it is undergoing Phase III clinical trials for this indication and breast cancer, as well as Phase II trials for prostate and head and neck cancer, and a Phase I glioma trial. Afatinib is not a first-line treatment; it is only used after other therapies have failed. In October 2010 a Phase III trial in NSCLC patients called Lux-Lung 5 began with this drug. Fall 2010 interim results suggested the drug extended progression-free survival threefold compared to placebo, but did not extend overall survival. In May 2012, the Phase IIb/III trial Lux-Lung 1 came to the same conclusion. Phase II results for breast cancer that over-expresses the protein human epidermal growth factor receptor 2 (Her2-positive breast cancer) were described as promising by the authors, with 19 of 41 patients achieving benefit from afatinib. Double-blind Phase III trials are under way to confirm or refute this finding. Her2-negative breast cancers showed limited or no response to the drug.
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9: Perera SA, Li D, Shimamura T, Raso MG, Ji H, Chen L, Borgman CL, Zaghlul S, Brandstetter KA, Kubo S, Takahashi M, Chirieac LR, Padera RF, Bronson RT, Shapiro GI, Greulich H, Meyerson M, Guertler U, Chesa PG, Solca F, Wistuba II, Wong KK. HER2YVMA drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy. Proc Natl Acad Sci U S A. 2009 Jan 13;106(2):474-9. Epub 2009 Jan 2. PubMed PMID: 19122144; PubMed Central PMCID: PMC2626727.
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