| Identification | Back Directory | [Name]
BIBW2992 DiMaleate | [CAS]
850140-73-7 | [Synonyms]
BIBW2992-MA2
BIBW2992 DiMaleate
Afatinib (diMaleate)
Afatinib double Maleate
Afatinib dimaleate, >=99%
Afatinib (BIBW2992) Dimaleate
Afatinib (diMaleate), BIBW2992
Afatinib dimaleate BIBW 2992MA2
(2E)-N-(4-[(3-chloro-4-fluorophenyl)aMino]-7-{[(3S)
(S,E)-N-(4-((3-Chloro-4-fluorophenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(d
(S,Z)-N-(4-((3-chloro-4-fluorophenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)-4-(dimethylamino)but-2-enamide dimaleate
N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[[(3S)-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4-(dimethylamino)-(2E)-2-butenamide,(2Z)-2-butenedioate (1:2)
2-ButenaMide, N-[4-[(3-chloro-4-fluorophenyl)aMino]-7-[[(3S)-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4-(diMethylaMino)-, (2E)-, (2Z)-2-butenedioate (1:2) | [EINECS(EC#)]
1308068-626-2 | [Molecular Formula]
C24H25ClFN5O3 | [MDL Number]
MFCD28969755 | [MOL File]
850140-73-7.mol | [Molecular Weight]
602.02 |
| Chemical Properties | Back Directory | [Melting point ]
>237oC (dec.) | [storage temp. ]
Refrigerator | [solubility ]
DMSO (Slightly), Methanol (Slightly) | [form ]
Solid | [color ]
White to Pale Yellow | [InChIKey]
LIENDGDDWJRJLO-LBXKZPGENA-N | [SMILES]
C(/C(=O)O)=C/C(=O)O.N(C1C=CC(F)=C(Cl)C=1)C1=NC=NC2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC1=2 |&1:25,r| |
| Hazard Information | Back Directory | [Definition]
ChEBI: A maleate salt obtained by combining afatinib with two molar equivalents of maleic acid. Used for the first-line treatment of patients with metastatic non-small cell lung cancer. | [Uses]
Afatinib Dimaleate (850140-73-7) is a salt of Afatinib {BIBW 2992), an aminocrotonylamino-substituted quinazoline derivative used for treating cancer and diseases of the respiratory tract, lungs, gastrointestinal tract, bile duct, and gallbladder. An anilino-quinazoline that irreversibly inhibits EGFR and HER2 kinase activity.
| [General Description]
Afatinib dimaleate (850140-73-7) is the dimaleate form of afatinib. It is a tyrosine kinase inhibitor of epidermal growth factor receptors (ERBB RECEPTORS) and an anti-angiogenic agent. Afatinib dimaleate has anti-tumour activity and is mainly used for the treatment of patients with metastatic non-small cell lung cancer (which has metastasised or spread to other parts of the body), or certain tumours with mutations in the EGFR gene and patients whose disease has worsened after platinum-based chemotherapy. It is also used for the treatment of esophageal squamous cell carcinoma (ESCC) and gastric cancer.
| [Biological Activity]
Afatinib dimaleate (850140-73-7) is an orally bioavailable and irreversible dual-specific inhibitor of the ErbB family (EGFR and HER2). IC50 are 0.4, 0.5, 10, 14, 1 nM for EGFRL858R, EGFRwt, EGFR L858R/T790M, ErbB2 (HER2) and ErbB4 (HER4), respectively. Afatinib dimaleate is available for cancer (esophageal squamous cell carcinoma (ESCC), non-small cell lung cancer (NSCLC) and gastric cancer) studies.
| [Synthesis]
Nitroquinazolinone (6), which is commercially available, was
first chlorinated with phosphorous oxychloride (POCl3) followed
by treatment with commercial 3-chloro-4-fluoroaniline (7) to
afford SNAr adduct 8 in 90% yield over two steps. Sulfonylation to afford 9 (86%) and subsequent displacement with (S)-tetrahydrofuran-
3-ol gave 10 in 90% yield. Raney¨CNickel reduction
of the nitro group delivered 11 in 97% yield, which set the stage
for the final side-chain functionalization. 2-(Diethoxyphosphoryl)
acetic acid and N,N0-carbonyldiimidazole (CDI) were pre-mixed
and added to aniline 11 to afford 12 in 70% isolated yield. Next, a
Horner¨CWadsworth¨CEmmons homologation gave the (E)-olefin
13 in quantitative yield, followed by maleate salt formation
(92%) to deliver the final API. The final five steps of this synthesis
have been successfully demonstrated on multi-kilogram scale.
| [storage]
Store at -20°C |
| Questions And Answer | Back Directory | [Description]
Afatinib dimaleate (Tovok; BIBW2992; Gilotrif) is a salt form of Afatinib. Afatinib is a second-generation, orally administered, irreversible inhibitor of the ErbB family of tyrosine kinases.
| [Mechanism of Action]
Afatinib (850140-73-7) downregulates ErbB signalling by covalently binding to the kinase domains of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER) 2 and HER4, resulting in irreversible inhibition of tyrosine kinase autophosphorylation; it also inhibits transphosphorylation of HER3. Afatinib is approved as monotherapy for the treatment of EGFR tyrosine kinase inhibitor (TKI)-na?ve adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating EGFR mutations in the EU, and for the first-line treatment of patients with metastatic NSCLC whose tumours have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by a US FDA-approved test in the US.
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