Use of amide compounds in combination with epidermal growth factor receptor inhibitor comprising gefitinib and/or erlotinib for the treatment of cancer e.g. lung cancer, colon cancer, bladder cancer, breast cancer and/or ovarian cancer

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This patent describes the use of specific amide compounds in combination with well-known epidermal growth factor receptor (EGFR) inhibitors, namely gefitinib and/or erlotinib, for treating various types of cancer. The invention proposes that combining these amide compounds, which act as cytohesin inhibitors, with EGFR inhibitors can enhance the effectiveness of cancer treatments.

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• Treatment of lung cancer using the new combination therapy.
• Treatment of colon cancer with improved efficacy.
• Application in bladder cancer therapy.
• Breast cancer treatment regimes employing the described drug combination.
• Ovarian cancer treatments incorporating this dual compound approach.
• Potential use in other cancers where EGFR inhibitors are relevant.

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• Potentially enhances the effectiveness of current EGFR inhibitor therapies (gefitinib/erlotinib).
• May help overcome or delay drug resistance in cancer treatments.
• Targets cancer through multiple pathways by combining cytohesin inhibition with EGFR inhibition.
• Provides a new therapeutic option for difficult-to-treat cancers.
• Increases the range of treatable cancers compared to single-drug therapies.

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Patent Abstract

Use of amide compounds (A1) comprising primary amide compounds (I) and/or secondary amide compounds (II) in combination with epidermal growth factor receptor inhibitor comprising gefitinib and/or erlotinib for the treatment of cancer, is claimed. Use of amide compounds (A1) comprising primary amide compounds of formula (A-C(=O)-NH-B1) (I) and/or secondary amide compounds of formula (D1-C(=O)-N(G1)-E1) (II) in combination with epidermal growth factor receptor inhibitor comprising gefitinib and/or erlotinib for the treatment of cancer, is claimed. A : linear or branched 1-10C-alkyl (optionally substituted with one or more halo comprising Cl, Br and/or F), linear or branched 2-10C-alkenyl, phenylsulfanylmethyl, (CH 3) 3C-CH 2-, 2-oxochromen-3-yl, (E)-styryl, 2-thienylmethyl or (hetero)aryl group of formula (a1)-(a8); B1 : 4-[[(E)-3-(2-furyl)prop-2-enoyl]amino]phenyl, 4-(thiophene-2-carbonylcarbamothioylamino)phenyl, 4-(2,3-dihydro-1,4-benzodioxine-6-carbonylamino)phenyl, 4-(1,3-benzodioxole-5-carbonylamino)phenyl, 4-carbamoylphenyl, carbamoyl, (2-phenoxyacetyl)amino, 5-phenyl-1,2,4-thiadiazol-3-yl, 2-furylmethyl, or (hetero)aryl group of formula (b1)-(b8); either D1 : phenyl, (3-phenyl-2,1-benzoxazole-5-carbonyl)oxymethyl, 2-thienylmethyl or (hetero)aryl group of formula (d1)-(d4); and E1 : linear or branched 1-10C-alkyl or 2-10C-alkenyl, 2-furylmethyl, tetrahydrofuran-2-ylmethyl or heteroaryl group of formula (e1); and G1 : linear or branched 1-10C-alkyl or 2-10C-alkenyl, [5-(2-furyl)-1,3,4-oxadiazol-2-yl]methyl, (4-oxo-3H-quinazolin-2-yl)methyl, 2-oxo-2-(4-phenyl-6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)ethyl, 1,3-benzodioxol-5-ylmethyl or heteroaryl group of formula (g1); or E1+G1+N : 5-7-membered aromatic or non-aromatic heterocycle comprising 4-carboxythiazolidin-3-yl, 2-oxo-3-(6-phenylthieno[2,3-d]pyrimidin-4-yl)sulfanyl-azepan-1-yl or of formula (eg1); or D1+G1+N : 5-7-membered aromatic or non-aromatic heterocycle comprising 5-nitro-1,3-dioxo-isoindolin-2-yl; R1 : H or linear or branched 1-10C-alkyl and/or 2-10C-alkenyl; R2 : linear or branched 1-10C-alkyl and/or 2-10C-alkenyl; R3 : linear or branched 1-10C-alkyl and/or 1-10C-alkoxy; R4 : H, CF 3and/or halo, preferably Cl, Br or F; and R5 : H and/or linear or branched 1-10C-alkoxy. [Image] [Image] [Image] [Image] ACTIVITY : Cytostatic. MECHANISM OF ACTION : Cytohesin inhibitor.