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A technology of compounds and solvates, applied in the field of treating cancer in mammals, can solve the problem of low frequency
Inactive Publication Date: 2012-09-12
GLAXO SMITHKLINE LLC
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Ultimately, the pathway can be genetically activated downstream of PI3K by DNA amplification or mutation of AKT; however, these genetic events occur with low frequency in human cancers
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[0102] Preparation of MEK inhibitors
[0103] MEK inhibitors suitable for use in the combinations according to the invention, in particular
[0110] It can be prepared according to International Patent Publication No. WO08 / 144463 (Example 345).
[0111] Compound A described in the experimental part refers to N-{3-[3-cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-6,8-dimethyl-2, dimethylsulfoxide solvate of 4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl}acetamide.
[0112] In v...
Embodiment 1
[0222] Example 1 - Capsule Composition
[0223] Oral dosage forms for administering the combinations of the invention are prepared by filling standard two-part hard gelatin capsules with the ingredients in the proportions shown in Table I below.
[0224] Table I
[0225]
[0226]
Embodiment 2
[0227] Example 2 - Capsule Composition
[0228] Oral dosage forms for administering one of the compounds of the invention are prepared by filling standard two-part hard gelatin capsules with the ingredients in the proportions shown in Table II below.
[0229] Table II
[0230]
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Abstract
The present invention relates to a method of treating cancer in a mammal and to pharmaceutical combinations useful in such treatment. In particular, the method relates to a novel combination comprising the MEK inhibitor: N -{3-[3-cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d / ]pyrimidin-1 (2H)-yl]phenyl}acetamide, or a pharmaceutically acceptable salt or solvate thereof, and the PI3 kinase inhibitor: 2,4-difluoro-N-{2-(methyloxy)-5-[4-(4-pyridazinyl)-6-quinolinyl]-3-pyridinyl}benzenesulfonamide, or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising the same, and methods of using such combinations in the treatment of cancer.
Description
technical field [0001] The present invention relates to methods of treating cancer in mammals, and to combinations useful in such treatment. Specifically, the method involves the inclusion of the MEK inhibitor: N-{3-[3-cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-6,8-dimethyl-2, 4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl}acetamide, or its pharmaceutically acceptable salt or solvent compounds, and PI3K inhibitors: 2,4-difluoro-N-{2-(methoxy)-5-[4-(4-pyridazinyl)-6-quinolinyl]-3-pyridyl} Novel combinations of benzenesulfonamides or pharmaceutically acceptable salts thereof, pharmaceutical compositions containing the combinations, and methods of using the combinations in the treatment of cancer. Background of the invention [0002] Effective treatment of hyperproliferative diseases, including cancer, has long been a goal of the field of oncology. In general, cancers arise from aberrations in the normal processes that control cell division, differenti...
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