NZ582929A - Derivatives of n-(arylamino) sulfonamides including polymorphs as inhibitors of mek as well as compositions, methods of use and methods for preparing the same - Google Patents

Info

Publication number

NZ582929A

NZ582929A NZ582929A NZ58292908A NZ582929A NZ 582929 A NZ582929 A NZ 582929A NZ 582929 A NZ582929 A NZ 582929A NZ 58292908 A NZ58292908 A NZ 58292908A NZ 582929 A NZ582929 A NZ 582929A

Authority

NZ

New Zealand

Prior art keywords

compound

composition

alkyl

cancer

additional embodiments

Prior art date

2007-07-30

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• 239000000203 mixture Substances 0.000 title claims abstract description 377
• 238000000034 method Methods 0.000 title claims abstract description 134
• 229940124530 sulfonamide Drugs 0.000 title description 27
• 150000003456 sulfonamides Chemical class 0.000 title description 10
• 239000003112 inhibitor Substances 0.000 title description 6
• 150000001875 compounds Chemical class 0.000 claims abstract description 623
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• 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 claims abstract description 55
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• 238000004519 manufacturing process Methods 0.000 claims abstract description 20
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 17
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• -1 dihydroxypropyl Chemical group 0.000 claims description 555
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 166
• 125000000217 alkyl group Chemical group 0.000 claims description 137
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 114
• 229910052739 hydrogen Inorganic materials 0.000 claims description 97
• 229910052731 fluorine Inorganic materials 0.000 claims description 81
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 79
• 150000003839 salts Chemical class 0.000 claims description 73
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 64
• 229910052794 bromium Inorganic materials 0.000 claims description 62
• 229910052740 iodine Inorganic materials 0.000 claims description 61
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 59
• 229910052799 carbon Inorganic materials 0.000 claims description 55
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 54
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• 125000000753 cycloalkyl group Chemical group 0.000 claims description 45
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• 125000005842 heteroatom Chemical group 0.000 claims description 40
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 40
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 38
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 38
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• 239000003937 drug carrier Substances 0.000 claims description 34
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 34
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 33
• 229920002785 Croscarmellose sodium Polymers 0.000 claims description 32
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 32
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• 238000011282 treatment Methods 0.000 claims description 27
• WMSPXQIQBQAWLL-UHFFFAOYSA-N cyclopropanesulfonamide Chemical compound NS(=O)(=O)C1CC1 WMSPXQIQBQAWLL-UHFFFAOYSA-N 0.000 claims description 26
• 125000003118 aryl group Chemical group 0.000 claims description 25
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• 238000011374 additional therapy Methods 0.000 claims description 20
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 20
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• 229940124647 MEK inhibitor Drugs 0.000 claims description 18
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 18
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• 238000000113 differential scanning calorimetry Methods 0.000 claims description 16
• 125000001153 fluoro group Chemical group F* 0.000 claims description 16
• VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 claims description 16
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• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 13
• 125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 claims description 13
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• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 13
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• 102000001291 MAP Kinase Kinase Kinase Human genes 0.000 claims description 9
• 108060006687 MAP kinase kinase kinase Proteins 0.000 claims description 9
• 238000009472 formulation Methods 0.000 claims description 9
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 9
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• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
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• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 7
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