NO324059B1 - Imidazolo-5-yl-2-anilino-pyrimidiner, fremstilling, farmasoytisk preparat inneholdende disse, samt anvendelse for fremstilling av medikament for inhibering av celleproliferasjon - Google Patents

Info

Publication number

NO324059B1

NO324059B1 NO20031006A NO20031006A NO324059B1 NO 324059 B1 NO324059 B1 NO 324059B1 NO 20031006 A NO20031006 A NO 20031006A NO 20031006 A NO20031006 A NO 20031006A NO 324059 B1 NO324059 B1 NO 324059B1

Authority

NO

Norway

Prior art keywords

sulfamoyl

formula

compound

alkyl

group

Prior art date

2000-09-05

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• -1 nitro, cyano, hydroxy, amino, carboxy, carbamoyl Chemical group 0.000 claims description 234
• 150000001875 compounds Chemical class 0.000 claims description 232
• 238000000034 method Methods 0.000 claims description 172
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 147
• 125000000217 alkyl group Chemical group 0.000 claims description 71
• 125000000623 heterocyclic group Chemical group 0.000 claims description 64
• 150000002148 esters Chemical class 0.000 claims description 49
• 239000001257 hydrogen Substances 0.000 claims description 49
• 229910052739 hydrogen Inorganic materials 0.000 claims description 49
• 150000003839 salts Chemical class 0.000 claims description 49
• 229910052799 carbon Inorganic materials 0.000 claims description 44
• 229910052757 nitrogen Inorganic materials 0.000 claims description 44
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 43
• 229910052736 halogen Inorganic materials 0.000 claims description 43
• 150000002367 halogens Chemical class 0.000 claims description 43
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 43
• 238000001727 in vivo Methods 0.000 claims description 40
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 31
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 29
• 206010028980 Neoplasm Diseases 0.000 claims description 27
• 239000003814 drug Substances 0.000 claims description 27
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
• 229920006395 saturated elastomer Polymers 0.000 claims description 26
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 25
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 24
• 238000011282 treatment Methods 0.000 claims description 23
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 22
• 125000003545 alkoxy group Chemical group 0.000 claims description 22
• 230000008569 process Effects 0.000 claims description 21
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 20
• 150000002431 hydrogen Chemical class 0.000 claims description 20
• 238000004519 manufacturing process Methods 0.000 claims description 20
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 19
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 19
• 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 17
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 17
• 238000006243 chemical reaction Methods 0.000 claims description 17
• 239000000460 chlorine Substances 0.000 claims description 15
• 229910052801 chlorine Inorganic materials 0.000 claims description 14
• 229910052717 sulfur Inorganic materials 0.000 claims description 14
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 13
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 13
• 125000006239 protecting group Chemical group 0.000 claims description 13
• 125000004429 atom Chemical group 0.000 claims description 12
• 201000011510 cancer Diseases 0.000 claims description 12
• 230000002401 inhibitory effect Effects 0.000 claims description 12
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 10
• GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 10
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 9
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 9
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
• 150000001412 amines Chemical class 0.000 claims description 8
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
• 229910052794 bromium Inorganic materials 0.000 claims description 8
• 208000032839 leukemia Diseases 0.000 claims description 8
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
• 229910052760 oxygen Inorganic materials 0.000 claims description 8
• 210000002307 prostate Anatomy 0.000 claims description 8
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 7
• 125000004434 sulfur atom Chemical group 0.000 claims description 7
• 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 6
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
• 210000000481 breast Anatomy 0.000 claims description 6
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• 230000012010 growth Effects 0.000 claims description 6
• RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 claims description 6
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• 125000002950 monocyclic group Chemical group 0.000 claims description 6
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• 238000002360 preparation method Methods 0.000 claims description 6
• 230000035755 proliferation Effects 0.000 claims description 6
• 239000011593 sulfur Substances 0.000 claims description 6
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 5
• 125000002619 bicyclic group Chemical group 0.000 claims description 5
• 208000035475 disorder Diseases 0.000 claims description 5
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 5
• 125000006125 ethylsulfonyl group Chemical group 0.000 claims description 5
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 5
• 229910052703 rhodium Inorganic materials 0.000 claims description 5
• 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 4
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 4
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
• 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 claims description 4
• 206010051113 Arterial restenosis Diseases 0.000 claims description 4
• 206010003210 Arteriosclerosis Diseases 0.000 claims description 4
• 201000001320 Atherosclerosis Diseases 0.000 claims description 4
• 208000037260 Atherosclerotic Plaque Diseases 0.000 claims description 4
• 208000023275 Autoimmune disease Diseases 0.000 claims description 4
• 208000020084 Bone disease Diseases 0.000 claims description 4
• 208000007766 Kaposi sarcoma Diseases 0.000 claims description 4
• 150000001204 N-oxides Chemical class 0.000 claims description 4
• 208000022873 Ocular disease Diseases 0.000 claims description 4
• 201000004681 Psoriasis Diseases 0.000 claims description 4
• 230000001154 acute effect Effects 0.000 claims description 4
• 208000038016 acute inflammation Diseases 0.000 claims description 4
• 230000006022 acute inflammation Effects 0.000 claims description 4
• 125000005236 alkanoylamino group Chemical group 0.000 claims description 4
• 230000015572 biosynthetic process Effects 0.000 claims description 4
• 230000001684 chronic effect Effects 0.000 claims description 4
• 208000037976 chronic inflammation Diseases 0.000 claims description 4
• 230000006020 chronic inflammation Effects 0.000 claims description 4
• 230000000893 fibroproliferative effect Effects 0.000 claims description 4
• 201000011066 hemangioma Diseases 0.000 claims description 4
• 208000017169 kidney disease Diseases 0.000 claims description 4
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 4
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 4
• 230000000306 recurrent effect Effects 0.000 claims description 4
• 210000001210 retinal vessel Anatomy 0.000 claims description 4
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
• 210000003491 skin Anatomy 0.000 claims description 4
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 3
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 3
• 125000001589 carboacyl group Chemical group 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 3
• 210000001519 tissue Anatomy 0.000 claims description 3
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 2
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
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• 125000004423 acyloxy group Chemical group 0.000 claims description 2
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• 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
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• MDUHIEIIDZPVRB-UHFFFAOYSA-N n-cyclopropyl-4-[[4-(3-ethyl-2-methylimidazol-4-yl)pyrimidin-2-yl]amino]benzenesulfonamide Chemical compound CCN1C(C)=NC=C1C1=CC=NC(NC=2C=CC(=CC=2)S(=O)(=O)NC2CC2)=N1 MDUHIEIIDZPVRB-UHFFFAOYSA-N 0.000 claims 1
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• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 126
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