NL1026329C2 - 2-Amino-pyridinederivaten toepasbaar voor de behandeling van ziekten. - Google Patents

Info

Publication number

NL1026329C2

NL1026329C2 NL1026329A NL1026329A NL1026329C2 NL 1026329 C2 NL1026329 C2 NL 1026329C2 NL 1026329 A NL1026329 A NL 1026329A NL 1026329 A NL1026329 A NL 1026329A NL 1026329 C2 NL1026329 C2 NL 1026329C2

Authority

NL

Netherlands

Prior art keywords

hydroxy

amino

propyl

phenyl

aminopyridin

Prior art date

2003-06-04

Links

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• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 28
• 238000011282 treatment Methods 0.000 title claims description 26
• 201000010099 disease Diseases 0.000 title claims description 21
• 150000003930 2-aminopyridines Chemical class 0.000 title claims description 12
• -1 Clf F Chemical group 0.000 claims description 594
• 229910052739 hydrogen Inorganic materials 0.000 claims description 421
• 150000001875 compounds Chemical class 0.000 claims description 282
• 238000002360 preparation method Methods 0.000 claims description 275
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 209
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 137
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 131
• 238000000034 method Methods 0.000 claims description 126
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 112
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 101
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 100
• 239000000203 mixture Substances 0.000 claims description 78
• 150000001412 amines Chemical class 0.000 claims description 66
• 239000002253 acid Substances 0.000 claims description 58
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 41
• 208000006673 asthma Diseases 0.000 claims description 40
• 150000003839 salts Chemical class 0.000 claims description 38
• 239000003814 drug Substances 0.000 claims description 30
• 150000001408 amides Chemical class 0.000 claims description 29
• 206010006451 bronchitis Diseases 0.000 claims description 29
• 125000000217 alkyl group Chemical group 0.000 claims description 28
• 239000000556 agonist Substances 0.000 claims description 27
• ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 claims description 24
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 22
• 230000000694 effects Effects 0.000 claims description 20
• 102000005962 receptors Human genes 0.000 claims description 17
• 108020003175 receptors Proteins 0.000 claims description 17
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 15
• 201000009267 bronchiectasis Diseases 0.000 claims description 15
• 229910052799 carbon Inorganic materials 0.000 claims description 15
• 239000005557 antagonist Substances 0.000 claims description 13
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 13
• 229910052731 fluorine Inorganic materials 0.000 claims description 12
• 210000003437 trachea Anatomy 0.000 claims description 12
• 229910052801 chlorine Inorganic materials 0.000 claims description 11
• 125000004464 hydroxyphenyl group Chemical group 0.000 claims description 11
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 10
• 239000003795 chemical substances by application Substances 0.000 claims description 10
• 125000006289 hydroxybenzyl group Chemical group 0.000 claims description 10
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• 230000001404 mediated effect Effects 0.000 claims description 10
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• 125000006239 protecting group Chemical group 0.000 claims description 9
• 229940124597 therapeutic agent Drugs 0.000 claims description 9
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
• 229910052736 halogen Inorganic materials 0.000 claims description 8
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• 229910052740 iodine Inorganic materials 0.000 claims description 8
• 230000008506 pathogenesis Effects 0.000 claims description 8
• 239000012453 solvate Substances 0.000 claims description 8
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 7
• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
• 125000004432 carbon atom Chemical group C* 0.000 claims description 7
• 125000006125 ethylsulfonyl group Chemical group 0.000 claims description 7
• 150000002367 halogens Chemical class 0.000 claims description 7
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 7
• 230000008569 process Effects 0.000 claims description 7
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• ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 claims description 7
• 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 6
• 239000003199 leukotriene receptor blocking agent Substances 0.000 claims description 6
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
• 125000002947 alkylene group Chemical group 0.000 claims description 5
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 5
• YEESKJGWJFYOOK-IJHYULJSSA-N leukotriene D4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@H](N)C(=O)NCC(O)=O YEESKJGWJFYOOK-IJHYULJSSA-N 0.000 claims description 5
• 125000006291 3-hydroxybenzyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(=C1[H])C([H])([H])* 0.000 claims description 4
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• 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 4
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• 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 4
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• 239000002464 receptor antagonist Substances 0.000 claims description 4
• 125000006290 2-hydroxybenzyl group Chemical group [H]OC1=C(C([H])=C([H])C([H])=C1[H])C([H])([H])* 0.000 claims description 3
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• 239000002465 adenosine A2a receptor agonist Substances 0.000 claims description 3
• 239000013566 allergen Substances 0.000 claims description 3
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
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• 208000007451 chronic bronchitis Diseases 0.000 claims description 3
• 230000001684 chronic effect Effects 0.000 claims description 3
• VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 claims description 3
• 208000015181 infectious disease Diseases 0.000 claims description 3
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• GWNVDXQDILPJIG-NXOLIXFESA-N leukotriene C4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O GWNVDXQDILPJIG-NXOLIXFESA-N 0.000 claims description 3
• 239000003681 muscarinic M3 receptor antagonist Substances 0.000 claims description 3
• 239000002587 phosphodiesterase IV inhibitor Substances 0.000 claims description 3
• 229960000278 theophylline Drugs 0.000 claims description 3
• 125000003944 tolyl group Chemical group 0.000 claims description 3
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
• ASPWWXIBCWONIM-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-2-benzazepin-8-ol Chemical compound C1CCNCC2=CC(O)=CC=C21 ASPWWXIBCWONIM-UHFFFAOYSA-N 0.000 claims description 2
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
• XKGMBJQFLBSAMN-NRFANRHFSA-N 3-[2-[[(2r)-2-(6-aminopyridin-3-yl)-2-hydroxyethyl]amino]-2-methylpropyl]-n-(3-hydroxyphenyl)benzamide Chemical compound C([C@H](O)C=1C=NC(N)=CC=1)NC(C)(C)CC(C=1)=CC=CC=1C(=O)NC1=CC=CC(O)=C1 XKGMBJQFLBSAMN-NRFANRHFSA-N 0.000 claims description 2
• 125000006500 3-trifluoromethoxy benzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC(F)(F)F)=C1[H])C([H])([H])* 0.000 claims description 2
• 102000004023 5-Lipoxygenase-Activating Proteins Human genes 0.000 claims description 2
• 108090000411 5-Lipoxygenase-Activating Proteins Proteins 0.000 claims description 2
• OIRDTQYFTABQOQ-CRKDRTNXSA-N 9-α-D-ribofuranosyl-9H-Purin-6-amine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-CRKDRTNXSA-N 0.000 claims description 2
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• VNYSSYRCGWBHLG-AMOLWHMGSA-N leukotriene B4 Chemical compound CCCCC\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCCC(O)=O VNYSSYRCGWBHLG-AMOLWHMGSA-N 0.000 claims description 2
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• 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 239000010409 thin film Substances 0.000 description 1
• 230000009974 thixotropic effect Effects 0.000 description 1
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• 229960002117 triamcinolone acetonide Drugs 0.000 description 1
• YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 description 1
• XWNXEWLCHSLQOI-UHFFFAOYSA-K trisodium;triacetate Chemical compound [Na+].[Na+].[Na+].CC([O-])=O.CC([O-])=O.CC([O-])=O XWNXEWLCHSLQOI-UHFFFAOYSA-K 0.000 description 1
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• 238000005406 washing Methods 0.000 description 1
• 239000003871 white petrolatum Substances 0.000 description 1
• 150000003751 zinc Chemical class 0.000 description 1
• XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1