CA2559533A1 - Phenylaminoethanol derivatives as beta2 receptor agonists - Google Patents

Info

Publication number

CA2559533A1

CA2559533A1 CA002559533A CA2559533A CA2559533A1 CA 2559533 A1 CA2559533 A1 CA 2559533A1 CA 002559533 A CA002559533 A CA 002559533A CA 2559533 A CA2559533 A CA 2559533A CA 2559533 A1 CA2559533 A1 CA 2559533A1

Authority

CA

Canada

Prior art keywords

formula

asthma

bronchitis

compound

compounds

Prior art date

2004-03-17

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 108010014499 beta-2 Adrenergic Receptors Proteins 0.000 title description 2
• ULZRKSDAMUWQEZ-UHFFFAOYSA-N 1-anilinoethanol Chemical class CC(O)NC1=CC=CC=C1 ULZRKSDAMUWQEZ-UHFFFAOYSA-N 0.000 title 1
• 102000016966 beta-2 Adrenergic Receptors Human genes 0.000 title 1
• 239000000018 receptor agonist Substances 0.000 title 1
• 229940044601 receptor agonist Drugs 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 210
• 239000000203 mixture Substances 0.000 claims abstract description 90
• 238000000034 method Methods 0.000 claims abstract description 53
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 27
• 201000010099 disease Diseases 0.000 claims abstract description 21
• 230000002757 inflammatory effect Effects 0.000 claims abstract description 9
• 208000035475 disorder Diseases 0.000 claims abstract description 6
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 45
• 208000006673 asthma Diseases 0.000 claims description 40
• 150000003839 salts Chemical class 0.000 claims description 40
• 239000000556 agonist Substances 0.000 claims description 28
• 206010006451 bronchitis Diseases 0.000 claims description 28
• 239000003814 drug Substances 0.000 claims description 27
• 238000011282 treatment Methods 0.000 claims description 23
• 102000005962 receptors Human genes 0.000 claims description 21
• 108020003175 receptors Proteins 0.000 claims description 21
• 201000009267 bronchiectasis Diseases 0.000 claims description 18
• 125000000217 alkyl group Chemical group 0.000 claims description 16
• 229940079593 drug Drugs 0.000 claims description 14
• 239000005557 antagonist Substances 0.000 claims description 12
• 229940124597 therapeutic agent Drugs 0.000 claims description 11
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 10
• 239000003112 inhibitor Substances 0.000 claims description 10
• 230000001404 mediated effect Effects 0.000 claims description 10
• 239000003795 chemical substances by application Substances 0.000 claims description 9
• 241000124008 Mammalia Species 0.000 claims description 8
• 201000010659 intrinsic asthma Diseases 0.000 claims description 8
• 230000008506 pathogenesis Effects 0.000 claims description 8
• 239000012453 solvate Substances 0.000 claims description 8
• 239000003199 leukotriene receptor blocking agent Substances 0.000 claims description 6
• ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 claims description 6
• 206010006482 Bronchospasm Diseases 0.000 claims description 5
• 230000007885 bronchoconstriction Effects 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
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 5
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
• 102000001381 Arachidonate 5-Lipoxygenase Human genes 0.000 claims description 4
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• 206010006458 Bronchitis chronic Diseases 0.000 claims description 4
• 206010014561 Emphysema Diseases 0.000 claims description 4
• 229940122694 Muscarinic M3 receptor antagonist Drugs 0.000 claims description 4
• 208000027771 Obstructive airways disease Diseases 0.000 claims description 4
• 230000001154 acute effect Effects 0.000 claims description 4
• 239000000812 cholinergic antagonist Substances 0.000 claims description 4
• 208000007451 chronic bronchitis Diseases 0.000 claims description 4
• 208000024711 extrinsic asthma Diseases 0.000 claims description 4
• 239000003681 muscarinic M3 receptor antagonist Substances 0.000 claims description 4
• 230000000414 obstructive effect Effects 0.000 claims description 4
• 229940044551 receptor antagonist Drugs 0.000 claims description 4
• 239000002464 receptor antagonist Substances 0.000 claims description 4
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 3
• 108090000695 Cytokines Proteins 0.000 claims description 3
• 102000004127 Cytokines Human genes 0.000 claims description 3
• 208000000059 Dyspnea Diseases 0.000 claims description 3
• 206010013975 Dyspnoeas Diseases 0.000 claims description 3
• 229940121948 Muscarinic receptor antagonist Drugs 0.000 claims description 3
• 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 claims description 3
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 3
• 101100545004 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) YSP2 gene Proteins 0.000 claims description 3
• 102000000551 Syk Kinase Human genes 0.000 claims description 3
• 108010016672 Syk Kinase Proteins 0.000 claims description 3
• 239000002465 adenosine A2a receptor agonist Substances 0.000 claims description 3
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 3
• 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 3
• 125000002947 alkylene group Chemical group 0.000 claims description 3
• 239000013566 allergen Substances 0.000 claims description 3
• 229940043355 kinase inhibitor Drugs 0.000 claims description 3
• 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 3
• 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
• 238000004519 manufacturing process Methods 0.000 claims description 3
• 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims description 3
• 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 claims description 3
• 239000002587 phosphodiesterase IV inhibitor Substances 0.000 claims description 3
• 239000003757 phosphotransferase inhibitor Substances 0.000 claims description 3
• 229960000278 theophylline Drugs 0.000 claims description 3
• XKNAGLMNQADBQE-UHFFFAOYSA-N 1-(5-tert-butyl-1,2-oxazol-3-yl)-3-(4-pyridin-4-yloxyphenyl)urea Chemical compound O1C(C(C)(C)C)=CC(NC(=O)NC=2C=CC(OC=3C=CN=CC=3)=CC=2)=N1 XKNAGLMNQADBQE-UHFFFAOYSA-N 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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• 208000035143 Bacterial infection Diseases 0.000 claims description 2
• 229940124638 COX inhibitor Drugs 0.000 claims description 2
• 101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 claims description 2
• 101100135868 Dictyostelium discoideum pde3 gene Proteins 0.000 claims description 2
• 102000015554 Dopamine receptor Human genes 0.000 claims description 2
• 108050004812 Dopamine receptor Proteins 0.000 claims description 2
• 208000004657 Exercise-Induced Asthma Diseases 0.000 claims description 2
• 206010017533 Fungal infection Diseases 0.000 claims description 2
• 229940122236 Histamine receptor antagonist Drugs 0.000 claims description 2
• 101001125071 Homo sapiens Neuromedin-K receptor Proteins 0.000 claims description 2
• 239000003458 I kappa b kinase inhibitor Substances 0.000 claims description 2
• 208000016300 Idiopathic chronic eosinophilic pneumonia Diseases 0.000 claims description 2
• 108010008212 Integrin alpha4beta1 Proteins 0.000 claims description 2
• 102000042838 JAK family Human genes 0.000 claims description 2
• 108091082332 JAK family Proteins 0.000 claims description 2
• 102000005741 Metalloproteases Human genes 0.000 claims description 2
• 108010006035 Metalloproteases Proteins 0.000 claims description 2
• 208000031888 Mycoses Diseases 0.000 claims description 2
• 108010040722 Neurokinin-2 Receptors Proteins 0.000 claims description 2
• 102100029409 Neuromedin-K receptor Human genes 0.000 claims description 2
• 229940123263 Phosphodiesterase 3 inhibitor Drugs 0.000 claims description 2
• 229940123333 Phosphodiesterase 5 inhibitor Drugs 0.000 claims description 2
• 101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 claims description 2
• 102100038277 Prostaglandin G/H synthase 1 Human genes 0.000 claims description 2
• 108050003243 Prostaglandin G/H synthase 1 Proteins 0.000 claims description 2
• 241000191940 Staphylococcus Species 0.000 claims description 2
• 102100037342 Substance-K receptor Human genes 0.000 claims description 2
• 239000000150 Sympathomimetic Substances 0.000 claims description 2
• 102000003141 Tachykinin Human genes 0.000 claims description 2
• 206010054094 Tumour necrosis Diseases 0.000 claims description 2
• 102000003990 Urokinase-type plasminogen activator Human genes 0.000 claims description 2
• 108090000435 Urokinase-type plasminogen activator Proteins 0.000 claims description 2
• 208000036142 Viral infection Diseases 0.000 claims description 2
• 206010047924 Wheezing Diseases 0.000 claims description 2
• 206010069351 acute lung injury Diseases 0.000 claims description 2
• 239000003470 adrenal cortex hormone Substances 0.000 claims description 2
• 239000000048 adrenergic agonist Substances 0.000 claims description 2
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• 230000000954 anitussive effect Effects 0.000 claims description 2
• 239000003242 anti bacterial agent Substances 0.000 claims description 2
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• 229940088710 antibiotic agent Drugs 0.000 claims description 2
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• 230000001580 bacterial effect Effects 0.000 claims description 2
• 208000022362 bacterial infectious disease Diseases 0.000 claims description 2
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• 201000009323 chronic eosinophilic pneumonia Diseases 0.000 claims description 2
• 229940111134 coxibs Drugs 0.000 claims description 2
• 229960000265 cromoglicic acid Drugs 0.000 claims description 2
• 239000003260 cyclooxygenase 1 inhibitor Substances 0.000 claims description 2
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• 239000000850 decongestant Substances 0.000 claims description 2
• 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 2
• 238000002651 drug therapy Methods 0.000 claims description 2
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• 230000007613 environmental effect Effects 0.000 claims description 2
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• 239000003172 expectorant agent Substances 0.000 claims description 2
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• 239000003276 histone deacetylase inhibitor Substances 0.000 claims description 2
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• 208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 2
• 230000002427 irreversible effect Effects 0.000 claims description 2
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• OTZRAYGBFWZKMX-JUDRUQEKSA-N leukotriene E4 Chemical compound CCCCCC=CCC=C\C=C\C=C\[C@@H](SC[C@H](N)C(O)=O)[C@@H](O)CCCC(O)=O OTZRAYGBFWZKMX-JUDRUQEKSA-N 0.000 claims description 2
• 239000011159 matrix material Substances 0.000 claims description 2
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• 229940066491 mucolytics Drugs 0.000 claims description 2
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• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 2
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• 230000001991 pathophysiological effect Effects 0.000 claims description 2
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• 239000002570 phosphodiesterase III inhibitor Substances 0.000 claims description 2
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• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 4
• 125000001475 halogen functional group Chemical group 0.000 claims 2
• 108010040718 Neurokinin-1 Receptors Proteins 0.000 claims 1
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• PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 claims 1
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• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 132
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• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 44
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• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 33
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
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• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 26
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
• KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 24
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