ZA200502359B - Indole derivatives as beta-2-agonists - Google Patents
Indole derivatives as beta-2-agonists Download PDFInfo
- Publication number
- ZA200502359B ZA200502359B ZA200502359A ZA200502359A ZA200502359B ZA 200502359 B ZA200502359 B ZA 200502359B ZA 200502359 A ZA200502359 A ZA 200502359A ZA 200502359 A ZA200502359 A ZA 200502359A ZA 200502359 B ZA200502359 B ZA 200502359B
- Authority
- ZA
- South Africa
- Prior art keywords
- hydroxy
- ethyl
- indole
- carboxamide
- amino
- Prior art date
Links
- 229940054051 antipsychotic indole derivative Drugs 0.000 title description 36
- 150000002475 indoles Chemical class 0.000 title description 36
- 229940124748 beta 2 agonist Drugs 0.000 title description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 67
- 150000001875 compounds Chemical class 0.000 claims description 54
- 229910052739 hydrogen Inorganic materials 0.000 claims description 51
- 239000001257 hydrogen Substances 0.000 claims description 50
- 150000003839 salts Chemical class 0.000 claims description 49
- 125000000217 alkyl group Chemical group 0.000 claims description 48
- 150000002431 hydrogen Chemical class 0.000 claims description 26
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- 239000012453 solvate Substances 0.000 claims description 23
- 239000000556 agonist Substances 0.000 claims description 21
- 208000006673 asthma Diseases 0.000 claims description 21
- 230000000155 isotopic effect Effects 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 15
- 201000010099 disease Diseases 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- -1 hydroxy, methyl Chemical group 0.000 claims description 13
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 238000011282 treatment Methods 0.000 claims description 11
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 7
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 6
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 6
- 230000001404 mediated effect Effects 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 4
- 206010006482 Bronchospasm Diseases 0.000 claims description 3
- 230000007885 bronchoconstriction Effects 0.000 claims description 3
- 230000002757 inflammatory effect Effects 0.000 claims description 3
- FDAKLYKEIOPOKK-XBBWARJSSA-N 5-[(2r)-2-[[(2r)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl]amino]propyl]-n-[2-(3-methoxyphenyl)ethyl]-1h-indole-2-carboxamide Chemical compound COC1=CC=CC(CCNC(=O)C=2NC3=CC=C(C[C@@H](C)NC[C@H](O)C=4C=C(CO)C(O)=CC=4)C=C3C=2)=C1 FDAKLYKEIOPOKK-XBBWARJSSA-N 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims description 2
- 239000013566 allergen Substances 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 206010006451 bronchitis Diseases 0.000 claims 14
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 10
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- 125000001475 halogen functional group Chemical group 0.000 claims 5
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- 230000008506 pathogenesis Effects 0.000 claims 4
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- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims 2
- 230000001154 acute effect Effects 0.000 claims 2
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims 2
- 208000007451 chronic bronchitis Diseases 0.000 claims 2
- 208000024711 extrinsic asthma Diseases 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
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- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- VFHUJFBEFDVZPJ-UHFFFAOYSA-N 1h-indole-2-carboxamide Chemical compound C1=CC=C2NC(C(=O)N)=CC2=C1 VFHUJFBEFDVZPJ-UHFFFAOYSA-N 0.000 claims 1
- 206010003557 Asthma exercise induced Diseases 0.000 claims 1
- 206010003645 Atopy Diseases 0.000 claims 1
- 208000035143 Bacterial infection Diseases 0.000 claims 1
- 208000000059 Dyspnea Diseases 0.000 claims 1
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- 208000004657 Exercise-Induced Asthma Diseases 0.000 claims 1
- 206010017533 Fungal infection Diseases 0.000 claims 1
- 208000016300 Idiopathic chronic eosinophilic pneumonia Diseases 0.000 claims 1
- 208000031888 Mycoses Diseases 0.000 claims 1
- 241000191940 Staphylococcus Species 0.000 claims 1
- 208000036142 Viral infection Diseases 0.000 claims 1
- 206010047924 Wheezing Diseases 0.000 claims 1
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- 230000001580 bacterial effect Effects 0.000 claims 1
- 208000022362 bacterial infectious disease Diseases 0.000 claims 1
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- 238000002651 drug therapy Methods 0.000 claims 1
- 230000007613 environmental effect Effects 0.000 claims 1
- 230000005713 exacerbation Effects 0.000 claims 1
- 208000024695 exercise-induced bronchoconstriction Diseases 0.000 claims 1
- 230000003325 follicular Effects 0.000 claims 1
- 230000002538 fungal effect Effects 0.000 claims 1
- 230000035874 hyperreactivity Effects 0.000 claims 1
- 208000015181 infectious disease Diseases 0.000 claims 1
- 230000002458 infectious effect Effects 0.000 claims 1
- 230000001524 infective effect Effects 0.000 claims 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims 1
- 230000002427 irreversible effect Effects 0.000 claims 1
- WTBGOYCHEVMMHF-CLYVBNDRSA-N n-[(2,6-dimethoxyphenyl)methyl]-5-[(2r)-2-[[(2r)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl]amino]propyl]-1h-indole-2-carboxamide Chemical compound COC1=CC=CC(OC)=C1CNC(=O)C1=CC2=CC(C[C@@H](C)NC[C@H](O)C=3C=C(CO)C(O)=CC=3)=CC=C2N1 WTBGOYCHEVMMHF-CLYVBNDRSA-N 0.000 claims 1
- 208000007892 occupational asthma Diseases 0.000 claims 1
- 230000001991 pathophysiological effect Effects 0.000 claims 1
- 230000000750 progressive effect Effects 0.000 claims 1
- 208000028172 protozoa infectious disease Diseases 0.000 claims 1
- 208000002815 pulmonary hypertension Diseases 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
- 230000009385 viral infection Effects 0.000 claims 1
- 238000000034 method Methods 0.000 description 25
- 239000002904 solvent Substances 0.000 description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 150000001412 amines Chemical class 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 125000005843 halogen group Chemical group 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 230000000172 allergic effect Effects 0.000 description 7
- 208000010668 atopic eczema Diseases 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- 108060003345 Adrenergic Receptor Proteins 0.000 description 6
- 102000017910 Adrenergic receptor Human genes 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 5
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
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- 239000000543 intermediate Substances 0.000 description 4
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- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 3
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- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical class C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP03290069A EP1440966A1 (de) | 2003-01-10 | 2003-01-10 | Zur Behandlung von Krankheiten geeignete Indolderivate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200502359B true ZA200502359B (en) | 2006-11-29 |
Family
ID=32524258
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200502359A ZA200502359B (en) | 2003-01-10 | 2005-03-22 | Indole derivatives as beta-2-agonists |
Country Status (2)
| Country | Link |
|---|---|
| EP (1) | EP1440966A1 (de) |
| ZA (1) | ZA200502359B (de) |
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10217006A1 (de) | 2002-04-16 | 2003-11-06 | Merck Patent Gmbh | Substituierte Indole |
| GB0401334D0 (en) | 2004-01-21 | 2004-02-25 | Novartis Ag | Organic compounds |
| GT200500281A (es) | 2004-10-22 | 2006-04-24 | Novartis Ag | Compuestos organicos. |
| GB0424284D0 (en) | 2004-11-02 | 2004-12-01 | Novartis Ag | Organic compounds |
| GB0426164D0 (en) | 2004-11-29 | 2004-12-29 | Novartis Ag | Organic compounds |
| GB0507577D0 (en) | 2005-04-14 | 2005-05-18 | Novartis Ag | Organic compounds |
| CA2618089A1 (en) | 2005-08-08 | 2007-02-15 | Argenta Discovery Ltd. | Bicyclo[2.2.]hept-7-ylamine derivatives and their uses |
| GB0516313D0 (en) | 2005-08-08 | 2005-09-14 | Argenta Discovery Ltd | Azole derivatives and their uses |
| EP1957530A2 (de) | 2005-10-21 | 2008-08-20 | Novartis AG | Menschliche antikörper gegen il13 und therapeutische verwendungen |
| GB0601951D0 (en) | 2006-01-31 | 2006-03-15 | Novartis Ag | Organic compounds |
| DK2013211T3 (da) | 2006-04-21 | 2012-07-02 | Novartis Ag | Purinderivater til anvendelse som adenosin-A2A-receptoragonister |
| CN101522682A (zh) | 2006-10-30 | 2009-09-02 | 诺瓦提斯公司 | 作为抗炎剂的杂环化合物 |
| DK2104535T3 (da) | 2007-01-10 | 2011-04-04 | Irm Llc | Forbindelser og sammensætninger som kanalaktiverende proteaseinhibitorer |
| JP2010518097A (ja) | 2007-02-09 | 2010-05-27 | アイアールエム・リミテッド・ライアビリティ・カンパニー | チャネル活性化プロテアーゼ阻害剤としての化合物および組成物 |
| CA2685546A1 (en) | 2007-05-07 | 2008-11-13 | Novartis Ag | Organic compounds |
| NZ585789A (en) | 2007-12-10 | 2012-03-30 | Novartis Ag | Pyrazine-2-carboxamide derivatives to treat diseases mediated by blockade of the epithelial sodium channel |
| PL2231642T3 (pl) | 2008-01-11 | 2014-04-30 | Novartis Ag | Pirymidyny jako inhibitory kinazy |
| MX2010013675A (es) | 2008-06-10 | 2011-02-15 | Novartis Ag | Derivados de pirazina como bloqueadores del canal de sodio epitelial. |
| US8236786B2 (en) | 2008-08-07 | 2012-08-07 | Pulmagen Therapeutics (Inflammation) Limited | Respiratory disease treatment |
| AU2009334597B2 (en) | 2008-12-30 | 2015-07-16 | Pulmagen Therapeutics (Inflammation) Limited | Sulfonamide compounds for the treatment of respiratory disorders |
| WO2010150014A1 (en) | 2009-06-24 | 2010-12-29 | Pulmagen Therapeutics (Inflammation) Limited | 5r- 5 -deuterated glitazones for respiratory disease treatment |
| EP2490687A1 (de) | 2009-10-22 | 2012-08-29 | Vertex Pharmaceuticals Incorporated | Zusammensetzungen für die behandlung von mukoviszidose und anderen chronischen erkrankungen |
| GB0918924D0 (en) | 2009-10-28 | 2009-12-16 | Vantia Ltd | Azaindole derivatives |
| GB0918923D0 (en) | 2009-10-28 | 2009-12-16 | Vantia Ltd | Aminothiazole derivatives |
| GB0918922D0 (en) | 2009-10-28 | 2009-12-16 | Vantia Ltd | Aminopyridine derivatives |
| WO2011098746A1 (en) | 2010-02-09 | 2011-08-18 | Pulmagen Therapeutics (Inflammation) Limited | Crystalline acid addition salts of ( 5r) -enanti0mer of pioglitazone |
| GB201002243D0 (en) | 2010-02-10 | 2010-03-31 | Argenta Therapeutics Ltd | Respiratory disease treatment |
| GB201002224D0 (en) | 2010-02-10 | 2010-03-31 | Argenta Therapeutics Ltd | Respiratory disease treatment |
| US8247436B2 (en) | 2010-03-19 | 2012-08-21 | Novartis Ag | Pyridine and pyrazine derivative for the treatment of CF |
| US8637516B2 (en) | 2010-09-09 | 2014-01-28 | Irm Llc | Compounds and compositions as TRK inhibitors |
| WO2012034095A1 (en) | 2010-09-09 | 2012-03-15 | Irm Llc | Compounds and compositions as trk inhibitors |
| US8372845B2 (en) | 2010-09-17 | 2013-02-12 | Novartis Ag | Pyrazine derivatives as enac blockers |
| MA34969B1 (fr) | 2011-02-25 | 2014-03-01 | Irm Llc | Composes et compositions en tant qu inibiteurs de trk |
| US8883819B2 (en) | 2011-09-01 | 2014-11-11 | Irm Llc | Bicyclic heterocycle derivatives for the treatment of pulmonary arterial hypertension |
| US9034879B2 (en) | 2011-09-16 | 2015-05-19 | Novartis Ag | Heterocyclic compounds for the treatment of CF |
| WO2013038381A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine/pyrazine amide derivatives |
| WO2013038373A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
| WO2013038378A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
| EP2755652B1 (de) | 2011-09-16 | 2021-06-02 | Novartis AG | N-substituierte heterocyclische carboxamide |
| US8809340B2 (en) | 2012-03-19 | 2014-08-19 | Novartis Ag | Crystalline form |
| US9073921B2 (en) | 2013-03-01 | 2015-07-07 | Novartis Ag | Salt forms of bicyclic heterocyclic derivatives |
| ES2761569T3 (es) | 2014-04-24 | 2020-05-20 | Novartis Ag | Derivados aminopiridínicos como inhibidores de fosfatidilinositol 3-cinasas |
| EA032075B1 (ru) | 2014-04-24 | 2019-04-30 | Новартис Аг | Производные аминопиразина в качестве ингибиторов фосфатидилинозитол-3-киназы |
| JP6404944B2 (ja) | 2014-04-24 | 2018-10-17 | ノバルティス アーゲー | ホスファチジルイノシトール３−キナーゼ阻害薬としてのピラジン誘導体 |
| AU2020290094B2 (en) | 2019-06-10 | 2024-01-18 | Novartis Ag | Pyridine and pyrazine derivative for the treatment of CF, COPD, and bronchiectasis |
| AR119819A1 (es) | 2019-08-28 | 2022-01-12 | Novartis Ag | Derivados de 1,3-fenil heteroarilo sustituidos y su uso en el tratamiento de enfermedades |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6514996B2 (en) * | 1995-05-19 | 2003-02-04 | Kyowa Hakko Kogyo Co., Ltd. | Derivatives of benzofuran or benzodioxole |
| EP0801060A1 (de) * | 1996-04-09 | 1997-10-15 | Pfizer Inc. | Heterocyclische Beta-3 adrenergische Angonisten |
| EP0822185A1 (de) * | 1996-07-31 | 1998-02-04 | Pfizer Inc. | Beta-3-adrenergische Agonisten als antidiabetische Mittel und als Mittel gegen Fettsucht |
-
2003
- 2003-01-10 EP EP03290069A patent/EP1440966A1/de not_active Withdrawn
-
2005
- 2005-03-22 ZA ZA200502359A patent/ZA200502359B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP1440966A1 (de) | 2004-07-28 |
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