CA2475633C - Heteroaryl compounds useful as inhibitors of gsk-3 - Google Patents
Heteroaryl compounds useful as inhibitors of gsk-3 Download PDFInfo
- Publication number
- CA2475633C CA2475633C CA2475633A CA2475633A CA2475633C CA 2475633 C CA2475633 C CA 2475633C CA 2475633 A CA2475633 A CA 2475633A CA 2475633 A CA2475633 A CA 2475633A CA 2475633 C CA2475633 C CA 2475633C
- Authority
- CA
- Canada
- Prior art keywords
- benzoimidazol
- furazan
- ring
- aliphatic
- optionally substituted
- Prior art date
- 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.)
- Expired - Fee Related
Links
- 125000001072 heteroaryl group Chemical group 0.000 title claims description 18
- 239000003112 inhibitor Substances 0.000 title abstract description 24
- 101150090422 gsk-3 gene Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 136
- 239000000203 mixture Substances 0.000 claims abstract description 129
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 101
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 78
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 43
- 229910052717 sulfur Chemical group 0.000 claims abstract description 38
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 37
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 37
- 125000001424 substituent group Chemical group 0.000 claims abstract description 37
- 239000011593 sulfur Chemical group 0.000 claims abstract description 37
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 36
- 239000001301 oxygen Chemical group 0.000 claims abstract description 36
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 36
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 32
- 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 claims abstract description 31
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 16
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 14
- 238000011282 treatment Methods 0.000 claims abstract description 14
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 13
- 206010052779 Transplant rejections Diseases 0.000 claims abstract description 7
- 208000035475 disorder Diseases 0.000 claims abstract description 7
- 102000002254 Glycogen Synthase Kinase 3 Human genes 0.000 claims abstract 2
- 125000001931 aliphatic group Chemical group 0.000 claims description 80
- -1 1,2-ethylenedioxy Chemical group 0.000 claims description 36
- 201000010099 disease Diseases 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 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 24
- 239000001257 hydrogen Substances 0.000 claims description 23
- 125000001118 alkylidene group Chemical group 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 21
- 125000003118 aryl group Chemical group 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 17
- 201000006417 multiple sclerosis Diseases 0.000 claims description 16
- 125000005843 halogen group Chemical group 0.000 claims description 15
- 150000002367 halogens Chemical class 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 14
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 12
- 229940124597 therapeutic agent Drugs 0.000 claims description 12
- 108010002481 Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Proteins 0.000 claims description 11
- 102000036243 Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Human genes 0.000 claims description 11
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- 206010020751 Hypersensitivity Diseases 0.000 claims description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
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- 201000000980 schizophrenia Diseases 0.000 claims description 10
- 125000005605 benzo group Chemical group 0.000 claims description 9
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 9
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 8
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- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
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- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 6
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- QEPDSNAEMKSMGN-UHFFFAOYSA-N chembl1329127 Chemical compound NC1=NON=C1C1=NC2=CC=CC=C2N1 QEPDSNAEMKSMGN-UHFFFAOYSA-N 0.000 claims description 6
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- 125000004423 acyloxy group Chemical group 0.000 claims description 5
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- 125000003838 furazanyl group Chemical group 0.000 claims description 5
- 125000001475 halogen functional group Chemical group 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
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- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 3
- GLQIZLCZHSQBLY-UHFFFAOYSA-N 2-(1h-benzimidazol-2-yl)-4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1C1=NC2=CC=CC=C2N1 GLQIZLCZHSQBLY-UHFFFAOYSA-N 0.000 claims 2
- JMSNVUTXNCLSSL-UHFFFAOYSA-N 2-[2-(4-amino-1,2,5-oxadiazol-3-yl)benzimidazol-1-yl]-n-(2,4-difluorophenyl)acetamide Chemical compound NC1=NON=C1C1=NC2=CC=CC=C2N1CC(=O)NC1=CC=C(F)C=C1F JMSNVUTXNCLSSL-UHFFFAOYSA-N 0.000 claims 2
- OIIBRYKPFULYFU-UHFFFAOYSA-N 2-[2-(4-amino-1,2,5-oxadiazol-3-yl)benzimidazol-1-yl]-n-(2,6-dimethylphenyl)acetamide Chemical compound CC1=CC=CC(C)=C1NC(=O)CN1C2=CC=CC=C2N=C1C1=NON=C1N OIIBRYKPFULYFU-UHFFFAOYSA-N 0.000 claims 2
- MWPXMWVHOXXWCY-UHFFFAOYSA-N 2-[2-(4-amino-1,2,5-oxadiazol-3-yl)benzimidazol-1-yl]-n-(2-phenylphenyl)acetamide Chemical compound NC1=NON=C1C1=NC2=CC=CC=C2N1CC(=O)NC1=CC=CC=C1C1=CC=CC=C1 MWPXMWVHOXXWCY-UHFFFAOYSA-N 0.000 claims 2
- RKDKILJBYDCMPH-UHFFFAOYSA-N 2-[2-(4-amino-1,2,5-oxadiazol-3-yl)benzimidazol-1-yl]-n-(3,4-difluorophenyl)acetamide Chemical compound NC1=NON=C1C1=NC2=CC=CC=C2N1CC(=O)NC1=CC=C(F)C(F)=C1 RKDKILJBYDCMPH-UHFFFAOYSA-N 0.000 claims 2
- CLAATNFGGLOUTN-UHFFFAOYSA-N 2-[2-(4-amino-1,2,5-oxadiazol-3-yl)benzimidazol-1-yl]-n-(3,4-dimethoxyphenyl)acetamide Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)CN1C2=CC=CC=C2N=C1C1=NON=C1N CLAATNFGGLOUTN-UHFFFAOYSA-N 0.000 claims 2
- IBQVTCXZQBZBDN-UHFFFAOYSA-N 2-[2-(4-amino-1,2,5-oxadiazol-3-yl)benzimidazol-1-yl]-n-(3-fluorophenyl)acetamide Chemical compound NC1=NON=C1C1=NC2=CC=CC=C2N1CC(=O)NC1=CC=CC(F)=C1 IBQVTCXZQBZBDN-UHFFFAOYSA-N 0.000 claims 2
- DLHZNLYFGBAMAP-UHFFFAOYSA-N 2-[2-(4-amino-1,2,5-oxadiazol-3-yl)benzimidazol-1-yl]-n-tert-butylacetamide Chemical compound N=1C2=CC=CC=C2N(CC(=O)NC(C)(C)C)C=1C1=NON=C1N DLHZNLYFGBAMAP-UHFFFAOYSA-N 0.000 claims 2
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- PZFLXZUSYPMQHT-UHFFFAOYSA-N 2-[[2-(4-amino-1,2,5-oxadiazol-3-yl)benzimidazol-1-yl]methyl]benzonitrile Chemical compound NC1=NON=C1C1=NC2=CC=CC=C2N1CC1=CC=CC=C1C#N PZFLXZUSYPMQHT-UHFFFAOYSA-N 0.000 claims 2
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- ZIHIDNWPEZFEMR-UHFFFAOYSA-N 4-(1-methylbenzimidazol-2-yl)-1,2,5-oxadiazol-3-amine Chemical compound N=1C2=CC=CC=C2N(C)C=1C1=NON=C1N ZIHIDNWPEZFEMR-UHFFFAOYSA-N 0.000 claims 2
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- KNJOGMJHNSVZCC-UHFFFAOYSA-N 4-[1-(2h-tetrazol-5-ylmethyl)benzimidazol-2-yl]-1,2,5-oxadiazol-3-amine Chemical compound NC1=NON=C1C1=NC2=CC=CC=C2N1CC1=NNN=N1 KNJOGMJHNSVZCC-UHFFFAOYSA-N 0.000 claims 2
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Landscapes
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| US35484302P | 2002-02-06 | 2002-02-06 | |
| US60/354,843 | 2002-02-06 | ||
| PCT/US2003/003655 WO2003066629A2 (en) | 2002-02-06 | 2003-02-06 | Heteroaryl compounds useful as inhibitors of gsk-3 |
Publications (2)
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| CA2475633A1 CA2475633A1 (en) | 2003-08-14 |
| CA2475633C true CA2475633C (en) | 2013-04-02 |
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| EP (2) | EP1472245A2 (OSRAM) |
| JP (2) | JP4656838B2 (OSRAM) |
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| RU (1) | RU2004126671A (OSRAM) |
| SG (1) | SG159380A1 (OSRAM) |
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| AU2003290346A1 (en) * | 2002-12-24 | 2004-07-22 | Biofocus Plc | Compound libraries of 2,3-substituted pyrazine derivatives capable of binding to g-protein coupled receptors |
| WO2004069160A2 (en) * | 2003-01-28 | 2004-08-19 | Smithkline Beecham Corporation | Chemical compounds |
| JP2006520794A (ja) | 2003-03-21 | 2006-09-14 | スミスクライン ビーチャム コーポレーション | 化合物 |
| CN100434428C (zh) * | 2003-05-23 | 2008-11-19 | 巴斯利尔药物股份公司 | 呋咱并苯并咪唑类化合物 |
| TWI372050B (en) | 2003-07-03 | 2012-09-11 | Astex Therapeutics Ltd | (morpholin-4-ylmethyl-1h-benzimidazol-2-yl)-1h-pyrazoles |
| AR045134A1 (es) * | 2003-07-29 | 2005-10-19 | Smithkline Beecham Plc | Compuesto de 1h - imidazo [4,5-c] piridin-ilo, composicion farmaceutica que lo comprende, proceso para prepararla, su uso para preparar dicha composicion farmaceutica, combinacion farmaceutica, uso de la combinacion farmaceutica para la preparacion de un medicamento, procedimientos para preparar dic |
| JP2007512230A (ja) | 2003-08-20 | 2007-05-17 | バーテックス ファーマシューティカルズ インコーポレイテッド | プロテインキナーゼ阻害剤として有用な（４−アミノ−１，２，５−オキサジアゾール−４−イル）−ヘテロ芳香族化合物 |
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| DE102004010207A1 (de) | 2004-03-02 | 2005-09-15 | Aventis Pharma S.A. | Neue 4-Benzimidazol-2-yl-pyridazin-3-on-Derivate |
| US7772271B2 (en) | 2004-07-14 | 2010-08-10 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| US7868037B2 (en) | 2004-07-14 | 2011-01-11 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| US7781478B2 (en) | 2004-07-14 | 2010-08-24 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| JP2008506702A (ja) | 2004-07-14 | 2008-03-06 | ピーティーシー セラピューティクス，インコーポレーテッド | Ｃ型肝炎を治療するための方法 |
| NZ553329A (en) | 2004-07-22 | 2010-09-30 | Ptc Therapeutics Inc | Thienopyridines for treating hepatitis C |
| US7674907B2 (en) * | 2004-07-23 | 2010-03-09 | Amgen Inc. | Furanopyridine derivatives and methods of use |
| WO2006034207A2 (en) * | 2004-09-17 | 2006-03-30 | Vanderbilt University | Use of gsk3 inhibitors in combination with radiation therapies |
| GB0422057D0 (en) * | 2004-10-05 | 2004-11-03 | Astrazeneca Ab | Novel compounds |
| US20060204980A1 (en) * | 2004-12-28 | 2006-09-14 | Altieri Dario C | Colorectal cancer therapies |
| TWI427077B (zh) | 2004-12-30 | 2014-02-21 | Astex Therapeutics Ltd | 吡唑化合物及其用途和含有彼之藥學組成物 |
| US20080312223A1 (en) | 2004-12-30 | 2008-12-18 | Astex Therapeutics Limited | Thiazole And Isothiazole Derivatives That Modulate The Activity Of CDK, GSK And Aurora Kinases |
| CA2599989A1 (en) * | 2005-03-03 | 2006-09-08 | Sirtris Pharmaceuticals, Inc. | N-phenyl benzamide derivatives as sirtuin modulators |
| DK1871374T3 (da) * | 2005-04-21 | 2011-12-05 | Merck Serono Sa | 2,3-substituerede pyrazinsulfonamider som CRTH2-inhibitorer |
| AU2006251832A1 (en) * | 2005-05-27 | 2006-11-30 | Queen's University At Kingston | Treatment of protein folding disorders |
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| US7625890B2 (en) | 2005-11-10 | 2009-12-01 | Smithkline Beecham Corp. | Substituted imidazo[4,5-c]pyridine compounds as Akt inhibitors |
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| AU2007351886A1 (en) * | 2006-06-23 | 2008-10-30 | Paratek Pharmaceuticals, Inc. | Transcription factor modulating compounds and methods of use thereof |
| JP5523829B2 (ja) | 2006-06-29 | 2014-06-18 | アステックス、セラピューティックス、リミテッド | 複合薬剤 |
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- 2003-02-06 EP EP10180554.7A patent/EP2322521B1/en not_active Expired - Lifetime
- 2003-02-06 RU RU2004126671/04A patent/RU2004126671A/ru not_active Application Discontinuation
- 2003-02-06 US US10/360,535 patent/US20040034037A1/en not_active Abandoned
- 2003-02-06 SG SG200605228-6A patent/SG159380A1/en unknown
- 2003-02-06 ES ES10180554.7T patent/ES2437391T3/es not_active Expired - Lifetime
-
2004
- 2004-09-06 NO NO20043726A patent/NO20043726L/no unknown
-
2007
- 2007-07-12 US US11/776,756 patent/US20070270420A1/en not_active Abandoned
-
2010
- 2010-02-26 JP JP2010043557A patent/JP2010132697A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP1472245A2 (en) | 2004-11-03 |
| RU2004126671A (ru) | 2005-04-10 |
| EP2322521A1 (en) | 2011-05-18 |
| PL372198A1 (en) | 2005-07-11 |
| JP4656838B2 (ja) | 2011-03-23 |
| JP2010132697A (ja) | 2010-06-17 |
| KR20040084896A (ko) | 2004-10-06 |
| AU2003215087A1 (en) | 2003-09-02 |
| WO2003066629A3 (en) | 2003-10-30 |
| CA2475633A1 (en) | 2003-08-14 |
| AU2003215087B2 (en) | 2009-07-16 |
| JP2005526028A (ja) | 2005-09-02 |
| US20070270420A1 (en) | 2007-11-22 |
| SG159380A1 (en) | 2010-03-30 |
| WO2003066629A2 (en) | 2003-08-14 |
| ES2437391T3 (es) | 2014-01-10 |
| US20040034037A1 (en) | 2004-02-19 |
| MXPA04007697A (es) | 2004-11-10 |
| NO20043726L (no) | 2004-11-08 |
| EP2322521B1 (en) | 2013-09-04 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20160208 |