AU2008304657B2 - Indole compounds bearing aryl or heteroaryl groups having sphingosine-1-phosphate (S1P) receptor biological activity - Google Patents
Indole compounds bearing aryl or heteroaryl groups having sphingosine-1-phosphate (S1P) receptor biological activity Download PDFInfo
- Publication number
- AU2008304657B2 AU2008304657B2 AU2008304657A AU2008304657A AU2008304657B2 AU 2008304657 B2 AU2008304657 B2 AU 2008304657B2 AU 2008304657 A AU2008304657 A AU 2008304657A AU 2008304657 A AU2008304657 A AU 2008304657A AU 2008304657 B2 AU2008304657 B2 AU 2008304657B2
- Authority
- AU
- Australia
- Prior art keywords
- heteroaryl
- substituted
- sphingosine
- compound
- aryl
- 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.)
- Ceased
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- 125000001072 heteroaryl group Chemical group 0.000 title claims abstract description 51
- 125000003118 aryl group Chemical group 0.000 title claims abstract description 30
- DUYSYHSSBDVJSM-KRWOKUGFSA-N sphingosine 1-phosphate Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)COP(O)(O)=O DUYSYHSSBDVJSM-KRWOKUGFSA-N 0.000 title description 18
- 230000004071 biological effect Effects 0.000 title description 4
- 125000001041 indolyl group Chemical group 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 47
- 102000011011 Sphingosine 1-phosphate receptors Human genes 0.000 claims abstract description 12
- 108050001083 Sphingosine 1-phosphate receptors Proteins 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 24
- 125000004432 carbon atom Chemical group C* 0.000 claims description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 23
- 208000002193 Pain Diseases 0.000 claims description 20
- 208000035475 disorder Diseases 0.000 claims description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 125000003342 alkenyl group Chemical group 0.000 claims description 13
- 125000000304 alkynyl group Chemical group 0.000 claims description 13
- -1 sulfoxy Chemical group 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 125000003107 substituted aryl group Chemical group 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 6
- 208000005298 acute pain Diseases 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
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- 238000004519 manufacturing process Methods 0.000 claims 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 claims description 4
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- 150000004820 halides Chemical class 0.000 claims description 4
- 125000001188 haloalkyl group Chemical group 0.000 claims description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
- 125000005702 oxyalkylene group Chemical group 0.000 claims description 4
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 4
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 4
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- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
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- 125000002252 acyl group Chemical group 0.000 claims description 3
- 125000004849 alkoxymethyl group Chemical group 0.000 claims description 3
- 125000003368 amide group Chemical group 0.000 claims description 3
- 125000004104 aryloxy group Chemical group 0.000 claims description 3
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 239000013078 crystal Chemical group 0.000 claims description 3
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- 125000004043 oxo group Chemical group O=* 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 150000002475 indoles Chemical class 0.000 abstract description 15
- 239000005557 antagonist Substances 0.000 abstract description 6
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- 239000000203 mixture Substances 0.000 description 11
- WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 description 10
- 125000001183 hydrocarbyl group Chemical group 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 8
- 150000003408 sphingolipids Chemical class 0.000 description 8
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 description 8
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- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
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- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 4
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- 239000000725 suspension Substances 0.000 description 4
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 3
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Ophthalmology & Optometry (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US97451107P | 2007-09-24 | 2007-09-24 | |
| US60/974,511 | 2007-09-24 | ||
| PCT/US2008/076792 WO2009042485A1 (en) | 2007-09-24 | 2008-09-18 | Indole compounds bearing aryl or heteroaryl groups having sphingosine-1-phosphate (s1p) receptor biological activity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2008304657A1 AU2008304657A1 (en) | 2009-04-02 |
| AU2008304657B2 true AU2008304657B2 (en) | 2013-09-05 |
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| AU2008304657A Ceased AU2008304657B2 (en) | 2007-09-24 | 2008-09-18 | Indole compounds bearing aryl or heteroaryl groups having sphingosine-1-phosphate (S1P) receptor biological activity |
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| EP (1) | EP2203424A1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP2010540543A (cg-RX-API-DMAC7.html) |
| KR (1) | KR20100067677A (cg-RX-API-DMAC7.html) |
| CN (1) | CN101918360A (cg-RX-API-DMAC7.html) |
| AU (1) | AU2008304657B2 (cg-RX-API-DMAC7.html) |
| BR (1) | BRPI0817397A2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2700539A1 (cg-RX-API-DMAC7.html) |
| RU (1) | RU2010112275A (cg-RX-API-DMAC7.html) |
| WO (1) | WO2009042485A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JPWO2006088246A1 (ja) * | 2005-02-18 | 2008-07-10 | 武田薬品工業株式会社 | Ｇｐｒ３４受容体機能調節剤 |
| US8524917B2 (en) * | 2007-01-11 | 2013-09-03 | Allergan, Inc. | 6-substituted indole-3-carboxylic acid amide compounds having sphingosine-1-phosphate (S1P) receptor antagonist biological activity |
| WO2012145236A1 (en) * | 2011-04-18 | 2012-10-26 | Allergan, Inc. | Substituted bicyclic methyl amine derivatives as sphingosine-1 phosphate receptors modulators |
| GB201603745D0 (en) * | 2016-03-04 | 2016-04-20 | Galapagos Nv | Novel compounds and pharmaceutical compositions thereof for the treatment of fibrosis |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007112322A2 (en) * | 2006-03-28 | 2007-10-04 | Allergan, Inc. | Indole compounds having sphingosine-1-phosphate (s1p) receptor agonist and/or antagonist biological activity |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4363912A (en) * | 1980-12-15 | 1982-12-14 | Pfizer Inc. | Indole thromboxane synthetase inhibitors |
| EP0146810A3 (de) | 1983-12-05 | 1987-05-13 | Solco Basel AG | Verfahren zur Herstellung von Sphingosinderivaten |
| US5110987A (en) | 1988-06-17 | 1992-05-05 | Emory University | Method of preparing sphingosine derivatives |
| NZ233285A (en) | 1989-04-18 | 1992-06-25 | Duphar Int Res | Imidazole-substituted carbamoyl-indoles and condensed analogues thereof and pharmaceutical compositions |
| US5294722A (en) | 1992-04-16 | 1994-03-15 | E. R. Squibb & Sons, Inc. | Process for the preparation of imidazoles useful in angiotensin II antagonism |
| US5403851A (en) | 1994-04-05 | 1995-04-04 | Interneuron Pharmaceuticals, Inc. | Substituted tryptamines, phenalkylamines and related compounds |
| US5639780A (en) * | 1995-05-22 | 1997-06-17 | Merck Frosst Canada, Inc. | N-benzyl indol-3-yl butanoic acid derivatives as cyclooxygenase inhibitors |
| US5811425A (en) * | 1997-03-04 | 1998-09-22 | Abbott Laboratories | Heterocyclic compounds as COX-2 inhibitors |
| EP1002790B1 (en) | 1997-03-12 | 2005-12-28 | Takara Bio Inc. | Sphingosine analogues |
| DE69835223T2 (de) | 1997-09-11 | 2007-05-31 | Takara Bio Inc., Otsu | Sphingosinderivate und medizinische zubereitung |
| US6358992B1 (en) * | 1998-11-25 | 2002-03-19 | Cell Pathways, Inc. | Method of inhibiting neoplastic cells with indole derivatives |
| FR2814073B1 (fr) * | 2000-09-21 | 2005-06-24 | Yang Ji Chemical Company Ltd | Composition pharmaceutique antifongique et/ou antiparasitaire et nouveaux derives de l'indole a titre de principes actifs d'une telle composition |
| PT1397130E (pt) | 2001-06-20 | 2007-11-13 | Wyeth Corp | Derivados ácidos de indole substituído como inibidores de inibidor 1 do activador de plasminogénio (pai-1) |
| EP1513522A2 (en) | 2002-01-18 | 2005-03-16 | Sri International | Methods of treating conditions associated with an edg receptor |
| ATE441654T1 (de) | 2002-01-18 | 2009-09-15 | Merck & Co Inc | Edg-rezeptoragonisten |
| US7323479B2 (en) | 2002-05-17 | 2008-01-29 | Celgene Corporation | Methods for treatment and management of brain cancer using 1-oxo-2-(2,6-dioxopiperidin-3-yl)-4-methylisoindoline |
| JP4505449B2 (ja) | 2003-02-11 | 2010-07-21 | アイアールエム・リミテッド・ライアビリティ・カンパニー | 新規二環式化合物および組成物 |
| EP1622860B1 (en) | 2003-04-30 | 2012-02-29 | Novartis AG | AMINO-PROPANOL DERIVATIVES AS SPHINGOSINE-1-PHOSPHATE RECEPTOR MODULATORs |
| MY150088A (en) | 2003-05-19 | 2013-11-29 | Irm Llc | Immunosuppressant compounds and compositions |
| US7582773B2 (en) * | 2003-09-25 | 2009-09-01 | Wyeth | Substituted phenyl indoles |
| EP1984334B1 (en) * | 2006-02-15 | 2014-04-09 | Allergan, Inc. | Indole-3-carboxylic acid amide, ester, thioamide and thiol ester compounds bearing aryl or heteroaryl groups having sphingosine-1-phosphate (s1p) receptor antagonist biological activity |
-
2008
- 2008-09-18 EP EP08833361A patent/EP2203424A1/en not_active Withdrawn
- 2008-09-18 JP JP2010527035A patent/JP2010540543A/ja active Pending
- 2008-09-18 KR KR1020107008739A patent/KR20100067677A/ko not_active Withdrawn
- 2008-09-18 WO PCT/US2008/076792 patent/WO2009042485A1/en not_active Ceased
- 2008-09-18 CN CN2008801163102A patent/CN101918360A/zh active Pending
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- 2008-09-18 AU AU2008304657A patent/AU2008304657B2/en not_active Ceased
- 2008-09-18 RU RU2010112275/04A patent/RU2010112275A/ru unknown
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- 2008-09-18 US US12/679,530 patent/US7888336B2/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007112322A2 (en) * | 2006-03-28 | 2007-10-04 | Allergan, Inc. | Indole compounds having sphingosine-1-phosphate (s1p) receptor agonist and/or antagonist biological activity |
Also Published As
| Publication number | Publication date |
|---|---|
| BRPI0817397A2 (pt) | 2015-04-07 |
| EP2203424A1 (en) | 2010-07-07 |
| US20100240614A1 (en) | 2010-09-23 |
| WO2009042485A1 (en) | 2009-04-02 |
| JP2010540543A (ja) | 2010-12-24 |
| RU2010112275A (ru) | 2011-11-10 |
| CA2700539A1 (en) | 2009-04-02 |
| CN101918360A (zh) | 2010-12-15 |
| AU2008304657A1 (en) | 2009-04-02 |
| US7888336B2 (en) | 2011-02-15 |
| KR20100067677A (ko) | 2010-06-21 |
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| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |