AU2002236730B2 - Benzenesulfonic acid indol-5-yl esters as antagonists of the 5-HT6 receptor - Google Patents
Benzenesulfonic acid indol-5-yl esters as antagonists of the 5-HT6 receptor Download PDFInfo
- Publication number
- AU2002236730B2 AU2002236730B2 AU2002236730A AU2002236730A AU2002236730B2 AU 2002236730 B2 AU2002236730 B2 AU 2002236730B2 AU 2002236730 A AU2002236730 A AU 2002236730A AU 2002236730 A AU2002236730 A AU 2002236730A AU 2002236730 B2 AU2002236730 B2 AU 2002236730B2
- Authority
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- Australia
- Prior art keywords
- ester
- methylpiperidin
- acid
- indol
- methyl
- 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
Links
- 108091005435 5-HT6 receptors Proteins 0.000 title claims abstract description 31
- 239000005557 antagonist Substances 0.000 title claims abstract description 14
- UXIVTIPEQSXFBC-UHFFFAOYSA-N 1h-indol-5-yl benzenesulfonate Chemical class C=1C=C2NC=CC2=CC=1OS(=O)(=O)C1=CC=CC=C1 UXIVTIPEQSXFBC-UHFFFAOYSA-N 0.000 title claims 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 231
- 238000000034 method Methods 0.000 claims description 105
- 229940092714 benzenesulfonic acid Drugs 0.000 claims description 81
- 238000002360 preparation method Methods 0.000 claims description 75
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 69
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 48
- -1 nitro, amino Chemical group 0.000 claims description 39
- 239000001257 hydrogen Substances 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- 239000002253 acid Substances 0.000 claims description 31
- HHSDIWAVOYCKAW-UHFFFAOYSA-N 2,6-difluorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=C(F)C=CC=C1F HHSDIWAVOYCKAW-UHFFFAOYSA-N 0.000 claims description 26
- 239000003814 drug Substances 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 21
- 208000024827 Alzheimer disease Diseases 0.000 claims description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 150000002148 esters Chemical class 0.000 claims description 18
- 208000010877 cognitive disease Diseases 0.000 claims description 17
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 16
- 125000005843 halogen group Chemical group 0.000 claims description 15
- 150000002431 hydrogen Chemical group 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 201000000980 schizophrenia Diseases 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- JIFAWAXKXDTUHW-UHFFFAOYSA-N 2-fluorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1F JIFAWAXKXDTUHW-UHFFFAOYSA-N 0.000 claims description 7
- 230000008485 antagonism Effects 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 claims description 3
- 229950000244 sulfanilic acid Drugs 0.000 claims description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 3
- 229920002554 vinyl polymer Polymers 0.000 claims description 3
- SPXOTSHWBDUUMT-UHFFFAOYSA-N 138-42-1 Chemical compound OS(=O)(=O)C1=CC=C([N+]([O-])=O)C=C1 SPXOTSHWBDUUMT-UHFFFAOYSA-N 0.000 claims description 2
- CVJVWHJVNYJTKA-UHFFFAOYSA-N 2,6-dichlorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=C(Cl)C=CC=C1Cl CVJVWHJVNYJTKA-UHFFFAOYSA-N 0.000 claims description 2
- WVSYONICNIDYBE-UHFFFAOYSA-N 4-fluorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(F)C=C1 WVSYONICNIDYBE-UHFFFAOYSA-N 0.000 claims description 2
- UBRJOJKCAVYQSH-UHFFFAOYSA-N 4-iodobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(I)C=C1 UBRJOJKCAVYQSH-UHFFFAOYSA-N 0.000 claims description 2
- JTBDAUNIHPKJQV-UHFFFAOYSA-N [1-benzyl-3-(1-methylpiperidin-4-yl)indol-5-yl] 2,6-difluorobenzenesulfonate Chemical compound C1CN(C)CCC1C(C1=CC(OS(=O)(=O)C=2C(=CC=CC=2F)F)=CC=C11)=CN1CC1=CC=CC=C1 JTBDAUNIHPKJQV-UHFFFAOYSA-N 0.000 claims 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- QYASBSHCEJENGL-UHFFFAOYSA-N 2,3,4-trifluorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(F)C(F)=C1F QYASBSHCEJENGL-UHFFFAOYSA-N 0.000 claims 1
- FRUWCRYDUOZXFA-UHFFFAOYSA-N 2,4-difluorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(F)C=C1F FRUWCRYDUOZXFA-UHFFFAOYSA-N 0.000 claims 1
- YODIPMROGSPCJQ-UHFFFAOYSA-N C1=C(C2CCN(C)CC2)C2=CC(OS(=O)(=O)C=3C(=CC=CC=3F)F)=CC(C)=C2N1C(C)C1=CC=CC=C1 Chemical compound C1=C(C2CCN(C)CC2)C2=CC(OS(=O)(=O)C=3C(=CC=CC=3F)F)=CC(C)=C2N1C(C)C1=CC=CC=C1 YODIPMROGSPCJQ-UHFFFAOYSA-N 0.000 claims 1
- YOPYLHIKNWDPGJ-UHFFFAOYSA-N C1=C(C2CCN(C)CC2)C2=CC(OS(=O)(=O)C=3C(=CC=CC=3F)F)=CC=C2N1C(C)C1=CC=CC=C1 Chemical compound C1=C(C2CCN(C)CC2)C2=CC(OS(=O)(=O)C=3C(=CC=CC=3F)F)=CC=C2N1C(C)C1=CC=CC=C1 YOPYLHIKNWDPGJ-UHFFFAOYSA-N 0.000 claims 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 1
- GFJSINCJLPAEBP-UHFFFAOYSA-N [1,7-dimethyl-3-(1-methylpiperidin-4-yl)indol-5-yl] benzenesulfonate Chemical compound C1CN(C)CCC1C(C1=C2)=CN(C)C1=C(C)C=C2OS(=O)(=O)C1=CC=CC=C1 GFJSINCJLPAEBP-UHFFFAOYSA-N 0.000 claims 1
- IHQUYRBHNOPXLO-UHFFFAOYSA-N [1-benzyl-3-(1-methylpiperidin-4-yl)indol-5-yl] benzenesulfonate Chemical compound C1CN(C)CCC1C(C1=CC(OS(=O)(=O)C=2C=CC=CC=2)=CC=C11)=CN1CC1=CC=CC=C1 IHQUYRBHNOPXLO-UHFFFAOYSA-N 0.000 claims 1
- GPVHAPQRXUVNLQ-UHFFFAOYSA-N [1-benzyl-7-methyl-3-(1-methylpiperidin-4-yl)indol-5-yl] 2,6-difluorobenzenesulfonate Chemical compound C1CN(C)CCC1C(C1=CC(OS(=O)(=O)C=2C(=CC=CC=2F)F)=CC(C)=C11)=CN1CC1=CC=CC=C1 GPVHAPQRXUVNLQ-UHFFFAOYSA-N 0.000 claims 1
- JOBZMYQSDSPXHL-UHFFFAOYSA-N [3-(1-methylpiperidin-4-yl)-1-propylindol-5-yl] 2,6-difluorobenzenesulfonate Chemical compound C12=CC(OS(=O)(=O)C=3C(=CC=CC=3F)F)=CC=C2N(CCC)C=C1C1CCN(C)CC1 JOBZMYQSDSPXHL-UHFFFAOYSA-N 0.000 claims 1
- BUVWOSLGQLYZLV-UHFFFAOYSA-N [7-methyl-3-(1-methylpiperidin-4-yl)-1-propylindol-5-yl] 2,6-difluorobenzenesulfonate Chemical compound C12=CC(OS(=O)(=O)C=3C(=CC=CC=3F)F)=CC(C)=C2N(CCC)C=C1C1CCN(C)CC1 BUVWOSLGQLYZLV-UHFFFAOYSA-N 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 279
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 215
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 139
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 137
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- 229940076263 indole Drugs 0.000 description 36
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- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 31
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 26
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Classifications
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- 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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- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
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Landscapes
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- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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| PCT/US2002/000502 WO2002060871A2 (en) | 2001-01-30 | 2002-01-17 | Benzenesulfonic acid indol-5-yl esters as antagonists of the 5-ht6 receptor |
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| MXPA06007415A (es) * | 2004-01-02 | 2007-01-26 | Suven Life Sciences Ltd | Inden [2, 1a] indenos e isoindol [2,1-a] indoles novedosos. |
| JP2009501705A (ja) * | 2005-07-05 | 2009-01-22 | アストラゼネカ・アクチエボラーグ | 新規化合物、その製造方法、中間体、医薬組成物、並びにアルツハイマー病、認知障害、統合失調症に伴う認識機能障害、肥満及びパーキンソン病のような5−ht6介在疾患の治療におけるそれらの使用 |
| JP2009515833A (ja) * | 2005-10-24 | 2009-04-16 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 3−ピペリジン−4−イル−インドールorl−1受容体モジュレーター |
| AU2007217040A1 (en) | 2006-02-17 | 2007-08-30 | Memory Pharmaceuticals Corporation | Compounds having 5-HT6 receptor affinity |
| AR061637A1 (es) * | 2006-06-26 | 2008-09-10 | Epix Delaware Inc | Composiciones y metodos de tratamiento de trastornos del snc |
| ATE537166T1 (de) * | 2006-10-27 | 2011-12-15 | Boehringer Ingelheim Int | Piperidylpropanthiole als ccr3-modulatoren |
| WO2008049875A1 (en) * | 2006-10-27 | 2008-05-02 | Boehringer Ingelheim International Gmbh | Novel substituted piperidyl-propane-thiols |
| JP2010515674A (ja) | 2007-01-08 | 2010-05-13 | スベン ライフ サイエンシズ リミティド | 5−(ヘテロシクリル)アルキル−n−(アリールスルホニル)インドール化合物および5−ht6リガンドとしてのそれらの使用 |
| CA2683124C (en) | 2007-05-03 | 2012-09-25 | Suven Life Sciences Limited | Aminoalkoxy aryl sulfonamide compounds and their use as 5-ht6 ligands |
| AU2008315309B2 (en) | 2007-10-26 | 2011-06-09 | Suven Life Sciences Limited | Amino arylsulfonamide compounds and their use as 5-HT6 ligands |
| US8318725B2 (en) | 2008-09-17 | 2012-11-27 | Suven Life Sciences Limited | Aryl indolyl sulfonamide compounds and their use as 5-HT6 ligands |
| ES2424036T3 (es) | 2008-09-17 | 2013-09-26 | Suven Life Sciences Limited | Compuestos de amina de arilsulfonamida y su uso como ligandos de 5-HT6 |
| US8563567B2 (en) | 2009-12-30 | 2013-10-22 | Arqule, Inc. | Substituted heterocyclic compounds |
| MX2012007783A (es) | 2010-01-05 | 2012-10-03 | Suven Life Sciences Ltd | Compuestos sulfona que actuan como ligandos del receptor 5-ht6. |
| KR101250606B1 (ko) * | 2011-01-24 | 2013-04-03 | 이화여자대학교 산학협력단 | 5-ht6 수용체 억제 작용을 갖는 신규한 벤조티아졸 및 벤즈이소티아졸유도체, 이의 제조 방법 및 이를 포함하는 약학적 조성물 |
| AU2012321345B2 (en) * | 2011-10-03 | 2016-03-17 | The University Of Utah Research Foundation | Application of 5-HT6 receptor antagonists for the alleviation of cognitive deficits of down syndrome |
| WO2015082499A2 (en) * | 2013-12-03 | 2015-06-11 | Iomet Pharma Ltd | Pharmaceutical compound |
| EP3166924B1 (en) | 2014-07-08 | 2019-02-20 | Sunshine Lake Pharma Co., Ltd. | Aromatic heterocyclic derivatives and pharmaceutical applications thereof |
| EP3250561A1 (en) * | 2015-01-30 | 2017-12-06 | Pfizer Inc | Sulfonamide-subsituted indole modulators of rorc2 and methods of use thereof |
| EP3331530A4 (en) * | 2015-08-03 | 2018-12-19 | Raze Therapeutics Inc. | Mthfd2 inhibitors and uses thereof |
| CN115521307B (zh) * | 2022-09-30 | 2023-09-22 | 甘肃皓天医药科技有限责任公司 | 一种5-卤代-7-氮杂吲哚的制备方法 |
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|---|---|---|---|---|
| RU2126399C1 (ru) * | 1991-11-25 | 1999-02-20 | Пфайзер Инк. | Производные индола, замещенные индолы и способ ингибирования 5ht1 рецептора серотонина |
| US5521196A (en) | 1994-10-05 | 1996-05-28 | Eli Lilly And Company | 5-HT1F agonists for the treatment of migraine |
| US5521197A (en) | 1994-12-01 | 1996-05-28 | Eli Lilly And Company | 3-<1-alkylenearyl>-4-<1,2,3,6-tetrahydropyridinyl>-and 3-<1-alkylenearyl>-4-piperidinyl-1h-indoles: new 5-HT1F agonists |
| DE4444864A1 (de) * | 1994-12-16 | 1996-06-20 | Bayer Ag | Verwendung von 5-Acyl-1,4-dihydropyridinen |
| PL322843A1 (en) | 1995-03-20 | 1998-02-16 | Lilly Co Eli | 5-substituted 3-91,2,3,6-tetrahydropyridin-4-yl)- and 3-9piperydin-4-4-yl0-1h-indoles nevel 5-htif natagonists |
| AU7261196A (en) | 1995-10-10 | 1997-04-30 | Eli Lilly And Company | N-{2-substituted-3-(2-aminoethyl)-1h-indol-5-yl}-amides: new 5-ht1f agonists |
| CA2268164A1 (en) | 1996-10-08 | 1998-04-16 | Yao-Chang Xu | New serotonin 5-ht1f agonists |
| US6133287A (en) | 1998-03-24 | 2000-10-17 | Allelix Biopharmaceuticals Inc. | Piperidine-indole compounds having 5-HT6 affinity |
| WO2000063203A1 (en) | 1999-04-21 | 2000-10-26 | Allelix Biopharmaceuticals Inc. | Piperidine-indole compounds having 5-ht6 affinity |
| ATE321751T1 (de) | 1999-07-28 | 2006-04-15 | Kirin Brewery | Harnstoffderivate als ccr-3 rezeptor-inhibitoren |
-
2002
- 2002-01-17 AU AU2002236730A patent/AU2002236730B2/en not_active Ceased
- 2002-01-17 WO PCT/US2002/000502 patent/WO2002060871A2/en not_active Ceased
- 2002-01-17 DE DE60214990T patent/DE60214990T2/de not_active Expired - Fee Related
- 2002-01-17 BR BR0206595-9A patent/BR0206595A/pt not_active IP Right Cessation
- 2002-01-17 CN CNB028043480A patent/CN1275967C/zh not_active Expired - Fee Related
- 2002-01-17 AT AT02703087T patent/ATE340795T1/de not_active IP Right Cessation
- 2002-01-17 JP JP2002561022A patent/JP2004526699A/ja active Pending
- 2002-01-17 CA CA002433351A patent/CA2433351A1/en not_active Abandoned
- 2002-01-17 EP EP02703087A patent/EP1377580B1/en not_active Expired - Lifetime
- 2002-01-17 US US10/466,969 patent/US7230011B2/en not_active Expired - Fee Related
- 2002-01-17 MX MXPA03006605A patent/MXPA03006605A/es active IP Right Grant
- 2002-01-17 ES ES02703087T patent/ES2272667T3/es not_active Expired - Lifetime
-
2007
- 2007-01-18 US US11/624,389 patent/US20070135484A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| BR0206595A (pt) | 2004-07-13 |
| MXPA03006605A (es) | 2003-09-22 |
| US7230011B2 (en) | 2007-06-12 |
| CA2433351A1 (en) | 2002-08-08 |
| WO2002060871A8 (en) | 2003-12-18 |
| US20040102481A1 (en) | 2004-05-27 |
| WO2002060871A3 (en) | 2003-09-12 |
| CN1489591A (zh) | 2004-04-14 |
| ES2272667T3 (es) | 2007-05-01 |
| EP1377580A2 (en) | 2004-01-07 |
| ATE340795T1 (de) | 2006-10-15 |
| WO2002060871A2 (en) | 2002-08-08 |
| DE60214990T2 (de) | 2007-04-05 |
| EP1377580B1 (en) | 2006-09-27 |
| JP2004526699A (ja) | 2004-09-02 |
| US20070135484A1 (en) | 2007-06-14 |
| CN1275967C (zh) | 2006-09-20 |
| DE60214990D1 (de) | 2006-11-09 |
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| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |