CA2544748A1 - Allosteric modulators of metabotropic glutamate receptors - Google Patents
Allosteric modulators of metabotropic glutamate receptors Download PDFInfo
- Publication number
- CA2544748A1 CA2544748A1 CA002544748A CA2544748A CA2544748A1 CA 2544748 A1 CA2544748 A1 CA 2544748A1 CA 002544748 A CA002544748 A CA 002544748A CA 2544748 A CA2544748 A CA 2544748A CA 2544748 A1 CA2544748 A1 CA 2544748A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- phenyl
- fluoro
- aryl
- piperidin
- 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.)
- Abandoned
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- 230000003281 allosteric effect Effects 0.000 title claims description 15
- 108010010914 Metabotropic glutamate receptors Proteins 0.000 title claims description 13
- 102000016193 Metabotropic glutamate receptors Human genes 0.000 title claims description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 267
- 208000015114 central nervous system disease Diseases 0.000 claims abstract description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 9
- 230000002265 prevention Effects 0.000 claims abstract description 9
- 102000012777 Metabotropic Glutamate 5 Receptor Human genes 0.000 claims abstract 3
- 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 claims abstract 3
- 125000003118 aryl group Chemical group 0.000 claims description 269
- 238000000034 method Methods 0.000 claims description 246
- 125000001072 heteroaryl group Chemical group 0.000 claims description 226
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 173
- -1 hydroxy, amino Chemical group 0.000 claims description 133
- 229910052736 halogen Inorganic materials 0.000 claims description 109
- 150000002367 halogens Chemical class 0.000 claims description 109
- 125000001424 substituent group Chemical group 0.000 claims description 108
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 106
- 229910052739 hydrogen Inorganic materials 0.000 claims description 92
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 91
- 239000001257 hydrogen Substances 0.000 claims description 90
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 90
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 89
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 73
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 51
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 49
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- 125000004429 atom Chemical group 0.000 claims description 32
- 150000001204 N-oxides Chemical class 0.000 claims description 30
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 26
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- 125000000753 cycloalkyl group Chemical group 0.000 claims description 25
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- 239000012453 solvate Substances 0.000 claims description 21
- 150000004677 hydrates Chemical class 0.000 claims description 20
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 14
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- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 14
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- 125000004103 aminoalkyl group Chemical group 0.000 claims description 10
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- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
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- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
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- 230000003287 optical effect Effects 0.000 claims description 3
- PSZICAUUIXXCES-AWEZNQCLSA-N (1,5-dimethylpyrazol-3-yl)-[(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound CN1C(C)=CC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C=2C=CC(F)=CC=2)=N1 PSZICAUUIXXCES-AWEZNQCLSA-N 0.000 claims description 2
- DTVMFUBCRPUKQW-INIZCTEOSA-N (4-fluoro-3-methylphenyl)-[(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=C(F)C(C)=CC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C=2C=CC(F)=CC=2)=C1 DTVMFUBCRPUKQW-INIZCTEOSA-N 0.000 claims description 2
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims description 2
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- SZAIFOWFJJIPFW-AWEZNQCLSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(3-methylthiophen-2-yl)methanone Chemical compound C1=CSC(C(=O)N2C[C@H](CCC2)C=2ON=C(N=2)C=2C=CC(F)=CC=2)=C1C SZAIFOWFJJIPFW-AWEZNQCLSA-N 0.000 claims description 2
- VYKNVFUTELGSOR-HNNXBMFYSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(4-methyl-2-pyrazin-2-yl-1,3-thiazol-5-yl)methanone Chemical compound N=1OC([C@H]2CCCN(C2)C(=O)C=2SC(=NC=2C)C=2N=CC=NC=2)=NC=1C1=CC=C(F)C=C1 VYKNVFUTELGSOR-HNNXBMFYSA-N 0.000 claims description 2
- BAFOZTRIMVNTHI-INIZCTEOSA-N [(3s)-3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]-(5-pyridin-2-ylthiophen-2-yl)methanone Chemical compound C1=CC(F)=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2SC(=CC=2)C=2N=CC=CC=2)=N1 BAFOZTRIMVNTHI-INIZCTEOSA-N 0.000 claims description 2
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- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 7
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- XNUMYFLOQVCEKO-AWEZNQCLSA-N (3,4-difluorophenyl)-[(3s)-3-[3-(4-nitrophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound C1=CC([N+](=O)[O-])=CC=C1C1=NOC([C@@H]2CN(CCC2)C(=O)C=2C=C(F)C(F)=CC=2)=N1 XNUMYFLOQVCEKO-AWEZNQCLSA-N 0.000 claims 1
- LYOFRRCBNWEVBY-UHFFFAOYSA-N (3-fluorophenyl)-[3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone (4-fluorophenyl)-[3-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone Chemical compound Fc1ccc(cc1)C(=O)N1CCCC(C1)c1nc(no1)-c1ccc(F)cc1.Fc1ccc(cc1)-c1noc(n1)C1CCCN(C1)C(=O)c1cccc(F)c1 LYOFRRCBNWEVBY-UHFFFAOYSA-N 0.000 claims 1
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- 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
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- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
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- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D401/02—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 containing two hetero rings
- C07D401/04—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 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- 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
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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| GB0325956.1 | 2003-11-06 | ||
| PCT/IB2004/003822 WO2005044797A1 (en) | 2003-11-06 | 2004-11-04 | Allosteric modulators of metabotropic glutamate receptors |
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-
2003
- 2003-11-06 GB GBGB0325956.1A patent/GB0325956D0/en not_active Ceased
-
2004
- 2004-04-11 UA UAA200605034A patent/UA83257C2/ru unknown
- 2004-11-04 CA CA002544748A patent/CA2544748A1/en not_active Abandoned
- 2004-11-04 US US10/578,589 patent/US7834035B2/en not_active Expired - Fee Related
- 2004-11-04 DE DE602004017213T patent/DE602004017213D1/de not_active Expired - Lifetime
- 2004-11-04 CN CN2004800383770A patent/CN1898206B/zh not_active Expired - Fee Related
- 2004-11-04 ES ES04798939T patent/ES2315722T3/es not_active Expired - Lifetime
- 2004-11-04 JP JP2006538992A patent/JP4880471B2/ja not_active Expired - Fee Related
- 2004-11-04 PT PT04798939T patent/PT1685105E/pt unknown
- 2004-11-04 RU RU2006119623/04A patent/RU2360902C2/ru not_active IP Right Cessation
- 2004-11-04 CN CN2011102046843A patent/CN102336749A/zh active Pending
- 2004-11-04 SI SI200430951T patent/SI1685105T1/sl unknown
- 2004-11-04 AT AT08017193T patent/ATE540024T1/de active
- 2004-11-04 PL PL04798939T patent/PL1685105T3/pl unknown
- 2004-11-04 AU AU2004287642A patent/AU2004287642A1/en not_active Abandoned
- 2004-11-04 EP EP08017193A patent/EP2030970B1/en not_active Expired - Lifetime
- 2004-11-04 DK DK04798939T patent/DK1685105T3/da active
- 2004-11-04 EP EP04798939A patent/EP1685105B1/en not_active Revoked
- 2004-11-04 WO PCT/IB2004/003822 patent/WO2005044797A1/en not_active Ceased
- 2004-11-04 AT AT04798939T patent/ATE411290T1/de active
-
2009
- 2009-01-14 CY CY20091100041T patent/CY1108703T1/el unknown
- 2009-03-17 RU RU2009109678/04A patent/RU2009109678A/ru not_active Application Discontinuation
-
2010
- 2010-10-06 US US12/899,542 patent/US8030331B2/en not_active Expired - Fee Related
-
2011
- 2011-09-30 US US13/251,197 patent/US8163775B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| UA83257C2 (en) | 2008-06-25 |
| JP4880471B2 (ja) | 2012-02-22 |
| ATE411290T1 (de) | 2008-10-15 |
| DE602004017213D1 (de) | 2008-11-27 |
| CY1108703T1 (el) | 2014-04-09 |
| EP1685105B1 (en) | 2008-10-15 |
| EP2030970B1 (en) | 2012-01-04 |
| HK1094204A1 (en) | 2007-03-23 |
| AU2004287642A1 (en) | 2005-05-19 |
| US20110112143A1 (en) | 2011-05-12 |
| ES2315722T3 (es) | 2009-04-01 |
| US20120022108A1 (en) | 2012-01-26 |
| CN1898206B (zh) | 2011-09-14 |
| WO2005044797A1 (en) | 2005-05-19 |
| ATE540024T1 (de) | 2012-01-15 |
| CN102336749A (zh) | 2012-02-01 |
| EP1685105A1 (en) | 2006-08-02 |
| US20070219187A1 (en) | 2007-09-20 |
| RU2006119623A (ru) | 2007-12-20 |
| US8030331B2 (en) | 2011-10-04 |
| EP2030970A1 (en) | 2009-03-04 |
| RU2360902C2 (ru) | 2009-07-10 |
| JP2007510713A (ja) | 2007-04-26 |
| US8163775B2 (en) | 2012-04-24 |
| PT1685105E (pt) | 2009-01-22 |
| CN1898206A (zh) | 2007-01-17 |
| SI1685105T1 (sl) | 2009-02-28 |
| PL1685105T3 (pl) | 2009-04-30 |
| RU2009109678A (ru) | 2010-09-27 |
| HK1128919A1 (en) | 2009-11-13 |
| GB0325956D0 (en) | 2003-12-10 |
| US7834035B2 (en) | 2010-11-16 |
| DK1685105T3 (da) | 2009-02-02 |
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| FZDE | Discontinued |
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