JP2009535316A - 二環式テトラヒドロピロール化合物 - Google Patents
二環式テトラヒドロピロール化合物 Download PDFInfo
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- JP2009535316A JP2009535316A JP2009507001A JP2009507001A JP2009535316A JP 2009535316 A JP2009535316 A JP 2009535316A JP 2009507001 A JP2009507001 A JP 2009507001A JP 2009507001 A JP2009507001 A JP 2009507001A JP 2009535316 A JP2009535316 A JP 2009535316A
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- branched
- alkyl
- monosubstituted
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- -1 Bicyclic tetrahydropyrrole compound Chemical class 0.000 title claims abstract description 76
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- 125000001424 substituent group Chemical group 0.000 claims description 255
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- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 187
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 170
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- 125000000623 heterocyclic group Chemical group 0.000 claims description 77
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 60
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- 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 27
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- QGKLPGKXAVVPOJ-UHFFFAOYSA-N pyrrolidin-3-one Chemical compound O=C1CCNC1 QGKLPGKXAVVPOJ-UHFFFAOYSA-N 0.000 claims description 7
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- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
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- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 claims description 3
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 3
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
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- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims 11
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- ZGJXAIOPBAMFSE-UHFFFAOYSA-N tert-butyl n-(4-ethynylphenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(C#C)C=C1 ZGJXAIOPBAMFSE-UHFFFAOYSA-N 0.000 description 1
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Landscapes
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP06384010A EP1849772A1 (en) | 2006-04-28 | 2006-04-28 | Bicyclic tetrahydropyrrole compounds |
| PCT/EP2007/003827 WO2007128459A1 (en) | 2006-04-28 | 2007-04-30 | Bicyclic tetrahydropyrrole compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2009535316A true JP2009535316A (ja) | 2009-10-01 |
| JP2009535316A5 JP2009535316A5 (enExample) | 2010-06-24 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009507001A Pending JP2009535316A (ja) | 2006-04-28 | 2007-04-30 | 二環式テトラヒドロピロール化合物 |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US8372990B2 (enExample) |
| EP (2) | EP1849772A1 (enExample) |
| JP (1) | JP2009535316A (enExample) |
| CN (1) | CN101421239A (enExample) |
| CA (1) | CA2641100A1 (enExample) |
| ES (1) | ES2573004T3 (enExample) |
| MX (1) | MX2008013478A (enExample) |
| WO (1) | WO2007128459A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009535315A (ja) * | 2006-04-28 | 2009-10-01 | ラボラトリオス・デル・ドクトル・エステベ・ソシエダッド・アノニマ | 二環式テトラヒドロピロール化合物 |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1849770A1 (en) * | 2006-04-28 | 2007-10-31 | Laboratorios Del Dr. Esteve, S.A. | Production process for bicyclic tetrahydropyrrole compounds |
| EP2070933A1 (en) * | 2007-12-07 | 2009-06-17 | Laboratorios del Dr. Esteve S.A. | Tricyclic triazolic compounds |
| EP2792679A1 (en) * | 2013-04-19 | 2014-10-22 | Laboratorios Del. Dr. Esteve, S.A. | Tricyclic triazolic compounds |
| US9540324B2 (en) | 2013-09-26 | 2017-01-10 | Luc Therapeutics, Inc. | Selective octahydro-cyclopenta[C] pyrrole negative modulators of NR2B |
| JO3579B1 (ar) | 2014-09-26 | 2020-07-05 | Luc Therapeutics Inc | مُعدِلات تفاغرية سالبة لمستقبل nr2b من المركب n-ألكيل أريل-5-أوكسي أريل-ثامن هيدرو-خماسي الحلقة [c] بيرول |
| CN105330588B (zh) * | 2015-10-16 | 2017-09-26 | 辽宁中医药大学 | 马齿苋中生物碱Oleracone及其提取分离方法 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0278659A (ja) * | 1988-09-12 | 1990-03-19 | Shionogi & Co Ltd | アザビシクロアルカン類化合物 |
| JPH07505143A (ja) * | 1992-02-14 | 1995-06-08 | ザ・デュポン・メルク・ファーマシュウティカル・カンパニー | 向精神性薬剤としてのヒドロイソインドリンおよびヒドロイソキノリン |
| JP2009535314A (ja) * | 2006-04-28 | 2009-10-01 | ラボラトリオス・デル・ドクトル・エステベ・ソシエダッド・アノニマ | 二環式テトラヒドロピロール化合物の製造方法 |
| JP2009535315A (ja) * | 2006-04-28 | 2009-10-01 | ラボラトリオス・デル・ドクトル・エステベ・ソシエダッド・アノニマ | 二環式テトラヒドロピロール化合物 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5491241A (en) * | 1993-10-18 | 1996-02-13 | Eli Lilly And Company | Bicyclic intermediates for excitatory amino acid receptor antagonists |
| DE4341403A1 (de) * | 1993-12-04 | 1995-06-08 | Basf Ag | N-substituierte 3-Azabicycloalkan-Derivate, ihre Herstellung und Verwendung |
| GB0218260D0 (en) * | 2002-08-06 | 2002-09-11 | Charterhouse Therapeutics Ltd | Improvements in pharmaceutically useful compounds |
| US20040044029A1 (en) * | 2002-08-14 | 2004-03-04 | Dart Michael J. | Azabicyclic compounds are central nervous system active agents |
| WO2007061741A2 (en) * | 2005-11-17 | 2007-05-31 | Arena Pharmaceuticals, Inc. | Modulators of the h3 receptor useful for the treatment of disorders related thereto |
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2006
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2007
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2012
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0278659A (ja) * | 1988-09-12 | 1990-03-19 | Shionogi & Co Ltd | アザビシクロアルカン類化合物 |
| JPH07505143A (ja) * | 1992-02-14 | 1995-06-08 | ザ・デュポン・メルク・ファーマシュウティカル・カンパニー | 向精神性薬剤としてのヒドロイソインドリンおよびヒドロイソキノリン |
| JP2009535314A (ja) * | 2006-04-28 | 2009-10-01 | ラボラトリオス・デル・ドクトル・エステベ・ソシエダッド・アノニマ | 二環式テトラヒドロピロール化合物の製造方法 |
| JP2009535315A (ja) * | 2006-04-28 | 2009-10-01 | ラボラトリオス・デル・ドクトル・エステベ・ソシエダッド・アノニマ | 二環式テトラヒドロピロール化合物 |
Non-Patent Citations (1)
| Title |
|---|
| JPN6012056212; ＪＥＯＮＧ，Ｎ． ｅｔ ａｌ: 'Ｐａｕｓｏｎ-Ｋｈａｎｄ-ｔｙｐｅ ｒｅａｃｔｉｏｎ ｍｅｄｉａｔｅｄｅ ｂｙ Ｒｈ（Ｉ） ｃａｔａｌｙｓｔｓ' Ｐｕｒｅ ａｎｄ Ａｐｐｌｉｅｄ Ｃｈｅｍｉｓｔｒｙ Ｖｏｌ．７４， Ｎｏ．１, 2002, ｐ．８５-９１ * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009535315A (ja) * | 2006-04-28 | 2009-10-01 | ラボラトリオス・デル・ドクトル・エステベ・ソシエダッド・アノニマ | 二環式テトラヒドロピロール化合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| US20130072456A1 (en) | 2013-03-21 |
| US8372990B2 (en) | 2013-02-12 |
| EP2029537A1 (en) | 2009-03-04 |
| WO2007128459A1 (en) | 2007-11-15 |
| ES2573004T3 (es) | 2016-06-03 |
| CN101421239A (zh) | 2009-04-29 |
| MX2008013478A (es) | 2008-10-29 |
| CA2641100A1 (en) | 2007-11-15 |
| EP1849772A1 (en) | 2007-10-31 |
| US20090318524A1 (en) | 2009-12-24 |
| US9271959B2 (en) | 2016-03-01 |
| EP2029537B1 (en) | 2016-03-02 |
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