CN102186840B - 哌啶化合物、含有该化合物的药物组合物及其用途 - Google Patents
哌啶化合物、含有该化合物的药物组合物及其用途 Download PDFInfo
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- CN102186840B CN102186840B CN200980140895.6A CN200980140895A CN102186840B CN 102186840 B CN102186840 B CN 102186840B CN 200980140895 A CN200980140895 A CN 200980140895A CN 102186840 B CN102186840 B CN 102186840B
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- Prior art keywords
- methyl
- piperidin
- amino
- chloro
- oxygen
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 11
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- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 240
- 150000001875 compounds Chemical class 0.000 claims description 219
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 121
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 91
- 239000001301 oxygen Substances 0.000 claims description 82
- 229910052760 oxygen Inorganic materials 0.000 claims description 82
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 77
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 70
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 32
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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
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- C07D211/30—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 with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom
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- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- Rheumatology (AREA)
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- Hydrogenated Pyridines (AREA)
Abstract
Description
实施例 | 增加值% | 实施例 | 增加值% |
2 | 42.6% | 56 | 134.7% |
3 | 71.1% | 57 | 29.0% |
4 | 74.1% | 58 | 48.3% |
5 | 76.1% | 59 | 48.0% |
8 | 51.6% | 60 | 14.2% |
9 | 55.8% | 61 | 44.3% |
13 | 14.0% | 62 | 17.9% |
15 | 78.7% | 63 | 24.4% |
16 | 53.6% | 64 | 7.3% |
17 | 22.1% | 65 | 93.1% |
23 | 55.8% | 66 | 84.1% |
24 | 71.1% | 68 | 52.9 |
27 | 48.5% | 70 | 67.5% |
29 | 61.3% | 71 | 63.7% |
31 | 79.3% | 72 | 48.1% |
32 | 40.0% | 74 | 46.7% |
33 | 115.2% | 83 | 42.5% |
35 | 105.5% | 88 | 44.1% |
36 | 55.2% | 89 | 45.3% |
37 | 70.7% | 96 | 105.0% |
38 | 49.1% | 97 | 71.4% |
39 | 40.0% | 98 | 63.6% |
40 | 51.6% | 99 | 47.5% |
41 | 24.3% | 100 | 46.1% |
42 | 42.7% | 103 | 88.8% |
43 | 46.1% | 104 | 81.0% |
45 | 51.4% | 111 | 37.2% |
46 | 45.9% | 121 | 46.8% |
47 | 25.9% | 122 | 6.8% |
48 | 3.5% | 123 | 56.8% |
49 | 17.8% | 124 | 45.6% |
50 | 3.9% | 126 | 93.3% |
51 | 122.1% | 127 | 11.3% |
52 | 131.0% | 129 | 5.4% |
53 | 28.4% | 135 | 90.3% |
54 | 89.2% | 136 | 64.1% |
55 | 66.7% | 146 | 83.0% |
Claims (3)
Priority Applications (2)
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CN201610090231.5A CN105646331B (zh) | 2008-10-14 | 2009-10-13 | 哌啶化合物、含有该化合物的药物组合物及其用途 |
CN201410234573.0A CN103980184B (zh) | 2008-10-14 | 2009-10-13 | 哌啶化合物、含有该化合物的药物组合物及其用途 |
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US10507008P | 2008-10-14 | 2008-10-14 | |
US61/105,070 | 2008-10-14 | ||
PCT/KR2009/005863 WO2010044585A2 (en) | 2008-10-14 | 2009-10-13 | Piperidine compounds, pharmaceutical composition comprising the same and its use |
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CN201410234573.0A Division CN103980184B (zh) | 2008-10-14 | 2009-10-13 | 哌啶化合物、含有该化合物的药物组合物及其用途 |
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CN201410234573.0A Active CN103980184B (zh) | 2008-10-14 | 2009-10-13 | 哌啶化合物、含有该化合物的药物组合物及其用途 |
CN200980140895.6A Active CN102186840B (zh) | 2008-10-14 | 2009-10-13 | 哌啶化合物、含有该化合物的药物组合物及其用途 |
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CN201410234573.0A Active CN103980184B (zh) | 2008-10-14 | 2009-10-13 | 哌啶化合物、含有该化合物的药物组合物及其用途 |
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US (5) | US8642772B2 (zh) |
EP (1) | EP2358702B1 (zh) |
JP (1) | JP5555243B2 (zh) |
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CN (3) | CN105646331B (zh) |
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PL (1) | PL2358702T3 (zh) |
RU (1) | RU2514827C2 (zh) |
WO (1) | WO2010044585A2 (zh) |
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KR101603487B1 (ko) * | 2008-06-05 | 2016-03-17 | 에스케이바이오팜 주식회사 | 3-치환된 프로판아민 화합물 |
US8101642B2 (en) | 2008-06-05 | 2012-01-24 | Sk Biopharmaceuticals Co., Ltd. | 3-substituted propanamine compounds |
US8642772B2 (en) | 2008-10-14 | 2014-02-04 | Sk Biopharmaceuticals Co., Ltd. | Piperidine compounds, pharmaceutical composition comprising the same and its use |
US8232315B2 (en) * | 2009-06-26 | 2012-07-31 | Sk Biopharmaceuticals Co., Ltd. | Methods for treating drug addiction and improving addiction-related behavior |
BR112012010648A2 (pt) | 2009-11-06 | 2020-12-01 | Sk Biopharmaceuticals Co., Ltd. | uso de compostos na preparação de composições farmacêuticas para tratar síndrome de fibromialgia e composição farmacêutica |
MX2012005258A (es) | 2009-11-06 | 2012-06-19 | Sk Biopharmaceuticals Co Ltd | El uso de un compuesto de carbamoilo para el tratamiento del trastorno de deficit de atencion/hiperactividad. |
KR101180174B1 (ko) * | 2010-04-23 | 2012-09-05 | 동아제약주식회사 | 신규한 벤즈아미드 유도체 |
US9610274B2 (en) | 2010-06-30 | 2017-04-04 | Sk Biopharmaceuticals Co., Ltd. | Methods for treating bipolar disorder |
US8623913B2 (en) | 2010-06-30 | 2014-01-07 | Sk Biopharmaceuticals Co., Ltd. | Methods for treating restless legs syndrome |
CN105636946B (zh) * | 2013-07-25 | 2017-12-19 | 东亚St 株式会社 | 制备苯甲酰胺衍生物的方法、用于制备苯甲酰胺的新型中间体以及制备新型中间体的方法 |
Family Cites Families (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR970702247A (ko) | 1994-03-30 | 1997-05-13 | 고야 마사시 | 벤조산 화합물 및 이들의 약제로서의 용도(benzoic acid compound and use thereof as medicine) |
KR100197892B1 (ko) | 1994-09-09 | 1999-06-15 | 남창우 | 신규한 페닐알킬아미노 카바메이트 화합물과 그의 제조방법 |
KR0173862B1 (ko) | 1995-02-11 | 1999-04-01 | 조규향 | O-카바모일-(d)-페닐알라닌올 화합물과 그의 약제학적으로 유용한 염 및 이들의 제조방법 |
US5756817C1 (en) | 1995-02-11 | 2001-04-17 | Sk Corp | O-carbamoyl-phenylananinol compounds their pharmaceutically useful salts and process for preparing the same |
IT1275903B1 (it) | 1995-03-14 | 1997-10-24 | Boehringer Ingelheim Italia | Esteri e ammidi della 1,4-piperidina disostituita |
KR0173863B1 (ko) | 1995-04-10 | 1999-04-01 | 조규향 | 페닐에 치환체가 있는 o-카바모일-페닐알라닌올 화합물과 그의 약제학적으로 유용한 염 및 이들의 제조방법 |
EP0873990A1 (en) * | 1995-09-22 | 1998-10-28 | Yoshitomi Pharmaceutical Industries, Ltd. | Benzoic acid compounds and medicinal use thereof |
GB9523526D0 (en) * | 1995-11-17 | 1996-01-17 | Zeneca Ltd | Therapeutic compounds |
TW402591B (en) | 1997-07-11 | 2000-08-21 | Janssen Pharmaceutica Nv | Monocyclic benzamides of 3- or 4-substituted 4-(aminomethyl)-piperidine derivatives |
US6294555B1 (en) | 1998-04-28 | 2001-09-25 | Dainippon Pharmaceutical Co., Ltd. | 1-[(1-Substituted-4-piperidinyl)methyl]-4-piperidine derivative, process for producing the same, medicinal compositions containing the same and intermediates of these compounds |
AU3113902A (en) | 2000-12-21 | 2002-07-01 | Bristol Myers Squibb Co | Thiazolyl inhibitors of tec family tyrosine kinases |
JP2005511478A (ja) * | 2001-04-03 | 2005-04-28 | メルク エンド カムパニー インコーポレーテッド | N−置換非アリール複素環アミジル系nmda/nr2b拮抗薬 |
CA2449249A1 (en) * | 2001-06-12 | 2002-12-19 | Merck & Co., Inc. | Nr2b receptor antagonists for the treatment or prevention of migraines |
MXPA03000145A (es) | 2002-01-07 | 2003-07-15 | Pfizer | Compuestos de oxo u oxi-piridina como moduladores de receptores 5-ht4. |
EP1543004A1 (en) | 2002-09-20 | 2005-06-22 | Pfizer Inc. | N-substituted piperidinyl-imidazopyridine compounds as 5-ht4 receptor modulators |
WO2004094418A1 (en) | 2003-04-21 | 2004-11-04 | Pfizer Inc. | Imidazopyridine compounds having 5-ht4 receptor agonistic activity and 5-ht3 receptor antagonistic activity |
WO2005021539A1 (en) | 2003-09-03 | 2005-03-10 | Pfizer Japan, Inc. | Benzimidazolone compounds having 5-ht4 receptor agonistic activity |
EP1689742B1 (en) * | 2003-11-24 | 2010-03-17 | Pfizer, Inc. | Quinolonecarboxylic acid compounds having 5-ht4 receptor agonistic activity |
JP4740152B2 (ja) * | 2003-12-23 | 2011-08-03 | セロドス アクスイェ セルスカブ | 末梢性5−ht受容体の修飾因子 |
JP4859672B2 (ja) * | 2004-01-29 | 2012-01-25 | ファイザー株式会社 | 5−ht4受容体作動活性を有する1−イソプロピル−2−オキソ−1,2−ジヒドロピリジン−3−カルボキサミド誘導体 |
WO2005092882A1 (en) | 2004-03-01 | 2005-10-06 | Pfizer Japan, Inc. | 4-amino-5-halogeno-benzamide derivatives as 5-ht4 receptor agonists for the treatment of gastrointestinal, cns, neurological and cardiovascular disorders |
EA200801608A1 (ru) | 2004-06-15 | 2008-10-30 | Пфайзер Инк. | Производные бензимидазолонкарбоновой кислоты |
JP2008509088A (ja) * | 2004-09-02 | 2008-03-27 | ファイザー株式会社 | ベンズイミダゾロンカルボン酸誘導体 |
NZ556627A (en) * | 2005-02-22 | 2010-09-30 | Pfizer | Oxyindole derivatives as 5HT4 receptor agonists |
CA2603939C (en) * | 2005-04-08 | 2013-08-27 | Pfizer Products Inc. | Bicyclic [3.1.0] heteroaryl amides as type i glycine transport inhibitors |
WO2007149929A1 (en) | 2006-06-23 | 2007-12-27 | Aryx Therapeutics, Inc. | Piperidine derivatives for the treatment of gastrointestinal and cns disorders |
US8642772B2 (en) | 2008-10-14 | 2014-02-04 | Sk Biopharmaceuticals Co., Ltd. | Piperidine compounds, pharmaceutical composition comprising the same and its use |
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2015
- 2015-01-23 HK HK15100788.9A patent/HK1200446A1/zh unknown
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2016
- 2016-08-26 US US15/248,872 patent/US9676718B2/en active Active
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2017
- 2017-06-09 US US15/618,252 patent/US10144709B2/en active Active
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2018
- 2018-11-29 US US16/204,364 patent/US20190092727A1/en not_active Abandoned
Non-Patent Citations (1)
Title |
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Synthesis and pharmacological evaluation of benzamide derivatives as selective 5-HT4 receptor agonists;Shuji Sonda et al.;《Bioorganic & Medicinal Chemistry》;20050319;第13卷;第3295-3308页 * |
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