JP2006514107A - ケモカイン受容体ccr5のモジュレーターとしての新規なピペリジン誘導体 - Google Patents
ケモカイン受容体ccr5のモジュレーターとしての新規なピペリジン誘導体 Download PDFInfo
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- JP2006514107A JP2006514107A JP2005502630A JP2005502630A JP2006514107A JP 2006514107 A JP2006514107 A JP 2006514107A JP 2005502630 A JP2005502630 A JP 2005502630A JP 2005502630 A JP2005502630 A JP 2005502630A JP 2006514107 A JP2006514107 A JP 2006514107A
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- Prior art keywords
- alkyl
- phenyl
- heteroaryl
- optionally substituted
- alkoxy
- Prior art date
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- 150000003053 piperidines Chemical class 0.000 title description 2
- 108700011778 CCR5 Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 221
- 238000000034 method Methods 0.000 claims abstract description 75
- 239000003814 drug Substances 0.000 claims abstract description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 610
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 201
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 171
- -1 R 13 Chemical compound 0.000 claims description 166
- 125000001072 heteroaryl group Chemical group 0.000 claims description 141
- 125000003545 alkoxy group Chemical group 0.000 claims description 94
- 229910052739 hydrogen Inorganic materials 0.000 claims description 67
- 239000002904 solvent Substances 0.000 claims description 67
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 63
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 49
- 125000003118 aryl group Chemical group 0.000 claims description 38
- 239000001257 hydrogen Substances 0.000 claims description 37
- 125000000623 heterocyclic group Chemical group 0.000 claims description 35
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 33
- 229910052717 sulfur Inorganic materials 0.000 claims description 32
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 26
- 239000012453 solvate Substances 0.000 claims description 25
- 125000004414 alkyl thio group Chemical group 0.000 claims description 24
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 22
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 21
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 18
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- 238000011282 treatment Methods 0.000 claims description 14
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- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
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- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 230000008878 coupling Effects 0.000 claims description 6
- 238000010168 coupling process Methods 0.000 claims description 6
- 238000005859 coupling reaction Methods 0.000 claims description 6
- 125000004434 sulfur atom Chemical group 0.000 claims description 6
- RZRJACCZWZTYJY-UHFFFAOYSA-N tert-butylsulfanyl n,n-dimethylcarbamodithioate Chemical compound CN(C)C(=S)SSC(C)(C)C RZRJACCZWZTYJY-UHFFFAOYSA-N 0.000 claims description 6
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 5
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 5
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 5
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 5
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- 125000001475 halogen functional group Chemical group 0.000 claims 14
- 125000005549 heteroarylene group Chemical group 0.000 claims 1
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- 239000000203 mixture Substances 0.000 abstract description 77
- 230000000694 effects Effects 0.000 abstract description 12
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- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 47
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 44
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 35
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
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- 125000001153 fluoro group Chemical group F* 0.000 description 26
- 239000012267 brine Substances 0.000 description 23
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
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- 239000000047 product Substances 0.000 description 21
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 20
- 206010039083 rhinitis Diseases 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 18
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 17
- 239000000377 silicon dioxide Substances 0.000 description 17
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- 125000001309 chloro group Chemical group Cl* 0.000 description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 16
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 15
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 15
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 13
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 13
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 13
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- 125000003831 tetrazolyl group Chemical group 0.000 description 13
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
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- Pain & Pain Management (AREA)
- AIDS & HIV (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
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Applications Claiming Priority (4)
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| SE0300499A SE0300499D0 (sv) | 2003-02-24 | 2003-02-24 | Chemical compounds |
| SE0301425A SE0301425D0 (sv) | 2003-05-15 | 2003-05-15 | Chemical compounds |
| PCT/SE2003/002008 WO2004056773A1 (en) | 2002-12-20 | 2003-12-18 | Novel piperidine derivatives as modulators of chemokine receptor ccr5 |
Publications (2)
| Publication Number | Publication Date |
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| JP2006514107A true JP2006514107A (ja) | 2006-04-27 |
| JP2006514107A5 JP2006514107A5 (enExample) | 2007-02-01 |
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| JP2005502630A Pending JP2006514107A (ja) | 2002-12-20 | 2003-12-18 | ケモカイン受容体ccr5のモジュレーターとしての新規なピペリジン誘導体 |
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| EP (1) | EP1572650A1 (enExample) |
| JP (1) | JP2006514107A (enExample) |
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| AR (1) | AR042628A1 (enExample) |
| AU (1) | AU2003288856B2 (enExample) |
| BR (1) | BR0317459A (enExample) |
| CA (1) | CA2508624A1 (enExample) |
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| CO (1) | CO5570665A2 (enExample) |
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| MX (1) | MXPA05006381A (enExample) |
| NZ (1) | NZ540780A (enExample) |
| PL (1) | PL377768A1 (enExample) |
| TW (1) | TW200505856A (enExample) |
| UY (1) | UY28139A1 (enExample) |
| WO (1) | WO2004056773A1 (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007500694A (ja) * | 2003-07-31 | 2007-01-18 | アストラゼネカ・アクチエボラーグ | Ccr5受容体モジュレーターとしてのピペリジン誘導体 |
| JP2007528867A (ja) * | 2003-07-16 | 2007-10-18 | アストラゼネカ・アクチエボラーグ | ケモカイン受容体活性のモジュレーターとして有用なピペリジンもしくは8−アザ−ビシクロ[3.2.1]オクタ−3−イル誘導体 |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE0103818D0 (sv) | 2001-11-15 | 2001-11-15 | Astrazeneca Ab | Chemical compounds |
| SE0301369D0 (sv) | 2003-05-09 | 2003-05-09 | Astrazeneca Ab | Chemical compounds |
| TW200610761A (en) * | 2004-04-23 | 2006-04-01 | Astrazeneca Ab | Chemical compounds |
| CN101001860A (zh) | 2004-06-09 | 2007-07-18 | 霍夫曼-拉罗奇有限公司 | 杂环抗病毒化合物 |
| SE0401657D0 (sv) * | 2004-06-24 | 2004-06-24 | Astrazeneca Ab | Chemical compounds |
| SE0401656D0 (sv) * | 2004-06-24 | 2004-06-24 | Astrazeneca Ab | Chemical compounds |
| US7665658B2 (en) | 2005-06-07 | 2010-02-23 | First Data Corporation | Dynamic aggregation of payment transactions |
| KR20080056220A (ko) | 2005-10-19 | 2008-06-20 | 에프. 호프만-라 로슈 아게 | 페닐-아세트아마이드 nnrt 저해제 |
| DE602007013573D1 (de) | 2006-08-16 | 2011-05-12 | Hoffmann La Roche | Nicht-nukleosidische reverse-transkriptase-hemmer |
| BRPI0717288A2 (pt) * | 2006-09-28 | 2013-10-15 | Arete Therapeutics Inc | Inibidores de epóxido hidrolase solúvel |
| RU2469032C2 (ru) | 2006-12-13 | 2012-12-10 | Ф.Хоффманн-Ля Рош Аг | Производные 2-(пиперидин-4-ил)-4-фенокси- или фениламинопиримидина в качестве ненуклеозидных ингибиторов обратной транскриптазы |
| WO2011079007A1 (en) | 2009-12-23 | 2011-06-30 | Ironwood Pharmaceuticals, Inc. | Crth2 modulators |
| WO2012009134A1 (en) | 2010-07-12 | 2012-01-19 | Ironwood Pharmaceuticals, Inc. | Crth2 modulators |
| US20130216552A1 (en) | 2010-07-12 | 2013-08-22 | Ironwood Pharmaceuticals, Inc. | Crth2 modulators |
| WO2018068296A1 (en) | 2016-10-14 | 2018-04-19 | Merck Sharp & Dohme Corp. | PIPERIDINE DERIVATIVES AS LIVER X RECEPTOR β AGONISTS, COMPOSITIONS, AND THEIR USE |
| US11629196B2 (en) | 2020-04-27 | 2023-04-18 | Incelldx, Inc. | Method of treating SARS-CoV-2-associated hypercytokinemia by administering a human monoclonal antibody (PRO-140) that inhibits CCR5/CCL5 binding interactions |
| CN113444065A (zh) * | 2021-06-29 | 2021-09-28 | 浙江得乐康食品股份有限公司 | 一种莽草酸磺化物及其制备方法 |
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| EP1467986A1 (en) * | 2002-01-17 | 2004-10-20 | Eli Lilly And Company | Aza-cyclic compounds as modulators of acetylcholine receptors |
-
2003
- 2003-12-17 AR ARP030104682A patent/AR042628A1/es not_active Application Discontinuation
- 2003-12-18 PL PL377768A patent/PL377768A1/pl not_active Application Discontinuation
- 2003-12-18 WO PCT/SE2003/002008 patent/WO2004056773A1/en not_active Ceased
- 2003-12-18 KR KR1020057011450A patent/KR20050084424A/ko not_active Withdrawn
- 2003-12-18 BR BR0317459-0A patent/BR0317459A/pt not_active IP Right Cessation
- 2003-12-18 US US10/539,859 patent/US20060189650A1/en not_active Abandoned
- 2003-12-18 CL CL200302678A patent/CL2003002678A1/es unknown
- 2003-12-18 MX MXPA05006381A patent/MXPA05006381A/es active IP Right Grant
- 2003-12-18 EP EP03781235A patent/EP1572650A1/en not_active Withdrawn
- 2003-12-18 NZ NZ540780A patent/NZ540780A/en unknown
- 2003-12-18 AU AU2003288856A patent/AU2003288856B2/en not_active Ceased
- 2003-12-18 CA CA002508624A patent/CA2508624A1/en not_active Abandoned
- 2003-12-18 JP JP2005502630A patent/JP2006514107A/ja active Pending
- 2003-12-19 TW TW092136170A patent/TW200505856A/zh unknown
- 2003-12-19 UY UY28139A patent/UY28139A1/es unknown
-
2005
- 2005-06-13 CO CO05057099A patent/CO5570665A2/es not_active Application Discontinuation
- 2005-07-18 IS IS7942A patent/IS7942A/is unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JPH06500093A (ja) * | 1990-08-06 | 1994-01-06 | スミス・クライン・アンド・フレンチ・ラボラトリース・リミテッド | N―ヒドロカルビル―4―置換ピペリジン、それらの調製およびカルシウム遮断薬としての使用 |
| JPH11147872A (ja) * | 1997-08-18 | 1999-06-02 | F Hoffmann La Roche Ag | Ccr−3受容体アンタゴニスト |
| WO2000076514A1 (en) * | 1999-06-11 | 2000-12-21 | Merck & Co., Inc. | Cyclopentyl modulators of chemokine receptor activity |
| WO2001087839A1 (en) * | 2000-05-17 | 2001-11-22 | Astrazeneca Ab | Pharmaceutically active piperidine derivatives, in particular as modulators of chemokine receptor activity |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2007528867A (ja) * | 2003-07-16 | 2007-10-18 | アストラゼネカ・アクチエボラーグ | ケモカイン受容体活性のモジュレーターとして有用なピペリジンもしくは8−アザ−ビシクロ[3.2.1]オクタ−3−イル誘導体 |
| JP2007500694A (ja) * | 2003-07-31 | 2007-01-18 | アストラゼネカ・アクチエボラーグ | Ccr5受容体モジュレーターとしてのピペリジン誘導体 |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20050084424A (ko) | 2005-08-26 |
| TW200505856A (en) | 2005-02-16 |
| IS7942A (is) | 2005-07-18 |
| CL2003002678A1 (es) | 2005-04-22 |
| AU2003288856B2 (en) | 2006-11-16 |
| NZ540780A (en) | 2008-04-30 |
| AU2003288856A1 (en) | 2004-07-14 |
| WO2004056773A1 (en) | 2004-07-08 |
| MXPA05006381A (es) | 2005-08-29 |
| US20060189650A1 (en) | 2006-08-24 |
| CO5570665A2 (es) | 2005-10-31 |
| CA2508624A1 (en) | 2004-07-08 |
| AR042628A1 (es) | 2005-06-29 |
| EP1572650A1 (en) | 2005-09-14 |
| BR0317459A (pt) | 2005-11-16 |
| UY28139A1 (es) | 2004-07-30 |
| PL377768A1 (pl) | 2006-02-20 |
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