JP2013534208A5 - - Google Patents
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- JP2013534208A5 JP2013534208A5 JP2013519642A JP2013519642A JP2013534208A5 JP 2013534208 A5 JP2013534208 A5 JP 2013534208A5 JP 2013519642 A JP2013519642 A JP 2013519642A JP 2013519642 A JP2013519642 A JP 2013519642A JP 2013534208 A5 JP2013534208 A5 JP 2013534208A5
- Authority
- JP
- Japan
- Prior art keywords
- hydrogen
- hydroxy
- methyl
- alkyl
- formula
- 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.)
- Granted
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- 229910052739 hydrogen Inorganic materials 0.000 claims description 215
- 239000001257 hydrogen Substances 0.000 claims description 215
- 150000002431 hydrogen Chemical group 0.000 claims description 145
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 133
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 101
- -1 hydroxyalkylamines Chemical group 0.000 claims description 96
- 125000003545 alkoxy group Chemical group 0.000 claims description 81
- 125000000217 alkyl group Chemical group 0.000 claims description 69
- 125000004423 acyloxy group Chemical group 0.000 claims description 66
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 57
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 54
- 150000001875 compounds Chemical class 0.000 claims description 45
- 125000003342 alkenyl group Chemical group 0.000 claims description 43
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 42
- 125000006431 methyl cyclopropyl group Chemical group 0.000 claims description 42
- 125000002252 acyl group Chemical group 0.000 claims description 37
- 125000003118 aryl group Chemical group 0.000 claims description 34
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 34
- 239000008194 pharmaceutical composition Substances 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 31
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 29
- 125000001072 heteroaryl group Chemical group 0.000 claims description 29
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
- 125000001475 halogen functional group Chemical group 0.000 claims description 27
- 229930194542 Keto Natural products 0.000 claims description 26
- 150000001412 amines Chemical class 0.000 claims description 26
- 125000000468 ketone group Chemical group 0.000 claims description 26
- 125000005354 acylalkyl group Chemical group 0.000 claims description 23
- 125000005041 acyloxyalkyl group Chemical group 0.000 claims description 23
- 208000002193 Pain Diseases 0.000 claims description 21
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 18
- 125000004104 aryloxy group Chemical group 0.000 claims description 18
- 125000002541 furyl group Chemical group 0.000 claims description 18
- 125000003944 tolyl group Chemical group 0.000 claims description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- 150000001408 amides Chemical class 0.000 claims description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 125000002837 carbocyclic group Chemical group 0.000 claims description 12
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 125000005082 alkoxyalkenyl group Chemical group 0.000 claims description 10
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 10
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 claims description 8
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- 150000003973 alkyl amines Chemical class 0.000 claims description 6
- 125000005233 alkylalcohol group Chemical group 0.000 claims description 6
- 150000004982 aromatic amines Chemical class 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims description 6
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 6
- 235000019441 ethanol Nutrition 0.000 claims description 6
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
- 125000001041 indolyl group Chemical group 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 208000000094 Chronic Pain Diseases 0.000 claims description 4
- 208000005298 acute pain Diseases 0.000 claims description 4
- 125000005157 alkyl carboxy group Chemical group 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 208000004296 neuralgia Diseases 0.000 claims description 4
- 208000021722 neuropathic pain Diseases 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- 230000000472 traumatic effect Effects 0.000 claims description 4
- JNWRCNXXCLSNJN-UHFFFAOYSA-N 1-(dimethylamino)cyclohexan-1-ol Chemical compound CN(C)C1(O)CCCCC1 JNWRCNXXCLSNJN-UHFFFAOYSA-N 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims 9
- 229910052799 carbon Inorganic materials 0.000 claims 2
- 125000004181 carboxyalkyl group Chemical group 0.000 claims 2
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 125000003368 amide group Chemical group 0.000 claims 1
- 150000001721 carbon Chemical group 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 description 39
- INAXVFBXDYWQFN-XHSDSOJGSA-N morphinan Chemical compound C1C2=CC=CC=C2[C@]23CCCC[C@H]3[C@@H]1NCC2 INAXVFBXDYWQFN-XHSDSOJGSA-N 0.000 description 18
- 0 *c1cc(CCN(*)[C@@]2CC3=CC=C(*)I(*)=C3)c2cc1 Chemical compound *c1cc(CCN(*)[C@@]2CC3=CC=C(*)I(*)=C3)c2cc1 0.000 description 11
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 3
- 239000012848 Dextrorphan Substances 0.000 description 1
- JAQUASYNZVUNQP-PVAVHDDUSA-N dextrorphan Chemical compound C1C2=CC=C(O)C=C2[C@@]23CCN(C)[C@@H]1[C@H]2CCCC3 JAQUASYNZVUNQP-PVAVHDDUSA-N 0.000 description 1
- 229950006878 dextrorphan Drugs 0.000 description 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12/837,545 | 2010-07-16 | ||
| US12/837,545 US20110015219A1 (en) | 2009-07-16 | 2010-07-16 | (+)-Morphinans as Antagonists of Toll-Like Receptor 9 and Therapeutic Uses Thereof |
| US12/975,407 | 2010-12-22 | ||
| PCT/US2010/061699 WO2012008984A1 (en) | 2010-07-16 | 2010-12-22 | (+)-morphinans as antagonists of toll-like receptor 9 and therapeutic uses thereof |
| US12/975,407 US9562014B2 (en) | 2009-07-16 | 2010-12-22 | (+)-morphinans as antagonists of toll-like receptor 9 and therapeutic uses thereof |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2013534208A JP2013534208A (ja) | 2013-09-02 |
| JP2013534208A5 true JP2013534208A5 (enExample) | 2014-01-30 |
| JP5911484B2 JP5911484B2 (ja) | 2016-04-27 |
Family
ID=43754707
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2013519642A Expired - Fee Related JP5911484B2 (ja) | 2010-07-16 | 2010-12-22 | トール様受容体９のアンタゴニストとしての（＋）−モルフィナンおよびその治療的使用 |
Country Status (8)
| Country | Link |
|---|---|
| US (3) | US9562014B2 (enExample) |
| EP (1) | EP2593095B1 (enExample) |
| JP (1) | JP5911484B2 (enExample) |
| AU (1) | AU2010357625B2 (enExample) |
| CA (1) | CA2768199C (enExample) |
| ES (1) | ES2728701T3 (enExample) |
| PL (1) | PL2593095T3 (enExample) |
| WO (1) | WO2012008984A1 (enExample) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011009020A2 (en) | 2009-07-16 | 2011-01-20 | Mallinckrodt Inc. | Compounds and compositions for use in phototherapy and in treatment of ocular neovascular disease and cancers |
| TR201809739T4 (tr) * | 2009-07-16 | 2018-07-23 | Mallinckrodt Llc | Toll benzeri reseptör 9 antagonistleri olarak (+)-morfinanlar ve bunların terapötik amaçlı kullanımları. |
| US10363251B2 (en) | 2009-07-16 | 2019-07-30 | Mallinckrodt Llc | (+)-morphinans as antagonists of toll-like receptor 9 and therapeutic uses thereof |
| ES2728701T3 (es) | 2010-07-16 | 2019-10-28 | Mallinckrodt Llc | (+)-Morfinanos como antagonistas del receptor 9 de tipo Toll y aplicaciones terapéuticas de los mismos |
| HK1197191A1 (en) | 2011-10-26 | 2015-01-09 | Kempharm, Inc. | Benzoic acid, benzoic acid derivatives and heteroaryl carboxylic acid conjugates of hydromorphone, prodrugs, methods of making and use thereof |
| CN102579444A (zh) * | 2012-01-21 | 2012-07-18 | 张有成 | 青藤碱在制备抑制肿瘤侵袭转移的药物中的应用 |
| GB201308440D0 (en) * | 2013-05-10 | 2013-06-19 | Dalgleish Angus | Therapeutic |
| ES2784690T3 (es) | 2013-12-05 | 2020-09-29 | Univ Bath | Nuevos compuestos opioides y sus usos |
| KR20170094251A (ko) | 2014-12-02 | 2017-08-17 | 켐팜 인코포레이티드 | 옥시모르폰의 벤조산, 벤조산 유도체 및 헤테로아릴 카르복실산 콘쥬게이트, 이의 전구 약물, 제조 방법 및 용도 |
| WO2016152965A1 (ja) * | 2015-03-24 | 2016-09-29 | 東レ株式会社 | 低アルブミン血症の改善剤 |
| US9757372B2 (en) * | 2015-03-25 | 2017-09-12 | Taiwanj Pharmaceuticals Co., Ltd. | Toll-like receptor 4 antagonists and use in autoimmune liver diseases |
| EP3377095B1 (en) | 2015-11-18 | 2020-01-01 | INSERM - Institut National de la Santé et de la Recherche Médicale | Methods and pharmaceutical compositions for treating rhabdomyolysis |
| JP2020504127A (ja) * | 2017-01-05 | 2020-02-06 | タイワンジェ ファーマシューティカルズ カンパニー リミテッドＴａｉｗａｎｊ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｃｏ．， Ｌｔｄ． | モルフィナン誘導体と自己免疫、炎症または感染に関連する障害の治療に用いるモルフィナン誘導体含有組成物 |
| WO2019018354A1 (en) * | 2017-07-18 | 2019-01-24 | Merck Patent Gmbh | ANTAGONISTS OF TLR7 / 8 AND USES THEREOF |
| AU2019224127B2 (en) * | 2018-02-23 | 2021-12-09 | Rhodes Technologies | Novel opioid compounds and uses thereof |
| CN109288840A (zh) * | 2018-11-23 | 2019-02-01 | 中国科学院长春应用化学研究所 | 二元纳曲酮衍生物的应用 |
| EP4125990A4 (en) * | 2020-03-24 | 2024-07-03 | University of Padova | MORPHINE ISOMERS AND THEIR STRUCTURAL MODIFICATIONS AS NMDAR ANTAGONISTS AND NEUROPLASTIGENS |
| CN115260098B (zh) * | 2022-06-09 | 2024-06-04 | 澳门科技大学 | Abcb5抑制剂在制备多耐药性类风湿性关节炎治疗药物中的应用 |
| WO2024204554A1 (ja) * | 2023-03-29 | 2024-10-03 | 日本ケミファ株式会社 | スピロ環状モルヒナン誘導体 |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS55133360A (en) * | 1979-04-03 | 1980-10-17 | Tatsuya Shono | Preparation of cyclic amine |
| US4521601A (en) * | 1981-05-20 | 1985-06-04 | The United States Of America As Represented By The Department Of Health & Human Services | Practical total synthesis unnatural enantiomers of opium-derived morphinans |
| HU197750B (en) * | 1984-07-17 | 1989-05-29 | Alkaloida Vegyeszeti Gyar | Process for n-demethylation of morphine alkaloids |
| US5668285A (en) * | 1986-10-31 | 1997-09-16 | The United States Of America As Represented By The Department Of Health And Human Services | Total synthesis of northebaine, normophine, noroxymorphone enantiomers and derivatives via N-Nor intermediates |
| PT95069B (pt) | 1989-08-24 | 1997-10-31 | Searle & Co | Processo para a preparacao de (+)-isomeros de derivados de endoetano/endoetanoepoximofinano, uteis como agentes anti-tussicos |
| JPH04273880A (ja) * | 1991-02-28 | 1992-09-30 | Ono Pharmaceut Co Ltd | ジヒドロモルヒネ誘導体 |
| US6323212B1 (en) | 1992-01-23 | 2001-11-27 | Toray Industries, Inc. | Morphinan derivative and its pharmaceutical applications |
| EP0663401B1 (en) * | 1993-07-23 | 2000-06-07 | Toray Industries, Inc. | Morphinan derivative and medicinal use |
| US5919826A (en) * | 1996-10-24 | 1999-07-06 | Algos Pharmaceutical Corporation | Method of alleviating pain |
| EP1359146B1 (en) | 2000-10-31 | 2008-04-09 | Rensselaer Polytechnic Institute | 4-aryl piperidines as opioid receptor binding agents |
| WO2002080918A1 (en) * | 2001-04-02 | 2002-10-17 | Toray Industries, Inc. | Remedial or prophylactic agent for frequent urination or urinary incontinence |
| US20040033253A1 (en) * | 2002-02-19 | 2004-02-19 | Ihor Shevchuk | Acyl opioid antagonists |
| GB2392670A (en) | 2002-09-03 | 2004-03-10 | Stylacats Ltd | (+)-Morphine production |
| US7238791B1 (en) * | 2005-12-16 | 2007-07-03 | Roche Diagnostics Operations, Inc. | 6-monoacetylmorphine derivatives useful in immunoassay |
| WO2007127624A1 (en) | 2006-04-26 | 2007-11-08 | The Uab Research Foundation | Reducing cancer cell invasion using an inhibitor of toll like receptor signaling |
| CN101066948B (zh) | 2007-05-30 | 2012-01-04 | 广东工业大学 | 青藤碱催化氢化还原制备氢化青藤碱的方法 |
| WO2009012005A1 (en) | 2007-07-17 | 2009-01-22 | Mallinckrodt Inc. | Preparation of n-alkylated opiates by reductive amination |
| MX2010001785A (es) | 2007-08-15 | 2010-03-10 | Idera Pharmaceuticals Inc | Moduladores de receptores tipo larga distancia. |
| US8883817B2 (en) * | 2007-10-18 | 2014-11-11 | Aiko Biotechnology | Combination analgesic employing opioid and neutral antagonist |
| US20110251229A1 (en) * | 2007-10-30 | 2011-10-13 | The Regents Of The University Of Colorado | (+)-opioids and methods of use |
| CN101896489A (zh) * | 2007-12-17 | 2010-11-24 | 马林克罗特公司 | 制备丁丙诺啡和丁丙诺啡的衍生物的方法 |
| EP2222642B1 (en) * | 2007-12-17 | 2014-02-12 | Mallinckrodt LLC | Process and compounds for the production of (+) opiates |
| CN101265266B (zh) | 2008-04-23 | 2011-12-14 | 南京大学 | 青藤碱衍生物及其制备方法和应用 |
| AU2009260303A1 (en) * | 2008-06-17 | 2009-12-23 | Mallinckrodt Inc. | Processes for the preparation of 6- beta-hydroxy morphinan compounds |
| CA2730111C (en) | 2008-07-10 | 2017-02-28 | Human Biomolecular Research Institute | Synthesis of metabolically stable agents for alcohol and drug abuse |
| EP2328899B1 (en) * | 2008-09-16 | 2018-01-24 | Mallinckrodt LLC | Processes for the synthesis of five and six membered heterocyclic rings |
| EP2344506B1 (en) | 2008-09-30 | 2016-02-10 | Mallinckrodt LLC | Processes for the alkylation of secondary amine groups of morphinan derivatives |
| ES2758831T3 (es) * | 2008-10-30 | 2020-05-06 | Gruenenthal Gmbh | Nuevas y potentes formas de dosificación de tapentadol |
| KR20100090155A (ko) * | 2009-02-05 | 2010-08-13 | 엘지전자 주식회사 | 이동 단말기 및 그의 프레즌스 정보 처리방법 |
| WO2010096790A1 (en) | 2009-02-23 | 2010-08-26 | Mallinckrodt Inc. | (+)-morphinananium n-oxides and processes for their production |
| JP2012518652A (ja) * | 2009-02-23 | 2012-08-16 | マリンクロッド インコーポレイテッド | （＋）−６−ヒドロキシ−モルフィナンまたは（＋）−６−アミノ−モルフィナン誘導体 |
| US8946419B2 (en) | 2009-02-23 | 2015-02-03 | Mallinckrodt Llc | (+)-6-hydroxy-morphinan or (+)-6-amino-morphinan derivatives |
| CN102803267A (zh) | 2009-06-11 | 2012-11-28 | 马林克罗特有限公司 | 通过催化氢转移的6-α-氨基N-取代的吗啡喃的制备 |
| TR201809739T4 (tr) * | 2009-07-16 | 2018-07-23 | Mallinckrodt Llc | Toll benzeri reseptör 9 antagonistleri olarak (+)-morfinanlar ve bunların terapötik amaçlı kullanımları. |
| ES2728701T3 (es) | 2010-07-16 | 2019-10-28 | Mallinckrodt Llc | (+)-Morfinanos como antagonistas del receptor 9 de tipo Toll y aplicaciones terapéuticas de los mismos |
-
2010
- 2010-12-22 ES ES10805351T patent/ES2728701T3/es active Active
- 2010-12-22 WO PCT/US2010/061699 patent/WO2012008984A1/en not_active Ceased
- 2010-12-22 EP EP10805351.3A patent/EP2593095B1/en active Active
- 2010-12-22 US US12/975,407 patent/US9562014B2/en active Active
- 2010-12-22 JP JP2013519642A patent/JP5911484B2/ja not_active Expired - Fee Related
- 2010-12-22 CA CA2768199A patent/CA2768199C/en active Active
- 2010-12-22 PL PL10805351T patent/PL2593095T3/pl unknown
- 2010-12-22 AU AU2010357625A patent/AU2010357625B2/en active Active
-
2016
- 2016-09-02 US US15/255,979 patent/US10604488B2/en active Active
-
2020
- 2020-02-03 US US16/779,796 patent/US11142502B2/en active Active
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