AU2010357625B2 - (+)-morphinans as antagonists of Toll-like receptor 9 and therapeutic uses thereof - Google Patents

(+)-morphinans as antagonists of Toll-like receptor 9 and therapeutic uses thereof Download PDF

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Publication number
AU2010357625B2
AU2010357625B2 AU2010357625A AU2010357625A AU2010357625B2 AU 2010357625 B2 AU2010357625 B2 AU 2010357625B2 AU 2010357625 A AU2010357625 A AU 2010357625A AU 2010357625 A AU2010357625 A AU 2010357625A AU 2010357625 B2 AU2010357625 B2 AU 2010357625B2
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hydrogen
hydroxy
compound
methyl
formula
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AU2010357625A1 (en
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David W. Berberich
Christopher W. Grote
Bobby N. Trawick
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Mallinckrodt LLC
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Mallinckrodt LLC
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
    • C07D217/18—Aralkyl radicals
    • C07D217/20—Aralkyl radicals with oxygen atoms directly attached to the aromatic ring of said aralkyl radical, e.g. papaverine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/485—Morphinan derivatives, e.g. morphine, codeine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/22—Bridged ring systems
    • C07D221/28—Morphinans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
    • C07D489/02—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
    • C07D489/06—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with a hetero atom directly attached in position 14
    • C07D489/08—Oxygen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
    • C07D489/09—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: containing 4aH-8, 9 c-Iminoethano- phenanthro [4, 5-b, c, d] furan ring systems condensed with carbocyclic rings or ring systems
    • C07D489/10—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: containing 4aH-8, 9 c-Iminoethano- phenanthro [4, 5-b, c, d] furan ring systems condensed with carbocyclic rings or ring systems with a bridge between positions 6 and 14

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Emergency Medicine (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
AU2010357625A 2010-07-16 2010-12-22 (+)-morphinans as antagonists of Toll-like receptor 9 and therapeutic uses thereof Active AU2010357625B2 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US12/837,545 US20110015219A1 (en) 2009-07-16 2010-07-16 (+)-Morphinans as Antagonists of Toll-Like Receptor 9 and Therapeutic Uses Thereof
US12/837,545 2010-07-16
US12/975,407 US9562014B2 (en) 2009-07-16 2010-12-22 (+)-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

Publications (2)

Publication Number Publication Date
AU2010357625A1 AU2010357625A1 (en) 2012-03-01
AU2010357625B2 true AU2010357625B2 (en) 2015-04-23

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AU2010357625A Active AU2010357625B2 (en) 2010-07-16 2010-12-22 (+)-morphinans as antagonists of Toll-like receptor 9 and therapeutic uses thereof

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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 (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10363251B2 (en) 2009-07-16 2019-07-30 Mallinckrodt Llc (+)-morphinans as antagonists of toll-like receptor 9 and therapeutic uses thereof
US8829020B2 (en) 2009-07-16 2014-09-09 Mallinckrodt Llc Compounds and compositions for use in phototherapy and in treatment of ocular neovascular disease and cancers
PL2453895T3 (pl) * 2009-07-16 2018-10-31 Mallinckrodt Llc (+)-morfinany jako antagonisty receptora toll-like 9 i ich zastosowania terapeutyczne
WO2012008984A1 (en) 2010-07-16 2012-01-19 Mallinckrodt Llc (+)-morphinans as antagonists of toll-like receptor 9 and therapeutic uses thereof
IN2014DN03009A (enExample) 2011-10-26 2015-05-08 Kempharm Inc
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
WO2015082932A1 (en) 2013-12-05 2015-06-11 The University Of Bath Novel opioid compounds and their uses
CA2969221C (en) 2014-12-02 2021-01-12 Travis Mickle Benzoic acid, benzoic acid derivatives and heteroaryl carboxylic acid conjugates of oxymorphone, prodrugs, methods of making and use thereof
JP6702184B2 (ja) * 2015-03-24 2020-05-27 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
US10653687B2 (en) 2015-11-18 2020-05-19 INSERM (Institut National de la Santé et de la Recherche Médicale Methods and pharmaceutical compostions for treating rhabdomyolysis
CN110290792A (zh) * 2017-01-05 2019-09-27 景凯生物科技股份有限公司 吗啡喃衍生物和其用于治疗自体免疫、发炎或感染相关的障碍的组合物
WO2019018354A1 (en) * 2017-07-18 2019-01-24 Merck Patent Gmbh ANTAGONISTS OF TLR7 / 8 AND USES THEREOF
CA3091826A1 (en) * 2018-02-23 2019-08-29 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
US12637411B2 (en) 2019-01-30 2026-05-26 Mggm Llc Structurally modified opioids for prevention and treatment of diseases and conditions
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
JP2026086955A (ja) * 2023-03-29 2026-05-27 日本ケミファ株式会社 スピロ環状モルヒナン誘導体

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009059048A2 (en) * 2007-10-30 2009-05-07 The Regents Of The University Of Colorado (+)-opioids and methods of use
WO2010096791A1 (en) * 2009-02-23 2010-08-26 Mallinckrodt Inc. (+)-6-hydroxy-morphinan or (+)-6-amino-morphinan derivatives
WO2010144641A1 (en) * 2009-06-11 2010-12-16 Mallinckrodt Inc. Preparation of 6-alpha-amino n-substituted morphinans by catalytic hydrogen transfer
WO2011009015A1 (en) * 2009-07-16 2011-01-20 Mallinckrodt Inc. (+) - morphinans as antagonists of toll-like receptor 9 and therapeutic uses thereof

Family Cites Families (31)

* Cited by examiner, † Cited by third party
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
JP2525552B2 (ja) * 1992-01-23 1996-08-21 東レ株式会社 モルヒナン誘導体および医薬用途
NZ268969A (en) * 1993-07-23 1997-06-24 Toray Industries Morphinan derivatives and pharmaceutical compositions
US5919826A (en) * 1996-10-24 1999-07-06 Algos Pharmaceutical Corporation Method of alleviating pain
ATE292625T1 (de) 2000-10-31 2005-04-15 Rensselaer Polytech Inst 8-substituierte 2,6-methano-3-benzazocine und 3- substituierte morphinane als opioidrezeptorbindende agenzien
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
EP2012772A1 (en) 2006-04-26 2009-01-14 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
JP2010533719A (ja) 2007-07-17 2010-10-28 マリンクロッド・インコーポレイテッド 還元的アミノ化によるｎ−アルキル化オピエートの調製
JP2010536787A (ja) 2007-08-15 2010-12-02 イデラ ファーマシューティカルズ インコーポレイテッド Ｔｏｌｌ様受容体モジュレータ
CA2702680A1 (en) * 2007-10-18 2009-04-23 Aiko Biotechnology Combination analgesic employing opioid and neutral antagonist
JP5688974B2 (ja) 2007-12-17 2015-03-25 マリンクロッド エルエルシー （＋）−オピエートの生成のためのプロセスおよび化合物
WO2009078986A1 (en) 2007-12-17 2009-06-25 Mallinckrodt Inc. Process for the preparation of buprenorphine and derivatives of buprenorphine
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
NZ589963A (en) 2008-06-17 2011-08-26 Mallinckrodt Inc Processes for the preparation of 6- beta-hydroxy morphinan compounds
EP2313400A4 (en) 2008-07-10 2011-12-28 Human Biomolecular Res Inst SYNTHESIS OF METABOLIC STRENGTHS FOR ALCOHOL AND DRUG ABUSE
NZ591756A (en) 2008-09-16 2013-04-26 Mallinckrodt Llc Processes for the synthesis of five and six membered heterocyclic rings
CN102227433B (zh) 2008-09-30 2015-01-07 马林克罗特有限公司 烷基化吗啡喃衍生物的仲胺基团的方法
SI2352494T1 (sl) * 2008-10-30 2019-12-31 Gruenenthal Gmbh Nove in potentne dozirne oblike tapentadola
KR20100090155A (ko) * 2009-02-05 2010-08-13 엘지전자 주식회사 이동 단말기 및 그의 프레즌스 정보 처리방법
US8946419B2 (en) 2009-02-23 2015-02-03 Mallinckrodt Llc (+)-6-hydroxy-morphinan or (+)-6-amino-morphinan derivatives
CN102325777B (zh) 2009-02-23 2015-08-12 马林克罗特公司 (+)-吗啡喃*n-氧化物及其制备方法
WO2012008984A1 (en) 2010-07-16 2012-01-19 Mallinckrodt Llc (+)-morphinans as antagonists of toll-like receptor 9 and therapeutic uses thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009059048A2 (en) * 2007-10-30 2009-05-07 The Regents Of The University Of Colorado (+)-opioids and methods of use
WO2010096791A1 (en) * 2009-02-23 2010-08-26 Mallinckrodt Inc. (+)-6-hydroxy-morphinan or (+)-6-amino-morphinan derivatives
WO2010144641A1 (en) * 2009-06-11 2010-12-16 Mallinckrodt Inc. Preparation of 6-alpha-amino n-substituted morphinans by catalytic hydrogen transfer
WO2011009015A1 (en) * 2009-07-16 2011-01-20 Mallinckrodt Inc. (+) - morphinans as antagonists of toll-like receptor 9 and therapeutic uses thereof

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
Fialip, J. et al, Life Sciences, 1996, vol. 59(11), pp. 133-139 *
Hutchinson, M.R. et al, European Journal of Neuroscience, 2008, vol. 28, pp. 20-29 *
Iijima, I. et al, Journal of Medicinal Chemistry, 1978, vol. 21(4), pp. 398 *
Iijima, I. et al, Journal of Organic Chemistry, 1978, vol. 43 (7), pp. 1462-1463 *
Watkins, L.R. et al, Brain, Behavior and Immunity, 2007, vol. 21, pp. 131-146 *
Watkins, L.R. et al, Trends in Pharmacological Sciences, 2009, vol. 30(11), pp. 581-591 *

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Publication number Publication date
WO2012008984A1 (en) 2012-01-19
CA2768199A1 (en) 2012-01-19
US11142502B2 (en) 2021-10-12
PL2593095T3 (pl) 2019-12-31
EP2593095B1 (en) 2019-03-27
JP2013534208A (ja) 2013-09-02
JP5911484B2 (ja) 2016-04-27
US20170029432A1 (en) 2017-02-02
ES2728701T3 (es) 2019-10-28
EP2593095A1 (en) 2013-05-22
US9562014B2 (en) 2017-02-07
US20200172488A1 (en) 2020-06-04
US10604488B2 (en) 2020-03-31
AU2010357625A1 (en) 2012-03-01
US20110136845A1 (en) 2011-06-09
CA2768199C (en) 2018-08-28

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