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

Info

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
Authority
AU
Australia
Prior art keywords
hydrogen
hydroxy
compound
methyl
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.)
Active
Application number
AU2010357625A
Other languages
English (en)
Other versions
AU2010357625A1 (en
Inventor
David W. Berberich
Christopher W. Grote
Bobby N. Trawick
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Mallinckrodt LLC
Original Assignee
Mallinckrodt LLC
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from US12/837,545 external-priority patent/US20110015219A1/en
Application filed by Mallinckrodt LLC filed Critical Mallinckrodt LLC
Publication of AU2010357625A1 publication Critical patent/AU2010357625A1/en
Application granted granted Critical
Publication of AU2010357625B2 publication Critical patent/AU2010357625B2/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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

Landscapes

  • 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)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Emergency Medicine (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (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 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 (2)

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

Family

ID=43754707

Family Applications (1)

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

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)

* Cited by examiner, † Cited by third party
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

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
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
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
US8946419B2 (en) 2009-02-23 2015-02-03 Mallinckrodt Llc (+)-6-hydroxy-morphinan or (+)-6-amino-morphinan derivatives
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

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 *

Also Published As

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

Similar Documents

Publication Publication Date Title
CA2768199C (en) (+)-morphinans as antagonists of toll-like receptor 9 and therapeutic uses thereof
AU2010273253B2 (en) (+) - morphinans as antagonists of Toll-like receptor 9 and therapeutic uses thereof
CA2782529C (en) Morphinan derivatives for the treatment of drug overdose
CA2787323C (en) Therapeutic or prophylactic agent for biliary tract diseases
US9597316B2 (en) Indole compounds for use in treating inflammation and cancer
US10363251B2 (en) (+)-morphinans as antagonists of toll-like receptor 9 and therapeutic uses thereof
EP2168580B1 (en) Remedy or preventive for schizophrenia
EP1844792A1 (en) Therapeutic agent for constipation
US20100331340A1 (en) Use of aryl piperazine derivatives in manufacturing medicants for treating pain
WO2025038406A1 (en) Design, synthesis, and biological evaluation of nitrogen-walk derivatives of nan as mu opioid receptor selective modulators
WO2014037381A1 (en) Method for treating pruritus

Legal Events

Date Code Title Description
FGA Letters patent sealed or granted (standard patent)