JPWO2011093441A1 - 胆道疾患の治療又は予防剤 - Google Patents
胆道疾患の治療又は予防剤 Download PDFInfo
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- JPWO2011093441A1 JPWO2011093441A1 JP2011505302A JP2011505302A JPWO2011093441A1 JP WO2011093441 A1 JPWO2011093441 A1 JP WO2011093441A1 JP 2011505302 A JP2011505302 A JP 2011505302A JP 2011505302 A JP2011505302 A JP 2011505302A JP WO2011093441 A1 JPWO2011093441 A1 JP WO2011093441A1
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- biliary tract
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- 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:
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
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- 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
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- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- Bioinformatics & Cheminformatics (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
また、鎮咳薬(特許文献2)、脳細胞保護薬(特許文献3)、止痒薬(特許文献4)、低ナトリウム血症治療薬(特許文献5)、ORL−1受容体拮抗薬(特許文献6)、神経因性疼痛治療薬(特許文献7)、角膜又は結膜用止痒薬(特許文献8)、精神神経疾患治療薬(特許文献9)、薬物依存治療薬(特許文献10)、敗血症治療薬(特許文献11)、多発性硬化症に伴う痒みの治療薬(特許文献12)、統合失調症治療薬(特許文献13)及びジスキネジア治療薬(特許文献14)などとしての用途も既に開示されている。しかしながら、胆道疾患の治療又は予防効果については、なんら開示されていない。
[1]下記一般式(I)
[2]一般式(I)において、R1がシクロプロピルメチル、シクロブチルメチル、シクロペンチルメチル又はシクロヘキシルメチルであり、R2がメチル、エチル又はプロピルである、[1]に記載の胆道疾患の治療又は予防剤。
[3]一般式(I)で表される化合物が(−)−17−(シクロプロピルメチル)−3,14β−ジヒドロキシ−4,5α−エポキシ−6β−[N−メチル−トランス−3−(3−フリル)アクリルアミド]モルヒナンである、[1]に記載の胆道疾患の治療又は予防剤。
[4]胆道疾患が、胆道閉塞、胆嚢障害、胆石症、膵炎、胆道ジスキネジー、胆管炎、胆嚢炎又は原発性胆汁性肝硬変である、[1]乃至[3]のいずれか一項記載の胆道疾患の治療又は予防剤。
[5]Oddi括約筋収縮を抑制することにより、胆道疾患の治療又は予防作用を発現する、[1]乃至[3]のいずれか一項記載の胆道疾患の治療又は予防剤。
[6]胆道疾患の治療又は予防のために用いる、下記一般式(I)
[7]下記一般式(I)
R1は炭素数1から5のアルキル、炭素数4から7のシクロアルキルアルキル、炭素数5から7のシクロアルケニルアルキル、炭素数6から12のアリール、炭素数7から13のアラルキル、炭素数4から7のアルケニル、アリル、フラン−2−イルアルキル(アルキル部の炭素数は1から5)又はチオフェン−2−イルアルキル(アルキル部の炭素数は1から5)を表す。
一般式(III)中の点線と実線の二重線は二重結合又は単結合を表し、単結合であることが好ましい。
R13が一緒になってオキソを表す化合物は、たとえば文献(Heterocycles,63,865(2004),Bioorg.Med.Chem.Lett.,5,1505(1995))に従って得られる10−オキソを有する化合物を原料として、これよりChem.Pharm.Bull.,52,664(2004)及び特許第2525552に記載の方法に従って製造することができる。さらに、一般式(1)で表される化合物のうちR12が水酸基でR13が水素である化合物は、Chem.Pharm.Bull.,52,664(2004)に記載の方法に従って製造することができる。
実施例1 ウサギOddi括約筋収縮に対する(−)−17−(シクロプロピルメチル)−3,14β−ジヒドロキシ−4,5α−エポキシ−6β−[N−メチル−トランス−3−(3−フリル)アクリルアミド]モルヒナン塩酸塩(化合物1)の効果
Wei JG et al.,World J. Gastroenterol.,6,102(2000)に記載の方法を一部変更し、Oddi括約筋の灌流抵抗圧変化を測定した。なお、Oddi括約筋の灌流抵抗圧変化はOddi括約筋の収縮変化のmotilityを反映する。
なお、化合物1の構造は下記式(II)で表される。
Claims (7)
- 一般式(I)において、R1がシクロプロピルメチル、シクロブチルメチル、シクロペンチルメチル又はシクロヘキシルメチルであり、R2がメチル、エチル又はプロピルである、請求項1記載の胆道疾患の治療又は予防剤。
- 一般式(I)で表される化合物が(−)−17−(シクロプロピルメチル)−3,14β−ジヒドロキシ−4,5α−エポキシ−6β−[N−メチル−トランス−3−(3−フリル)アクリルアミド]モルヒナンである、請求項1記載の胆道疾患の治療又は予防剤。
- 胆道疾患が、胆道閉塞、胆嚢障害、胆石症、膵炎、胆道ジスキネジー、胆管炎、胆嚢炎又は原発性胆汁性肝硬変である、請求項1乃至3のいずれか一項記載の胆道疾患の治療又は予防剤。
- Oddi括約筋収縮を抑制することにより、胆道疾患の治療又は予防作用を発現する、請求項1乃至3のいずれか一項記載の胆道疾患の治療又は予防剤。
Priority Applications (1)
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JP2011505302A JP5867081B2 (ja) | 2010-01-29 | 2011-01-28 | 胆道疾患の治療又は予防剤 |
Applications Claiming Priority (4)
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JP2010018730 | 2010-01-29 | ||
JP2010018730 | 2010-01-29 | ||
PCT/JP2011/051737 WO2011093441A1 (ja) | 2010-01-29 | 2011-01-28 | 胆道疾患の治療又は予防剤 |
JP2011505302A JP5867081B2 (ja) | 2010-01-29 | 2011-01-28 | 胆道疾患の治療又は予防剤 |
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JPWO2011093441A1 true JPWO2011093441A1 (ja) | 2013-06-06 |
JP5867081B2 JP5867081B2 (ja) | 2016-02-24 |
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Country | Link |
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US (1) | US10131672B2 (ja) |
EP (1) | EP2529739B1 (ja) |
JP (1) | JP5867081B2 (ja) |
KR (1) | KR101732042B1 (ja) |
CN (1) | CN102711759B (ja) |
AU (1) | AU2011211223B2 (ja) |
BR (1) | BR112012018765B1 (ja) |
CA (1) | CA2787323C (ja) |
ES (1) | ES2582628T3 (ja) |
MX (1) | MX362830B (ja) |
MY (1) | MY173491A (ja) |
PL (1) | PL2529739T3 (ja) |
RU (1) | RU2554857C2 (ja) |
TW (1) | TWI477505B (ja) |
WO (1) | WO2011093441A1 (ja) |
Families Citing this family (8)
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EP2630150B1 (en) * | 2010-10-19 | 2017-04-12 | Memorial Sloan-Kettering Cancer Center | 6-amido derivatives of 4,5a-epoxymorphinans for treatment of pain |
MX2013008749A (es) | 2011-01-31 | 2013-10-17 | Toray Industries | Agente terapeutico o profilactico para caquexia. |
EP4212532A3 (en) | 2015-04-30 | 2023-09-27 | Memorial Sloan Kettering Cancer Center | Mitragynine analogs and uses thereof |
CN106110220B (zh) * | 2016-08-22 | 2020-01-07 | 陕西盘龙药业集团股份有限公司 | 一种治疗胆道疾病的中成药的制备工艺 |
EP3761982A4 (en) | 2018-03-08 | 2021-12-15 | Victoria Link Ltd | TREATMENT OF DEMYELINIZATION DISEASES |
EP3826635A4 (en) | 2018-07-23 | 2022-04-27 | Trevi Therapeutics, Inc. | TREATMENT OF CHRONIC COUGH, DIFFICULT BREATHING AND DYSPNEA |
WO2020205735A1 (en) * | 2019-03-29 | 2020-10-08 | Humanwell Pharmaceutical US | Novel morphinans useful for treating medical disorders |
IL309232A (en) | 2021-06-14 | 2024-02-01 | Scorpion Therapeutics Inc | History of urea which can be used to treat cancer |
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ES2121988T3 (es) | 1992-01-23 | 1998-12-16 | Toray Industries | Derivado de morfinano y uso medicinal. |
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NZ287243A (en) * | 1994-05-31 | 1997-12-19 | Mallinckrodt Chemical Inc | Process for production of nalbuphine form alpha-noroxymorphol |
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Publication number | Publication date |
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RU2012136826A (ru) | 2014-03-10 |
MY173491A (en) | 2020-01-29 |
EP2529739A1 (en) | 2012-12-05 |
CA2787323A1 (en) | 2011-08-04 |
US10131672B2 (en) | 2018-11-20 |
ES2582628T3 (es) | 2016-09-14 |
EP2529739A4 (en) | 2015-03-11 |
AU2011211223A1 (en) | 2012-09-20 |
CN102711759A (zh) | 2012-10-03 |
MX362830B (es) | 2019-02-14 |
WO2011093441A1 (ja) | 2011-08-04 |
US20130203797A1 (en) | 2013-08-08 |
KR101732042B1 (ko) | 2017-05-02 |
MX2012008509A (es) | 2012-08-31 |
PL2529739T3 (pl) | 2016-12-30 |
RU2554857C2 (ru) | 2015-06-27 |
TWI477505B (zh) | 2015-03-21 |
JP5867081B2 (ja) | 2016-02-24 |
CN102711759B (zh) | 2015-05-13 |
KR20120139713A (ko) | 2012-12-27 |
TW201200521A (en) | 2012-01-01 |
BR112012018765B1 (pt) | 2019-09-03 |
BR112012018765A2 (pt) | 2016-05-03 |
EP2529739B1 (en) | 2016-07-13 |
AU2011211223B2 (en) | 2014-10-23 |
CA2787323C (en) | 2017-08-29 |
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