CN1939915A - 喹啉衍生物 - Google Patents
喹啉衍生物 Download PDFInfo
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- CN1939915A CN1939915A CNA2006101357990A CN200610135799A CN1939915A CN 1939915 A CN1939915 A CN 1939915A CN A2006101357990 A CNA2006101357990 A CN A2006101357990A CN 200610135799 A CN200610135799 A CN 200610135799A CN 1939915 A CN1939915 A CN 1939915A
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- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title 1
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title 1
- 208000010412 Glaucoma Diseases 0.000 claims abstract description 8
- 239000003814 drug Substances 0.000 claims abstract description 8
- 208000001491 myopia Diseases 0.000 claims abstract description 7
- 230000004379 myopia Effects 0.000 claims abstract description 6
- 238000002360 preparation method Methods 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 38
- 150000003839 salts Chemical group 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 7
- 239000003513 alkali Substances 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 230000003287 optical effect Effects 0.000 claims description 2
- RFQDDXWZZVRLKO-UHFFFAOYSA-N benzo[g]quinoline Chemical class N1=CC=CC2=CC3=CC=CC=C3C=C21 RFQDDXWZZVRLKO-UHFFFAOYSA-N 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 230000004410 intraocular pressure Effects 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
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- JRTGLDQQKSHCTM-UHFFFAOYSA-N C1=CC=C2C=C3C(O)=CC=CC3=CC2=N1 Chemical compound C1=CC=C2C=C3C(O)=CC=CC3=CC2=N1 JRTGLDQQKSHCTM-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
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- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- QJMIKHWBGQHYPT-UHFFFAOYSA-N 1,2,3,4,4a,5,5a,6-octahydrobenzo[g]quinoline Chemical compound C1=CCC2CC(CCCN3)C3=CC2=C1 QJMIKHWBGQHYPT-UHFFFAOYSA-N 0.000 description 1
- OXFSTTJBVAAALW-UHFFFAOYSA-N 1,3-dihydroimidazole-2-thione Chemical class SC1=NC=CN1 OXFSTTJBVAAALW-UHFFFAOYSA-N 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- ANBBXQWFNXMHLD-UHFFFAOYSA-N aluminum;sodium;oxygen(2-) Chemical compound [O-2].[O-2].[Na+].[Al+3] ANBBXQWFNXMHLD-UHFFFAOYSA-N 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
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- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
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- 238000002347 injection Methods 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000002997 ophthalmic solution Substances 0.000 description 1
- 229940054534 ophthalmic solution Drugs 0.000 description 1
- CMHHMUWAYWTMGS-UHFFFAOYSA-N oxybuprocaine Chemical compound CCCCOC1=CC(C(=O)OCCN(CC)CC)=CC=C1N CMHHMUWAYWTMGS-UHFFFAOYSA-N 0.000 description 1
- 229960003502 oxybuprocaine Drugs 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910001388 sodium aluminate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/10—Ophthalmic agents for accommodation disorders, e.g. myopia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
本发明涉及新的苯并[g]喹啉衍生物、它们的制备、它们作为药物用于治疗青光眼和近视的用途。
Description
本申请为分案申请，原申请的申请号为03805360.8，申请日为2003年3月6日，发明名称为“喹啉衍生物”。
本发明涉及新的苯并[g]喹啉衍生物、它们的制备、它们作为药物的用途以及包含它们的药物组合物。
本发明涉及选自式Ia化合物的化合物，
其中A和Q各自为H或一起形成另外的键，并且其中3位上的不对称中心可以是外消旋的，或者可以是光学活性形式，并且其中R为式Ib或Ic，
并且其中R1为烷基，所述化合物可以是游离碱或酸加成盐形式。
在一个优选的方面，A和Q各自为H。在另一个优选的方面，A和Q一起形成另外的键。
式Ia中3位上的取代基CH2-R优选为3R构型，条件是A和Q各自为H。
R1优选选自含1至4个碳原子的烷基。因此，在此所用的烷基特别是C1-C4-烷基，例如正丁基、仲丁基、叔丁基、正丙基、异丙基，或者特别是甲基或乙基。
在一个更优选的方面，R1为C1-烷基，例如甲基。
更具体而言，本发明涉及选自式I化合物和式II化合物的化合物，
其中式I中的取代基CH2-S-咪唑为3R构型，所述化合物可以是游离碱或酸加成盐形式。
本发明的一个甚至更优选的方面是以上所定义的式I化合物。还非常优选的是以上所定义的式II化合物。
可以用已知的方法由游离碱制备酸加成盐，反之亦然。
用于本发明的适宜的酸加成盐包括例如盐酸盐。
式Ia、I和II的化合物及其生理学可接受的酸加成盐在下文中称为本发明的化合物，它们在动物试验中表现出有价值的药理学性质，因此可用作药物。
现有技术：
与最接近的现有技术、例如EP 912’553相比，本发明的化合物表现出有利的药理学性质。
本发明的详细描述：
具体而言，本发明的化合物在10至100μM的浓度下使家兔的眼内压(IOP)降低。将约2.5kg的雄性家兔固定在笼中，保持其头部可自由活动。将含有供试化合物的溶液应用于右眼，并将安慰剂溶液应用于左眼(各2滴，即约40μl)。首先用含有盐酸奥布卡因(0.4％)和荧光素(0.05％)的溶液将眼麻醉，在施用后的各种时间间隔(10、20、30、60、90、120、180和240分钟)测定眼压，在此使用了Goldberg的压平眼压计。
令人惊奇的是，本发明的化合物表现出强的降IOP功效、极佳的可耐受性和长的作用持续时间，因此特别可用于治疗青光眼和近视。在一个优选的方面，其涉及治疗青光眼。
对于上述适应症，适宜的剂量当然将根据例如所用的化合物、宿主、施用方式以及所治疗病症的严重程度而改变。但是，通常显示在动物中可获得满意结果的日剂量为约0.1至约10mg/kg动物体重。在较大的哺乳动物例如人中，适用的日剂量为约5至约200mg、优选约10至约100mg所述化合物，所述剂量可以以每天不超过4次的分剂量或以缓释形式方便地施用。
本发明的化合物可以以游离形式或以可药用盐形式施用。所述的盐可以以常规方法制备，并且表现出与游离化合物相同等级的活性。
因此，本发明提供了用作药物、例如在治疗青光眼和近视中用作药物的本发明的化合物。
此外，本发明提供了包含本发明的化合物以及至少一种可药用稀释剂或载体的药物组合物。所述组合物可以以常规方法配制。单位剂量形式含有例如约0.25至约50mg本发明的化合物。
本发明的化合物可以以任何常规途径施用，例如可以例如以注射用溶液剂或混悬剂形式经胃肠外施用，或者例如以片剂或胶囊剂形式经肠、优选口服施用。
更优选地，它们以约0.002至0.02％的眼用溶液形式局部应用于眼。
眼用赋形剂是这样的物质：使得所述化合物可以与眼表面保持接触足够长的时间以使化合物渗透入眼的角膜和内部区域。
可药用的眼用赋形剂可以是例如软膏、植物油或包囊材料。
根据前述内容，本发明还提供了在治疗青光眼和近视中用作药物的本发明的化合物。
此外，本发明提供了本发明的化合物在制备用于治疗青光眼和近视的药物中的用途。
还有另一个方面，本发明提供了用于在需要所述治疗的个体中治疗青光眼和近视的方法，其包括向所述个体施用治疗有效量的本发明的化合物。
实施例1：
[3R，4aR，10aR]-1-甲基-3β-羟甲基-6-甲氧基-1，2，3，4，4aα，5，10，10aβ-八氢苯并[g]喹啉
在氩气、室温下，在1小时内向5.78g(20mM)[3R，4aR，10aR]-1-甲基-3β-甲氧基羰基-6-甲氧基-1，2，3，4，4aα，5，10，10aβ-八氢苯并[g]喹啉于100ml甲苯中的溶液中滴加12ml SDBA(二氢-双-(2-甲氧基乙氧基)铝酸钠)的溶液(70％，在甲苯中，42mM)。然后，向用冰冷却的反应混合物中滴加10mlNaOH(30％)。将沉淀出来的结晶滤出、用水和甲苯洗涤并干燥。得到的标题化合物m.p.为148℃；[α]20 D＝-120°(c＝0.425，在乙醇中)。
实施例2
[3R，4aR，10aR]-1-甲基-3β-甲磺酰基氧基甲基-6-甲氧基-1，2，3，4，4aα，5，10，10aβ-八氢苯并[g]喹啉
在室温下，将12ml(153mM)甲磺酰氯滴加至20g(76.5mM)实施例1下所获得的化合物于150ml吡啶中的溶液中。用冰冷却将温度保持在45℃以下。在室温下搅拌2小时后，在0℃下用饱和KHCO3将溶液调至pH 7-8，并用乙酸乙酯萃取。用Na2SO4干燥后，过滤并蒸发浓缩，获得标题化合物，为米黄色结晶，将其直接用于下一步骤。
实施例3
将2g(5.9mmol)实施例2中所获得的甲磺酸酯和1g(8.8mM)1-甲基-2-巯基-咪唑于30ml二甲基甲酰胺中的溶液与2ml 10N NaOH混合，并在60℃下搅拌3小时。将得到的混悬液通过在真空下蒸发进行浓缩，然后用乙酸乙酯/异丙醇(9∶1)萃取。用Na2SO4干燥后，过滤，并在真空下除去溶剂，获得式I化合物的甲基醚，然后将其直接用于下一步骤。
实施例4＝＞式I化合物：
在-50℃下，向1.76g(5mmol)实施例1中所获得的化合物于10ml二氯甲烷中的溶液中，缓慢滴加25ml三溴化硼(1摩尔浓度，在二氯甲烷中)。将混悬液在室温下搅拌3小时、用氨水中和并用乙酸乙酯/异丙醇(9∶1)萃取。将萃取物用硫酸钠干燥、过滤并在真空下除去溶剂。加入于甲醇中的过量的盐酸，直至达到pH＝1。然后逐渐除去溶剂，直至发生结晶。将盐酸盐用甲醇/乙醇(1∶1)进行重结晶，m.p.272-274℃。αD 20＝-38°(c＝0.375，在乙醇/水中)。C19H25N3OS(2HCl)，MW＝416.4。
实施例5：
在0℃下，向4g(15.4mM)1，2，4aS-反式-5，10，10a-六氢-6-甲氧基-1-甲基-3-羟甲基-苯并[g]喹啉(参见登记号201869-32-1，Chem.Abstr.)于40ml甲苯中的溶液中，缓慢滴加1.3ml(17.9mM)亚硫酰氯。将混悬液在室温下搅拌12小时。形成的氯化物自动结晶。过滤并用甲苯洗涤后，将产物直接用于下一步骤。
实施例6：
在-70℃下，向4g(17.6mM)实施例5中所获得的氯化物于100ml二氯甲烷中的溶液中，缓慢加入50.5ml 1摩尔浓度的三溴化硼的二氯甲烷溶液。将混悬液在室温下搅拌3小时、用NaHCO3中和并用乙酸乙酯/异丙醇(9∶1)萃取。用Na2SO4干燥后，过滤并蒸发浓缩，将相应的6-羟基-苯并[g]喹啉衍生物直接用于下一步骤。
实施例7＝＞(式II化合物)
将930mg(3.5mM)实施例6的6-羟基-苯并[g]喹啉衍生物和705mg(4.2mM)噻唑并[4，5-b]吡啶-2-硫醇于30ml二甲基甲酰胺中的溶液与10NNaOH混合，并在室温下搅拌1小时。将得到的混悬液通过在真空下蒸发进行浓缩，然后用乙酸乙酯/异丙醇(9∶1)萃取。用Na2SO4干燥后，过滤，并在真空下除去溶剂，将得到的残余物在硅胶上用比例为40∶55∶5的二氯甲烷/乙酸乙酯/甲醇进行色谱分离。然后，通过加入于乙醇中的HCl、然后蒸发，将纯化后的物质转化为盐酸盐。用甲醇/乙醇进行重结晶，得到盐酸盐形式的式II化合物，m.p.为240℃(分解)，αD 20＝-101°(c＝0.405，在乙醇/水中)。C21H21N3OS2(HCl)，MW＝432.01。
Claims (3)
1.游离碱或酸加成盐形式的式Ia化合物，
其中A和Q各自为H或一起形成另外的键，并且其中3位上的不对称中心可以是外消旋的，或者可以是光学活性形式，并且其中R为式Ib，
其中R1为具有1至4个碳原子的烷基。
2.包含权利要求1的化合物和至少一种可药用的稀释剂或载体的药物组合物。
3.权利要求1的游离碱或酸加成盐形式的化合物在制备用于治疗青光眼和近视的药物中的用途。
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| US10729710B2 (en) | 2017-11-24 | 2020-08-04 | H. Lundbeck A/S | Catecholamine prodrugs for use in the treatment of Parkinson's disease |
| US11168056B2 (en) | 2019-05-20 | 2021-11-09 | H. Lundbeck A/S | Process for the manufacturing of (6aR,10aR)-7-propyl-6,6a,7,8,9,10,10a,11-octahydro-[1,3]dioxolo[4′,5′:5,6]benzo[1,2-G]quinoline and (4aR,10aR)-1-propyl-1,2,3,4,4a,5,10,10a-octahydro-benzo[G]quinoline-6,7-diol |
| US11111263B2 (en) | 2019-05-20 | 2021-09-07 | H. Lundbeck A/S | Process for the manufacture of (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid |
| US11130775B2 (en) | 2019-05-20 | 2021-09-28 | H. Lundbeck A/S | Solid forms of (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4A,5,10,10A-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid |
| US11104697B2 (en) | 2019-05-20 | 2021-08-31 | H. Lundbeck A/S | Process for the manufacture of (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(((4AR,10AR)-7-hydroxy-1- propyl-1,2,3,4,4A,5,10,10A-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-2-carboxylic acid |
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| GB9326010D0 (en) * | 1993-12-21 | 1994-02-23 | Sandoz Ltd | Improvements in or relating to organic compounds |
| TW378209B (en) * | 1996-07-08 | 2000-01-01 | Novartis Ag | Benzo[g]quinoline derivatives, their preparation and the pharmaceutical composition containing them |
| PE20030240A1 (es) * | 2001-07-09 | 2003-04-16 | Novartis Ag | DERIVADOS DE BENZO [g] QUINOLINA |
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