JPWO2020234275A5 - - Google Patents
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- JPWO2020234275A5 JPWO2020234275A5 JP2021560668A JP2021560668A JPWO2020234275A5 JP WO2020234275 A5 JPWO2020234275 A5 JP WO2020234275A5 JP 2021560668 A JP2021560668 A JP 2021560668A JP 2021560668 A JP2021560668 A JP 2021560668A JP WO2020234275 A5 JPWO2020234275 A5 JP WO2020234275A5
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- 150000003839 salts Chemical class 0.000 claims description 30
- 150000001875 compounds Chemical class 0.000 claims description 28
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- -1 (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a, 5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyltriacetate Chemical compound 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 208000024827 Alzheimer disease Diseases 0.000 claims description 6
- 208000023105 Huntington disease Diseases 0.000 claims description 6
- 208000018737 Parkinson disease Diseases 0.000 claims description 6
- 208000005793 Restless legs syndrome Diseases 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 230000004770 neurodegeneration Effects 0.000 claims description 6
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 5
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 5
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000004550 quinolin-6-yl group Chemical group N1=CC=CC2=CC(=CC=C12)* 0.000 claims description 5
- 201000000980 schizophrenia Diseases 0.000 claims description 5
- 208000011117 substance-related disease Diseases 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- PAUPBQZUPVEKRT-NTGJKAENSA-N CCCN1CCC[C@H]2[C@H]1CC3=C(C2)C(=C(C=C3)O[C@H]4[C@@H]([C@H]([C@@H]([C@H](O4)CO)O)O)O)O[C@H]5[C@@H]([C@H]([C@@H]([C@H](O5)CO)O)O)O Chemical compound CCCN1CCC[C@H]2[C@H]1CC3=C(C2)C(=C(C=C3)O[C@H]4[C@@H]([C@H]([C@@H]([C@H](O4)CO)O)O)O)O[C@H]5[C@@H]([C@H]([C@@H]([C@H](O5)CO)O)O)O PAUPBQZUPVEKRT-NTGJKAENSA-N 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000008203 oral pharmaceutical composition Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 10
- 229940079593 drug Drugs 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
Description
［１］[1]
式（Ｉｄ） Formula (Id)
（式中、Ｒ１及びＲ２は、以下のａ）～ｃ）：(Wherein, R1 and R2 are the following a) to c):
ａ）Ｒ１は、Ｈ、Ｃ１～Ｃ６アルキル、ベンジル及び直鎖－Ｃ（Ｏ）Ｃ１～Ｃ６アルキルから選択され、及びＲ２は、以下の置換基（ｉ）であること、又はa) R1 is selected from H, C1-C6 alkyl, benzyl and linear —C(O)C1-C6 alkyl, and R2 is the following substituent (i), or
ｂ）Ｒ１は、以下の置換基（ｉ）であり、及びＲ２は、Ｈ、Ｃ１～Ｃ６アルキル、ベンジル及び直鎖－Ｃ（Ｏ）Ｃ１～Ｃ６アルキルから選択されること、又はb) R1 is the following substituent (i) and R2 is selected from H, C1-C6 alkyl, benzyl and linear —C(O)C1-C6 alkyl, or
ｃ）Ｒ１及びＲ２は、両方とも以下の置換基（ｉ）c) R1 and R2 are both the following substituents (i)
によって表されることto be represented by
に従い、in accordance with
Ｒ３は、Ｈ及び－Ｃ（Ｏ）Ｃ１～Ｃ６アルキルから選択され、R3 is selected from H and —C(O)C1-C6 alkyl;
＊は、結合点を示し、* indicates the point of attachment,
置換基（ｉ）上の結合点での炭素原子は、Ｓ立体配置であり、the carbon atom at the point of attachment on substituent (i) is in the S configuration;
ただし、Ｒ１又はＲ２の一方が置換基（ｉ）であり、及びＲ３がＨである場合、Ｒ１又はＲ２の他方は、直鎖－Ｃ（Ｏ）Ｃ１～Ｃ６アルキルであることができない）provided that when one of R1 or R2 is a substituent (i) and R3 is H, the other of R1 or R2 cannot be linear —C(O)C1-C6 alkyl)
による化合物又はその薬剤として許容される塩。or a pharmaceutically acceptable salt thereof.
［２］[2]
Ｒ１は、Ｈ、Ｃ１～Ｃ６アルキル、ベンジル及び直鎖－Ｃ（Ｏ）Ｃ１～Ｃ６アルキルから選択され、及びＲ２は、置換基（ｉ）である、［２］に記載の化合物又はその薬剤として許容される塩。 R1 is selected from H, C1-C6 alkyl, benzyl and linear —C(O)C1-C6 alkyl, and R2 is substituent (i), as a compound or agent thereof according to [2] acceptable salt.
［３］[3]
Ｒ１は、置換基（ｉ）であり、及びＲ２は、Ｈ、Ｃ１～Ｃ６アルキル、ベンジル及び直鎖－Ｃ（Ｏ）Ｃ１～Ｃ６アルキルから選択される、［２］に記載の化合物又はその薬剤として許容される塩。 The compound according to [2] or a drug thereof, wherein R1 is a substituent (i) and R2 is selected from H, C1-C6 alkyl, benzyl and linear —C(O)C1-C6 alkyl Salts that are acceptable as
［４］[4]
Ｒ１及びＲ２は、両方とも置換基（ｉ）によって表される、［２］に記載の化合物又はその薬剤として許容される塩。 The compound of [2] or a pharmaceutically acceptable salt thereof, wherein both R1 and R2 are represented by substituent (i).
［５］[5]
Ｒ１又はＲ２は、－Ｃ（Ｏ）メチルである、［２］～［４］のいずれか一項に記載の化合物又はその薬剤として許容される塩。 The compound or a pharmaceutically acceptable salt thereof according to any one of [2] to [4], wherein R1 or R2 is -C(O)methyl.
［６］[6]
Ｒ３は、－Ｃ（Ｏ）メチルである、［１］～［５］のいずれか一項に記載の化合物又はその薬剤として許容される塩。 The compound or a pharmaceutically acceptable salt thereof according to any one of [1] to [5], wherein R3 is -C(O)methyl.
［７］[7]
Ｒ３は、Ｈである、［１］～［５］のいずれか一項に記載の化合物又はその薬剤として許容される塩。 The compound or a pharmaceutically acceptable salt thereof according to any one of [1] to [5], wherein R3 is H.
［８］[8]
Ｒ１及びＲ２の一方は、Ｈであり、Ｒ１及びＲ２の一方は、置換基（ｉ）であり、Ｒ３は、Ｈである、［１］又は［５］に記載の化合物又はその薬剤として許容される塩。 one of R1 and R2 is H, one of R1 and R2 is substituent (i), and R3 is H, the compound according to [1] or [5] or an acceptable drug thereof salt.
［９］[9]
（２Ｒ，３Ｒ，４Ｓ，５Ｒ，６Ｓ）－２－（アセトキシメチル）－６－（（（４ａＲ，１０ａＲ）－７－（ベンジルオキシ）－１－プロピル－１，２，３，４，４ａ，５，１０，１０ａ－オクタヒドロベンゾ［ｇ］キノリン－６－イル）オキシ）テトラヒドロ－２Ｈ－ピラン－３，４，５－トリイルトリアセテート； (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a, 5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyltriacetate;
（２Ｒ，３Ｒ，４Ｓ，５Ｒ，６Ｓ）－２－（アセトキシメチル）－６－（（（４ａＲ，１０ａＲ）－７－ヒドロキシ－１－プロピル－１，２，３，４，４ａ，５，１０，１０ａ－オクタヒドロベンゾ［ｇ］キノリン－６－イル）オキシ）テトラヒドロ－２Ｈ－ピラン－３，４，５－トリイルトリアセテート；(2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10 , 10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyltriacetate;
（２Ｓ，３Ｒ，４Ｓ，５Ｒ，６Ｒ）－２－（（（４ａＲ，１０ａＲ）－７－アセトキシ－１－プロピル－１，２，３，４，４ａ，５，１０，１０ａ－オクタヒドロベンゾ［ｇ］キノリン－６－イル）オキシ）－６－（アセトキシメチル）テトラヒドロ－２Ｈ－ピラン－３，４，５－トリイルトリアセテート；(2S,3R,4S,5R,6R)-2-(((4aR,10aR)-7-acetoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[ g] quinolin-6-yl)oxy)-6-(acetoxymethyl)tetrahydro-2H-pyran-3,4,5-triyltriacetate;
（２Ｓ，３Ｒ，４Ｓ，５Ｓ，６Ｒ）－２－（（（４ａＲ，１０ａＲ）－７－ヒドロキシ－１－プロピル－１，２，３，４，４ａ，５，１０，１０ａ－オクタヒドロベンゾ［ｇ］キノリン－６－イル）オキシ）－６－（ヒドロキシメチル）テトラヒドロ－２Ｈ－ピラン－３，４，５－トリオール；(2S,3R,4S,5S,6R)-2-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[ g]quinolin-6-yl)oxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;
（２Ｒ，３Ｒ，４Ｓ，５Ｒ，６Ｓ）－２－（アセトキシメチル）－６－（（（４ａＲ，１０ａＲ）－６－ヒドロキシ－１－プロピル－１，２，３，４，４ａ，５，１０，１０ａ－オクタヒドロベンゾ［ｇ］キノリン－７－イル）オキシ）テトラヒドロ－２Ｈ－ピラン－３，４，５－トリイルトリアセテート；(2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((4aR,10aR)-6-hydroxy-1-propyl-1,2,3,4,4a,5,10 , 10a-octahydrobenzo[g]quinolin-7-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyltriacetate;
（２Ｓ，３Ｒ，４Ｓ，５Ｒ，６Ｒ）－２－（（（４ａＲ，１０ａＲ）－６－アセトキシ－１－プロピル－１，２，３，４，４ａ，５，１０，１０ａ－オクタヒドロベンゾ［ｇ］キノリン－７－イル）オキシ）－６－（アセトキシメチル）テトラヒドロ－２Ｈ－ピラン－３，４，５－トリイルトリアセテート；(2S,3R,4S,5R,6R)-2-(((4aR,10aR)-6-acetoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[ g] quinolin-7-yl)oxy)-6-(acetoxymethyl)tetrahydro-2H-pyran-3,4,5-triyltriacetate;
（２Ｓ，３Ｒ，４Ｓ，５Ｓ，６Ｒ）－２－（（（４ａＲ，１０ａＲ）－６－ヒドロキシ－１－プロピル－１，２，３，４，４ａ，５，１０，１０ａ－オクタヒドロベンゾ［ｇ］キノリン－７－イル）オキシ）－６－（ヒドロキシメチル）テトラヒドロ－２Ｈ－ピラン－３，４，５－トリオール；(2S,3R,4S,5S,6R)-2-(((4aR,10aR)-6-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[ g]quinolin-7-yl)oxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;
［（２Ｒ，３Ｒ，４Ｓ，５Ｒ，６Ｓ）－６－［［（４ａＲ，１０ａＲ）－１－プロピル－６－［（２Ｓ，３Ｒ，４Ｓ，５Ｒ，６Ｒ）－３，４，５－トリアセトキシ－６－（アセトキシメチル）テトラヒドロピラン－２－イル］オキシ－３，４，４ａ，５，１０，１０ａ－ヘキサヒドロ－２Ｈ－ベンゾ［ｇ］キノリン－７－イル］オキシ］－３，４，５－トリアセトキシ－テトラヒドロピラン－２－イル］メチルアセテート；及び[(2R,3R,4S,5R,6S)-6-[[(4aR,10aR)-1-propyl-6-[(2S,3R,4S,5R,6R)-3,4,5-triacetoxy -6-(acetoxymethyl)tetrahydropyran-2-yl]oxy-3,4,4a,5,10,10a-hexahydro-2H-benzo[g]quinolin-7-yl]oxy]-3,4,5 -triacetoxy-tetrahydropyran-2-yl]methyl acetate; and
（２Ｒ，２’Ｒ，３Ｓ，３’Ｓ，４Ｓ，４’Ｓ，５Ｒ，５’Ｒ，６Ｓ，６’Ｓ）－６，６’－（（（４ａＲ，１０ａＲ）－１－プロピル－１，２，３，４，４ａ，５，１０，１０ａ－オクタヒドロベンゾ［ｇ］キノリン－６，７－ジイル）ビス（オキシ））ビス（２－（ヒドロキシメチル）テトラヒドロ－２Ｈ－ピラン－３，４，５－トリオール）(2R,2′R,3S,3′S,4S,4′S,5R,5′R,6S,6′S)-6,6′-(((4aR,10aR)-1-propyl-1 , 2,3,4,4a,5,10,10a-octahydrobenzo[g]quinoline-6,7-diyl)bis(oxy))bis(2-(hydroxymethyl)tetrahydro-2H-pyran-3, 4,5-triol)
からなる群から選択される、［１］に記載の化合物又は前記化合物のいずれかの薬剤として許容される塩。The compound of [1] or a pharmaceutically acceptable salt of any of said compounds, selected from the group consisting of:
［１０］[10]
薬物として使用するための、［１］～［９］のいずれか一項に記載の化合物又はその薬剤として許容される塩。 A compound according to any one of [1] to [9] or a pharmaceutically acceptable salt thereof for use as a drug.
［１１］[11]
治療有効量の、［１］～［９］のいずれか一項に記載の化合物又はその薬剤として許容される塩と、１種又は複数の薬剤として許容される賦形剤とを含む医薬組成物。 A pharmaceutical composition comprising a therapeutically effective amount of the compound of any one of [1] to [9] or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients .
［１２］[12]
経口投与のための錠剤又はカプセル剤などの経口医薬組成物である、［１１］に記載の医薬組成物。 The pharmaceutical composition according to [11], which is an oral pharmaceutical composition such as tablets or capsules for oral administration.
［１３］[13]
パーキンソン病、ハンチントン病、下肢静止不能症候群若しくはアルツハイマー病などの神経変性疾患若しくは障害又は精神分裂病、注意欠陥多動障害若しくは薬物嗜癖などの神経精神患若しくは障害の治療で使用するための、［１］～［９］のいずれか一項に記載の化合物又はその薬剤として許容される塩。 for use in the treatment of neurodegenerative diseases or disorders such as Parkinson's disease, Huntington's disease, restless leg syndrome or Alzheimer's disease, or neuropsychiatric diseases or disorders such as schizophrenia, attention deficit hyperactivity disorder or substance addiction [1 ] to [9] or a pharmaceutically acceptable salt thereof.
［１４］[14]
パーキンソン病、ハンチントン病、下肢静止不能症候群若しくはアルツハイマー病などの神経変性疾患若しくは障害又は精神分裂病、注意欠陥多動障害若しくは薬物嗜癖などの神経精神患若しくは障害の治療の方法であって、治療有効量の、［１］～［９］のいずれか一項に記載の化合物又はその薬剤として許容される塩を、それを必要とする患者に投与することを含む方法。 A method of treating a neurodegenerative disease or disorder such as Parkinson's disease, Huntington's disease, restless leg syndrome or Alzheimer's disease, or a neuropsychiatric disease or disorder such as schizophrenia, attention deficit hyperactivity disorder or drug addiction, wherein the treatment is effective A method comprising administering an amount of the compound of any one of [1] to [9] or a pharmaceutically acceptable salt thereof to a patient in need thereof.
［１５］[15]
パーキンソン病、ハンチントン病、下肢静止不能症候群若しくはアルツハイマー病などの神経変性疾患若しくは障害の治療のための、又は精神分裂病、注意欠陥多動障害若しくは薬物嗜癖などの神経精神疾患若しくは障害の治療のための薬物の製造における、［１］～［９］のいずれか一項に記載の化合物又はその薬剤として許容される塩の使用。 For the treatment of neurodegenerative diseases or disorders such as Parkinson's disease, Huntington's disease, restless leg syndrome or Alzheimer's disease, or for the treatment of neuropsychiatric diseases or disorders such as schizophrenia, attention deficit hyperactivity disorder or substance addiction Use of the compound according to any one of [1] to [9] or a pharmaceutically acceptable salt thereof in the manufacture of a drug of
Claims (19)
（式中、Ｒ１及びＲ２は、以下のａ）～ｃ）：
ａ）Ｒ１は、Ｈ、Ｃ１～Ｃ６アルキル、ベンジル及び直鎖－Ｃ（Ｏ）Ｃ１～Ｃ６アルキルから選択され、及びＲ２は、以下の置換基（ｉ）であること、又は
ｂ）Ｒ１は、以下の置換基（ｉ）であり、及びＲ２は、Ｈ、Ｃ１～Ｃ６アルキル、ベンジル及び直鎖－Ｃ（Ｏ）Ｃ１～Ｃ６アルキルから選択されること、又は
ｃ）Ｒ１及びＲ２は、両方とも以下の置換基（ｉ）
によって表されること
に従い、
Ｒ３は、Ｈ及び－Ｃ（Ｏ）Ｃ１～Ｃ６アルキルから選択され、
＊は、結合点を示し、
置換基（ｉ）上の結合点での炭素原子は、Ｓ立体配置であり、
ただし、Ｒ１又はＲ２の一方が置換基（ｉ）であり、及びＲ３がＨである場合、Ｒ１又はＲ２の他方は、直鎖－Ｃ（Ｏ）Ｃ１～Ｃ６アルキルであることができない）
による化合物又はその薬剤として許容される塩。 Formula (Id)
(Wherein, R1 and R2 are the following a) to c):
a) R1 is selected from H, C 1 -C 6 alkyl, benzyl and linear —C(O)C 1 -C 6 alkyl and R2 is the following substituent (i), or b ) R1 is the following substituent (i) and R2 is selected from H, C 1 -C 6 alkyl, benzyl and linear —C(O)C 1 -C 6 alkyl, or c ) R1 and R2 are both the following substituents (i)
according to being represented by
R3 is selected from H and —C(O)C 1 -C 6 alkyl;
* indicates the point of attachment,
the carbon atom at the point of attachment on substituent (i) is in the S configuration;
provided that when one of R1 or R2 is a substituent (i) and R3 is H, the other of R1 or R2 cannot be linear —C(O)C 1 -C 6 alkyl)
or a pharmaceutically acceptable salt thereof.
（２Ｒ，３Ｒ，４Ｓ，５Ｒ，６Ｓ）－２－（アセトキシメチル）－６－（（（４ａＲ，１０ａＲ）－７－ヒドロキシ－１－プロピル－１，２，３，４，４ａ，５，１０，１０ａ－オクタヒドロベンゾ［ｇ］キノリン－６－イル）オキシ）テトラヒドロ－２Ｈ－ピラン－３，４，５－トリイルトリアセテート；
（２Ｓ，３Ｒ，４Ｓ，５Ｒ，６Ｒ）－２－（（（４ａＲ，１０ａＲ）－７－アセトキシ－１－プロピル－１，２，３，４，４ａ，５，１０，１０ａ－オクタヒドロベンゾ［ｇ］キノリン－６－イル）オキシ）－６－（アセトキシメチル）テトラヒドロ－２Ｈ－ピラン－３，４，５－トリイルトリアセテート；
（２Ｓ，３Ｒ，４Ｓ，５Ｓ，６Ｒ）－２－（（（４ａＲ，１０ａＲ）－７－ヒドロキシ－１－プロピル－１，２，３，４，４ａ，５，１０，１０ａ－オクタヒドロベンゾ［ｇ］キノリン－６－イル）オキシ）－６－（ヒドロキシメチル）テトラヒドロ－２Ｈ－ピラン－３，４，５－トリオール；
（２Ｒ，３Ｒ，４Ｓ，５Ｒ，６Ｓ）－２－（アセトキシメチル）－６－（（（４ａＲ，１０ａＲ）－６－ヒドロキシ－１－プロピル－１，２，３，４，４ａ，５，１０，１０ａ－オクタヒドロベンゾ［ｇ］キノリン－７－イル）オキシ）テトラヒドロ－２Ｈ－ピラン－３，４，５－トリイルトリアセテート；
（２Ｓ，３Ｒ，４Ｓ，５Ｒ，６Ｒ）－２－（（（４ａＲ，１０ａＲ）－６－アセトキシ－１－プロピル－１，２，３，４，４ａ，５，１０，１０ａ－オクタヒドロベンゾ［ｇ］キノリン－７－イル）オキシ）－６－（アセトキシメチル）テトラヒドロ－２Ｈ－ピラン－３，４，５－トリイルトリアセテート；
（２Ｓ，３Ｒ，４Ｓ，５Ｓ，６Ｒ）－２－（（（４ａＲ，１０ａＲ）－６－ヒドロキシ－１－プロピル－１，２，３，４，４ａ，５，１０，１０ａ－オクタヒドロベンゾ［ｇ］キノリン－７－イル）オキシ）－６－（ヒドロキシメチル）テトラヒドロ－２Ｈ－ピラン－３，４，５－トリオール；
［（２Ｒ，３Ｒ，４Ｓ，５Ｒ，６Ｓ）－６－［［（４ａＲ，１０ａＲ）－１－プロピル－６－［（２Ｓ，３Ｒ，４Ｓ，５Ｒ，６Ｒ）－３，４，５－トリアセトキシ－６－（アセトキシメチル）テトラヒドロピラン－２－イル］オキシ－３，４，４ａ，５，１０，１０ａ－ヘキサヒドロ－２Ｈ－ベンゾ［ｇ］キノリン－７－イル］オキシ］－３，４，５－トリアセトキシ－テトラヒドロピラン－２－イル］メチルアセテート；及び
（２Ｒ，２’Ｒ，３Ｓ，３’Ｓ，４Ｓ，４’Ｓ，５Ｒ，５’Ｒ，６Ｓ，６’Ｓ）－６，６’－（（（４ａＲ，１０ａＲ）－１－プロピル－１，２，３，４，４ａ，５，１０，１０ａ－オクタヒドロベンゾ［ｇ］キノリン－６，７－ジイル）ビス（オキシ））ビス（２－（ヒドロキシメチル）テトラヒドロ－２Ｈ－ピラン－３，４，５－トリオール）
からなる群から選択される、請求項１に記載の化合物又は前記化合物のいずれかの薬剤として許容される塩。 (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((4aR,10aR)-7-(benzyloxy)-1-propyl-1,2,3,4,4a, 5,10,10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyltriacetate;
(2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10 , 10a-octahydrobenzo[g]quinolin-6-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyltriacetate;
(2S,3R,4S,5R,6R)-2-(((4aR,10aR)-7-acetoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[ g] quinolin-6-yl)oxy)-6-(acetoxymethyl)tetrahydro-2H-pyran-3,4,5-triyltriacetate;
(2S,3R,4S,5S,6R)-2-(((4aR,10aR)-7-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[ g]quinolin-6-yl)oxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;
(2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((4aR,10aR)-6-hydroxy-1-propyl-1,2,3,4,4a,5,10 , 10a-octahydrobenzo[g]quinolin-7-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyltriacetate;
(2S,3R,4S,5R,6R)-2-(((4aR,10aR)-6-acetoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[ g] quinolin-7-yl)oxy)-6-(acetoxymethyl)tetrahydro-2H-pyran-3,4,5-triyltriacetate;
(2S,3R,4S,5S,6R)-2-(((4aR,10aR)-6-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[ g]quinolin-7-yl)oxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol;
[(2R,3R,4S,5R,6S)-6-[[(4aR,10aR)-1-propyl-6-[(2S,3R,4S,5R,6R)-3,4,5-triacetoxy -6-(acetoxymethyl)tetrahydropyran-2-yl]oxy-3,4,4a,5,10,10a-hexahydro-2H-benzo[g]quinolin-7-yl]oxy]-3,4,5 -triacetoxy-tetrahydropyran-2-yl]methyl acetate; and (2R,2'R,3S,3'S,4S,4'S,5R,5'R,6S,6'S)-6,6 '-(((4aR,10aR)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinoline-6,7-diyl)bis(oxy))bis (2-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol)
2. A compound according to claim 1, or a pharmaceutically acceptable salt of any of said compounds, selected from the group consisting of:
（２Ｓ，３Ｒ，４Ｓ，５Ｓ，６Ｒ）－２－（（（４ａＲ，１０ａＲ）－６－ヒドロキシ－１－プロピル－１，２，３，４，４ａ，５，１０，１０ａ－オクタヒドロベンゾ［ｇ］キノリン－７－イル）オキシ）－６－（ヒドロキシメチル）テトラヒドロ－２Ｈ－ピラン－３，４，５－トリオール；及び(2S,3R,4S,5S,6R)-2-(((4aR,10aR)-6-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[ g]quinolin-7-yl)oxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; and
（２Ｒ，２’Ｒ，３Ｓ，３’Ｓ，４Ｓ，４’Ｓ，５Ｒ，５’Ｒ，６Ｓ，６’Ｓ）－６，６’－（（（４ａＲ，１０ａＲ）－１－プロピル－１，２，３，４，４ａ，５，１０，１０ａ－オクタヒドロベンゾ［ｇ］キノリン－６，７－ジイル）ビス（オキシ））ビス（２－（ヒドロキシメチル）テトラヒドロ－２Ｈ－ピラン－３，４，５－トリオール）(2R,2′R,3S,3′S,4S,4′S,5R,5′R,6S,6′S)-6,6′-(((4aR,10aR)-1-propyl-1 , 2,3,4,4a,5,10,10a-octahydrobenzo[g]quinoline-6,7-diyl)bis(oxy))bis(2-(hydroxymethyl)tetrahydro-2H-pyran-3, 4,5-triol)
からなる群から選択される、請求項１に記載の化合物又は前記化合物のいずれかの薬剤として許容される塩。2. A compound according to claim 1, or a pharmaceutically acceptable salt of any of said compounds, selected from the group consisting of:
の、請求項１に記載の化合物又はその薬剤として許容される塩。or a pharmaceutically acceptable salt thereof according to claim 1.
の、請求項１に記載の化合物又はその薬剤として許容される塩。or a pharmaceutically acceptable salt thereof according to claim 1.
の、請求項１に記載の化合物又はその薬剤として許容される塩。or a pharmaceutically acceptable salt thereof according to claim 1.
for the treatment of neurodegenerative diseases or disorders selected from Parkinson's disease , Huntington's disease, restless leg syndrome and Alzheimer 's disease; Use of a compound according to any one of claims 1-13, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment of disorders.
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| 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 |
| 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 |
| 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 |
| 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 |
| US20240025857A1 (en) | 2020-11-17 | 2024-01-25 | H. Lundbeck A/S | New catecholamine prodrugs for use in the treatment of parkinson's disease |
| AU2023259559A1 (en) | 2022-04-25 | 2024-10-31 | Integrative Research Laboratories Sweden Ab | NOVEL 1,2,3,4,4a,5,6,7,8,9,10,10a-DODECAHYDROBENZO[G]QUINOLIN-6-OL COMPOUNDS AND USES THEREOF |
| WO2023208867A1 (en) | 2022-04-25 | 2023-11-02 | Integrative Research Laboratories Sweden Ab | NOVEL 1,2,3,4,4a,5,8,9,10,10a-DECAHYDROBENZO[G]QUINOLIN-6(7H)-ONE COMPOUNDS AND USES THEREOF |
| WO2023208869A1 (en) | 2022-04-25 | 2023-11-02 | Integrative Research Laboratories Sweden Ab | NOVEL ESTERS OF 1,2,3,4,4a,5,6,7,8,9,10,10a-DODECAHYDROBENZO[G]QUINOLIN-6-OL COMPOUNDS AND USES THEREOF |
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| US4543256A (en) | 1982-03-17 | 1985-09-24 | Northeastern University | (-)-10,1L Methylenedioxy-N-N-propylnoraporphine and methods employing it for inhibiting the effects of epileptic seizures and for prevention and treatment of duodenal ulcers |
| GB2344819A (en) * | 1998-12-18 | 2000-06-21 | Portela & Ca Sa | 2-Phenyl-1-(3,4-dihydroxy-5-nitrophenyl)-1-ethanones |
| SE0001438D0 (en) | 2000-04-18 | 2000-04-18 | Axon Chemicals Bv | New chemical compounds and their use in therapy |
| SE0102036D0 (en) | 2001-06-08 | 2001-06-08 | Axon Biochemicals Bv | Pharmaceutical formulation for the efficient administration of apomorphine, 6aR- (-) -N- Propyl- norapomorphine and their derivatives and pro-drugs thereof |
| GB2377934B (en) * | 2001-07-25 | 2005-01-12 | Portela & Ca Sa | Method for the nitration of phenolic compounds |
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| US7101912B2 (en) | 2002-12-06 | 2006-09-05 | Xenoport, Inc. | Carbidopa prodrugs and derivatives, and compositions and uses thereof |
| WO2006056604A1 (en) | 2004-11-25 | 2006-06-01 | Evolva Ag | Levodopa glycosyl derivatives, methods of preparation and use |
| EP1870097A1 (en) * | 2006-06-15 | 2007-12-26 | Newron Pharmaceuticals S.p.A. | Alpha-aminoamide derivatives useful in the treatment of cognitive disorders |
| TWI404702B (en) * | 2007-08-31 | 2013-08-11 | Lundbeck & Co As H | Catecholamine derivatives and prodrugs thereof |
| US8129530B2 (en) * | 2007-08-31 | 2012-03-06 | H. Lundbeck A/S | Catecholamine derivatives and prodrugs thereof |
| TW201036949A (en) | 2009-02-27 | 2010-10-16 | Lundbeck & Co As H | Treatment of dyskinesia related disorders |
| WO2011143721A1 (en) * | 2010-05-21 | 2011-11-24 | Gosforth Centre (Holdings) Pty Ltd | Compositions and methods for treating neurodegenerative disorders |
| CN117653649A (en) | 2017-11-24 | 2024-03-08 | H.隆德贝克有限公司 | Novel catecholamine prodrugs for the treatment of parkinson's disease |
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