TWI738767B - 胺基酸衍生物之前藥 - Google Patents
胺基酸衍生物之前藥 Download PDFInfo
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- TWI738767B TWI738767B TW106112946A TW106112946A TWI738767B TW I738767 B TWI738767 B TW I738767B TW 106112946 A TW106112946 A TW 106112946A TW 106112946 A TW106112946 A TW 106112946A TW I738767 B TWI738767 B TW I738767B
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- Taiwan
- Prior art keywords
- carbonyl
- oxy
- hexane
- fluoro
- amino
- Prior art date
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- 239000000651 prodrug Substances 0.000 title abstract description 31
- 229940002612 prodrug Drugs 0.000 title abstract description 31
- 150000003862 amino acid derivatives Chemical class 0.000 title abstract description 5
- 150000003839 salts Chemical class 0.000 claims abstract description 54
- 206010008118 cerebral infarction Diseases 0.000 claims abstract description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 11
- 201000010099 disease Diseases 0.000 claims abstract description 9
- 208000019022 Mood disease Diseases 0.000 claims abstract description 8
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 7
- 208000019901 Anxiety disease Diseases 0.000 claims abstract description 7
- 208000020925 Bipolar disease Diseases 0.000 claims abstract description 7
- 206010048962 Brain oedema Diseases 0.000 claims abstract description 7
- 208000030814 Eating disease Diseases 0.000 claims abstract description 7
- 208000019454 Feeding and Eating disease Diseases 0.000 claims abstract description 7
- 206010019196 Head injury Diseases 0.000 claims abstract description 7
- 208000023105 Huntington disease Diseases 0.000 claims abstract description 7
- 206010061218 Inflammation Diseases 0.000 claims abstract description 7
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 7
- 208000006752 brain edema Diseases 0.000 claims abstract description 7
- 208000010877 cognitive disease Diseases 0.000 claims abstract description 7
- 235000014632 disordered eating Nutrition 0.000 claims abstract description 7
- 206010013663 drug dependence Diseases 0.000 claims abstract description 7
- 206010015037 epilepsy Diseases 0.000 claims abstract description 7
- 230000004054 inflammatory process Effects 0.000 claims abstract description 7
- 208000019116 sleep disease Diseases 0.000 claims abstract description 7
- 208000011117 substance-related disease Diseases 0.000 claims abstract description 7
- 201000006474 Brain Ischemia Diseases 0.000 claims abstract description 6
- 206010008120 Cerebral ischaemia Diseases 0.000 claims abstract description 6
- 208000012239 Developmental disease Diseases 0.000 claims abstract description 6
- 230000003449 preventive effect Effects 0.000 claims abstract 3
- 150000001875 compounds Chemical class 0.000 claims description 365
- -1 3,4-difluorophenyl Chemical group 0.000 claims description 86
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 84
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 63
- KPNFHMCCBRGOKU-UHFFFAOYSA-N bicyclo[3.1.0]hexane-6-carboxylic acid Chemical compound C1CCC2C(C(=O)O)C21 KPNFHMCCBRGOKU-UHFFFAOYSA-N 0.000 claims description 52
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 48
- GBLRQXKSCRCLBZ-AJSYEDJNSA-N (1S,2R,1'S,2'R)-doxacurium Chemical compound COC1=C(OC)C(OC)=CC(C[C@@H]2[N@@+](CCC3=C2C(=C(OC)C(OC)=C3)OC)(C)CCCOC(=O)CCC(=O)OCCC[N@+]2(C)[C@H](C3=C(OC)C(OC)=C(OC)C=C3CC2)CC=2C=C(OC)C(OC)=C(OC)C=2)=C1 GBLRQXKSCRCLBZ-AJSYEDJNSA-N 0.000 claims description 30
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 28
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 claims description 11
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 9
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 8
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 8
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 claims description 8
- 125000001153 fluoro group Chemical group F* 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 7
- SNXOMRRYFYTWCF-RFVFKLTOSA-N (1R,2R,3R,5R,6R)-2-(adamantane-1-carbonyloxymethoxycarbonyl)-2-amino-3-[(3,4-difluorophenyl)methoxy]-6-fluorobicyclo[3.1.0]hexane-6-carboxylic acid Chemical compound N[C@@]1([C@H]2[C@@H](C[C@H]1OCc1ccc(F)c(F)c1)[C@]2(F)C(O)=O)C(=O)OCOC(=O)C12CC3CC(CC(C3)C1)C2 SNXOMRRYFYTWCF-RFVFKLTOSA-N 0.000 claims description 6
- FZFBEVRXOFJFPI-SENXAPQXSA-N N[C@@]1([C@@H]2[C@]([C@@H]2C[C@H]1OCC1=CC=C(C=C1)C)(C(=O)O)F)C(=O)O[C@@H](C)OC(=O)C12CC3CC(CC(C1)C3)C2 Chemical compound N[C@@]1([C@@H]2[C@]([C@@H]2C[C@H]1OCC1=CC=C(C=C1)C)(C(=O)O)F)C(=O)O[C@@H](C)OC(=O)C12CC3CC(CC(C1)C3)C2 FZFBEVRXOFJFPI-SENXAPQXSA-N 0.000 claims description 6
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 6
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 6
- BSUBXBXNFNRXLH-VLBIBGDSSA-N (1R,2R,3R,5R,6R)-2-[(1S)-1-(adamantane-1-carbonyloxy)ethoxy]carbonyl-2-amino-3-[(3,4-difluorophenyl)methoxy]-6-fluorobicyclo[3.1.0]hexane-6-carboxylic acid Chemical compound C[C@H](OC(=O)[C@@]1(N)[C@H]2[C@@H](C[C@H]1OCc1ccc(F)c(F)c1)[C@]2(F)C(O)=O)OC(=O)C12CC3CC(CC(C3)C1)C2 BSUBXBXNFNRXLH-VLBIBGDSSA-N 0.000 claims description 5
- 125000001072 heteroaryl group Chemical group 0.000 claims description 5
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
- FXAUGNLOKIBSSI-IOEMREFESA-N (1R,2R,3R,5R,6R)-2-amino-6-fluoro-2-[1-[(1S,2R,5S)-5-methyl-2-propan-2-ylcyclohexyl]oxycarbonyloxyethoxycarbonyl]-3-propoxybicyclo[3.1.0]hexane-6-carboxylic acid Chemical compound N[C@@]1([C@@H]2[C@]([C@@H]2C[C@H]1OCCC)(C(=O)O)F)C(=O)OC(C)OC(=O)O[C@@H]1[C@H](CC[C@@H](C1)C)C(C)C FXAUGNLOKIBSSI-IOEMREFESA-N 0.000 claims description 4
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 4
- GQZRDISSNBHANR-BIAYIWCMSA-N N[C@@]1([C@@H]2[C@]([C@@H]2C[C@H]1OCC=1C=NC(=CC=1)Cl)(C(=O)O)F)C(=O)O[C@@H](C)OC(=O)C12CC3CC(CC(C1)C3)C2 Chemical compound N[C@@]1([C@@H]2[C@]([C@@H]2C[C@H]1OCC=1C=NC(=CC=1)Cl)(C(=O)O)F)C(=O)O[C@@H](C)OC(=O)C12CC3CC(CC(C1)C3)C2 GQZRDISSNBHANR-BIAYIWCMSA-N 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- FXAUGNLOKIBSSI-QPNZBKOUSA-N (1R,2R,3R,5R,6R)-2-amino-6-fluoro-2-[(1R)-1-[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl]oxycarbonyloxyethoxy]carbonyl-3-propoxybicyclo[3.1.0]hexane-6-carboxylic acid Chemical compound CCCO[C@@H]1C[C@@H]2[C@@H]([C@@]2(F)C(O)=O)[C@]1(N)C(=O)O[C@@H](C)OC(=O)O[C@@H]1C[C@H](C)CC[C@H]1C(C)C FXAUGNLOKIBSSI-QPNZBKOUSA-N 0.000 claims description 3
- DGWDIPLWNUBSCL-UMLCVQKRSA-N (1R,2R,3R,5R,6R)-2-amino-6-fluoro-3-[(4-fluorophenyl)methoxy]-2-[1-[[(1S,2R,4S)-1,7,7-trimethyl-2-bicyclo[2.2.1]heptanyl]oxycarbonyloxy]ethoxycarbonyl]bicyclo[3.1.0]hexane-6-carboxylic acid Chemical compound CC(OC(=O)O[C@@H]1C[C@@H]2CC[C@@]1(C)C2(C)C)OC(=O)[C@@]1(N)[C@H]2[C@@H](C[C@H]1OCc1ccc(F)cc1)[C@]2(F)C(O)=O DGWDIPLWNUBSCL-UMLCVQKRSA-N 0.000 claims description 3
- PAXOWJOGPVZJKG-MBQZEHINSA-N (1R,2R,3R,5R,6R)-2-amino-6-fluoro-3-propoxy-2-[1-[[(1S,2R,4S)-1,7,7-trimethyl-2-bicyclo[2.2.1]heptanyl]oxycarbonyloxy]ethoxycarbonyl]bicyclo[3.1.0]hexane-6-carboxylic acid Chemical compound N[C@@]1([C@@H]2[C@]([C@@H]2C[C@H]1OCCC)(C(=O)O)F)C(=O)OC(C)OC(=O)O[C@H]1[C@]2(CC[C@@H](C1)C2(C)C)C PAXOWJOGPVZJKG-MBQZEHINSA-N 0.000 claims description 3
- SUMBAGQHELWXAH-VGRWTXIISA-N N[C@@]1([C@@H]2[C@]([C@@H]2C[C@H]1OC1CCCC1)(C(=O)O)F)C(=O)O[C@@H](C)OC(=O)C12CC3CC(CC(C1)C3)C2 Chemical compound N[C@@]1([C@@H]2[C@]([C@@H]2C[C@H]1OC1CCCC1)(C(=O)O)F)C(=O)O[C@@H](C)OC(=O)C12CC3CC(CC(C1)C3)C2 SUMBAGQHELWXAH-VGRWTXIISA-N 0.000 claims description 3
- LADLKLQNZRWJGI-BZVMJTILSA-N N[C@@]1([C@@H]2[C@]([C@@H]2C[C@H]1OCC1=CC=C(C=C1)F)(C(=O)O)F)C(=O)OCOC(=O)C1CCCCC1 Chemical compound N[C@@]1([C@@H]2[C@]([C@@H]2C[C@H]1OCC1=CC=C(C=C1)F)(C(=O)O)F)C(=O)OCOC(=O)C1CCCCC1 LADLKLQNZRWJGI-BZVMJTILSA-N 0.000 claims description 3
- WWJZRSRKLBMSGQ-VACIJKKBSA-N N[C@@]1([C@@H]2[C@]([C@@H]2C[C@H]1OCC1=NC(=CC=C1)Cl)(C(=O)O)F)C(=O)O[C@@H](C)OC(=O)O[C@H]1[C@@H](CC[C@H](C1)C)C(C)C Chemical compound N[C@@]1([C@@H]2[C@]([C@@H]2C[C@H]1OCC1=NC(=CC=C1)Cl)(C(=O)O)F)C(=O)O[C@@H](C)OC(=O)O[C@H]1[C@@H](CC[C@H](C1)C)C(C)C WWJZRSRKLBMSGQ-VACIJKKBSA-N 0.000 claims description 3
- GTGBFHLAGTYUFQ-YDEGJAPISA-N N[C@@]1([C@@H]2[C@]([C@@H]2C[C@H]1OCC1=NC=C(C=C1)Cl)(C(=O)O)F)C(=O)O[C@@H](C)OC(=O)C12CC3CC(CC(C1)C3)C2 Chemical compound N[C@@]1([C@@H]2[C@]([C@@H]2C[C@H]1OCC1=NC=C(C=C1)Cl)(C(=O)O)F)C(=O)O[C@@H](C)OC(=O)C12CC3CC(CC(C1)C3)C2 GTGBFHLAGTYUFQ-YDEGJAPISA-N 0.000 claims description 3
- ZMBVCYCLPCIXOD-XAVQWOHHSA-N N[C@@]1([C@@H]2[C@]([C@@H]2C[C@H]1O[C@H](C)C1=CC(=C(C=C1)F)OC)(C(=O)O)F)C(=O)O[C@@H](C)OC(=O)C12CC3CC(CC(C1)C3)C2 Chemical compound N[C@@]1([C@@H]2[C@]([C@@H]2C[C@H]1O[C@H](C)C1=CC(=C(C=C1)F)OC)(C(=O)O)F)C(=O)O[C@@H](C)OC(=O)C12CC3CC(CC(C1)C3)C2 ZMBVCYCLPCIXOD-XAVQWOHHSA-N 0.000 claims description 3
- JXWVNRMWMYRSKM-VCSLONGPSA-N N[C@]([C@@H]([C@H]1C2)[C@]1(C(O)=O)F)([C@@H]2OCC(C=C1)=CC=C1F)C(OCOCC1=CC=CC=C1)=O Chemical compound N[C@]([C@@H]([C@H]1C2)[C@]1(C(O)=O)F)([C@@H]2OCC(C=C1)=CC=C1F)C(OCOCC1=CC=CC=C1)=O JXWVNRMWMYRSKM-VCSLONGPSA-N 0.000 claims description 3
- 238000004132 cross linking Methods 0.000 claims description 3
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 238000006467 substitution reaction Methods 0.000 claims description 3
- OCBOIIPOESZRHG-VPTDYQRQSA-N N[C@@]1([C@@H]2[C@]([C@@H]2C[C@H]1OCC1=CC(=CC=C1)F)(C(=O)O)F)C(=O)O[C@@H](C)OC(=O)O[C@H]1[C@@H](CC[C@H](C1)C)C(C)C Chemical compound N[C@@]1([C@@H]2[C@]([C@@H]2C[C@H]1OCC1=CC(=CC=C1)F)(C(=O)O)F)C(=O)O[C@@H](C)OC(=O)O[C@H]1[C@@H](CC[C@H](C1)C)C(C)C OCBOIIPOESZRHG-VPTDYQRQSA-N 0.000 claims description 2
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- 229940124597 therapeutic agent Drugs 0.000 claims 2
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Classifications
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- C07C229/46—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino or carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C229/50—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino or carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups and carboxyl groups bound to carbon atoms being part of the same condensed ring system
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- C07C255/45—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C255/47—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of rings being part of condensed ring systems
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
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- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/61—Halogen atoms or nitro radicals
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
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- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
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- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
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- C07C2602/36—Systems containing two condensed rings the rings having more than two atoms in common
- C07C2602/42—Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing seven carbon atoms
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| ES2886442T3 (es) * | 2016-04-18 | 2021-12-20 | Taisho Pharmaceutical Co Ltd | Profármaco de derivado de aminoácido |
| JP7314494B2 (ja) * | 2017-10-17 | 2023-07-26 | 大正製薬株式会社 | アミノ酸誘導体のプロドラッグを含有する医薬 |
| JP7436385B2 (ja) * | 2018-04-24 | 2024-02-21 | ヴィーブ ヘルスケア ユーケー(ナンバー5)リミテッド | Hiv成熟阻害活性を有する化合物 |
| CN109180712B (zh) * | 2018-08-08 | 2020-12-25 | 南京医科大学 | 一类2-茨醇的芳基硼酸酯衍生物及其应用 |
| CN108948077B (zh) * | 2018-08-09 | 2020-10-13 | 东华理工大学 | 一种α-磷酰化的α-氨基酸酯类化合物及其合成方法 |
| WO2022114135A1 (ja) * | 2020-11-26 | 2022-06-02 | 大正製薬株式会社 | アミノ酸誘導体の結晶形及びその製造方法 |
| CN112409443B (zh) * | 2021-01-25 | 2021-04-27 | 潍坊科技学院 | 一种脯氨酸茨醇衍生物及其制备方法和在制备治疗心脑血管类疾病的药物中的应用 |
| CN114805104A (zh) * | 2021-01-29 | 2022-07-29 | 南京宁丹新药技术有限公司 | 一类氨基水杨酸类衍生物及其用途 |
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| DK1459765T3 (da) * | 2001-12-27 | 2008-10-06 | Taisho Pharmaceutical Co Ltd | 6-fluorbicyclo 3.1.0 hexan-derivater |
| ES2394175T3 (es) | 2003-06-26 | 2013-01-23 | Taisho Pharmaceutical Co., Ltd | Derivado de éster 2-amino-biciclo[3.1.0]hexano-2, 6-dicarboxílico |
| EP2502903A4 (en) | 2009-11-19 | 2013-04-17 | Taisho Pharmaceutical Co Ltd | METHOD FOR PRODUCING A 3-ALKOXY-2-AMINO-6-FLUORBICYCLO- [3.1.0-] HEXANE-2,6-DICARBOXYLIC ACID DERIVATIVE AND A INTERMEDIATE PRODUCT THEREOF |
| TWI520935B (zh) | 2010-11-18 | 2016-02-11 | 美國禮來大藥廠 | 作為mGluR2/3拮抗劑之4-經取代-3-苯基磺醯基甲基-雙環[3.1.0]己烷化合物 |
| WO2013062680A1 (en) | 2011-10-25 | 2013-05-02 | Braincells, Inc. | Novel compounds and compositions thereof for treating nervous system disorders |
| BR112014029478B1 (pt) | 2012-06-01 | 2023-01-17 | Taisho Pharmaceutical Co., Ltd | Compostos, fármacos de aminoácido contendo flúor e uso destes |
| US20150119345A1 (en) | 2013-10-29 | 2015-04-30 | Lumena Pharmaceuticals, Inc. | Bile acid recycling inhibitors for treatment of gastrointestinal infections |
| ES2886442T3 (es) * | 2016-04-18 | 2021-12-20 | Taisho Pharmaceutical Co Ltd | Profármaco de derivado de aminoácido |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012068041A1 (en) * | 2010-11-18 | 2012-05-24 | Eli Lilly And Company | 4-SUBSTITUTED-3-BENZYLOXY-BICYCLO[3.1.0]HEXANE COMPOUNDS AS mGluR 2/3 ANTAGONISTS |
Non-Patent Citations (2)
| Title |
|---|
| AkitoYasuhara et al., "Prodrugs of 3-(3,4-dichlorobenzyloxy)-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (): A potent and orally active group II mGluR antagonist with antidepressant-like potential", Bioorganic & Medicinal Chemistry, Volume 14, Issue 12, 15 June 2006, Pages 4193-4207. * |
| AkitoYasuhara et al., "Prodrugs of 3-(3,4-dichlorobenzyloxy)-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (MGS0039): A potent and orally active group II mGluR antagonist with antidepressant-like potential", Bioorganic & Medicinal Chemistry, Volume 14, Issue 12, 15 June 2006, Pages 4193-4207. |
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