ES2435651T3 - Agonistas de MGLU2 - Google Patents
Agonistas de MGLU2 Download PDFInfo
- Publication number
- ES2435651T3 ES2435651T3 ES10798419T ES10798419T ES2435651T3 ES 2435651 T3 ES2435651 T3 ES 2435651T3 ES 10798419 T ES10798419 T ES 10798419T ES 10798419 T ES10798419 T ES 10798419T ES 2435651 T3 ES2435651 T3 ES 2435651T3
- Authority
- ES
- Spain
- Prior art keywords
- amino
- hexane
- bicyclo
- triazol
- ylsulfanyl
- 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
Links
- 102100036837 Metabotropic glutamate receptor 2 Human genes 0.000 title description 20
- 101001071429 Homo sapiens Metabotropic glutamate receptor 2 Proteins 0.000 title description 19
- 239000000556 agonist Substances 0.000 title description 18
- 150000001875 compounds Chemical class 0.000 claims abstract description 155
- 150000003839 salts Chemical class 0.000 claims abstract description 91
- -1 (2S) -2-amino-4-methylsulfanyl-butanoyl Chemical group 0.000 claims abstract description 49
- 239000001257 hydrogen Substances 0.000 claims abstract description 39
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 39
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 31
- 125000003412 L-alanyl group Chemical group [H]N([H])[C@@](C([H])([H])[H])(C(=O)[*])[H] 0.000 claims abstract description 11
- 125000003440 L-leucyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C(C([H])([H])[H])([H])C([H])([H])[H] 0.000 claims abstract description 7
- 239000012453 solvate Substances 0.000 claims abstract description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 45
- 239000002253 acid Substances 0.000 claims description 39
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 38
- MWECKFISVWUYDM-UHFFFAOYSA-N bicyclo[3.1.0]hexane-2,6-dicarboxylic acid Chemical compound C1CC(C(O)=O)C2C(C(=O)O)C21 MWECKFISVWUYDM-UHFFFAOYSA-N 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 17
- 201000000980 schizophrenia Diseases 0.000 claims description 15
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- 208000020016 psychiatric disease Diseases 0.000 claims description 12
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- 208000029364 generalized anxiety disease Diseases 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- YCQVGZVFFKDBHR-SQARDTNNSA-N (1r,2s,4r,5r,6r)-2-[[(2s)-2-amino-4-methylsulfanylbutanoyl]amino]-4-(1h-1,2,4-triazol-5-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylic acid Chemical compound S([C@@H]1C[C@@]([C@@H]2[C@H]([C@@H]21)C(O)=O)(NC(=O)[C@@H](N)CCSC)C(O)=O)C1=NN=CN1 YCQVGZVFFKDBHR-SQARDTNNSA-N 0.000 claims description 6
- JENKYOUHNBMHEG-JRICUUGESA-N (1r,2s,4r,5r,6r)-2-[[(2s)-2-amino-4-methylpentanoyl]amino]-4-(1h-1,2,4-triazol-5-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylic acid Chemical compound S([C@@H]1C[C@@]([C@@H]2[C@H]([C@@H]21)C(O)=O)(NC(=O)[C@@H](N)CC(C)C)C(O)=O)C1=NN=CN1 JENKYOUHNBMHEG-JRICUUGESA-N 0.000 claims description 5
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- 230000001225 therapeutic effect Effects 0.000 claims description 4
- KCOXOYTVOWOBEG-CQDVULCKSA-N (1r,2s,4r,5r,6r)-2-[(2-aminoacetyl)amino]-4-(1h-1,2,4-triazol-5-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylic acid;hydrochloride Chemical compound Cl.S([C@@H]1C[C@@]([C@@H]2[C@H]([C@@H]21)C(O)=O)(NC(=O)CN)C(O)=O)C1=NN=CN1 KCOXOYTVOWOBEG-CQDVULCKSA-N 0.000 claims description 3
- QWUWMCYKGHVNAV-UHFFFAOYSA-N 1,2-dihydrostilbene Chemical group C=1C=CC=CC=1CCC1=CC=CC=C1 QWUWMCYKGHVNAV-UHFFFAOYSA-N 0.000 claims description 3
- JAPMJSVZDUYFKL-UHFFFAOYSA-N bicyclo[3.1.0]hexane Chemical compound C1CCC2CC21 JAPMJSVZDUYFKL-UHFFFAOYSA-N 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- SGEXVXMPLDCNCK-OUXKRIEPSA-N (1r,2s,4r,5r,6r)-2-[[(2s)-2-amino-4-methylsulfanylbutanoyl]amino]-4-(1h-1,2,4-triazol-5-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylic acid;hydrochloride Chemical compound Cl.S([C@@H]1C[C@@]([C@@H]2[C@H]([C@@H]21)C(O)=O)(NC(=O)[C@@H](N)CCSC)C(O)=O)C1=NN=CN1 SGEXVXMPLDCNCK-OUXKRIEPSA-N 0.000 claims description 2
- BBGHHIUQOKQCBW-LDZWZCGGSA-N (1r,2s,4r,5r,6r)-2-[[(2s)-2-aminopropanoyl]amino]-4-(1h-1,2,4-triazol-5-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylic acid Chemical compound S([C@@H]1C[C@@]([C@@H]2[C@H]([C@@H]21)C(O)=O)(NC(=O)[C@@H](N)C)C(O)=O)C=1N=CNN=1 BBGHHIUQOKQCBW-LDZWZCGGSA-N 0.000 claims description 2
- ANUFAWHRSIJTHW-UHFFFAOYSA-N 2-methylheptanedioic acid Chemical compound OC(=O)C(C)CCCCC(O)=O ANUFAWHRSIJTHW-UHFFFAOYSA-N 0.000 claims description 2
- 239000004615 ingredient Substances 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- VUHJHXJVPNGWPT-ODIFVZITSA-N (1r,2s,4r,5r,6r)-2-[[(2s)-2-amino-4-methylpentanoyl]amino]-4-(1h-1,2,4-triazol-5-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylic acid;hydrochloride Chemical compound Cl.S([C@@H]1C[C@@]([C@@H]2[C@H]([C@@H]21)C(O)=O)(NC(=O)[C@@H](N)CC(C)C)C(O)=O)C1=NN=CN1 VUHJHXJVPNGWPT-ODIFVZITSA-N 0.000 claims 1
- ZZBVHBLTFIJABC-KXHOBWMPSA-N (1r,2s,4r,5r,6r)-2-[[(2s)-2-aminopropanoyl]amino]-4-(1h-1,2,4-triazol-5-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylic acid;hydrochloride Chemical compound Cl.S([C@@H]1C[C@@]([C@@H]2[C@H]([C@@H]21)C(O)=O)(NC(=O)[C@@H](N)C)C(O)=O)C=1N=CNN=1 ZZBVHBLTFIJABC-KXHOBWMPSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 59
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- 229940002612 prodrug Drugs 0.000 description 42
- 239000000651 prodrug Substances 0.000 description 42
- 239000007787 solid Substances 0.000 description 39
- 125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 29
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 28
- 238000003756 stirring Methods 0.000 description 28
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 210000004027 cell Anatomy 0.000 description 27
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 24
- 239000012141 concentrate Substances 0.000 description 23
- 238000000034 method Methods 0.000 description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 238000003556 assay Methods 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 241000700159 Rattus Species 0.000 description 20
- 238000002360 preparation method Methods 0.000 description 19
- 238000012360 testing method Methods 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 241000282414 Homo sapiens Species 0.000 description 17
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- 238000011534 incubation Methods 0.000 description 15
- 241000699670 Mus sp. Species 0.000 description 14
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
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- 239000003981 vehicle Substances 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
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- 239000012267 brine Substances 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- YSOWRGMLMZQSBX-AVUIYAGVSA-N (1r,2s,4r,5r,6r)-2-amino-4-(1h-1,2,4-triazol-5-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylic acid Chemical compound S([C@@H]1C[C@@]([C@@H]2[C@H]([C@@H]21)C(O)=O)(N)C(O)=O)C1=NN=CN1 YSOWRGMLMZQSBX-AVUIYAGVSA-N 0.000 description 8
- 102000046014 Peptide Transporter 1 Human genes 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
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- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
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- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
- C07D249/12—Oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/24—Antidepressants
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP09382290 | 2009-12-21 | ||
| EP09382290 | 2009-12-21 | ||
| US30523910P | 2010-02-17 | 2010-02-17 | |
| US305239P | 2010-02-17 | ||
| PCT/US2010/060371 WO2011084437A1 (en) | 2009-12-21 | 2010-12-15 | Mglu2 agonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2435651T3 true ES2435651T3 (es) | 2013-12-20 |
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| ES10798419T Active ES2435651T3 (es) | 2009-12-21 | 2010-12-15 | Agonistas de MGLU2 |
Country Status (35)
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3533797B1 (en) | 2010-02-17 | 2023-12-20 | Takeda Pharmaceutical Company Limited | Heterocyclic compound |
| CN103209954B (zh) * | 2010-11-18 | 2015-09-02 | 伊莱利利公司 | 作为mGluR2/3拮抗剂的4-取代的-3-苄氧基-双环[3.1.0]己烷化合物 |
| AR083845A1 (es) * | 2010-11-18 | 2013-03-27 | Lilly Co Eli | COMPUESTOS 3-FENILSULFANILMETIL-BICICLO[3.1.0]HEXANO 4-SUSTITUIDOS COMO ANTAGONISTAS DE mGluR2/3 |
| KR101598679B1 (ko) | 2011-06-17 | 2016-02-29 | 일라이 릴리 앤드 캄파니 | mGlu2 수용체 효능제로서의 비시클로(3.1.0)헥산-2,6-디카르복실산 유도체 |
| AR089718A1 (es) | 2012-02-01 | 2014-09-10 | Lilly Co Eli | AGONISTAS DE mGlu2/3 |
| US10154988B2 (en) | 2012-11-14 | 2018-12-18 | The Johns Hopkins University | Methods and compositions for treating schizophrenia |
| ME03518B (me) | 2014-01-21 | 2020-04-20 | Janssen Pharmaceutica Nv | Kombinacije koje obuhvataju pozitivne alosterične modulatore ili ortosterične agoniste metabotropnog glutamatergičnog receptora podtipa 2 i njihova primjena |
| PL3096790T3 (pl) * | 2014-01-21 | 2020-01-31 | Janssen Pharmaceutica, N.V. | Kombinacje zawierające pozytywne modulatory allosteryczne lub agonistów ortosterycznych metabotropowego receptora glutaminergicznego podtypu 2 i ich zastosowanie |
| NZ735973A (en) | 2015-04-01 | 2023-06-30 | Akebia Therapeutics Inc | Compositions and methods for treating anemia |
| WO2021216530A1 (en) | 2020-04-20 | 2021-10-28 | Akebia Therapeutics, Inc. | Treatment of viral infections, of organ injury, and of related conditions using a hif prolyl hydroxylase inhibitor or a hif-alpha stabilizer |
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| US5576323A (en) * | 1993-12-03 | 1996-11-19 | Eli Lilly And Company | Excitatory amino acid receptor antagonists |
| GB9605429D0 (en) * | 1995-11-16 | 1996-05-15 | Lilly Co Eli | Excitatory amino acid receptor antagonists |
| US5688826A (en) * | 1995-11-16 | 1997-11-18 | Eli Lilly And Company | Excitatory amino acid derivatives |
| ZA983930B (en) | 1997-05-14 | 1999-11-08 | Lilly Co Eli | Excitatory amino acid receptor modulators. |
| WO2002055485A1 (en) * | 2001-01-11 | 2002-07-18 | Eli Lilly And Company | Prodrugs of excitatory amino acids |
| US7256217B2 (en) * | 2001-01-11 | 2007-08-14 | Eli Lilly And Company | Prodrugs of excitatory amino acids |
| WO2002068380A1 (en) * | 2001-02-22 | 2002-09-06 | Eli Lilly And Company | Synthetic excitatory amino acids |
| HRP20041179B1 (hr) * | 2002-06-11 | 2012-11-30 | Eli Lilly And Company | Prekursorski oblici lijekova za aminokiseline s pobuđivačkom aktivnosti |
| US7381746B2 (en) * | 2003-06-26 | 2008-06-03 | Taisho Pharmaceutical Co., Ltd. | 2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivative |
| CN103209954B (zh) * | 2010-11-18 | 2015-09-02 | 伊莱利利公司 | 作为mGluR2/3拮抗剂的4-取代的-3-苄氧基-双环[3.1.0]己烷化合物 |
| AR083845A1 (es) * | 2010-11-18 | 2013-03-27 | Lilly Co Eli | COMPUESTOS 3-FENILSULFANILMETIL-BICICLO[3.1.0]HEXANO 4-SUSTITUIDOS COMO ANTAGONISTAS DE mGluR2/3 |
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