ES2734405T3 - Moduladores de receptores NMDA de espiro-lactama y sus usos - Google Patents
Moduladores de receptores NMDA de espiro-lactama y sus usos Download PDFInfo
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- ES2734405T3 ES2734405T3 ES14703747T ES14703747T ES2734405T3 ES 2734405 T3 ES2734405 T3 ES 2734405T3 ES 14703747 T ES14703747 T ES 14703747T ES 14703747 T ES14703747 T ES 14703747T ES 2734405 T3 ES2734405 T3 ES 2734405T3
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- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 title description 30
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 title description 30
- 150000001875 compounds Chemical class 0.000 claims abstract description 377
- -1 9-fluorenylmethyloxycarbonyl Chemical group 0.000 claims abstract description 123
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 67
- 125000001424 substituent group Chemical group 0.000 claims abstract description 49
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 41
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 40
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 38
- 125000006413 ring segment Chemical group 0.000 claims abstract description 34
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 33
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 33
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 32
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 27
- 125000005843 halogen group Chemical group 0.000 claims abstract description 26
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 26
- 150000003839 salts Chemical class 0.000 claims abstract description 24
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 23
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 23
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 22
- 150000002367 halogens Chemical class 0.000 claims abstract description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 11
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 10
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 8
- 125000006677 (C1-C3) haloalkoxy group Chemical group 0.000 claims abstract description 7
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 6
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 6
- 125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims abstract description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims abstract description 5
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 5
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 5
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims abstract description 5
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 39
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 17
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 16
- 201000000980 schizophrenia Diseases 0.000 claims description 13
- 125000004429 atom Chemical group 0.000 claims description 10
- 125000002947 alkylene group Chemical group 0.000 claims description 9
- 208000024827 Alzheimer disease Diseases 0.000 claims description 8
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 8
- 208000019901 Anxiety disease Diseases 0.000 claims description 7
- 150000001204 N-oxides Chemical class 0.000 claims description 7
- 230000036506 anxiety Effects 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 6
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 4
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical group C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical group C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 2
- 125000002393 azetidinyl group Chemical group 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 238000001990 intravenous administration Methods 0.000 claims description 2
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical group C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- CIISBYKBBMFLEZ-UHFFFAOYSA-N 1,2-oxazolidine Chemical group C1CNOC1 CIISBYKBBMFLEZ-UHFFFAOYSA-N 0.000 claims 1
- CZSRXHJVZUBEGW-UHFFFAOYSA-N 1,2-thiazolidine Chemical group C1CNSC1 CZSRXHJVZUBEGW-UHFFFAOYSA-N 0.000 claims 1
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical group C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 claims 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical group N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 claims 1
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical group N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 claims 1
- 125000001963 4 membered heterocyclic group Chemical group 0.000 claims 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical group C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 claims 1
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical group C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 claims 1
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical group C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 claims 1
- SEEPANYCNGTZFQ-UHFFFAOYSA-N sulfadiazine Chemical group C1=CC(N)=CC=C1S(=O)(=O)NC1=NC=CC=N1 SEEPANYCNGTZFQ-UHFFFAOYSA-N 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 62
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract description 29
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract description 21
- 125000001188 haloalkyl group Chemical group 0.000 abstract description 11
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 abstract description 8
- 125000003545 alkoxy group Chemical group 0.000 abstract description 8
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 abstract description 8
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 246
- 239000000243 solution Substances 0.000 description 244
- 239000011541 reaction mixture Substances 0.000 description 202
- 238000003786 synthesis reaction Methods 0.000 description 170
- 230000015572 biosynthetic process Effects 0.000 description 169
- 230000002829 reductive effect Effects 0.000 description 159
- 238000005160 1H NMR spectroscopy Methods 0.000 description 154
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 150
- 238000003756 stirring Methods 0.000 description 138
- 239000007858 starting material Substances 0.000 description 133
- 239000012044 organic layer Substances 0.000 description 129
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 112
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 108
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 106
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 103
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 100
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 97
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 95
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 88
- 235000019439 ethyl acetate Nutrition 0.000 description 75
- 239000007832 Na2SO4 Substances 0.000 description 74
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 74
- 229910052938 sodium sulfate Inorganic materials 0.000 description 74
- 235000011152 sodium sulphate Nutrition 0.000 description 74
- 239000007787 solid Substances 0.000 description 74
- 239000013058 crude material Substances 0.000 description 71
- 239000012267 brine Substances 0.000 description 59
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 59
- 238000010898 silica gel chromatography Methods 0.000 description 55
- 239000000460 chlorine Substances 0.000 description 48
- 239000000203 mixture Substances 0.000 description 48
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 45
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 34
- 238000006243 chemical reaction Methods 0.000 description 34
- 238000004440 column chromatography Methods 0.000 description 34
- 238000004128 high performance liquid chromatography Methods 0.000 description 33
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 32
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
- 239000006188 syrup Substances 0.000 description 30
- 235000020357 syrup Nutrition 0.000 description 30
- VYYVWXALPOFDLK-UHFFFAOYSA-N tert-butyl 2-propylhexanoate Chemical compound CCCCC(CCC)C(=O)OC(C)(C)C VYYVWXALPOFDLK-UHFFFAOYSA-N 0.000 description 30
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 30
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 29
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 29
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 27
- 239000011734 sodium Substances 0.000 description 27
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 24
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 24
- 239000007788 liquid Substances 0.000 description 23
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 239000012298 atmosphere Substances 0.000 description 21
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 21
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- 239000012299 nitrogen atmosphere Substances 0.000 description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 18
- IQPWGJWLDXLEMF-ODLMARSHSA-N (2s,3r)-3-hydroxy-2-[5-[(2-methylpropan-2-yl)oxycarbonyl]-3-oxo-2,5-diazaspiro[3.4]octan-2-yl]butanoic acid Chemical compound O=C1N([C@@H]([C@H](O)C)C(O)=O)CC11N(C(=O)OC(C)(C)C)CCC1 IQPWGJWLDXLEMF-ODLMARSHSA-N 0.000 description 16
- GDEBINCKVAQTKX-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonyl]-2-(phenylmethoxymethyl)pyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCCC1(C(O)=O)COCC1=CC=CC=C1 GDEBINCKVAQTKX-UHFFFAOYSA-N 0.000 description 16
- RYSMMYRGSNWYHF-UHFFFAOYSA-N 2-(hydroxymethyl)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCCC1(CO)C(O)=O RYSMMYRGSNWYHF-UHFFFAOYSA-N 0.000 description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
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- 208000024891 symptom Diseases 0.000 description 14
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 12
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 12
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- 229930195712 glutamate Natural products 0.000 description 10
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- 239000002904 solvent Substances 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
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- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 9
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- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 6
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- LCFRGHPLZRCMIF-UHFFFAOYSA-N 2-(1-hydroxyethyl)-5-methyl-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC(O)C1(C(O)=O)CCC(C)N1C(=O)OC(C)(C)C LCFRGHPLZRCMIF-UHFFFAOYSA-N 0.000 description 5
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
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Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2011003015A (es) | 2008-09-18 | 2011-11-18 | Univ Northwestern | Moduladores del receptor de n-metil-d-aspartato, y usos de los mismos. |
| EP3514158B1 (en) * | 2013-01-29 | 2022-10-12 | Aptinyx Inc. | Spiro-lactam nmda receptor modulators and uses thereof |
| PE20151438A1 (es) | 2013-01-29 | 2015-10-10 | Naurex Inc | Moduladores de receptores nmda de espiro-lactama y sus usos |
| MX2015009785A (es) | 2013-01-29 | 2016-04-04 | Aptinyx Inc | Moduladores de receptores nmda de espiro-lactama y sus usos. |
| US9828384B2 (en) | 2013-01-29 | 2017-11-28 | Aptinyx Inc. | Spiro-lactam NMDA receptor modulators and uses thereof |
| KR20150110787A (ko) * | 2013-01-29 | 2015-10-02 | 노렉스, 인크. | 스피로-락탐 nmda 수용체 조절인자 및 그의 용도 |
| WO2017201285A1 (en) * | 2016-05-19 | 2017-11-23 | Aptinyx Inc. | Spiro-lactam nmda receptor modulators and uses thereof |
| WO2017201283A1 (en) * | 2016-05-19 | 2017-11-23 | Aptinyx Inc. | Spiro-lactam nmda receptor modulators and uses thereof |
| KR102465758B1 (ko) | 2016-08-01 | 2022-11-09 | 앱티닉스 인크. | 스피로-락탐 nmda 수용체 조정제 및 그의 용도 |
| ES2973283T3 (es) | 2016-08-01 | 2024-06-19 | Tenacia Biotechnology Hong Kong Co Ltd | Moduladores de receptores de NMDA espirolactámicos y usos de los mismos |
| WO2018026792A1 (en) | 2016-08-01 | 2018-02-08 | Aptinyx Inc. | Spiro-lactam and bis-spiro-lactam nmda receptor modulators and uses thereof |
| KR102538803B1 (ko) | 2016-08-01 | 2023-06-01 | 앱티닉스 인크. | 스피로-락탐 nmda 조정제 및 그의 사용 방법 |
| JP7036792B2 (ja) | 2016-08-01 | 2022-03-15 | アプティニックス インコーポレイテッド | スピロ－ラクタムｎｍｄａ受容体修飾因子およびその使用 |
| WO2019152685A1 (en) * | 2018-01-31 | 2019-08-08 | Aptinyx Inc. | Spiro-lactam nmda receptor modulators and methods of using same |
| CN112204031B (zh) | 2018-01-31 | 2024-05-24 | 元羿生物科技(香港)有限公司 | 螺-内酰胺nmda受体调节剂及其用途 |
| AU2019215049A1 (en) * | 2018-01-31 | 2020-09-17 | Aptinyx Inc. | Spiro-lactam NMDA receptor modulators and uses thereof |
| WO2019152696A1 (en) * | 2018-01-31 | 2019-08-08 | Aptinyx Inc. | Spiro-lactam nmda receptor modulators and uses thereof |
| WO2019152688A1 (en) * | 2018-01-31 | 2019-08-08 | Aptinyx Inc. | Spiro-lactam nmda receptor modulators and uses thereof |
| EP3959205B1 (en) | 2019-04-26 | 2025-11-12 | Merck Sharp & Dohme LLC | Process for the preparation of intermediates useful for making (2s,5r)-7-oxo-n-piperidin-4-yl-6-(sulfoxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide |
| EP4484431A3 (en) | 2019-06-24 | 2025-03-26 | Naurex Inc. | Processes and intermediates for producing diazaspiro lactam compounds |
| CN114364380A (zh) * | 2019-06-24 | 2022-04-15 | 诺雷克斯股份有限公司 | (s)-2-((2s,3r)-1-氨基-3-羟基-1-氧代丁烷-2-基)-1-氧代-2,5-二氮杂螺[3.4]辛烷-5-甲酸叔丁酯的固体形式及其制备方法 |
| CA3148922A1 (en) * | 2019-08-01 | 2021-02-04 | Aptinyx Inc. | Methods of treating disorders associated with elevated levels of antibodies that interact with the nmda receptor |
| US12012413B2 (en) | 2019-11-11 | 2024-06-18 | Tenacia Biotechnology (Hong Kong) Co., Limited | Methods of treating painful diabetic peripheral neuropathy |
| CN113956183B (zh) * | 2021-10-28 | 2023-06-20 | 成都市科隆化学品有限公司 | 一种Boc-Ser(Bzl)-OH及其制备方法 |
Family Cites Families (106)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0180398A1 (en) | 1984-10-26 | 1986-05-07 | The Regents Of The University Of California | Synthesis of beta-lactam |
| CA1305177C (en) | 1987-06-30 | 1992-07-14 | Yasufumi Ohfune | Carboxycyclopropylglycine and process for producing the same |
| US4904681A (en) | 1987-12-01 | 1990-02-27 | G. D. Searle & Co. | D-cycloserine and its prodrugs as cognitive enhancers |
| EP0360390A1 (en) | 1988-07-25 | 1990-03-28 | Glaxo Group Limited | Spirolactam derivatives |
| US5061721A (en) | 1989-03-15 | 1991-10-29 | G. D. Searle & Co. | Composition containing d-cycloserine and d-alanine for memory and learning enhancement or treatment of a cognitive or psychotic disorder |
| US5086072A (en) | 1990-06-18 | 1992-02-04 | The United States Of America As Represented By The Department Of Health And Human Services | Treatment of mood disorders with functional antagonists of the glycine/nmda receptor complex |
| CA2058975C (en) | 1990-10-30 | 2000-06-06 | Shuichi Kasai | Antiinflammatory gel preparation |
| US5168103A (en) | 1991-01-22 | 1992-12-01 | American Home Products Corporation | [[2-(amino-3,4-dioxo-1-cyclobuten-1-yl) amino]alkyl]-acid derivatives |
| FR2692268B1 (fr) | 1992-06-15 | 1994-08-19 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides ayant une activité de récepteur NMDA, acides nucléiques codant pour ces polypeptides et utilisations. |
| SE9301667D0 (sv) | 1993-05-14 | 1993-05-14 | Kabi Pharmacia Ab | New use |
| US5523323A (en) | 1993-09-14 | 1996-06-04 | Maccecchini; Maria-Luisa | Use of partial agonists of the NMDA receptor to reduce opiate induced tolerance and dependence |
| US5605911A (en) | 1995-01-31 | 1997-02-25 | Washington University | Use of alpha-2 adrenergic drugs to prevent adverse effects of NMDA receptor hypofunction (NRH) |
| US6335358B1 (en) | 1995-04-12 | 2002-01-01 | President And Fellows Of Harvard College | Lactacystin analogs |
| US5741778A (en) | 1996-03-19 | 1998-04-21 | Amgen Inc. | Method for treating Huntington's disease using glial cell line-derived neurotrophic factor (GDNF) protein product |
| US5763393A (en) | 1996-05-17 | 1998-06-09 | Neurotherapeutics L.P. | Neuroactive peptides |
| IL127332A0 (en) | 1996-06-07 | 1999-09-22 | Zeneca Ltd | Peptide derivatives |
| EP0918859A1 (en) | 1996-08-02 | 1999-06-02 | ZymoGenetics, Inc. | Testis-specific insulin homolog polypeptides |
| US5902815A (en) | 1996-09-03 | 1999-05-11 | Washington University | Use of 5HT-2A serotonin agonists to prevent adverse effects of NMDA receptor hypofunction |
| JP3955345B2 (ja) | 1996-09-27 | 2007-08-08 | サントリー株式会社 | 新規アミノ酸ダイジハーベイン |
| AU1585999A (en) | 1997-11-12 | 1999-05-31 | Neurotherapeutics | Methods for the detection and treatment of disease using a glycosyltransferase |
| US5952389A (en) | 1998-01-13 | 1999-09-14 | Synchroneuron | Methods of treating tardive dyskinesia and other movement disorders |
| US6007841A (en) | 1998-03-13 | 1999-12-28 | Algos Pharmaceutical Corporation | Analgesic composition and method for treating pain |
| US6274314B1 (en) | 1998-04-02 | 2001-08-14 | Nyxis Neurotherapies, Inc. | Diagnostic assay for the modified nucleosides pseudouridine, 7-methyladenosine, or 1-methyladenosine |
| US6197820B1 (en) | 1998-04-06 | 2001-03-06 | Uab Research Foundation | Use of phenylglycine derivatives to decrease neuronal death caused by brain tumors and brain lesions |
| US6025471A (en) | 1998-06-03 | 2000-02-15 | Deghenghi; Romano | Diazaspiro, azepino and azabicyclo therapeutic peptides |
| WO2000027790A1 (en) | 1998-11-11 | 2000-05-18 | Smithkline Beecham P.L.C. | Mutilin compounds |
| AU1724000A (en) | 1998-11-12 | 2000-05-29 | Nyxis, Inc. | Diagnostic assay for cancer |
| US20030064921A1 (en) | 1999-10-27 | 2003-04-03 | The Regents Of The University Of California | Methods and compounds for modulating melanocortin receptor ligand binding and activity |
| WO2001036685A2 (en) | 1999-11-17 | 2001-05-25 | Nyxis Neurotherapies, Inc. | Differential gene expression in cancer |
| AU782678B2 (en) | 2000-02-01 | 2005-08-18 | Agy Therapeutics, Inc. | Interaction of NMDA receptor with protein tyrosine phosphatase |
| JP2001261679A (ja) | 2000-03-21 | 2001-09-26 | Mitsui Chemicals Inc | ピロリジノン誘導体及びそれらの製造方法並びに該化合物を含有する医薬 |
| AU2001268467A1 (en) | 2000-06-14 | 2001-12-24 | Nyxis Neurotherapies, Inc. | Identification of genes and compounds for treatment of cancer |
| WO2001098367A2 (en) | 2000-06-22 | 2001-12-27 | Nyxis Neurotherapies, Inc. | Neuroactive peptides for treatment of hypoxia and related conditions |
| GB0018272D0 (en) | 2000-07-25 | 2000-09-13 | Vernalis Research Limited | Chemical compounds IV |
| IL145209A0 (en) | 2000-09-06 | 2002-06-30 | Pfizer Prod Inc | Pharmaceutical combinations for the treatment of stroke and traumatic brain injury |
| EP1186303A3 (en) | 2000-09-06 | 2003-12-10 | Pfizer Products Inc. | Pharmaceutical combinations, for the treatment of stroke and traumatic brain injury, containing a neutrophil inhibiting factor and an selective NMDA-NR2B receptor antagonist |
| UA73619C2 (en) | 2000-12-13 | 2005-08-15 | Pfizer Prod Inc | Stable pharmaceutical compositions of nmda receptor agonist (variants) and method of treatment |
| WO2002047535A2 (en) | 2000-12-14 | 2002-06-20 | Nyxis Neurotherapies, Inc. | High throughput assay to detect inhibitors of the map kinase pathway |
| WO2002072005A2 (en) | 2001-03-07 | 2002-09-19 | University Of Utah Research Foundation | Linear y-carboxyglutamate rich conotoxins |
| WO2002072609A2 (en) | 2001-03-12 | 2002-09-19 | Nyxis Neurotherapies, Inc | Neuroactive peptides for prevention and/or treatment of hypoxia and neuropathic pain |
| US20030022253A1 (en) | 2001-07-25 | 2003-01-30 | Nyxis Neurotherapies, Inc. | Method for identifying, isolating and producing neuroactive binding agents and binding agents derived thereby |
| EP2078718A1 (en) | 2002-07-05 | 2009-07-15 | Targacept, Inc. | N-aryl diazaspiracyclic compounds and methods of preparation and use thereof |
| US7273889B2 (en) | 2002-09-25 | 2007-09-25 | Innovative Drug Delivery Systems, Inc. | NMDA receptor antagonist formulation with reduced neurotoxicity |
| CA2573951A1 (en) | 2003-07-18 | 2005-01-27 | Virochem Pharma Inc. | Spiro compounds and methods for the modulation of chemokine receptor activity |
| CA2534909A1 (en) | 2003-08-08 | 2005-02-17 | The Burnham Institute | P16 mediated regulation of nmda receptors |
| US7662856B2 (en) | 2003-08-29 | 2010-02-16 | The University Of Houston System | Compositions having antimycrobial activity including a hydroxamate or a hydroxamate and a hydroxlyamine |
| GB0323204D0 (en) | 2003-10-03 | 2003-11-05 | Novartis Ag | Organic compounds |
| US20050096311A1 (en) | 2003-10-30 | 2005-05-05 | Cns Response | Compositions and methods for treatment of nervous system disorders |
| EP1683797A1 (en) | 2003-11-13 | 2006-07-26 | Ono Pharmaceutical Co., Ltd. | Heterocyclic spiro compound |
| AU2004313693B2 (en) | 2004-01-08 | 2010-08-26 | F. Hoffmann-La Roche Ag | Diaza-spiropiperidine derivatives |
| WO2006034196A1 (en) | 2004-09-17 | 2006-03-30 | Lifelike Biomatic Inc. | Compositions for enhancing memory and methods therefor |
| CN101090902B (zh) | 2004-10-13 | 2013-05-29 | 默沙东公司 | Cgrp受体拮抗剂 |
| PL2030622T3 (pl) | 2005-03-24 | 2011-07-29 | Univ Emory | Wskazanie dawkowania progesteronu w leczeniu urazowego uszkodzenia mózgu |
| WO2007025141A2 (en) | 2005-08-26 | 2007-03-01 | Wisconsin Alumni Research Foundation | Poly-beta-peptides from functionalized beta-lactam monomers and antibacterial compositions containing same |
| AR059224A1 (es) * | 2006-01-31 | 2008-03-19 | Jerini Ag | Compuestos para la inhibicion de integrinas y uso de estas |
| WO2007103719A2 (en) | 2006-03-03 | 2007-09-13 | Incyte Corporation | MODULATORS OF 11-β HYDROXYL STEROID DEHYDROGENASE TYPE 1, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USING THE SAME |
| US7884080B2 (en) | 2006-09-15 | 2011-02-08 | Schering Plough Corporation | Azetidinone derivatives and methods of use thereof |
| JP2008188285A (ja) | 2007-02-06 | 2008-08-21 | Bridgestone Corp | バックパッド及び車両用シート |
| CN101066945B (zh) | 2007-05-25 | 2010-05-19 | 中国科学院上海有机化学研究所 | 一种合成3-位取代内酰胺类化合物的方法 |
| CN101125817B (zh) | 2007-08-03 | 2011-09-14 | 中国科学院上海有机化学研究所 | 一种合成高对映选择性醛基取代小环胺类化合物和光学活性3-位取代内酰胺类化合物的方法 |
| US20090054392A1 (en) | 2007-08-20 | 2009-02-26 | Wyeth | Naphthylpyrimidine, naphthylpyrazine and naphthylpyridazine analogs and their use as agonists of the wnt-beta-catenin cellular messaging system |
| WO2009039390A2 (en) | 2007-09-20 | 2009-03-26 | Naurex Inc. | The development of glycobiology-based therapeutics for the treatment of brain tumors |
| CA2716375C (en) | 2008-02-20 | 2018-05-29 | The Children's Hospital Of Philadelphia | Genetic alterations associated with autism and the autistic phenotype and methods of use thereof for the diagnosis and treatmemt of autism |
| US20110105480A1 (en) | 2008-06-24 | 2011-05-05 | Keith Freehauf | Pharmaceutical transdermal compositions and method for treating inflammation in cattle |
| CA2728730A1 (en) | 2008-06-27 | 2009-12-30 | Neurosearch A/S | Novel tetramethyl substituted piperidine derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
| AU2009278075B2 (en) | 2008-08-07 | 2013-07-04 | F. Hoffmann-La Roche Ag | Process for the preparation of a macrocycle |
| GB0814991D0 (en) | 2008-08-15 | 2008-09-24 | Glaxo Group Ltd | Compounds |
| MX2011003015A (es) | 2008-09-18 | 2011-11-18 | Univ Northwestern | Moduladores del receptor de n-metil-d-aspartato, y usos de los mismos. |
| WO2010065709A2 (en) | 2008-12-03 | 2010-06-10 | Amin Khan | Hydroxamic acid derivatives, preparation and therapeutic uses thereof |
| DE102009001460B4 (de) | 2009-03-11 | 2010-12-02 | Zf Friedrichshafen Ag | Ölbehälter |
| US8329904B2 (en) | 2009-05-12 | 2012-12-11 | Hoffmann-La Roche Inc. | Azacyclic derivatives |
| US20120178695A1 (en) | 2009-07-02 | 2012-07-12 | Joseph Moskal | Methods of treating neuropathic pain |
| US8951968B2 (en) | 2009-10-05 | 2015-02-10 | Northwestern University | Methods of treating depression and other related diseases |
| WO2011044089A2 (en) | 2009-10-05 | 2011-04-14 | Joseph Moskal | Methods of treating depression and other related diseases |
| WO2011068927A2 (en) | 2009-12-04 | 2011-06-09 | Abbott Laboratories | 11-β-HYDROXYSTEROID DEHYDROGENASE TYPE 1 (11B-HSD1) INHIBITORS AND USES THEREOF |
| KR101692275B1 (ko) | 2010-02-11 | 2017-01-04 | 노오쓰웨스턴 유니버시티 | ２차 구조 안정화된 ｎｍｄａ 수용체 조절제 및 그의 용도 |
| BR112012020142A2 (pt) | 2010-02-11 | 2020-08-18 | Northwestern University | moduladores do receptor de nmda com estrutura secundária estabilizada e usos dos mesmos. |
| UY33227A (es) | 2010-02-19 | 2011-09-30 | Novartis Ag | Compuestos de pirrolopirimidina como inhibidores de la cdk4/6 |
| US8097634B2 (en) | 2010-04-15 | 2012-01-17 | Hoffmann-La Roche Inc. | Azacyclic derivatives |
| GB201007789D0 (en) | 2010-05-10 | 2010-06-23 | Glaxo Group Ltd | Novel Compound |
| CN102267995A (zh) | 2010-06-04 | 2011-12-07 | 艾琪康医药科技（上海）有限公司 | 一种制备二氮杂螺环化合物的方法 |
| WO2012021712A1 (en) | 2010-08-12 | 2012-02-16 | Tetraphase Pharmaceuticals, Inc. | Tetracycline analogs |
| US9737531B2 (en) | 2012-07-12 | 2017-08-22 | Glytech, Llc | Composition and method for treatment of depression and psychosis in humans |
| AU2012229172B2 (en) | 2011-03-14 | 2017-02-09 | Alkahest, Inc. | Benzodioxane inhibitors of leukotriene production |
| CA2834286A1 (en) | 2011-04-27 | 2012-11-01 | Northwestern University | Methods of treating alzheimer's disease, huntington's disease, autism, and other disorders |
| WO2013001448A1 (en) | 2011-06-27 | 2013-01-03 | Koninklijke Philips Electronics N.V. | Ultrasound transducer assembly and method of manufacturing the same |
| CN104109151B (zh) | 2011-07-27 | 2017-04-12 | 阿斯利康(瑞典)有限公司 | N‑(2‑{2‑二甲氨基乙基‑甲氨基}‑4‑甲氧基‑5‑{[4‑(1‑甲基吲哚‑3‑基)嘧啶‑2‑基]氨基}苯基)丙‑2‑烯酰胺的甲磺酸盐的多晶型 |
| KR20150110787A (ko) | 2013-01-29 | 2015-10-02 | 노렉스, 인크. | 스피로-락탐 nmda 수용체 조절인자 및 그의 용도 |
| EP3514158B1 (en) | 2013-01-29 | 2022-10-12 | Aptinyx Inc. | Spiro-lactam nmda receptor modulators and uses thereof |
| US9828384B2 (en) | 2013-01-29 | 2017-11-28 | Aptinyx Inc. | Spiro-lactam NMDA receptor modulators and uses thereof |
| PE20151438A1 (es) | 2013-01-29 | 2015-10-10 | Naurex Inc | Moduladores de receptores nmda de espiro-lactama y sus usos |
| MX2015009785A (es) | 2013-01-29 | 2016-04-04 | Aptinyx Inc | Moduladores de receptores nmda de espiro-lactama y sus usos. |
| JO3517B1 (ar) | 2014-01-17 | 2020-07-05 | Novartis Ag | ان-ازاسبيرو الكان حلقي كبديل مركبات اريل-ان مغايرة وتركيبات لتثبيط نشاط shp2 |
| GB201416346D0 (en) | 2014-09-16 | 2014-10-29 | Shire Internat Gmbh | Spirocyclic derivatives |
| WO2017201285A1 (en) | 2016-05-19 | 2017-11-23 | Aptinyx Inc. | Spiro-lactam nmda receptor modulators and uses thereof |
| WO2017201283A1 (en) | 2016-05-19 | 2017-11-23 | Aptinyx Inc. | Spiro-lactam nmda receptor modulators and uses thereof |
| KR102538803B1 (ko) | 2016-08-01 | 2023-06-01 | 앱티닉스 인크. | 스피로-락탐 nmda 조정제 및 그의 사용 방법 |
| JP7036792B2 (ja) | 2016-08-01 | 2022-03-15 | アプティニックス インコーポレイテッド | スピロ－ラクタムｎｍｄａ受容体修飾因子およびその使用 |
| ES2973283T3 (es) | 2016-08-01 | 2024-06-19 | Tenacia Biotechnology Hong Kong Co Ltd | Moduladores de receptores de NMDA espirolactámicos y usos de los mismos |
| KR102465758B1 (ko) | 2016-08-01 | 2022-11-09 | 앱티닉스 인크. | 스피로-락탐 nmda 수용체 조정제 및 그의 용도 |
| WO2018026792A1 (en) | 2016-08-01 | 2018-02-08 | Aptinyx Inc. | Spiro-lactam and bis-spiro-lactam nmda receptor modulators and uses thereof |
| AU2019215049A1 (en) | 2018-01-31 | 2020-09-17 | Aptinyx Inc. | Spiro-lactam NMDA receptor modulators and uses thereof |
| CN112204031B (zh) | 2018-01-31 | 2024-05-24 | 元羿生物科技(香港)有限公司 | 螺-内酰胺nmda受体调节剂及其用途 |
| US20210308101A1 (en) | 2019-11-11 | 2021-10-07 | Aptinyx Inc. | Methods of treating fibromyalgia |
| US12012413B2 (en) | 2019-11-11 | 2024-06-18 | Tenacia Biotechnology (Hong Kong) Co., Limited | Methods of treating painful diabetic peripheral neuropathy |
| CA3161742A1 (en) | 2019-12-04 | 2021-06-10 | Aptinyx Inc. | Methods of treating cognitive impairment associated with neurodegenerative disease |
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