ES2703904T3 - Moduladores del receptor de NMDA y usos de los mismos - Google Patents
Moduladores del receptor de NMDA y usos de los mismos Download PDFInfo
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- ES2703904T3 ES2703904T3 ES12844456T ES12844456T ES2703904T3 ES 2703904 T3 ES2703904 T3 ES 2703904T3 ES 12844456 T ES12844456 T ES 12844456T ES 12844456 T ES12844456 T ES 12844456T ES 2703904 T3 ES2703904 T3 ES 2703904T3
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- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 title description 42
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 title description 42
- 150000001875 compounds Chemical class 0.000 claims abstract description 344
- -1 -OH Chemical group 0.000 claims abstract description 200
- 229910052736 halogen Chemical group 0.000 claims abstract description 91
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- 125000001424 substituent group Chemical group 0.000 claims abstract description 82
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 67
- 239000001257 hydrogen Substances 0.000 claims abstract description 64
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 46
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 18
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 13
- 150000004677 hydrates Chemical class 0.000 claims abstract description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 55
- 238000000034 method Methods 0.000 claims description 32
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 201000000980 schizophrenia Diseases 0.000 claims description 12
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- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 9
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- YWINCLIZVLSGLF-LGKHCZOZSA-N amino (2S,3R)-3-hydroxy-2-[[(2S)-1-[(2S)-1-[(2R)-3-hydroxy-2-(phenylmethoxycarbonylamino)propanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]butanoate Chemical compound C(C1=CC=CC=C1)OC(N[C@@H](C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(N[C@H](C(=O)ON)[C@@H](C)O)=O)CO)=O YWINCLIZVLSGLF-LGKHCZOZSA-N 0.000 description 37
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- VBNALPYAVIAHCI-ONSCTEFMSA-N amino (2S)-3-hydroxy-2-[[(2S)-1-[(2S)-1-[(2R,3S)-3-hydroxy-2-(phenylmethoxycarbonylamino)butanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]propanoate Chemical compound C(C1=CC=CC=C1)OC(N[C@@H](C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(N[C@H](C(=O)ON)CO)=O)[C@H](C)O)=O VBNALPYAVIAHCI-ONSCTEFMSA-N 0.000 description 33
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- 125000001072 heteroaryl group Chemical group 0.000 description 31
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- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 26
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 25
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- 241001465754 Metazoa Species 0.000 description 23
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 22
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 22
- 238000004296 chiral HPLC Methods 0.000 description 22
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 22
- 230000027928 long-term synaptic potentiation Effects 0.000 description 22
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 21
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 21
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- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 20
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 20
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- 238000005481 NMR spectroscopy Methods 0.000 description 19
- WVSDBKNTLMWQTQ-SNPRPXQTSA-N benzyl (2s)-2-[[(2s,3r)-3-hydroxy-1-methoxy-1-oxobutan-2-yl]carbamoyl]pyrrolidine-1-carboxylate Chemical compound COC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H]1CCCN1C(=O)OCC1=CC=CC=C1 WVSDBKNTLMWQTQ-SNPRPXQTSA-N 0.000 description 19
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 19
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- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 17
- 125000003118 aryl group Chemical group 0.000 description 17
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- ZBDQHSHVSLIFAR-SVRRBLITSA-N (2s,3r)-3-acetyloxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC(=O)O[C@H](C)[C@@H](C(O)=O)NC(=O)OC(C)(C)C ZBDQHSHVSLIFAR-SVRRBLITSA-N 0.000 description 16
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 16
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| US8951968B2 (en) | 2009-10-05 | 2015-02-10 | Northwestern University | Methods of treating depression and other related diseases |
| CA2789331C (en) | 2010-02-11 | 2017-11-07 | Northwestern University | Secondary structure stabilized nmda receptor modulators and uses thereof |
| KR101692275B1 (ko) | 2010-02-11 | 2017-01-04 | 노오쓰웨스턴 유니버시티 | ２차 구조 안정화된 ｎｍｄａ 수용체 조절제 및 그의 용도 |
| US20150158903A1 (en) | 2011-09-08 | 2015-06-11 | Sage Therapeutics, Inc. | Neuroactive steroids, compositions, and uses thereof |
| PE20151436A1 (es) | 2013-01-29 | 2015-10-10 | Naurex Inc | Moduladores de receptores nmda de espiro-lactama y sus usos |
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