ES2822830T3 - Antagonistas selectivos de NR2B - Google Patents
Antagonistas selectivos de NR2B Download PDFInfo
- Publication number
- ES2822830T3 ES2822830T3 ES16787974T ES16787974T ES2822830T3 ES 2822830 T3 ES2822830 T3 ES 2822830T3 ES 16787974 T ES16787974 T ES 16787974T ES 16787974 T ES16787974 T ES 16787974T ES 2822830 T3 ES2822830 T3 ES 2822830T3
- Authority
- ES
- Spain
- Prior art keywords
- compound
- mmol
- column
- alkyl
- pharmaceutically acceptable
- 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
- 108010038912 Retinoid X Receptors Proteins 0.000 title description 13
- 239000005557 antagonist Substances 0.000 title description 4
- 102000034527 Retinoid X Receptors Human genes 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 79
- -1 amino acid esters Chemical group 0.000 claims abstract description 37
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims abstract description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 22
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 21
- 125000001424 substituent group Chemical group 0.000 claims abstract description 21
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 10
- 239000001257 hydrogen Substances 0.000 claims abstract description 10
- 150000002148 esters Chemical class 0.000 claims abstract description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 8
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 8
- 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 6
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 5
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 5
- 125000004438 haloalkoxy group Chemical group 0.000 claims abstract description 5
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 5
- 239000002253 acid Substances 0.000 claims abstract description 4
- 125000005907 alkyl ester group Chemical group 0.000 claims abstract description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 4
- 150000003009 phosphonic acids Chemical group 0.000 claims abstract description 4
- 239000000651 prodrug Chemical group 0.000 claims abstract description 4
- 229940002612 prodrug Drugs 0.000 claims abstract description 4
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 32
- 125000005843 halogen group Chemical group 0.000 claims description 13
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims description 5
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 5
- 208000004296 neuralgia Diseases 0.000 claims description 5
- 208000021722 neuropathic pain Diseases 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 208000020401 Depressive disease Diseases 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 208000018737 Parkinson disease Diseases 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 150000003053 piperidines Chemical group 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 abstract 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 132
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 105
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 80
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 43
- 239000006184 cosolvent Substances 0.000 description 41
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 38
- 239000000203 mixture Substances 0.000 description 37
- 239000011541 reaction mixture Substances 0.000 description 37
- 239000000047 product Substances 0.000 description 34
- 239000000243 solution Substances 0.000 description 31
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 26
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 25
- 238000000746 purification Methods 0.000 description 25
- 238000005160 1H NMR spectroscopy Methods 0.000 description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- 239000012043 crude product Substances 0.000 description 20
- 239000003643 water by type Substances 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 18
- 238000002347 injection Methods 0.000 description 18
- 239000007924 injection Substances 0.000 description 18
- 239000000872 buffer Substances 0.000 description 15
- 239000007787 solid Substances 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- 102100022630 Glutamate receptor ionotropic, NMDA 2B Human genes 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- 238000004128 high performance liquid chromatography Methods 0.000 description 12
- 238000011068 loading method Methods 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
- 239000003814 drug Substances 0.000 description 11
- 230000014759 maintenance of location Effects 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 10
- 238000005481 NMR spectroscopy Methods 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 239000013058 crude material Substances 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 230000001681 protective effect Effects 0.000 description 10
- 239000012528 membrane Substances 0.000 description 9
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 239000005695 Ammonium acetate Substances 0.000 description 7
- 235000019257 ammonium acetate Nutrition 0.000 description 7
- 229940043376 ammonium acetate Drugs 0.000 description 7
- UFDHFCFMDKCNHY-UHFFFAOYSA-N 4-bromo-2-[(4-methylphenyl)methyl]oxazinan-3-one Chemical compound CC1=CC=C(CN2OCCC(Br)C2=O)C=C1 UFDHFCFMDKCNHY-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 108091006146 Channels Proteins 0.000 description 5
- 230000027455 binding Effects 0.000 description 5
- 210000003169 central nervous system Anatomy 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000009182 swimming Effects 0.000 description 5
- PSXAMPZZTNVYRP-UHFFFAOYSA-N 4-[4-(5-hydroxypyridin-2-yl)piperazin-1-yl]-2-[(4-methylphenyl)methyl]-1,2-oxazolidin-3-one Chemical compound OC=1C=CC(=NC=1)N1CCN(CC1)C1C(N(OC1)CC1=CC=C(C=C1)C)=O PSXAMPZZTNVYRP-UHFFFAOYSA-N 0.000 description 4
- 229920000856 Amylose Polymers 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 229940024606 amino acid Drugs 0.000 description 4
- 239000000935 antidepressant agent Substances 0.000 description 4
- 229940005513 antidepressants Drugs 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 239000001913 cellulose Substances 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 235000019253 formic acid Nutrition 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- OIBISEAEGMVEPG-UHFFFAOYSA-N n-[(4-methylphenyl)methyl]hydroxylamine Chemical compound CC1=CC=C(CNO)C=C1 OIBISEAEGMVEPG-UHFFFAOYSA-N 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- AGOSGCWATIJZHQ-UHFFFAOYSA-N tert-butyl [(2-methylpropan-2-yl)oxycarbonylamino] carbonate Chemical compound CC(C)(C)OC(=O)NOC(=O)OC(C)(C)C AGOSGCWATIJZHQ-UHFFFAOYSA-N 0.000 description 4
- YUKBQUJZGFSWNY-SNVBAGLBSA-N (4R)-4-amino-2-[(4-methylphenyl)methyl]-1,2-oxazolidin-3-one Chemical compound N[C@H]1C(N(OC1)CC1=CC=C(C=C1)C)=O YUKBQUJZGFSWNY-SNVBAGLBSA-N 0.000 description 3
- NVNPLEPBDPJYRZ-UHFFFAOYSA-N 1-(bromomethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CBr)C=C1 NVNPLEPBDPJYRZ-UHFFFAOYSA-N 0.000 description 3
- FPMFDMCHCNBOAE-MCOCGALXSA-N 2-[(4-chlorophenyl)methyl]-4-[(3S,4S)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl]oxazinan-3-one Chemical compound OC1=CC=C(C=C1)[C@@H]1CCN(C[C@H]1F)C1CCON(CC2=CC=C(Cl)C=C2)C1=O FPMFDMCHCNBOAE-MCOCGALXSA-N 0.000 description 3
- IHWNSMGEPWAHER-UHFFFAOYSA-N 2-[(4-chlorophenyl)methyl]-4-[3-fluoro-4-(3-fluoro-4-hydroxyphenyl)piperidin-1-yl]oxazinan-3-one Chemical compound OC1=C(F)C=C(C=C1)C1CCN(CC1F)C1CCON(CC2=CC=C(Cl)C=C2)C1=O IHWNSMGEPWAHER-UHFFFAOYSA-N 0.000 description 3
- NXDMPSWVSBJLBA-MCOCGALXSA-N 4-[(3S,4S)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl]-2-[(4-fluorophenyl)methyl]oxazinan-3-one Chemical compound OC1=CC=C(C=C1)[C@@H]1CCN(C[C@H]1F)C1CCON(CC2=CC=C(F)C=C2)C1=O NXDMPSWVSBJLBA-MCOCGALXSA-N 0.000 description 3
- JWFRNGYOYFWLSJ-UHFFFAOYSA-N 4-[3-fluoro-4-(3-fluoro-4-hydroxyphenyl)piperidin-1-yl]-2-[(4-fluorophenyl)methyl]oxazinan-3-one Chemical compound OC1=C(F)C=C(C=C1)C1CCN(CC1F)C1CCON(CC2=CC=C(F)C=C2)C1=O JWFRNGYOYFWLSJ-UHFFFAOYSA-N 0.000 description 3
- KNLAYFWTYNWJDW-UHFFFAOYSA-N 4-[4-(5-hydroxypyridin-2-yl)piperazin-1-yl]-2-[(4-methylphenyl)methyl]oxazinan-3-one Chemical compound CC1=CC=C(CN2OCCC(N3CCN(CC3)C3=NC=C(O)C=C3)C2=O)C=C1 KNLAYFWTYNWJDW-UHFFFAOYSA-N 0.000 description 3
- BBNCALBVVXJSMD-UHFFFAOYSA-N 4-[4-(5-hydroxypyridin-2-yl)piperidin-1-yl]-2-[(4-methylphenyl)methyl]-1,2-oxazolidin-3-one Chemical compound OC=1C=CC(=NC=1)C1CCN(CC1)C1C(N(OC1)CC1=CC=C(C=C1)C)=O BBNCALBVVXJSMD-UHFFFAOYSA-N 0.000 description 3
- XJGZSMIDMGYHSU-UHFFFAOYSA-N 4-bromo-2-[(4-fluorophenyl)methyl]-1,2-oxazolidin-3-one Chemical compound BrC1C(N(OC1)CC1=CC=C(C=C1)F)=O XJGZSMIDMGYHSU-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 3
- 230000001430 anti-depressive effect Effects 0.000 description 3
- 125000002619 bicyclic group Chemical group 0.000 description 3
- 229960003299 ketamine Drugs 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 210000002381 plasma Anatomy 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- IQKCCYIMXLKTDN-SBSPUUFOSA-N (4R)-4-amino-2-[(4-fluorophenyl)methyl]-1,2-oxazolidin-3-one hydrochloride Chemical compound Cl.N[C@@H]1CON(Cc2ccc(F)cc2)C1=O IQKCCYIMXLKTDN-SBSPUUFOSA-N 0.000 description 2
- WZRKSPFYXUXINF-UHFFFAOYSA-N 1-(bromomethyl)-4-methylbenzene Chemical compound CC1=CC=C(CBr)C=C1 WZRKSPFYXUXINF-UHFFFAOYSA-N 0.000 description 2
- WYZLYWUZERABRL-UHFFFAOYSA-N 2,4-dibromobutanoyl chloride Chemical compound ClC(=O)C(Br)CCBr WYZLYWUZERABRL-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- LFAIBZXNQLLZCD-LKXRKSRJSA-N 4-[(3R,4R)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl]-2-[(4-methylphenyl)methyl]oxazinan-3-one Chemical compound CC1=CC=C(CN2OCCC(N3CC[C@@H]([C@@H](F)C3)C3=CC=C(O)C=C3)C2=O)C=C1 LFAIBZXNQLLZCD-LKXRKSRJSA-N 0.000 description 2
- LFAIBZXNQLLZCD-UGGDCYSXSA-N 4-[(3S,4S)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl]-2-[(4-methylphenyl)methyl]oxazinan-3-one Chemical compound CC1=CC=C(CN2OCCC(N3CC[C@H]([C@H](F)C3)C3=CC=C(O)C=C3)C2=O)C=C1 LFAIBZXNQLLZCD-UGGDCYSXSA-N 0.000 description 2
- RWWRVFJUUHSBLX-UHFFFAOYSA-N 4-[3-fluoro-4-(3-fluoro-4-hydroxyphenyl)piperidin-1-yl]-2-[(4-methylphenyl)methyl]oxazinan-3-one Chemical compound CC1=CC=C(CN2OCCC(N3CCC(C(F)C3)C3=CC(F)=C(O)C=C3)C2=O)C=C1 RWWRVFJUUHSBLX-UHFFFAOYSA-N 0.000 description 2
- JMIWZCWXOJZQIV-UHFFFAOYSA-N 4-[4-(5-hydroxypyridin-2-yl)piperidin-1-yl]-2-[(4-methylphenyl)methyl]oxazinan-3-one Chemical compound CC1=CC=C(CN2OCCC(N3CCC(CC3)C3=NC=C(O)C=C3)C2=O)C=C1 JMIWZCWXOJZQIV-UHFFFAOYSA-N 0.000 description 2
- HLMJQVDGESNAMK-UHFFFAOYSA-N 4-bromo-2-[(4-methylphenyl)methyl]-1,2-oxazolidin-3-one Chemical compound BrC1C(N(OC1)CC1=CC=C(C=C1)C)=O HLMJQVDGESNAMK-UHFFFAOYSA-N 0.000 description 2
- 102100028628 Bombesin receptor subtype-3 Human genes 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- OJRUSAPKCPIVBY-KQYNXXCUSA-N C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N Chemical compound C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N OJRUSAPKCPIVBY-KQYNXXCUSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 101000695054 Homo sapiens Bombesin receptor subtype-3 Proteins 0.000 description 2
- 101001047090 Homo sapiens Potassium voltage-gated channel subfamily H member 2 Proteins 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 102000004310 Ion Channels Human genes 0.000 description 2
- 108090000862 Ion Channels Proteins 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 2
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 2
- 102000038100 NR2 subfamily Human genes 0.000 description 2
- 108020002076 NR2 subfamily Proteins 0.000 description 2
- PGXHBINJZDOSIH-SECBINFHSA-N N[C@H]1C(N(OC1)CC1=CC=C(C=C1)F)=O Chemical compound N[C@H]1C(N(OC1)CC1=CC=C(C=C1)F)=O PGXHBINJZDOSIH-SECBINFHSA-N 0.000 description 2
- 102100022807 Potassium voltage-gated channel subfamily H member 2 Human genes 0.000 description 2
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 210000003050 axon Anatomy 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 229940125758 compound 15 Drugs 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- 238000000265 homogenisation Methods 0.000 description 2
- 239000011539 homogenization buffer Substances 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 208000024714 major depressive disease Diseases 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- BGQHUMGDKKVWMB-UHFFFAOYSA-N n-[(4-chlorophenyl)methyl]hydroxylamine Chemical compound ONCC1=CC=C(Cl)C=C1 BGQHUMGDKKVWMB-UHFFFAOYSA-N 0.000 description 2
- OERSFCWDCVETCJ-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]hydroxylamine Chemical compound ONCC1=CC=C(F)C=C1 OERSFCWDCVETCJ-UHFFFAOYSA-N 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 210000004129 prosencephalon Anatomy 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 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 2
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 2
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- 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 1
- XFPBJWAHCIEXMF-OAQYLSRUSA-N (4R)-2-[(4-fluorophenyl)methyl]-4-[4-(4-methoxyphenyl)piperidin-1-yl]-1,2-oxazolidin-3-one Chemical compound FC1=CC=C(CN2OC[C@H](C2=O)N2CCC(CC2)C2=CC=C(C=C2)OC)C=C1 XFPBJWAHCIEXMF-OAQYLSRUSA-N 0.000 description 1
- KQNBRMUBPRGXSL-UHFFFAOYSA-N 1-(bromomethyl)-4-chlorobenzene Chemical compound ClC1=CC=C(CBr)C=C1 KQNBRMUBPRGXSL-UHFFFAOYSA-N 0.000 description 1
- QEMSVZNTSXPFJA-HNAYVOBHSA-N 1-[(1s,2s)-1-hydroxy-1-(4-hydroxyphenyl)propan-2-yl]-4-phenylpiperidin-4-ol Chemical compound C1([C@H](O)[C@H](C)N2CCC(O)(CC2)C=2C=CC=CC=2)=CC=C(O)C=C1 QEMSVZNTSXPFJA-HNAYVOBHSA-N 0.000 description 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- QFTXNHSEWOULGJ-UHFFFAOYSA-N 2-[(4-fluorophenyl)methyl]-4-[4-(4-hydroxyphenyl)piperidin-1-yl]-1,2-oxazolidin-3-one Chemical compound FC1=CC=C(CN2OCC(C2=O)N2CCC(CC2)C2=CC=C(C=C2)O)C=C1 QFTXNHSEWOULGJ-UHFFFAOYSA-N 0.000 description 1
- XFPBJWAHCIEXMF-UHFFFAOYSA-N 2-[(4-fluorophenyl)methyl]-4-[4-(4-methoxyphenyl)piperidin-1-yl]-1,2-oxazolidin-3-one Chemical compound FC1=CC=C(CN2OCC(C2=O)N2CCC(CC2)C2=CC=C(C=C2)OC)C=C1 XFPBJWAHCIEXMF-UHFFFAOYSA-N 0.000 description 1
- KAGYZTGOXOCFJN-UHFFFAOYSA-N 2-[(4-methylphenyl)methyl]-4-[4-(5-phenylmethoxypyridin-2-yl)piperazin-1-yl]-1,2-oxazolidin-3-one Chemical compound C(C1=CC=CC=C1)OC=1C=CC(=NC=1)N1CCN(CC1)C1C(N(OC1)CC1=CC=C(C=C1)C)=O KAGYZTGOXOCFJN-UHFFFAOYSA-N 0.000 description 1
- VXZBYIWNGKSFOJ-UHFFFAOYSA-N 2-[4-[5-(2,3-dihydro-1H-inden-2-ylamino)pyrazin-2-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC=1N=CC(=NC=1)C=1C=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2 VXZBYIWNGKSFOJ-UHFFFAOYSA-N 0.000 description 1
- RBLBLNARISWZTL-UHFFFAOYSA-N 3-(4-methoxyphenyl)pentane-1,5-diol Chemical compound COC1=CC=C(C(CCO)CCO)C=C1 RBLBLNARISWZTL-UHFFFAOYSA-N 0.000 description 1
- HGAPKINVUOUWJG-WDEREUQCSA-N 4-[(3S,4S)-3-fluoropiperidin-4-yl]phenol Chemical compound F[C@@H]1CNCC[C@H]1C1=CC=C(C=C1)O HGAPKINVUOUWJG-WDEREUQCSA-N 0.000 description 1
- TYMSZYLMXQIIJM-UHFFFAOYSA-N 4-[4-(4-hydroxyphenyl)piperidin-1-yl]-2-[(4-methylphenyl)methyl]oxazinan-3-one Chemical compound Cc1ccc(CN2OCCC(N3CCC(CC3)c3ccc(O)cc3)C2=O)cc1 TYMSZYLMXQIIJM-UHFFFAOYSA-N 0.000 description 1
- QFDFQYCFWTXMNA-UHFFFAOYSA-N 4-[4-(4-methoxyphenyl)piperidin-1-yl]-2-[(4-methylphenyl)methyl]-1,2-oxazolidin-3-one Chemical compound COC1=CC=C(C=C1)C1CCN(CC1)C1C(N(OC1)CC1=CC=C(C=C1)C)=O QFDFQYCFWTXMNA-UHFFFAOYSA-N 0.000 description 1
- CJSYQTPDBBUBDS-UHFFFAOYSA-N 4-bromo-2-[(4-chlorophenyl)methyl]morpholin-3-one Chemical compound BrN1C(C(OCC1)CC1=CC=C(C=C1)Cl)=O CJSYQTPDBBUBDS-UHFFFAOYSA-N 0.000 description 1
- YEYGGDQPVMXRDN-UHFFFAOYSA-N 4-bromo-2-[(4-fluorophenyl)methyl]morpholin-3-one Chemical compound BrN1C(C(OCC1)CC1=CC=C(C=C1)F)=O YEYGGDQPVMXRDN-UHFFFAOYSA-N 0.000 description 1
- SJISCEAZUHNOMD-UHFFFAOYSA-N 4-phenylcyclohexan-1-amine Chemical compound C1CC(N)CCC1C1=CC=CC=C1 SJISCEAZUHNOMD-UHFFFAOYSA-N 0.000 description 1
- ZDEWVCFSCQUKTE-UHFFFAOYSA-N 4-piperidin-4-ylphenol Chemical compound C1=CC(O)=CC=C1C1CCNCC1 ZDEWVCFSCQUKTE-UHFFFAOYSA-N 0.000 description 1
- CLBZAZFGEWOCGK-UHFFFAOYSA-N 6-piperidin-4-ylpyridin-3-ol Chemical compound N1=CC(O)=CC=C1C1CCNCC1 CLBZAZFGEWOCGK-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- JLKDJSXBUPSWAB-UHFFFAOYSA-N CC(C)(C)OC(N(Cc(cc1)ccc1F)OC(OC(C)(C)C)=O)=O Chemical compound CC(C)(C)OC(N(Cc(cc1)ccc1F)OC(OC(C)(C)C)=O)=O JLKDJSXBUPSWAB-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- LFAIBZXNQLLZCD-ATKRNPRHSA-N Cc1ccc(CN(C2=O)OCCC2N(CCC2c(cc3)ccc3O)C[C@H]2F)cc1 Chemical compound Cc1ccc(CN(C2=O)OCCC2N(CCC2c(cc3)ccc3O)C[C@H]2F)cc1 LFAIBZXNQLLZCD-ATKRNPRHSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- DYDCUQKUCUHJBH-UWTATZPHSA-N D-Cycloserine Chemical compound N[C@@H]1CONC1=O DYDCUQKUCUHJBH-UWTATZPHSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102100029458 Glutamate receptor ionotropic, NMDA 2A Human genes 0.000 description 1
- 102100022631 Glutamate receptor ionotropic, NMDA 2C Human genes 0.000 description 1
- 102100022626 Glutamate receptor ionotropic, NMDA 2D Human genes 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 102000034570 NR1 subfamily Human genes 0.000 description 1
- 108020001305 NR1 subfamily Proteins 0.000 description 1
- 108091008644 NR2D Proteins 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- IGSHUIPOKIEKJL-UHFFFAOYSA-N Oc1ccc(C(CC2)CCN2C(CON2Cc(cc3)ccc3F)C2=O)nc1 Chemical compound Oc1ccc(C(CC2)CCN2C(CON2Cc(cc3)ccc3F)C2=O)nc1 IGSHUIPOKIEKJL-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 208000018452 Torsade de pointes Diseases 0.000 description 1
- 208000002363 Torsades de Pointes Diseases 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 229950010850 acistrate Drugs 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 230000008856 allosteric binding Effects 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229910052797 bismuth Inorganic materials 0.000 description 1
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- RECBFDWSXWAXHY-IAGOWNOFSA-N cerc-301 Chemical compound C1=CC(C)=CC=C1COC(=O)N1C[C@@H](F)[C@@H](CNC=2N=CC=CN=2)CC1 RECBFDWSXWAXHY-IAGOWNOFSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 230000010485 coping Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000007267 depressive like behavior Effects 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 230000007831 electrophysiology Effects 0.000 description 1
- 238000002001 electrophysiology Methods 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000012048 forced swim test Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940097042 glucuronate Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 108091008634 hepatocyte nuclear factors 4 Proteins 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 230000002102 hyperpolarization Effects 0.000 description 1
- 230000002631 hypothermal effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 230000028161 membrane depolarization Effects 0.000 description 1
- XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229940126662 negative allosteric modulator Drugs 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229910052717 sulfur Chemical group 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- VNNOMGVHZFZWLD-RXMQYKEDSA-N tert-butyl n-[(4r)-3-oxo-1,2-oxazolidin-4-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H]1CONC1=O VNNOMGVHZFZWLD-RXMQYKEDSA-N 0.000 description 1
- 108091008646 testicular receptors Proteins 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 229950005135 traxoprodil Drugs 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5355—Non-condensed oxazines and containing further heterocyclic rings
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/09—Geometrical isomers
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN3309DE2015 | 2015-10-14 | ||
| PCT/US2016/056716 WO2017066368A1 (en) | 2015-10-14 | 2016-10-13 | Selective nr2b antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2822830T3 true ES2822830T3 (es) | 2021-05-05 |
Family
ID=57208377
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES16787974T Active ES2822830T3 (es) | 2015-10-14 | 2016-10-13 | Antagonistas selectivos de NR2B |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US10501451B2 (enExample) |
| EP (1) | EP3362447B1 (enExample) |
| JP (1) | JP6843853B2 (enExample) |
| KR (1) | KR20180064507A (enExample) |
| CN (1) | CN108368101B (enExample) |
| AU (1) | AU2016340239A1 (enExample) |
| BR (1) | BR112018007181A2 (enExample) |
| CA (1) | CA3001894A1 (enExample) |
| EA (1) | EA201890764A1 (enExample) |
| ES (1) | ES2822830T3 (enExample) |
| IL (1) | IL258611A (enExample) |
| MX (1) | MX2018004257A (enExample) |
| WO (1) | WO2017066368A1 (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112018006537A2 (pt) * | 2015-10-14 | 2018-10-16 | Bristol-Myers Squibb Company | antagonistas seletivos de nr2b |
| US11104670B2 (en) * | 2018-10-17 | 2021-08-31 | Boehringer Ingelheim International Gmbh | 4-pyrimidin-5-ylmethyl-morpholine derivatives and the use thereof as medicament |
| CN112888685B (zh) * | 2018-10-17 | 2023-09-22 | 勃林格殷格翰国际有限公司 | 4-吡嗪-2-基甲基-吗啉衍生物及其作为药物的用途 |
| JP7093469B2 (ja) * | 2018-10-17 | 2022-06-29 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ４－ピリジニルメチル－モルホリン誘導体および医薬としてのその使用 |
| US12398143B2 (en) | 2019-06-04 | 2025-08-26 | Boehringer Ingelheim International Gmbh | Imidazopyrazine derivatives and the use thereof as medicament |
| TW202237103A (zh) * | 2020-12-04 | 2022-10-01 | 瑞士商諾華公司 | 用於治療抑鬱症的ｎｒ２ｂ－ｎｍｄａ受體ｎａｍ之劑量方案 |
| CN113620896A (zh) * | 2021-08-31 | 2021-11-09 | 青岛科技大学 | 2-(2-氯苯基)甲基-4,4-二甲基-3-异恶唑酮的制备方法 |
| CN116063200A (zh) * | 2022-12-12 | 2023-05-05 | 华南理工大学 | 一种异噁唑啉宠物用杀虫剂氟雷拉纳中间体及其制备方法 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6476041B1 (en) | 1999-10-29 | 2002-11-05 | Merck & Co., Inc. | 1,4 substituted piperidinyl NMDA/NR2B antagonists |
| US7022728B2 (en) | 2001-03-09 | 2006-04-04 | Abbott Laboratories | Benzimidazoles that are useful in treating male sexual dysfunction |
| WO2003035641A1 (en) | 2001-10-22 | 2003-05-01 | Shionogi & Co., Ltd. | Novel carbamoylpyrrolidone derivative |
| MXPA05013151A (es) | 2003-06-04 | 2006-03-17 | Merck & Co Inc | 3-fluoro-piperidinas como antagonistas de n-metil-d-aspartato/nr2b. |
| JP2007508288A (ja) | 2003-10-08 | 2007-04-05 | ファイザー株式会社 | 縮合ラクタム化合物 |
| US20070185168A1 (en) * | 2004-04-07 | 2007-08-09 | Takai Haruki S | Piperidine derivatives |
| JPWO2006137465A1 (ja) * | 2005-06-24 | 2009-01-22 | 塩野義製薬株式会社 | 含窒素複素環誘導体 |
| US7935706B2 (en) | 2006-02-23 | 2011-05-03 | Shionogi & Co., Ltd. | Nitrogen-containing heterocycle derivatives substituted with cyclic group |
| CN101815518B (zh) | 2007-06-29 | 2013-01-09 | 埃莫里大学 | 用于神经保护的nmda受体拮抗剂 |
| JP2009067784A (ja) * | 2007-08-21 | 2009-04-02 | Shionogi & Co Ltd | 環式基で置換された含窒素複素環誘導体を含有する鎮痛剤 |
| US9101612B2 (en) * | 2010-02-11 | 2015-08-11 | Northwestern University | Secondary structure stabilized NMDA receptor modulators and uses thereof |
| US9221796B2 (en) * | 2014-01-09 | 2015-12-29 | Bristol-Myers Squibb Company | Selective NR2B antagonists |
| US9187506B2 (en) * | 2014-01-09 | 2015-11-17 | Bristol-Myers Squibb Company | (R)-3-((3S,4S)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one and its prodrugs for the treatment of psychiatric disorders |
-
2016
- 2016-10-13 AU AU2016340239A patent/AU2016340239A1/en not_active Abandoned
- 2016-10-13 US US15/767,385 patent/US10501451B2/en active Active
- 2016-10-13 CA CA3001894A patent/CA3001894A1/en not_active Abandoned
- 2016-10-13 WO PCT/US2016/056716 patent/WO2017066368A1/en not_active Ceased
- 2016-10-13 ES ES16787974T patent/ES2822830T3/es active Active
- 2016-10-13 KR KR1020187013128A patent/KR20180064507A/ko active Pending
- 2016-10-13 EA EA201890764A patent/EA201890764A1/ru unknown
- 2016-10-13 EP EP16787974.1A patent/EP3362447B1/en active Active
- 2016-10-13 JP JP2018519276A patent/JP6843853B2/ja not_active Expired - Fee Related
- 2016-10-13 MX MX2018004257A patent/MX2018004257A/es unknown
- 2016-10-13 BR BR112018007181A patent/BR112018007181A2/pt not_active Application Discontinuation
- 2016-10-13 CN CN201680073103.8A patent/CN108368101B/zh active Active
-
2018
- 2018-04-10 IL IL258611A patent/IL258611A/en unknown
-
2019
- 2019-12-09 US US16/707,382 patent/US10954225B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| EA201890764A1 (ru) | 2018-09-28 |
| WO2017066368A1 (en) | 2017-04-20 |
| EP3362447B1 (en) | 2020-08-26 |
| EP3362447A1 (en) | 2018-08-22 |
| BR112018007181A2 (pt) | 2018-10-16 |
| IL258611A (en) | 2018-06-28 |
| MX2018004257A (es) | 2018-05-16 |
| CA3001894A1 (en) | 2017-04-20 |
| AU2016340239A1 (en) | 2018-05-31 |
| JP6843853B2 (ja) | 2021-03-17 |
| US10501451B2 (en) | 2019-12-10 |
| CN108368101A (zh) | 2018-08-03 |
| KR20180064507A (ko) | 2018-06-14 |
| US20180312495A1 (en) | 2018-11-01 |
| US20200115370A1 (en) | 2020-04-16 |
| US10954225B2 (en) | 2021-03-23 |
| JP2018530582A (ja) | 2018-10-18 |
| CN108368101B (zh) | 2022-03-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2822830T3 (es) | Antagonistas selectivos de NR2B | |
| ES2548135T3 (es) | Heterociclos condensados que contienen nitrógeno y composiciones de los mismos como inhibidores de quinasa | |
| ES2672992T3 (es) | Compuesto aromático | |
| DK3092224T3 (en) | SELECTIVE NR2B ANTAGONISTS | |
| ES2707525T3 (es) | Compuestos de 6,7-dihidropirazolo[1,5-a]pirazin-4(5H)-ona y su uso como moduladores alostéricos negativos de receptores de mGlu2 | |
| BR112020017644A2 (pt) | Piperidinil-3-(arilóxi)propanamidas e propanoatos | |
| ES2548284T3 (es) | Compuestos novedosos como ligandos del receptor H3 de histamina | |
| ES2750868T3 (es) | Derivados de fluoroindol como moduladores alostéricos positivos del receptor muscarínico M1 | |
| EP3233077A1 (en) | Dopamine d2 receptor ligands | |
| ES2818254T3 (es) | Antagonistas selectivos de NR2B | |
| US20110207709A1 (en) | Modulators of serotonin receptor |