ES2316184T3 - 1-(3-heteroarilpropil- o -prop-2-enil)-4-bencilpiperidinas como antagonistas del receptor nmda. - Google Patents
1-(3-heteroarilpropil- o -prop-2-enil)-4-bencilpiperidinas como antagonistas del receptor nmda. Download PDFInfo
- Publication number
- ES2316184T3 ES2316184T3 ES99915568T ES99915568T ES2316184T3 ES 2316184 T3 ES2316184 T3 ES 2316184T3 ES 99915568 T ES99915568 T ES 99915568T ES 99915568 T ES99915568 T ES 99915568T ES 2316184 T3 ES2316184 T3 ES 2316184T3
- Authority
- ES
- Spain
- Prior art keywords
- piperidin
- acid
- fluorbenzyl
- disease
- propenyl
- 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.)
- Expired - Lifetime
Links
- 239000005557 antagonist Substances 0.000 title claims description 9
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 title description 5
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- KSTICMFAFQGYSN-UHFFFAOYSA-N 5-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]prop-1-enyl]-1,3-dihydrobenzimidazol-2-one Chemical compound C1=CC(F)=CC=C1CC1CCN(CC=CC=2C=C3NC(=O)NC3=CC=2)CC1 KSTICMFAFQGYSN-UHFFFAOYSA-N 0.000 claims abstract description 7
- DCWVSMOSBUAONF-UHFFFAOYSA-N 5-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]prop-1-enyl]-1,3-dihydroindol-2-one Chemical compound C1=CC(F)=CC=C1CC1CCN(CC=CC=2C=C3CC(=O)NC3=CC=2)CC1 DCWVSMOSBUAONF-UHFFFAOYSA-N 0.000 claims abstract description 7
- GRCRMRUZDNKSBD-UHFFFAOYSA-N 6-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]prop-1-enyl]-3h-1,3-benzothiazol-2-one Chemical compound C1=CC(F)=CC=C1CC1CCN(CC=CC=2C=C3SC(=O)NC3=CC=2)CC1 GRCRMRUZDNKSBD-UHFFFAOYSA-N 0.000 claims abstract description 7
- CQYRNVNODQPZDL-UHFFFAOYSA-N 6-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]prop-1-enyl]-3h-1,3-benzoxazol-2-one Chemical compound C1=CC(F)=CC=C1CC1CCN(CC=CC=2C=C3OC(=O)NC3=CC=2)CC1 CQYRNVNODQPZDL-UHFFFAOYSA-N 0.000 claims abstract description 3
- YNWAFHDAQQTVIT-UHFFFAOYSA-N 6-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]-3h-1,3-benzoxazol-2-one Chemical compound C1=CC(F)=CC=C1CC1CCN(CCCC=2C=C3OC(=O)NC3=CC=2)CC1 YNWAFHDAQQTVIT-UHFFFAOYSA-N 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 44
- 201000010099 disease Diseases 0.000 claims description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 9
- 150000001413 amino acids Chemical class 0.000 claims description 8
- 208000024827 Alzheimer disease Diseases 0.000 claims description 7
- 208000023105 Huntington disease Diseases 0.000 claims description 7
- 208000018737 Parkinson disease Diseases 0.000 claims description 7
- 208000028017 Psychotic disease Diseases 0.000 claims description 7
- 206010008118 cerebral infarction Diseases 0.000 claims description 7
- 206010015037 epilepsy Diseases 0.000 claims description 7
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 7
- 201000000980 schizophrenia Diseases 0.000 claims description 7
- 201000006474 Brain Ischemia Diseases 0.000 claims description 6
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- 208000010125 myocardial infarction Diseases 0.000 claims description 6
- 230000000626 neurodegenerative effect Effects 0.000 claims description 4
- 239000002552 dosage form Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 230000004770 neurodegeneration Effects 0.000 claims description 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 3
- 239000012439 solid excipient Substances 0.000 claims 1
- 239000002253 acid Substances 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- -1 for example Chemical class 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 239000013543 active substance Substances 0.000 description 12
- 239000000047 product Substances 0.000 description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 150000007513 acids Chemical class 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 229940024606 amino acid Drugs 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 5
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 5
- 239000000443 aerosol Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- UYNVMODNBIQBMV-UHFFFAOYSA-N 4-[1-hydroxy-2-[4-(phenylmethyl)-1-piperidinyl]propyl]phenol Chemical compound C1CC(CC=2C=CC=CC=2)CCN1C(C)C(O)C1=CC=C(O)C=C1 UYNVMODNBIQBMV-UHFFFAOYSA-N 0.000 description 4
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- 229960003998 ifenprodil Drugs 0.000 description 4
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 4
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 235000011007 phosphoric acid Nutrition 0.000 description 4
- WLJVNTCWHIRURA-UHFFFAOYSA-N pimelic acid Chemical compound OC(=O)CCCCCC(O)=O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000003380 propellant Substances 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- PFNFFQXMRSDOHW-UHFFFAOYSA-N spermine Chemical compound NCCCNCCCCNCCCN PFNFFQXMRSDOHW-UHFFFAOYSA-N 0.000 description 4
- 239000007921 spray Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- 230000000699 topical effect Effects 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 239000008298 dragée Substances 0.000 description 3
- 239000000975 dye Substances 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 150000002430 hydrocarbons Chemical class 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 150000003053 piperidines Chemical class 0.000 description 3
- 229920000768 polyamine Polymers 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 229940099259 vaseline Drugs 0.000 description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- OXQGTIUCKGYOAA-UHFFFAOYSA-N 2-Ethylbutanoic acid Chemical compound CCC(CC)C(O)=O OXQGTIUCKGYOAA-UHFFFAOYSA-N 0.000 description 2
- ASSKVPFEZFQQNQ-UHFFFAOYSA-N 2-benzoxazolinone Chemical compound C1=CC=C2OC(O)=NC2=C1 ASSKVPFEZFQQNQ-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- JLAKCHGEEBPDQI-UHFFFAOYSA-N 4-(4-fluorobenzyl)piperidine Chemical compound C1=CC(F)=CC=C1CC1CCNCC1 JLAKCHGEEBPDQI-UHFFFAOYSA-N 0.000 description 2
- OJKWWANXBGLGQN-UHFFFAOYSA-N 4-[(4-fluorophenyl)methyl]piperidine;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1CC1CCNCC1 OJKWWANXBGLGQN-UHFFFAOYSA-N 0.000 description 2
- YZHPRSMPPPJPII-UHFFFAOYSA-N 5-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]-1,3-dihydrobenzimidazol-2-one Chemical compound C1=CC(F)=CC=C1CC1CCN(CCCC=2C=C3NC(=O)NC3=CC=2)CC1 YZHPRSMPPPJPII-UHFFFAOYSA-N 0.000 description 2
- TZPYHSABVMEQJM-UHFFFAOYSA-N 5-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]-1,3-dihydroindol-2-one Chemical compound C1=CC(F)=CC=C1CC1CCN(CCCC=2C=C3CC(=O)NC3=CC=2)CC1 TZPYHSABVMEQJM-UHFFFAOYSA-N 0.000 description 2
- KAKDFWWFSZIEIX-UHFFFAOYSA-N 6-(3-chloropropyl)-3h-1,3-benzoxazol-2-one Chemical compound ClCCCC1=CC=C2NC(=O)OC2=C1 KAKDFWWFSZIEIX-UHFFFAOYSA-N 0.000 description 2
- VXFJVYLYMPVVTQ-UHFFFAOYSA-N 6-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]-2-methylprop-1-enyl]-3h-1,3-benzoxazol-2-one Chemical compound C=1C=C2NC(=O)OC2=CC=1C=C(C)CN(CC1)CCC1CC1=CC=C(F)C=C1 VXFJVYLYMPVVTQ-UHFFFAOYSA-N 0.000 description 2
- OVQXQXYBFNPNTP-UHFFFAOYSA-N 6-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]prop-1-enyl]-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=CC(F)=CC=C1CC1CCN(CC=CC=2C=C3CCC(=O)NC3=CC=2)CC1 OVQXQXYBFNPNTP-UHFFFAOYSA-N 0.000 description 2
- FWYRCNFWCMKNTJ-UHFFFAOYSA-N 6-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]propanoyl]-3h-1,3-benzoxazol-2-one Chemical compound C1=CC(F)=CC=C1CC1CCN(CCC(=O)C=2C=C3OC(=O)NC3=CC=2)CC1 FWYRCNFWCMKNTJ-UHFFFAOYSA-N 0.000 description 2
- KUKQWVAVMDIKGW-UHFFFAOYSA-N 6-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]-2,3-dihydro-1,3-benzoxazole Chemical compound C1=CC(F)=CC=C1CC1CCN(CCCC=2C=C3OCNC3=CC=2)CC1 KUKQWVAVMDIKGW-UHFFFAOYSA-N 0.000 description 2
- NXIMVTKEDFLFOG-UHFFFAOYSA-N 6-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]-3h-1,3-benzothiazol-2-one Chemical compound C1=CC(F)=CC=C1CC1CCN(CCCC=2C=C3SC(=O)NC3=CC=2)CC1 NXIMVTKEDFLFOG-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- 229940127523 NMDA Receptor Antagonists Drugs 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- BYUMYPPGJBLEIS-UHFFFAOYSA-N acetic acid;propane-1,2,3-triol Chemical compound CC(O)=O.CC(O)=O.CC(O)=O.OCC(O)CO BYUMYPPGJBLEIS-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- 150000003938 benzyl alcohols Chemical class 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 2
- 239000006196 drop Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 2
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 239000000174 gluconic acid Substances 0.000 description 2
- 235000012208 gluconic acid Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 239000003906 humectant Substances 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 235000015110 jellies Nutrition 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 239000001630 malic acid Substances 0.000 description 2
- 235000011090 malic acid Nutrition 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 2
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical compound C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 2
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 2
- 229960003512 nicotinic acid Drugs 0.000 description 2
- 235000001968 nicotinic acid Nutrition 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 150000003016 phosphoric acids Chemical class 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- 239000006215 rectal suppository Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 229940063675 spermine Drugs 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 238000002560 therapeutic procedure Methods 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
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- GGUSQTSTQSHJAH-UHFFFAOYSA-N 1-(4-chlorophenyl)-2-[4-(4-fluorobenzyl)piperidin-1-yl]ethanol Chemical compound C=1C=C(Cl)C=CC=1C(O)CN(CC1)CCC1CC1=CC=C(F)C=C1 GGUSQTSTQSHJAH-UHFFFAOYSA-N 0.000 description 1
- NZVZVGPYTICZBZ-UHFFFAOYSA-N 1-benzylpiperidine Chemical class C=1C=CC=CC=1CN1CCCCC1 NZVZVGPYTICZBZ-UHFFFAOYSA-N 0.000 description 1
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
- JWBYYIVNNQPQHL-UHFFFAOYSA-N 6-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]-2-methylpropyl]-3h-1,3-benzoxazol-2-one Chemical compound C=1C=C2NC(=O)OC2=CC=1CC(C)CN(CC1)CCC1CC1=CC=C(F)C=C1 JWBYYIVNNQPQHL-UHFFFAOYSA-N 0.000 description 1
- QVAIDYMCUIMKGK-UHFFFAOYSA-N 6-[3-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]-3,4-dihydro-1h-quinolin-2-one Chemical compound C1=CC(F)=CC=C1CC1CCN(CCCC=2C=C3CCC(=O)NC3=CC=2)CC1 QVAIDYMCUIMKGK-UHFFFAOYSA-N 0.000 description 1
- 102000015404 Amino Acid Receptors Human genes 0.000 description 1
- 108010025177 Amino Acid Receptors Proteins 0.000 description 1
- 206010002660 Anoxia Diseases 0.000 description 1
- 241000976983 Anoxia Species 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010048962 Brain oedema Diseases 0.000 description 1
- 101100283604 Caenorhabditis elegans pigk-1 gene Proteins 0.000 description 1
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 1
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- LBOJYSIDWZQNJS-JKSUJKDBSA-N LSM-5387 Chemical compound C12=CC=CC=C2[C@@]2(C)C3=CC=CC=C3C[C@@H]1N2 LBOJYSIDWZQNJS-JKSUJKDBSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- 235000009470 Theobroma cacao Nutrition 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000007953 anoxia Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 208000006752 brain edema Diseases 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 239000012154 double-distilled water Substances 0.000 description 1
- 229950005455 eliprodil Drugs 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000009711 regulatory function Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- C07D413/06—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 carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19812331 | 1998-03-20 | ||
| DE19812331A DE19812331A1 (de) | 1998-03-20 | 1998-03-20 | Piperidinderivate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2316184T3 true ES2316184T3 (es) | 2009-04-01 |
Family
ID=7861717
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES99915568T Expired - Lifetime ES2316184T3 (es) | 1998-03-20 | 1999-03-11 | 1-(3-heteroarilpropil- o -prop-2-enil)-4-bencilpiperidinas como antagonistas del receptor nmda. |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US6548516B1 (https=) |
| EP (1) | EP1068202B1 (https=) |
| JP (1) | JP4451565B2 (https=) |
| KR (1) | KR20010042047A (https=) |
| CN (1) | CN1123571C (https=) |
| AR (1) | AR014747A1 (https=) |
| AT (1) | ATE416173T1 (https=) |
| AU (1) | AU747900B2 (https=) |
| BR (1) | BR9908902A (https=) |
| CA (1) | CA2324339C (https=) |
| DE (2) | DE19812331A1 (https=) |
| DK (1) | DK1068202T3 (https=) |
| ES (1) | ES2316184T3 (https=) |
| HU (1) | HUP0101220A3 (https=) |
| ID (1) | ID26125A (https=) |
| NO (1) | NO20004668L (https=) |
| PL (1) | PL342732A1 (https=) |
| PT (1) | PT1068202E (https=) |
| RU (1) | RU2217429C2 (https=) |
| SK (1) | SK13692000A3 (https=) |
| WO (1) | WO1999048891A1 (https=) |
| ZA (1) | ZA992191B (https=) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2409006A1 (en) | 2000-05-31 | 2001-12-06 | Warner-Lambert Company | Biciclic cyclohexylamines and their use as nmda receptor antogonists |
| JP2003535851A (ja) * | 2000-06-06 | 2003-12-02 | ワーナー−ランバート・カンパニー、リミテッド、ライアビリティ、カンパニー | 二環式シクロヘキシルアミン類およびそれらのｎｍｄａ受容体アンタゴニストとしての使用 |
| JP2004516295A (ja) | 2000-12-21 | 2004-06-03 | ワーナー−ランバート・カンパニー、リミテッド、ライアビリティ、カンパニー | サブタイプ選択的なｎ−メチル−ｄ−アスパラギン酸拮抗薬としてのピペリジン誘導体 |
| MXPA02002749A (es) | 2001-03-27 | 2002-10-28 | Warner Lambert Co | Derivados de ciclohexilamina como antagonistas del subtipo selectivo del n-metil-d-aspartato. |
| DE10248067A1 (de) * | 2002-10-07 | 2004-04-15 | Proteosys Ag | Heteroarylpropyl-Piperazine und Heteroarylpropyl-Piperidine |
| US7732162B2 (en) | 2003-05-05 | 2010-06-08 | Probiodrug Ag | Inhibitors of glutaminyl cyclase for treating neurodegenerative diseases |
| EP2089383B1 (en) | 2006-11-09 | 2015-09-16 | Probiodrug AG | 3-hydr0xy-1,5-dihydr0-pyrr0l-2-one derivatives as inhibitors of glutaminyl cyclase for the treatment of ulcer, cancer and other diseases |
| US9126987B2 (en) | 2006-11-30 | 2015-09-08 | Probiodrug Ag | Inhibitors of glutaminyl cyclase |
| AU2008220785B2 (en) | 2007-03-01 | 2013-02-21 | Vivoryon Therapeutics N.V. | New use of glutaminyl cyclase inhibitors |
| JP5667440B2 (ja) | 2007-04-18 | 2015-02-12 | プロビオドルグ エージー | グルタミニルシクラーゼ阻害剤としてのチオ尿素誘導体 |
| JP5934645B2 (ja) | 2009-09-11 | 2016-06-15 | プロビオドルグ エージー | グルタミニルシクラーゼ阻害剤としてのヘテロ環式誘導体 |
| CA2784119A1 (en) | 2009-12-15 | 2011-06-23 | Neurop, Inc. | Compounds for the treatment of neurologic disorders |
| WO2011107530A2 (en) | 2010-03-03 | 2011-09-09 | Probiodrug Ag | Novel inhibitors |
| JP5688745B2 (ja) | 2010-03-10 | 2015-03-25 | プロビオドルグ エージー | グルタミニルシクラーゼ（ｑｃ、ｅｃ２．３．２．５）の複素環阻害剤 |
| WO2011131748A2 (en) | 2010-04-21 | 2011-10-27 | Probiodrug Ag | Novel inhibitors |
| CN102133198B (zh) * | 2011-03-09 | 2012-02-08 | 北京四环科宝制药有限公司 | 一种酒石酸艾芬地尔冻干粉针剂及其制备方法 |
| EP2686313B1 (en) | 2011-03-16 | 2016-02-03 | Probiodrug AG | Benzimidazole derivatives as inhibitors of glutaminyl cyclase |
| CN103965188A (zh) * | 2013-01-29 | 2014-08-06 | 中山大学 | 含硒多奈哌齐类似物 |
| RS61688B1 (sr) | 2015-04-29 | 2021-05-31 | Janssen Pharmaceutica Nv | Azabenzimidazoli i njihiova upotreba kao modulatori ampa receptora |
| US10604484B2 (en) * | 2015-04-29 | 2020-03-31 | Janssen Pharmaceutica Nv | Indolone compounds and their use as AMPA receptor modulators |
| ES2812698T3 (es) | 2017-09-29 | 2021-03-18 | Probiodrug Ag | Inhibidores de glutaminil ciclasa |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PH17194A (en) * | 1980-03-06 | 1984-06-19 | Otsuka Pharma Co Ltd | Novel carbostyril derivatives,and pharmaceutical composition containing the same |
| JP3084729B2 (ja) * | 1990-06-15 | 2000-09-04 | 横河電機株式会社 | デジタルオシロスコープ |
| TW281670B (https=) * | 1993-09-02 | 1996-07-21 | Hoffmann La Roche | |
| FR2717810B1 (fr) * | 1994-03-22 | 1996-04-26 | Adir | Nouvelles aminoalkyl benzoxazolinones et benzothiazolinones, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent. |
| WO1996002250A1 (en) | 1994-07-20 | 1996-02-01 | Acea Pharmaceuticals Inc. | Haloperidol analogs and the use thereof |
| ATE174915T1 (de) | 1994-10-31 | 1999-01-15 | Merck Patent Gmbh | Benzylpiperidinderivate mit hoher affinität zu bindungsstellen von aminosäure-rezeptoren |
| ZA9610745B (en) | 1995-12-22 | 1997-06-24 | Warner Lambert Co | 4-Subsituted piperidine analogs and their use as subtype selective nmda receptor antagonists |
| DE19643790A1 (de) | 1996-10-30 | 1998-05-07 | Merck Patent Gmbh | Benzoxazol-Derivat |
-
1998
- 1998-03-20 DE DE19812331A patent/DE19812331A1/de not_active Withdrawn
-
1999
- 1999-03-11 PT PT99915568T patent/PT1068202E/pt unknown
- 1999-03-11 AU AU34105/99A patent/AU747900B2/en not_active Ceased
- 1999-03-11 CN CN99804190A patent/CN1123571C/zh not_active Expired - Fee Related
- 1999-03-11 PL PL99342732A patent/PL342732A1/xx not_active Application Discontinuation
- 1999-03-11 CA CA002324339A patent/CA2324339C/en not_active Expired - Fee Related
- 1999-03-11 WO PCT/EP1999/001573 patent/WO1999048891A1/de not_active Ceased
- 1999-03-11 US US09/646,185 patent/US6548516B1/en not_active Expired - Fee Related
- 1999-03-11 KR KR1020007010387A patent/KR20010042047A/ko not_active Withdrawn
- 1999-03-11 AT AT99915568T patent/ATE416173T1/de not_active IP Right Cessation
- 1999-03-11 EP EP99915568A patent/EP1068202B1/de not_active Expired - Lifetime
- 1999-03-11 DE DE59914921T patent/DE59914921D1/de not_active Expired - Lifetime
- 1999-03-11 ES ES99915568T patent/ES2316184T3/es not_active Expired - Lifetime
- 1999-03-11 SK SK1369-2000A patent/SK13692000A3/sk unknown
- 1999-03-11 JP JP2000537874A patent/JP4451565B2/ja not_active Expired - Fee Related
- 1999-03-11 DK DK99915568T patent/DK1068202T3/da active
- 1999-03-11 RU RU2000126475/04A patent/RU2217429C2/ru not_active IP Right Cessation
- 1999-03-11 HU HU0101220A patent/HUP0101220A3/hu unknown
- 1999-03-11 ID IDW20002091A patent/ID26125A/id unknown
- 1999-03-11 BR BR9908902-5A patent/BR9908902A/pt not_active IP Right Cessation
- 1999-03-18 ZA ZA9902191A patent/ZA992191B/xx unknown
- 1999-03-19 AR ARP990101208A patent/AR014747A1/es not_active Application Discontinuation
-
2000
- 2000-09-19 NO NO20004668A patent/NO20004668L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP1068202B1 (de) | 2008-12-03 |
| ATE416173T1 (de) | 2008-12-15 |
| WO1999048891A1 (de) | 1999-09-30 |
| JP4451565B2 (ja) | 2010-04-14 |
| HUP0101220A2 (hu) | 2002-05-29 |
| SK13692000A3 (sk) | 2001-02-12 |
| AU3410599A (en) | 1999-10-18 |
| JP2002507613A (ja) | 2002-03-12 |
| BR9908902A (pt) | 2000-11-28 |
| US6548516B1 (en) | 2003-04-15 |
| EP1068202A1 (de) | 2001-01-17 |
| NO20004668D0 (no) | 2000-09-19 |
| CA2324339C (en) | 2010-01-12 |
| AU747900B2 (en) | 2002-05-30 |
| HUP0101220A3 (en) | 2003-08-28 |
| PL342732A1 (en) | 2001-07-02 |
| NO20004668L (no) | 2000-09-19 |
| RU2217429C2 (ru) | 2003-11-27 |
| DE59914921D1 (de) | 2009-01-15 |
| CA2324339A1 (en) | 1999-09-30 |
| PT1068202E (pt) | 2009-03-06 |
| ZA992191B (en) | 1999-09-29 |
| KR20010042047A (ko) | 2001-05-25 |
| DE19812331A1 (de) | 1999-09-23 |
| ID26125A (id) | 2000-11-23 |
| CN1293673A (zh) | 2001-05-02 |
| AR014747A1 (es) | 2001-03-28 |
| DK1068202T3 (da) | 2009-03-16 |
| CN1123571C (zh) | 2003-10-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2316184T3 (es) | 1-(3-heteroarilpropil- o -prop-2-enil)-4-bencilpiperidinas como antagonistas del receptor nmda. | |
| ES2315483T3 (es) | Amidas ciclicas. | |
| ES2272331T3 (es) | Derivados de pirrol como inhibidores de la fosfodiesterasa vii. | |
| JP2941309B2 (ja) | 化合物 | |
| MX2014014563A (es) | Formas solidas de un compuesto antiviral. | |
| CN110343090B (zh) | 喹唑啉衍生物盐型晶型及制备方法和应用 | |
| ES2200968T3 (es) | Compuestos de imidazol como inhibidores de fosfodiesterasa vii. | |
| ES2197466T3 (es) | Oxazolidinonas como antagonistas de 5ht2a. | |
| AU2016205187B2 (en) | Concise synthesis of urea derivatives of amphotericin B | |
| JP3057095B2 (ja) | イサチン誘導体、その製造方法及びその使用方法 | |
| ES2243313T3 (es) | Derivados de isoxazol como inhibidores de la fosfodiesterasa vii. | |
| JP2011503145A (ja) | 新規な１，４−ジアザ−ビシクロ［３．２．２］ノニルピリミジン誘導体及びその医学的使用 | |
| ES2319421T3 (es) | Benzofuran oxietilaminas como farmacos antidepresivos y farmacos asioliticos. | |
| CZ2003809A3 (cs) | Derivát arylpiperazinu, způsob jeho přípravy, jeho použití jako psychofarmaka a farmaceutický prostředek, který ho obsahuje | |
| CZ147999A3 (cs) | 6-{3-[4-(4-Fluorbenzyl)piperidin-1-yl]propionyl}-3H-benzoxazol-2-on, způsob jeho přípravy a farmaceutický prostředek, který ho obsahuje | |
| ES2380123T3 (es) | Derivados de oxafenantreno | |
| CA3238090A1 (en) | Htt modulators for treating huntington's disease | |
| ES2304599T3 (es) | Derivados de bencofurano y su empleo como antidepresivos y ansioliticos. | |
| ES2280824T3 (es) | Benzodioxepinas substituidas. | |
| MXPA00009090A (en) | 1-(3-heteroarylpropyl- or -prop-2-enyl)-4-benzylpiperidines used as nmda receptor antagonists | |
| US10793558B2 (en) | Quinoline oxadiazoles as cytoprotective agents | |
| RU2322438C2 (ru) | Азаспиросоединения для лечения болей | |
| MXPA99003834A (en) | Benzoxazole derivative with an affinity to binding sites of amino acid receptors | |
| ME00521B (me) | Derivati imidazola sa afinitetom prema aktivnosti alfa 2 receptora | |
| WO2024158862A1 (en) | Thiourea antioxcompounds with neuroprotective activity |