JPH078869B2 - イミダゾジアゼピン誘導体類 - Google Patents
イミダゾジアゼピン誘導体類Info
- Publication number
- JPH078869B2 JPH078869B2 JP4179406A JP17940692A JPH078869B2 JP H078869 B2 JPH078869 B2 JP H078869B2 JP 4179406 A JP4179406 A JP 4179406A JP 17940692 A JP17940692 A JP 17940692A JP H078869 B2 JPH078869 B2 JP H078869B2
- Authority
- JP
- Japan
- Prior art keywords
- benzodiazepine
- imidazo
- triazolo
- fluoro
- formula
- 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
- BMGXAZCDDYTVFV-UHFFFAOYSA-N imidazo[4,5-c]diazepine Chemical class C1=CN=NC2=NC=NC2=C1 BMGXAZCDDYTVFV-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 107
- 239000000126 substance Substances 0.000 claims description 64
- -1 heteroaroyloxy Chemical group 0.000 claims description 59
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical class N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 claims description 54
- 125000000217 alkyl group Chemical group 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 36
- 229910052757 nitrogen Chemical group 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 23
- 125000000623 heterocyclic group Chemical group 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 150000003254 radicals Chemical class 0.000 claims description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 14
- 150000001412 amines Chemical class 0.000 claims description 12
- 102000004300 GABA-A Receptors Human genes 0.000 claims description 11
- 108090000839 GABA-A Receptors Proteins 0.000 claims description 11
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 11
- 229940079593 drug Drugs 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 150000001721 carbon Chemical group 0.000 claims description 10
- 150000002431 hydrogen Chemical class 0.000 claims description 10
- 150000007514 bases Chemical class 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 9
- 208000019901 Anxiety disease Diseases 0.000 claims description 8
- 206010010904 Convulsion Diseases 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000002252 acyl group Chemical group 0.000 claims description 7
- 230000036506 anxiety Effects 0.000 claims description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims description 6
- 206010002091 Anaesthesia Diseases 0.000 claims description 6
- 208000014644 Brain disease Diseases 0.000 claims description 6
- 206010039966 Senile dementia Diseases 0.000 claims description 6
- 238000013019 agitation Methods 0.000 claims description 6
- 230000037005 anaesthesia Effects 0.000 claims description 6
- 125000003435 aroyl group Chemical group 0.000 claims description 6
- 150000002527 isonitriles Chemical class 0.000 claims description 6
- 150000002923 oximes Chemical class 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 201000000980 schizophrenia Diseases 0.000 claims description 6
- 208000019116 sleep disease Diseases 0.000 claims description 6
- 206010001497 Agitation Diseases 0.000 claims description 5
- 230000008485 antagonism Effects 0.000 claims description 5
- 125000004423 acyloxy group Chemical group 0.000 claims description 4
- 125000005128 aryl amino alkyl group Chemical group 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 206010015037 epilepsy Diseases 0.000 claims description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 206010010356 Congenital anomaly Diseases 0.000 claims description 2
- 208000032274 Encephalopathy Diseases 0.000 claims description 2
- 208000028329 epileptic seizure Diseases 0.000 claims description 2
- 210000004185 liver Anatomy 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- KYARBIJYVGJZLB-UHFFFAOYSA-N 7-amino-4-hydroxy-2-naphthalenesulfonic acid Chemical compound OC1=CC(S(O)(=O)=O)=CC2=CC(N)=CC=C21 KYARBIJYVGJZLB-UHFFFAOYSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 220
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 214
- 238000002844 melting Methods 0.000 description 205
- 230000008018 melting Effects 0.000 description 204
- 239000000203 mixture Substances 0.000 description 198
- 239000000243 solution Substances 0.000 description 182
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 164
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 123
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 120
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 113
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 100
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 75
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 75
- 239000011541 reaction mixture Substances 0.000 description 69
- 229920006395 saturated elastomer Polymers 0.000 description 63
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 54
- 239000013078 crystal Substances 0.000 description 54
- 235000017557 sodium bicarbonate Nutrition 0.000 description 54
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 54
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
- 238000006243 chemical reaction Methods 0.000 description 51
- 238000010992 reflux Methods 0.000 description 48
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 47
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 41
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 41
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 37
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 36
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 35
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 34
- 238000012360 testing method Methods 0.000 description 34
- 238000003756 stirring Methods 0.000 description 32
- 239000000725 suspension Substances 0.000 description 31
- 239000000741 silica gel Substances 0.000 description 29
- 229910002027 silica gel Inorganic materials 0.000 description 29
- 239000012074 organic phase Substances 0.000 description 28
- GYVGXEWAOAAJEU-UHFFFAOYSA-N n,n,4-trimethylaniline Chemical compound CN(C)C1=CC=C(C)C=C1 GYVGXEWAOAAJEU-UHFFFAOYSA-N 0.000 description 27
- 239000008346 aqueous phase Substances 0.000 description 26
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 26
- BSGOHMQXEGBBHL-UHFFFAOYSA-N 3h-[1,2,4]triazolo[1,5-d][1,4]benzodiazepine Chemical compound C1=CN2NC=NC2=C2C=CC=CC2=N1 BSGOHMQXEGBBHL-UHFFFAOYSA-N 0.000 description 25
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 25
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 25
- 238000000354 decomposition reaction Methods 0.000 description 25
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- 239000000284 extract Substances 0.000 description 23
- 239000000706 filtrate Substances 0.000 description 23
- 239000011780 sodium chloride Substances 0.000 description 23
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 22
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 21
- 239000000047 product Substances 0.000 description 20
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 20
- 238000010828 elution Methods 0.000 description 19
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 18
- XQJLNZCMZBXUPJ-UHFFFAOYSA-N N1=CNN2C=CN=C3C(=C21)C=C(C=C3)C(=O)O Chemical compound N1=CNN2C=CN=C3C(=C21)C=C(C=C3)C(=O)O XQJLNZCMZBXUPJ-UHFFFAOYSA-N 0.000 description 18
- 238000001953 recrystallisation Methods 0.000 description 17
- 239000002585 base Substances 0.000 description 16
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 16
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
- 239000002026 chloroform extract Substances 0.000 description 14
- 239000002904 solvent Substances 0.000 description 13
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 11
- 239000012442 inert solvent Substances 0.000 description 11
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- RVHBVNJPRSUQAF-UHFFFAOYSA-N N1=CNN2C=CN=C3C(=C21)C=C(C=C3)C(N)=NO Chemical compound N1=CNN2C=CN=C3C(=C21)C=C(C=C3)C(N)=NO RVHBVNJPRSUQAF-UHFFFAOYSA-N 0.000 description 10
- 235000011114 ammonium hydroxide Nutrition 0.000 description 10
- OMCUPXRCMTUDHI-UHFFFAOYSA-N n'-hydroxycyclopropanecarboximidamide Chemical compound ON=C(N)C1CC1 OMCUPXRCMTUDHI-UHFFFAOYSA-N 0.000 description 10
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 10
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 9
- 239000013543 active substance Substances 0.000 description 9
- FPULFENIJDPZBX-UHFFFAOYSA-N ethyl 2-isocyanoacetate Chemical compound CCOC(=O)C[N+]#[C-] FPULFENIJDPZBX-UHFFFAOYSA-N 0.000 description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 9
- 229910000104 sodium hydride Inorganic materials 0.000 description 9
- 239000012312 sodium hydride Substances 0.000 description 9
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 8
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 8
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- 229910021529 ammonia Inorganic materials 0.000 description 8
- 238000001035 drying Methods 0.000 description 8
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 8
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 8
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 8
- 239000011591 potassium Substances 0.000 description 8
- 229910052700 potassium Inorganic materials 0.000 description 8
- 239000000829 suppository Substances 0.000 description 8
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 7
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 7
- 150000001735 carboxylic acids Chemical class 0.000 description 7
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 6
- OLVGHJPGWVFCIL-UHFFFAOYSA-N N1=CNN2C=CN=C3C(=C21)C=C(C=C3)C#N Chemical compound N1=CNN2C=CN=C3C(=C21)C=C(C=C3)C#N OLVGHJPGWVFCIL-UHFFFAOYSA-N 0.000 description 6
- 239000000969 carrier Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 6
- 239000002480 mineral oil Substances 0.000 description 6
- 235000010446 mineral oil Nutrition 0.000 description 6
- ZNKRVPGGUVZLTG-UHFFFAOYSA-N 5-(chloromethyl)-[1,2,4]triazolo[4,3-c]quinazoline Chemical compound C1=CC=C2C3=NN=CN3C(CCl)=NC2=C1 ZNKRVPGGUVZLTG-UHFFFAOYSA-N 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- SIGXBBGZEQHNBC-UHFFFAOYSA-N N1=CNN2C=CN=C3C(=C21)C=C(C=C3)C(=O)N Chemical compound N1=CNN2C=CN=C3C(=C21)C=C(C=C3)C(=O)N SIGXBBGZEQHNBC-UHFFFAOYSA-N 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 239000000470 constituent Substances 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 5
- 239000007903 gelatin capsule Substances 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 5
- 239000008188 pellet Substances 0.000 description 5
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 5
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 5
- QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- 229920002261 Corn starch Polymers 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- YZGQDNOIGFBYKF-UHFFFAOYSA-N Ethoxyacetic acid Chemical compound CCOCC(O)=O YZGQDNOIGFBYKF-UHFFFAOYSA-N 0.000 description 4
- 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 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- BHIIGRBMZRSDRI-UHFFFAOYSA-N [chloro(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(Cl)OC1=CC=CC=C1 BHIIGRBMZRSDRI-UHFFFAOYSA-N 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 239000008120 corn starch Substances 0.000 description 4
- 239000002027 dichloromethane extract Substances 0.000 description 4
- LJGKKJWPDGDDEH-UHFFFAOYSA-N ethyl 1H-1,2-benzodiazepine-3-carboxylate Chemical compound C(C)OC(=O)C1=NNC2=C(C=C1)C=CC=C2 LJGKKJWPDGDDEH-UHFFFAOYSA-N 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000012065 filter cake Substances 0.000 description 4
- 230000002440 hepatic effect Effects 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 125000004430 oxygen atom Chemical group O* 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 4
- 229920005862 polyol Polymers 0.000 description 4
- 150000003077 polyols Chemical class 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- LMUVYJCAFWGNSY-VIFPVBQESA-N (3s)-5-(2-chlorophenyl)-3-methyl-7-nitro-1,3-dihydro-1,4-benzodiazepin-2-one Chemical compound N([C@H](C(NC1=CC=C(C=C11)[N+]([O-])=O)=O)C)=C1C1=CC=CC=C1Cl LMUVYJCAFWGNSY-VIFPVBQESA-N 0.000 description 3
- KHTQWEDOAADBCL-UHFFFAOYSA-N 15-fluoro-2,4,8,9-tetrazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(13),3,5,9,11,14,16-heptaene-5-carboxylic acid Chemical compound C1N2N=CC=C2C2=CC(F)=CC=C2N2C=NC(C(=O)O)=C21 KHTQWEDOAADBCL-UHFFFAOYSA-N 0.000 description 3
- HZABUXCSZMLBHU-UHFFFAOYSA-N 1H-1,4-benzodiazepine-3-carboxylic acid Chemical compound C1=NC(C(=O)O)=CNC2=CC=CC=C21 HZABUXCSZMLBHU-UHFFFAOYSA-N 0.000 description 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 3
- QOFBIYUXTUCZMO-UHFFFAOYSA-N 3-bromo-2-(1h-imidazol-2-yl)aniline Chemical compound NC1=CC=CC(Br)=C1C1=NC=CN1 QOFBIYUXTUCZMO-UHFFFAOYSA-N 0.000 description 3
- HTNUUDFQRYBJPH-UHFFFAOYSA-N 3-methoxypropanehydrazide Chemical compound COCCC(=O)NN HTNUUDFQRYBJPH-UHFFFAOYSA-N 0.000 description 3
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 3
- LRKWILPMCIMYSF-UHFFFAOYSA-N 3h-triazolo[1,5-d][1,4]benzodiazepine Chemical compound C1=CN2NN=CC2=C2C=CC=CC2=N1 LRKWILPMCIMYSF-UHFFFAOYSA-N 0.000 description 3
- YMKVQGFJEMOPCH-UHFFFAOYSA-N 4,5-dichloro-2-(chloromethyl)quinazoline Chemical compound ClC1=CC=CC2=NC(CCl)=NC(Cl)=C21 YMKVQGFJEMOPCH-UHFFFAOYSA-N 0.000 description 3
- PMBABTLGYWFWBZ-UHFFFAOYSA-N 4-chloro-2-(chloromethyl)quinazoline Chemical compound C1=CC=CC2=NC(CCl)=NC(Cl)=C21 PMBABTLGYWFWBZ-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- CSIFOXDCAVOCTR-UHFFFAOYSA-N C1=CNN2C=CN=C3C(=C21)C=CC=C3 Chemical compound C1=CNN2C=CN=C3C(=C21)C=CC=C3 CSIFOXDCAVOCTR-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 3
- ANMRRIHZGBFEQS-UHFFFAOYSA-N N1=CNN2C=CN=CC=C21 Chemical compound N1=CNN2C=CN=CC=C21 ANMRRIHZGBFEQS-UHFFFAOYSA-N 0.000 description 3
- UMOMOMGVVBVJQP-UHFFFAOYSA-N [2-(chloromethyl)quinazolin-4-yl]hydrazine Chemical compound C1=CC=C2C(NN)=NC(CCl)=NC2=C1 UMOMOMGVVBVJQP-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 238000001994 activation Methods 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 150000003857 carboxamides Chemical class 0.000 description 3
- SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
- 230000006806 disease prevention Effects 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 229960004381 flumazenil Drugs 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229950002184 meclonazepam Drugs 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- JIRJHEXNDQBKRZ-UHFFFAOYSA-N phosgene oxime Chemical compound ON=C(Cl)Cl JIRJHEXNDQBKRZ-UHFFFAOYSA-N 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
- 235000019260 propionic acid Nutrition 0.000 description 3
- 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 3
- 239000002002 slurry Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 239000001993 wax Substances 0.000 description 3
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- PWDBPRUUCLFXQN-UHFFFAOYSA-N 10-bromo-2,3-dihydroimidazo[1,2-c]quinazoline Chemical compound N1=CN2CCN=C2C2=C1C=CC=C2Br PWDBPRUUCLFXQN-UHFFFAOYSA-N 0.000 description 2
- RPEKYNNITUPYLJ-UHFFFAOYSA-N 10-chloro-5-(chloromethyl)-[1,2,4]triazolo[4,3-c]quinazoline Chemical compound C1=CC(Cl)=C2C3=NN=CN3C(CCl)=NC2=C1 RPEKYNNITUPYLJ-UHFFFAOYSA-N 0.000 description 2
- PUOHCCBMZXVOKN-UHFFFAOYSA-N 15-fluoro-2,4,8,9-tetrazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(13),3,5,9,11,14,16-heptaene-5-carbonitrile Chemical compound C1C2=C(C#N)N=CN2C2=CC=C(F)C=C2C2=CC=NN21 PUOHCCBMZXVOKN-UHFFFAOYSA-N 0.000 description 2
- DAZIFHWGSWYNLG-UHFFFAOYSA-N 15-fluoro-N'-hydroxy-2,4,8,9-tetrazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(13),3,5,9,11,14,16-heptaene-5-carboximidamide Chemical compound C1N2N=CC=C2C2=CC(F)=CC=C2N2C=NC(C(=NO)N)=C21 DAZIFHWGSWYNLG-UHFFFAOYSA-N 0.000 description 2
- DBMMUCPRSCZDSF-UHFFFAOYSA-N 2,5-dimethylquinazolin-4-amine Chemical compound CC1=NC(N)=C2C(C)=CC=CC2=N1 DBMMUCPRSCZDSF-UHFFFAOYSA-N 0.000 description 2
- GWTYYHXEYIUTGY-UHFFFAOYSA-N 2-(1h-imidazol-2-yl)-3-methylaniline Chemical compound CC1=CC=CC(N)=C1C1=NC=CN1 GWTYYHXEYIUTGY-UHFFFAOYSA-N 0.000 description 2
- DMOQHEWCUXULLO-UHFFFAOYSA-N 2-(2,6-dimethylanilino)acetic acid Chemical compound CC1=CC=CC(C)=C1NCC(O)=O DMOQHEWCUXULLO-UHFFFAOYSA-N 0.000 description 2
- QYRDWARBHMCOAG-UHFFFAOYSA-N 2-amino-5-chlorobenzonitrile Chemical compound NC1=CC=C(Cl)C=C1C#N QYRDWARBHMCOAG-UHFFFAOYSA-N 0.000 description 2
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 2
- KOHBEDRJXKOYHL-UHFFFAOYSA-N 2-methoxy-n-methylethanamine Chemical compound CNCCOC KOHBEDRJXKOYHL-UHFFFAOYSA-N 0.000 description 2
- IHCCAYCGZOLTEU-UHFFFAOYSA-N 3-furoic acid Chemical compound OC(=O)C=1C=COC=1 IHCCAYCGZOLTEU-UHFFFAOYSA-N 0.000 description 2
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
- BLJFNIZOARXJLZ-UHFFFAOYSA-N 4,6-dichloro-2-(chloromethyl)quinazoline Chemical compound C1=C(Cl)C=CC2=NC(CCl)=NC(Cl)=C21 BLJFNIZOARXJLZ-UHFFFAOYSA-N 0.000 description 2
- YDKQDRVHPQVDJR-UHFFFAOYSA-N 4-chloro-2,5-dimethylquinazoline Chemical compound CC1=NC(Cl)=C2C(C)=CC=CC2=N1 YDKQDRVHPQVDJR-UHFFFAOYSA-N 0.000 description 2
- ANLNVUDMKOGLGM-UHFFFAOYSA-N 4-chloro-2-(chloromethyl)-6-fluoroquinazoline Chemical compound N1=C(CCl)N=C(Cl)C2=CC(F)=CC=C21 ANLNVUDMKOGLGM-UHFFFAOYSA-N 0.000 description 2
- CTGWKVLYJSVSDC-UHFFFAOYSA-N 4-chloro-2-(chloromethyl)-6-methylquinazoline Chemical compound N1=C(CCl)N=C(Cl)C2=CC(C)=CC=C21 CTGWKVLYJSVSDC-UHFFFAOYSA-N 0.000 description 2
- SEMYRGBWYGGIPZ-UHFFFAOYSA-N 4-chloro-2-(chloromethyl)thieno[2,3-d]pyrimidine Chemical compound ClCC1=NC(Cl)=C2C=CSC2=N1 SEMYRGBWYGGIPZ-UHFFFAOYSA-N 0.000 description 2
- NRPFNQUDKRYCNX-UHFFFAOYSA-N 4-methoxyphenylacetic acid Chemical compound COC1=CC=C(CC(O)=O)C=C1 NRPFNQUDKRYCNX-UHFFFAOYSA-N 0.000 description 2
- OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 2
- QTHIPJPCIUZJDN-UHFFFAOYSA-N 5,10-dimethylimidazo[1,2-c]quinazoline Chemical compound N1=C(C)N2C=CN=C2C2=C1C=CC=C2C QTHIPJPCIUZJDN-UHFFFAOYSA-N 0.000 description 2
- GWAURELTCSFLPZ-UHFFFAOYSA-N 5-(chloromethyl)-9-fluoro-[1,2,4]triazolo[4,3-c]quinazoline Chemical compound N1=C(CCl)N2C=NN=C2C2=CC(F)=CC=C21 GWAURELTCSFLPZ-UHFFFAOYSA-N 0.000 description 2
- BNHLKLMFUAAWOB-UHFFFAOYSA-N 5-(chloromethyl)pyrazolo[1,5-c]quinazoline Chemical compound C1=CC=C2C3=CC=NN3C(CCl)=NC2=C1 BNHLKLMFUAAWOB-UHFFFAOYSA-N 0.000 description 2
- RYYTVTDOTKUTGI-UHFFFAOYSA-N 5-(chloromethyl)thieno[2,3-e][1,2,4]triazolo[4,3-c]-pyrimidine Chemical compound C12=NN=CN2C(CCl)=NC2=C1SC=C2 RYYTVTDOTKUTGI-UHFFFAOYSA-N 0.000 description 2
- YDFBMOHNHXKEGO-UHFFFAOYSA-N 6-chloro-5h-[1,2,4]triazolo[1,5-d][1,4]benzodiazepine Chemical compound C1C(Cl)=NC2=CC=CC=C2C2=NC=NN21 YDFBMOHNHXKEGO-UHFFFAOYSA-N 0.000 description 2
- WMPSQXLZNFEYEP-UHFFFAOYSA-N 6-fluoro-1h-quinazoline-4-thione Chemical compound N1=CNC(=S)C2=CC(F)=CC=C21 WMPSQXLZNFEYEP-UHFFFAOYSA-N 0.000 description 2
- KTDSCWHNCWKYKQ-UHFFFAOYSA-N 7-[(2,4-dimethoxyphenyl)methyl]thieno[3,2-e][1,4]diazepine-5,8-dione Chemical compound COC1=CC(OC)=CC=C1CC1C(=O)C(N=CC=NC2=O)=C2S1 KTDSCWHNCWKYKQ-UHFFFAOYSA-N 0.000 description 2
- COIVTBPVOIEHOZ-UHFFFAOYSA-N 7H-thieno[3,2-e][1,4]diazepine-7-carboxylic acid Chemical compound N1=CC=NC=C2C1=CC(S2)C(=O)O COIVTBPVOIEHOZ-UHFFFAOYSA-N 0.000 description 2
- WLZWOOPMKHGYMG-UHFFFAOYSA-N 8-chloro-13-thia-3,5,6,9-tetrazatricyclo[8.3.0.02,6]trideca-1(10),2,4,8,11-pentaene Chemical compound C12=NC=NN2CC(Cl)=NC2=C1SC=C2 WLZWOOPMKHGYMG-UHFFFAOYSA-N 0.000 description 2
- OWBRUXHCTYTWSG-UHFFFAOYSA-N 9-fluoro-[1,2,4]triazolo[1,5-c]quinazoline Chemical compound N1=CN2N=CN=C2C2=CC(F)=CC=C21 OWBRUXHCTYTWSG-UHFFFAOYSA-N 0.000 description 2
- 208000024255 Audiogenic seizures Diseases 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- SRCCPPZIBRRAAD-UHFFFAOYSA-N C(C)OC(=O)C=1C=CC=2C(=C3N(C=CN=2)NC=N3)C=1 Chemical compound C(C)OC(=O)C=1C=CC=2C(=C3N(C=CN=2)NC=N3)C=1 SRCCPPZIBRRAAD-UHFFFAOYSA-N 0.000 description 2
- UDBBADDZBSXSLT-UHFFFAOYSA-N C1=CNN2C=CN=C3C(=C21)C=CC=C3C(=O)O Chemical compound C1=CNN2C=CN=C3C(=C21)C=CC=C3C(=O)O UDBBADDZBSXSLT-UHFFFAOYSA-N 0.000 description 2
- AVRKSHFWKBNKBU-UHFFFAOYSA-N CCOC(=O)C1=CNC=CC=N1 Chemical compound CCOC(=O)C1=CNC=CC=N1 AVRKSHFWKBNKBU-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 239000012448 Lithium borohydride Substances 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- HDWMPJAIVPSONF-UHFFFAOYSA-N N'-hydroxy-2,4,8,9-tetrazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(17),3,5,9,11,13,15-heptaene-5-carboximidamide Chemical compound C1N2N=CC=C2C2=CC=CC=C2N2C=NC(C(=NO)N)=C21 HDWMPJAIVPSONF-UHFFFAOYSA-N 0.000 description 2
- FFDGPVCHZBVARC-UHFFFAOYSA-N N,N-dimethylglycine Chemical compound CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 description 2
- OKJIRPAQVSHGFK-UHFFFAOYSA-N N-acetylglycine Chemical compound CC(=O)NCC(O)=O OKJIRPAQVSHGFK-UHFFFAOYSA-N 0.000 description 2
- OPKOKAMJFNKNAS-UHFFFAOYSA-N N-methylethanolamine Chemical compound CNCCO OPKOKAMJFNKNAS-UHFFFAOYSA-N 0.000 description 2
- LQYPDTIAAQKWFJ-UHFFFAOYSA-N NC(C(C1=NC=C2)=CC=CC1=C1N2NC=C1)=O Chemical compound NC(C(C1=NC=C2)=CC=CC1=C1N2NC=C1)=O LQYPDTIAAQKWFJ-UHFFFAOYSA-N 0.000 description 2
- OALBZMHHQBKPHQ-UHFFFAOYSA-N OC(C1=CC2=C3N=CNN3C=CN=C2S1)=O Chemical compound OC(C1=CC2=C3N=CNN3C=CN=C2S1)=O OALBZMHHQBKPHQ-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 101100386054 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) CYS3 gene Proteins 0.000 description 2
- 206010043994 Tonic convulsion Diseases 0.000 description 2
- ZDEZTQCRUYAIDI-UHFFFAOYSA-N [2-(chloromethyl)-6-methylquinazolin-4-yl]hydrazine Chemical compound N1=C(CCl)N=C(NN)C2=CC(C)=CC=C21 ZDEZTQCRUYAIDI-UHFFFAOYSA-N 0.000 description 2
- HIDXBHFOQRSGOE-UHFFFAOYSA-N [2-(chloromethyl)thieno[3,2-d]pyrimidin-4-yl]hydrazine Chemical compound NNC1=NC(CCl)=NC2=C1SC=C2 HIDXBHFOQRSGOE-UHFFFAOYSA-N 0.000 description 2
- KGECIFTURWRQOZ-UHFFFAOYSA-N [5-chloro-2-(chloromethyl)quinazolin-4-yl]hydrazine Chemical compound C1=CC(Cl)=C2C(NN)=NC(CCl)=NC2=C1 KGECIFTURWRQOZ-UHFFFAOYSA-N 0.000 description 2
- QFTZOMGQMRLAFJ-UHFFFAOYSA-N [6-chloro-2-(chloromethyl)quinazolin-4-yl]hydrazine Chemical compound C1=C(Cl)C=C2C(NN)=NC(CCl)=NC2=C1 QFTZOMGQMRLAFJ-UHFFFAOYSA-N 0.000 description 2
- ATYJDIJXODZHDG-UHFFFAOYSA-N [K].CCOC(=O)C[N+]#[C-] Chemical compound [K].CCOC(=O)C[N+]#[C-] ATYJDIJXODZHDG-UHFFFAOYSA-N 0.000 description 2
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 2
- 150000008046 alkali metal hydrides Chemical class 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000002249 anxiolytic agent Substances 0.000 description 2
- 230000000949 anxiolytic effect Effects 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 229940049706 benzodiazepine Drugs 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 150000001733 carboxylic acid esters Chemical class 0.000 description 2
- AKRXCNKGZVHBKU-UHFFFAOYSA-N chembl576667 Chemical compound C1C2=CN=CN2C2=CC=CC=C2C2=NC=NN12 AKRXCNKGZVHBKU-UHFFFAOYSA-N 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 150000002168 ethanoic acid esters Chemical class 0.000 description 2
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 2
- MOYMDXWTHALRHV-UHFFFAOYSA-N ethyl 1H-1,4-benzodiazepine-3-carboxylate Chemical compound C1=NC(C(=O)OCC)=CNC2=CC=CC=C21 MOYMDXWTHALRHV-UHFFFAOYSA-N 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- OFBIFZUFASYYRE-UHFFFAOYSA-N flumazenil Chemical compound C1N(C)C(=O)C2=CC(F)=CC=C2N2C=NC(C(=O)OCC)=C21 OFBIFZUFASYYRE-UHFFFAOYSA-N 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 125000001072 heteroaryl group Chemical group 0.000 description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 2
- 150000007928 imidazolide derivatives Chemical class 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 description 2
- RMNGWHROFLDKAF-UHFFFAOYSA-N n-(2,2-dimethoxyethyl)-2,5-dimethylquinazolin-4-amine Chemical compound C1=CC(C)=C2C(NCC(OC)OC)=NC(C)=NC2=C1 RMNGWHROFLDKAF-UHFFFAOYSA-N 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 125000004043 oxo group Chemical group O=* 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 description 2
- 229960003424 phenylacetic acid Drugs 0.000 description 2
- 239000003279 phenylacetic acid Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 101150035983 str1 gene Proteins 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- IQSYKHVFMYGJER-UHFFFAOYSA-N tert-butyl 2-isocyanoacetate Chemical compound CC(C)(C)OC(=O)C[N+]#[C-] IQSYKHVFMYGJER-UHFFFAOYSA-N 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 description 1
- JBCFJMYPJJWIRG-UHFFFAOYSA-N 1,3-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=COC=N1 JBCFJMYPJJWIRG-UHFFFAOYSA-N 0.000 description 1
- WHOSTRMGZDFYCI-UHFFFAOYSA-N 1-(2,2-dimethyl-1,3-dioxolan-4-yl)-n-methylmethanamine Chemical compound CNCC1COC(C)(C)O1 WHOSTRMGZDFYCI-UHFFFAOYSA-N 0.000 description 1
- VNZLQLYBRIOLFZ-UHFFFAOYSA-N 1-(2-methoxyphenyl)piperazine Chemical compound COC1=CC=CC=C1N1CCNCC1 VNZLQLYBRIOLFZ-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- IWWCCNVRNHTGLV-UHFFFAOYSA-N 1-phenylcyclopropane-1-carboxylic acid Chemical compound C=1C=CC=CC=1C1(C(=O)O)CC1 IWWCCNVRNHTGLV-UHFFFAOYSA-N 0.000 description 1
- GWCSATTUAOHJDK-UHFFFAOYSA-N 1-prop-2-ynylpiperazine Chemical compound C#CCN1CCNCC1 GWCSATTUAOHJDK-UHFFFAOYSA-N 0.000 description 1
- QNPSFHTXYVRPRK-UHFFFAOYSA-N 10-bromoimidazo[1,2-c]quinazoline Chemical compound N1=CN2C=CN=C2C2=C1C=CC=C2Br QNPSFHTXYVRPRK-UHFFFAOYSA-N 0.000 description 1
- PIFFTRGZZVTNGC-UHFFFAOYSA-N 15-fluoro-2,4,8,9-tetrazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(13),3,5,9,11,14,16-heptaene-5-carboxamide Chemical compound C1N2N=CC=C2C2=CC(F)=CC=C2N2C=NC(C(=O)N)=C21 PIFFTRGZZVTNGC-UHFFFAOYSA-N 0.000 description 1
- JKBGUEZBPXVKTB-UHFFFAOYSA-N 16-fluoro-2,4,8,9,11-pentazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(13),3,5,9,11,14,16-heptaene Chemical compound FC1=CC2=C(C=3N(CC=4N2C=NC=4)N=CN=3)C=C1 JKBGUEZBPXVKTB-UHFFFAOYSA-N 0.000 description 1
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
- FZJLREPRIOUQQO-UHFFFAOYSA-N 1h-1,4-benzodiazepine;hydrochloride Chemical compound Cl.N1C=CN=CC2=CC=CC=C12 FZJLREPRIOUQQO-UHFFFAOYSA-N 0.000 description 1
- JYOCYCDSXDFBGV-UHFFFAOYSA-N 1h-1,4-diazepine-7-carbonitrile Chemical compound N#CC1=CC=NC=CN1 JYOCYCDSXDFBGV-UHFFFAOYSA-N 0.000 description 1
- XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical compound O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 description 1
- QHTTXSWWWSYDRY-UHFFFAOYSA-N 1h-thieno[3,2-d][1,3]oxazine-2,4-dione Chemical compound O=C1OC(=O)NC2=C1SC=C2 QHTTXSWWWSYDRY-UHFFFAOYSA-N 0.000 description 1
- DTIQMWFEKCDHQR-UHFFFAOYSA-N 1h-triazolo[1,5-d][1,4]diazepine Chemical compound C1=NC=CN2NN=CC2=C1 DTIQMWFEKCDHQR-UHFFFAOYSA-N 0.000 description 1
- VNKWLNRKUBZUJX-UHFFFAOYSA-N 2,4,8,9-tetrazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(17),3,5,9,11,13,15-heptaene-5-carbonitrile Chemical compound C1N2N=CC=C2C2=CC=CC=C2N2C=NC(C#N)=C21 VNKWLNRKUBZUJX-UHFFFAOYSA-N 0.000 description 1
- PQCFNULCLDXSEN-UHFFFAOYSA-N 2,4,8,9-tetrazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(17),3,5,9,11,13,15-heptaene-5-carboxamide Chemical compound C1N2N=CC=C2C2=CC=CC=C2N2C=NC(C(=O)N)=C21 PQCFNULCLDXSEN-UHFFFAOYSA-N 0.000 description 1
- MAIUQLMRBVVPPM-UHFFFAOYSA-N 2,4,8,9-tetrazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(17),3,5,9,11,13,15-heptaene-5-carboxylic acid Chemical compound C1N2N=CC=C2C2=CC=CC=C2N2C=NC(C(=O)O)=C21 MAIUQLMRBVVPPM-UHFFFAOYSA-N 0.000 description 1
- ODVLMCWNGKLROU-UHFFFAOYSA-N 2-(1,3-benzodioxol-5-yl)acetic acid Chemical compound OC(=O)CC1=CC=C2OCOC2=C1 ODVLMCWNGKLROU-UHFFFAOYSA-N 0.000 description 1
- WQINSVOOIJDOLJ-UHFFFAOYSA-N 2-(1,3-dioxoisoindol-2-yl)acetic acid Chemical compound C1=CC=C2C(=O)N(CC(=O)O)C(=O)C2=C1 WQINSVOOIJDOLJ-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- RPTRFSADOICSSK-UHFFFAOYSA-N 2-(2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1F RPTRFSADOICSSK-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- IVEWTCACRDEAOB-UHFFFAOYSA-N 2-(2-methoxyphenyl)acetic acid Chemical compound COC1=CC=CC=C1CC(O)=O IVEWTCACRDEAOB-UHFFFAOYSA-N 0.000 description 1
- RZWGTXHSYZGXKF-UHFFFAOYSA-N 2-(2-methylphenyl)acetic acid Chemical compound CC1=CC=CC=C1CC(O)=O RZWGTXHSYZGXKF-UHFFFAOYSA-N 0.000 description 1
- YEAUYVGUXSZCFI-UHFFFAOYSA-N 2-(3-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(F)=C1 YEAUYVGUXSZCFI-UHFFFAOYSA-N 0.000 description 1
- MGKPFALCNDRSQD-UHFFFAOYSA-N 2-(4-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(F)C=C1 MGKPFALCNDRSQD-UHFFFAOYSA-N 0.000 description 1
- GXXXUZIRGXYDFP-UHFFFAOYSA-N 2-(4-methylphenyl)acetic acid Chemical compound CC1=CC=C(CC(O)=O)C=C1 GXXXUZIRGXYDFP-UHFFFAOYSA-N 0.000 description 1
- DLMFKSKTOVIVGR-UHFFFAOYSA-N 2-(chloromethyl)-n-(2,2-dimethoxyethyl)quinazolin-4-amine Chemical compound C1=CC=C2C(NCC(OC)OC)=NC(CCl)=NC2=C1 DLMFKSKTOVIVGR-UHFFFAOYSA-N 0.000 description 1
- ZTXZPRVWTCOQNC-UHFFFAOYSA-N 2-(chloromethyl)quinazoline Chemical compound C1=CC=CC2=NC(CCl)=NC=C21 ZTXZPRVWTCOQNC-UHFFFAOYSA-N 0.000 description 1
- FHOMLQYOXKEAOD-UHFFFAOYSA-N 2-(chloromethyl)thieno[3,2-d]pyrimidine Chemical compound ClCC1=NC=C2SC=CC2=N1 FHOMLQYOXKEAOD-UHFFFAOYSA-N 0.000 description 1
- LKUZWHWTXFALOC-UHFFFAOYSA-N 2-(methylamino)ethyl carbamate Chemical compound CNCCOC(N)=O LKUZWHWTXFALOC-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- AJVOIZUSHCYQHZ-UHFFFAOYSA-N 2-[(2,4-dimethoxyphenyl)methylazaniumyl]acetate Chemical compound COC1=CC=C(CNCC(O)=O)C(OC)=C1 AJVOIZUSHCYQHZ-UHFFFAOYSA-N 0.000 description 1
- DOCYGBLUJABNHM-UHFFFAOYSA-N 2-[(2,5,6,6-tetramethylcyclohexa-2,4-dien-1-yl)amino]acetonitrile Chemical compound CC1=CC=C(C)C(C)(C)C1NCC#N DOCYGBLUJABNHM-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- BLXXCCIBGGBDHI-UHFFFAOYSA-N 2-[3-(trifluoromethyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(C(F)(F)F)=C1 BLXXCCIBGGBDHI-UHFFFAOYSA-N 0.000 description 1
- ZMTIBXQPXBUWPQ-UHFFFAOYSA-N 2-[4-(trifluoromethoxy)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=C(OC(F)(F)F)C=C1 ZMTIBXQPXBUWPQ-UHFFFAOYSA-N 0.000 description 1
- HNORVZDAANCHAY-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=C(C(F)(F)F)C=C1 HNORVZDAANCHAY-UHFFFAOYSA-N 0.000 description 1
- MYTRAZSITAGUJX-UHFFFAOYSA-N 2-[4-[(4-bromophenyl)methoxy]phenyl]acetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1OCC1=CC=C(Br)C=C1 MYTRAZSITAGUJX-UHFFFAOYSA-N 0.000 description 1
- VPSXHKGJZJCWLV-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-(1-ethylpiperidin-4-yl)oxypyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)OC1CCN(CC1)CC VPSXHKGJZJCWLV-UHFFFAOYSA-N 0.000 description 1
- APLNAFMUEHKRLM-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(3,4,6,7-tetrahydroimidazo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)N=CN2 APLNAFMUEHKRLM-UHFFFAOYSA-N 0.000 description 1
- CBWFTZNMONHKNZ-UHFFFAOYSA-N 2-[methyl(phenylmethoxycarbonyl)amino]acetic acid Chemical compound OC(=O)CN(C)C(=O)OCC1=CC=CC=C1 CBWFTZNMONHKNZ-UHFFFAOYSA-N 0.000 description 1
- MEJVTQKBWPYBFG-UHFFFAOYSA-N 2-amino-6-chlorobenzonitrile Chemical compound NC1=CC=CC(Cl)=C1C#N MEJVTQKBWPYBFG-UHFFFAOYSA-N 0.000 description 1
- PKOMYWHVCYHAHW-UHFFFAOYSA-N 2-amino-6-methylbenzonitrile Chemical compound CC1=CC=CC(N)=C1C#N PKOMYWHVCYHAHW-UHFFFAOYSA-N 0.000 description 1
- LYIIBVSRGJSHAV-UHFFFAOYSA-N 2-aminoacetaldehyde Chemical compound NCC=O LYIIBVSRGJSHAV-UHFFFAOYSA-N 0.000 description 1
- HLCPWBZNUKCSBN-UHFFFAOYSA-N 2-aminobenzonitrile Chemical compound NC1=CC=CC=C1C#N HLCPWBZNUKCSBN-UHFFFAOYSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- XVGHZFWFGXDIOU-UHFFFAOYSA-N 2-aminothiophene-3-carbonitrile Chemical compound NC=1SC=CC=1C#N XVGHZFWFGXDIOU-UHFFFAOYSA-N 0.000 description 1
- IZQAUUVBKYXMET-UHFFFAOYSA-N 2-bromoethanamine Chemical compound NCCBr IZQAUUVBKYXMET-UHFFFAOYSA-N 0.000 description 1
- WMPTYRGXBUYONY-UHFFFAOYSA-N 2-chloroquinazoline Chemical compound C1=CC=CC2=NC(Cl)=NC=C21 WMPTYRGXBUYONY-UHFFFAOYSA-N 0.000 description 1
- KVVDRQDTODKIJD-UHFFFAOYSA-N 2-cyclopropylacetic acid Chemical compound OC(=O)CC1CC1 KVVDRQDTODKIJD-UHFFFAOYSA-N 0.000 description 1
- 125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- BWLBGMIXKSTLSX-UHFFFAOYSA-N 2-hydroxyisobutyric acid Chemical compound CC(C)(O)C(O)=O BWLBGMIXKSTLSX-UHFFFAOYSA-N 0.000 description 1
- 125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 1
- 125000006179 2-methyl benzyl group Chemical group [H]C1=C([H])C(=C(C([H])=C1[H])C([H])([H])*)C([H])([H])[H] 0.000 description 1
- IVJXAWDIBZSHMG-UHFFFAOYSA-N 2-methyl-2-pyridin-3-yloxypropanoic acid Chemical compound OC(=O)C(C)(C)OC1=CC=CN=C1 IVJXAWDIBZSHMG-UHFFFAOYSA-N 0.000 description 1
- XWAVPOFYNPXXEL-UHFFFAOYSA-N 2-phenylmethoxypropanoic acid Chemical compound OC(=O)C(C)OCC1=CC=CC=C1 XWAVPOFYNPXXEL-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- SMJRBWINMFUUDS-UHFFFAOYSA-N 2-thienylacetic acid Chemical compound OC(=O)CC1=CC=CS1 SMJRBWINMFUUDS-UHFFFAOYSA-N 0.000 description 1
- RCNOGGGBSSVMAS-UHFFFAOYSA-N 2-thiophen-3-ylacetic acid Chemical compound OC(=O)CC=1C=CSC=1 RCNOGGGBSSVMAS-UHFFFAOYSA-N 0.000 description 1
- VSFNAZLYGOOSEY-UHFFFAOYSA-N 3-(1H-imidazol-1-yl)propanoic acid Chemical compound OC(=O)CCN1C=CN=C1 VSFNAZLYGOOSEY-UHFFFAOYSA-N 0.000 description 1
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 1
- CSBJIXVKDCZBPF-UHFFFAOYSA-N 3-(5-oxopyrrolidin-2-yl)propanoic acid Chemical compound OC(=O)CCC1CCC(=O)N1 CSBJIXVKDCZBPF-UHFFFAOYSA-N 0.000 description 1
- LEGPZHPSIPPYIO-UHFFFAOYSA-N 3-Methoxyphenylacetic acid Chemical compound COC1=CC=CC(CC(O)=O)=C1 LEGPZHPSIPPYIO-UHFFFAOYSA-N 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-M 3-Methylbutanoic acid Natural products CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 1
- WHBIWWYTGXQXSD-UHFFFAOYSA-N 3-ethyl-1,2-oxazole-5-carboxylic acid Chemical compound CCC=1C=C(C(O)=O)ON=1 WHBIWWYTGXQXSD-UHFFFAOYSA-N 0.000 description 1
- 125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 1
- GJMPSRSMBJLKKB-UHFFFAOYSA-N 3-methylphenylacetic acid Chemical compound CC1=CC=CC(CC(O)=O)=C1 GJMPSRSMBJLKKB-UHFFFAOYSA-N 0.000 description 1
- ZZEWMYILWXCRHZ-UHFFFAOYSA-N 3-phenylbutyric acid Chemical compound OC(=O)CC(C)C1=CC=CC=C1 ZZEWMYILWXCRHZ-UHFFFAOYSA-N 0.000 description 1
- OZGUGVRKYBSDBN-UHFFFAOYSA-N 3-phenylmethoxypropanoic acid Chemical compound OC(=O)CCOCC1=CC=CC=C1 OZGUGVRKYBSDBN-UHFFFAOYSA-N 0.000 description 1
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000006495 3-trifluoromethyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])*)C(F)(F)F 0.000 description 1
- VZJCLNWCJGKJOI-UHFFFAOYSA-N 4-ethoxybutanoic acid Chemical compound CCOCCCC(O)=O VZJCLNWCJGKJOI-UHFFFAOYSA-N 0.000 description 1
- MBVFRSJFKMJRHA-UHFFFAOYSA-N 4-fluoro-1-benzofuran-7-carbaldehyde Chemical compound FC1=CC=C(C=O)C2=C1C=CO2 MBVFRSJFKMJRHA-UHFFFAOYSA-N 0.000 description 1
- MVCZGAMTHVLYJZ-UHFFFAOYSA-N 4-fluoro-2-(1h-1,2,4-triazol-5-yl)aniline Chemical compound NC1=CC=C(F)C=C1C1=NNC=N1 MVCZGAMTHVLYJZ-UHFFFAOYSA-N 0.000 description 1
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 description 1
- KMQLIDDEQAJAGJ-UHFFFAOYSA-N 4-oxo-4-phenylbutyric acid Chemical compound OC(=O)CCC(=O)C1=CC=CC=C1 KMQLIDDEQAJAGJ-UHFFFAOYSA-N 0.000 description 1
- QZLNSNIHXKQIIS-UHFFFAOYSA-N 4-pentoxyaniline Chemical compound CCCCCOC1=CC=C(N)C=C1 QZLNSNIHXKQIIS-UHFFFAOYSA-N 0.000 description 1
- 125000000173 4-trifluoromethoxy benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC(F)(F)F)C([H])([H])* 0.000 description 1
- 125000001318 4-trifluoromethylbenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])*)C(F)(F)F 0.000 description 1
- UMYPCMXFKYIENJ-UHFFFAOYSA-N 5-(chloromethyl)-9-fluoropyrazolo[1,5-c]quinazoline Chemical compound N1=C(CCl)N2N=CC=C2C2=CC(F)=CC=C21 UMYPCMXFKYIENJ-UHFFFAOYSA-N 0.000 description 1
- CGOXJTRFBKABIX-UHFFFAOYSA-N 5-(chloromethyl)-9-methyl-[1,2,4]triazolo[4,3-c]quinazoline Chemical compound N1=C(CCl)N2C=NN=C2C2=CC(C)=CC=C21 CGOXJTRFBKABIX-UHFFFAOYSA-N 0.000 description 1
- QGHJLGZHULRQAJ-UHFFFAOYSA-N 5-bromo-1h-quinazolin-4-one Chemical compound N1=CNC(=O)C2=C1C=CC=C2Br QGHJLGZHULRQAJ-UHFFFAOYSA-N 0.000 description 1
- XCVRQUJTALTMRU-UHFFFAOYSA-N 5-bromo-4-chloroquinazoline Chemical compound C1=CC(Br)=C2C(Cl)=NC=NC2=C1 XCVRQUJTALTMRU-UHFFFAOYSA-N 0.000 description 1
- BGHGVAKKIBOJGS-UHFFFAOYSA-N 5-cyclopropyl-3-(isocyanomethyl)-1,2,4-oxadiazole Chemical compound [C-]#[N+]CC1=NOC(C2CC2)=N1 BGHGVAKKIBOJGS-UHFFFAOYSA-N 0.000 description 1
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
- WQBIFZCGCYZTOE-UHFFFAOYSA-N 5-thia-1,8,10,11,15-pentazatetracyclo[11.3.0.02,6.07,11]hexadeca-2(6),3,7,9,13,15-hexaene-14-carboxylic acid Chemical compound OC(=O)C=1N=CN2C=1CN1N=CN=C1C1=C2C=CS1 WQBIFZCGCYZTOE-UHFFFAOYSA-N 0.000 description 1
- KSERCNWUTVIQJO-UHFFFAOYSA-N 6-chloro-10-fluoro-5h-triazolo[1,5-d][1,4]benzodiazepine Chemical compound N1=C(Cl)CN2N=NC=C2C2=CC(F)=CC=C21 KSERCNWUTVIQJO-UHFFFAOYSA-N 0.000 description 1
- RURSQRZXNZWFML-UHFFFAOYSA-N 6-chloro-10-methyl-5h-[1,2,4]triazolo[1,5-d][1,4]benzodiazepine Chemical compound N1=C(Cl)CN2N=CN=C2C2=CC(C)=CC=C21 RURSQRZXNZWFML-UHFFFAOYSA-N 0.000 description 1
- SLGAPWSWRLDIMS-UHFFFAOYSA-N 6-fluoro-1,3-benzoxazine-2,4-dione Chemical compound O1C(=O)NC(=O)C2=CC(F)=CC=C21 SLGAPWSWRLDIMS-UHFFFAOYSA-N 0.000 description 1
- WCSMZAHKVXOYLH-UHFFFAOYSA-N 6-fluoro-1h-quinazolin-4-one Chemical compound N1C=NC(=O)C2=CC(F)=CC=C21 WCSMZAHKVXOYLH-UHFFFAOYSA-N 0.000 description 1
- BYZXOYSEYWCLOK-UHFFFAOYSA-N 6-fluoro-1h-quinolin-4-one Chemical compound C1=C(F)C=C2C(O)=CC=NC2=C1 BYZXOYSEYWCLOK-UHFFFAOYSA-N 0.000 description 1
- UMILXGOHFPOWKE-UHFFFAOYSA-N 7-(chloromethyl)-10-thia-3,4,6,8-tetrazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7,11-pentaene Chemical compound C12=NN=CN2C(CCl)=NC2=C1C=CS2 UMILXGOHFPOWKE-UHFFFAOYSA-N 0.000 description 1
- WTCJJEJMYYASNT-UHFFFAOYSA-N 7-chloro-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid Chemical compound C12=NC(Cl)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1=CC=C(F)C=C1F WTCJJEJMYYASNT-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- LIUMNBVCHBTLKH-UHFFFAOYSA-N 7h-thieno[3,2-e][1,4]diazepine Chemical compound N1=CC=NC2=CCSC2=C1 LIUMNBVCHBTLKH-UHFFFAOYSA-N 0.000 description 1
- KBIATCKJTLCSNS-UHFFFAOYSA-N 8h-diimidazo[1,5-a:1',2'-d]thieno[2,3-f][1,4]diazepine-7-carboxylic acid Chemical compound OC(=O)C=1N=CN2C=1CN1C=CN=C1C1=C2C=CS1 KBIATCKJTLCSNS-UHFFFAOYSA-N 0.000 description 1
- JOZNXHMSEPHUCI-UHFFFAOYSA-N 9h-1,2-benzodiazepine-8-carboxylic acid Chemical compound C1=CC=NN=C2CC(C(=O)O)=CC=C21 JOZNXHMSEPHUCI-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ITLAKNFGERUNEH-UHFFFAOYSA-N C(C)(C)(C)[K].[N+](#[C-])CC(=O)O Chemical compound C(C)(C)(C)[K].[N+](#[C-])CC(=O)O ITLAKNFGERUNEH-UHFFFAOYSA-N 0.000 description 1
- UKUNBYLPNPJYJC-UHFFFAOYSA-N C1=CNN2C=CN=C3C(=C21)C=CC=C3C#N Chemical compound C1=CNN2C=CN=C3C(=C21)C=CC=C3C#N UKUNBYLPNPJYJC-UHFFFAOYSA-N 0.000 description 1
- ULPGILSJTCMQRE-UHFFFAOYSA-N C1=NNN2C=CN=C3C(=C21)C=C(C=C3)C(=O)N Chemical compound C1=NNN2C=CN=C3C(=C21)C=C(C=C3)C(=O)N ULPGILSJTCMQRE-UHFFFAOYSA-N 0.000 description 1
- PYTQREKNMLMUOR-UHFFFAOYSA-N CC1=CC=CC=2C=3N(CC=4N(C21)C=NC4)C=CN3 Chemical compound CC1=CC=CC=2C=3N(CC=4N(C21)C=NC4)C=CN3 PYTQREKNMLMUOR-UHFFFAOYSA-N 0.000 description 1
- IWCZYBLUYGJDGW-UHFFFAOYSA-N CCOC(=O)C1=NNC=CC=C1 Chemical compound CCOC(=O)C1=NNC=CC=C1 IWCZYBLUYGJDGW-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 239000005973 Carvone Substances 0.000 description 1
- XZXMKWHOTRTUHI-UHFFFAOYSA-N Cl.N1=CNN2C=CN=C3C(=C21)C=CC=C3 Chemical compound Cl.N1=CNN2C=CN=C3C(=C21)C=CC=C3 XZXMKWHOTRTUHI-UHFFFAOYSA-N 0.000 description 1
- NHXRLJVBHLWAKU-UHFFFAOYSA-N ClCC1=NC2=CC=C(C=C2C=N1)C Chemical compound ClCC1=NC2=CC=C(C=C2C=N1)C NHXRLJVBHLWAKU-UHFFFAOYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- HJTAOMUKKDUKQJ-UHFFFAOYSA-N FC1=NC2=CC=CC=C2C(=N1)NN Chemical compound FC1=NC2=CC=CC=C2C(=N1)NN HJTAOMUKKDUKQJ-UHFFFAOYSA-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
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- XTUVJUMINZSXGF-UHFFFAOYSA-N N-methylcyclohexylamine Chemical compound CNC1CCCCC1 XTUVJUMINZSXGF-UHFFFAOYSA-N 0.000 description 1
- PAMIQIKDUOTOBW-UHFFFAOYSA-N N-methylcyclohexylamine Natural products CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 1
- WCYFLKKGNOFYOO-UHFFFAOYSA-N N1=CNN2C=CN=C3C(=C21)C=C(C=C3)C=NO Chemical compound N1=CNN2C=CN=C3C(=C21)C=C(C=C3)C=NO WCYFLKKGNOFYOO-UHFFFAOYSA-N 0.000 description 1
- AKKVSOMZLPPJCS-UHFFFAOYSA-N N1=CNN2C=CN=C3C(=C21)C=C(C=C3)C=O Chemical compound N1=CNN2C=CN=C3C(=C21)C=C(C=C3)C=O AKKVSOMZLPPJCS-UHFFFAOYSA-N 0.000 description 1
- JWKZAXIRWSZRTD-UHFFFAOYSA-N N1=CNN2C=CN=C3C(=C21)C=C(C=C3)CO Chemical compound N1=CNN2C=CN=C3C(=C21)C=C(C=C3)CO JWKZAXIRWSZRTD-UHFFFAOYSA-N 0.000 description 1
- HQELUXZGVPNGCN-UHFFFAOYSA-N N1C=CN=CC=C1C(=O)OCC Chemical compound N1C=CN=CC=C1C(=O)OCC HQELUXZGVPNGCN-UHFFFAOYSA-N 0.000 description 1
- HAWDKDMAJURFGV-UHFFFAOYSA-N N1C=CN=CC=C1C(N)=NO Chemical compound N1C=CN=CC=C1C(N)=NO HAWDKDMAJURFGV-UHFFFAOYSA-N 0.000 description 1
- VXFQMXNYPUNWJM-UHFFFAOYSA-N N1N=CC=2N1C=C(N=CC2)C(N)=NO Chemical compound N1N=CC=2N1C=C(N=CC2)C(N)=NO VXFQMXNYPUNWJM-UHFFFAOYSA-N 0.000 description 1
- NONRGTLWVIAXJM-UHFFFAOYSA-N N=1C=NN2C=CN(C3=C(C21)SC=C3)C#N Chemical compound N=1C=NN2C=CN(C3=C(C21)SC=C3)C#N NONRGTLWVIAXJM-UHFFFAOYSA-N 0.000 description 1
- KBRGERWJWOLZLK-UHFFFAOYSA-N N=1C=NN2C=CN(C3=C(C21)SC=C3)C(=O)O Chemical compound N=1C=NN2C=CN(C3=C(C21)SC=C3)C(=O)O KBRGERWJWOLZLK-UHFFFAOYSA-N 0.000 description 1
- PPBKMMAYSAYRMB-UHFFFAOYSA-N N=1C=NN2C=CN(C=CC21)C(=O)N Chemical compound N=1C=NN2C=CN(C=CC21)C(=O)N PPBKMMAYSAYRMB-UHFFFAOYSA-N 0.000 description 1
- OSFQAQXLEQXHHD-UHFFFAOYSA-N NC(N(C=CN1N=CN=C11)C2=C1SC=C2)=O Chemical compound NC(N(C=CN1N=CN=C11)C2=C1SC=C2)=O OSFQAQXLEQXHHD-UHFFFAOYSA-N 0.000 description 1
- HXIWFMKFZCWXKD-UHFFFAOYSA-N OC(=O)C1=CNC=CC=N1 Chemical compound OC(=O)C1=CNC=CC=N1 HXIWFMKFZCWXKD-UHFFFAOYSA-N 0.000 description 1
- YHNUEWZPQPLIBM-UHFFFAOYSA-N S1C=CC2=C1C=1N(CC=3N2C=NC3)N=CN1 Chemical compound S1C=CC2=C1C=1N(CC=3N2C=NC3)N=CN1 YHNUEWZPQPLIBM-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229910000831 Steel Inorganic materials 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
- 229930006000 Sucrose Natural products 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 238000001793 Wilcoxon signed-rank test Methods 0.000 description 1
- XUFCBCHWTOAVAA-UHFFFAOYSA-N [1,2,4]triazolo[4,3-c]pyrimidine Chemical compound C1=CN=CN2C=NN=C21 XUFCBCHWTOAVAA-UHFFFAOYSA-N 0.000 description 1
- YSCFOWHLQMFKEP-UHFFFAOYSA-L [K+].[N+](#[C-])CC(=O)[O-].[K+].[N+](#[C-])CC(=O)[O-] Chemical compound [K+].[N+](#[C-])CC(=O)[O-].[K+].[N+](#[C-])CC(=O)[O-] YSCFOWHLQMFKEP-UHFFFAOYSA-L 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000005041 acyloxyalkyl group Chemical group 0.000 description 1
- 229960003767 alanine Drugs 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 125000005530 alkylenedioxy group Chemical group 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 230000002921 anti-spasmodic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 125000004659 aryl alkyl thio group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 150000001557 benzodiazepines Chemical class 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N beta-methyl-butyric acid Natural products CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 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
- 230000005587 bubbling Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- PVEOYINWKBTPIZ-UHFFFAOYSA-N but-3-enoic acid Chemical compound OC(=O)CC=C PVEOYINWKBTPIZ-UHFFFAOYSA-N 0.000 description 1
- CFQORFKYBKZNLD-UHFFFAOYSA-N butyl 2-isocyanoacetate Chemical class CCCCOC(=O)C[N+]#[C-] CFQORFKYBKZNLD-UHFFFAOYSA-N 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- QSKWJTXWJJOJFP-UHFFFAOYSA-N chloroform;ethoxyethane Chemical compound ClC(Cl)Cl.CCOCC QSKWJTXWJJOJFP-UHFFFAOYSA-N 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 description 1
- 108700003601 dimethylglycine Proteins 0.000 description 1
- HXBZCHYDLURWIZ-UHFFFAOYSA-N diphenyl hydrogen phosphate;hydrochloride Chemical compound Cl.C=1C=CC=CC=1OP(=O)(O)OC1=CC=CC=C1 HXBZCHYDLURWIZ-UHFFFAOYSA-N 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- CLLYAFZCYGRLGE-UHFFFAOYSA-N dithiadiphosphetane Chemical compound P1PSS1 CLLYAFZCYGRLGE-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- HINMIVNEVWWBAW-UHFFFAOYSA-N ethyl 13-(2,2-dimethoxyethylamino)-5-thia-1,8,12-triazatricyclo[8.3.0.02,6]trideca-2(6),3,7,10,12-pentaene-11-carboxylate Chemical compound COC(CNC1=NC(=C2N1C1=C(C=NC2)SC=C1)C(=O)OCC)OC HINMIVNEVWWBAW-UHFFFAOYSA-N 0.000 description 1
- SRBRWLUDWBSZQE-UHFFFAOYSA-N ethyl 6-(2,2-diethoxyethylamino)-8-fluoro-4h-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate Chemical compound CCOC(OCC)CNC1=NCC2=C(C(=O)OCC)N=CN2C2=CC=C(F)C=C12 SRBRWLUDWBSZQE-UHFFFAOYSA-N 0.000 description 1
- JGRJMGSKDINEDD-UHFFFAOYSA-N ethyl 6-(2,2-dimethoxyethylamino)-4h-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate Chemical compound C1N=C(NCC(OC)OC)C2=CC=CC=C2N2C=NC(C(=O)OCC)=C21 JGRJMGSKDINEDD-UHFFFAOYSA-N 0.000 description 1
- HTMYORIIBDGUIJ-UHFFFAOYSA-N ethyl 6-sulfanylidene-4,5-dihydroimidazo[1,5-a][1,4]benzodiazepine-3-carboxylate Chemical compound C1NC(=S)C2=CC=CC=C2N2C=NC(C(=O)OCC)=C21 HTMYORIIBDGUIJ-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- CUICPJOPYVMUPK-UHFFFAOYSA-N ethyl n-tert-butylcarbamate Chemical compound CCOC(=O)NC(C)(C)C CUICPJOPYVMUPK-UHFFFAOYSA-N 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000005553 heteroaryloxy group Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000002440 hydroxy compounds Chemical class 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229960004903 invert sugar Drugs 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- MDHYFUPTSWXVIA-UHFFFAOYSA-N methyl 2-amino-5-methylbenzoate Chemical compound COC(=O)C1=CC(C)=CC=C1N MDHYFUPTSWXVIA-UHFFFAOYSA-N 0.000 description 1
- NYXHSRNBKJIQQG-UHFFFAOYSA-N methyl n-methylcarbamate Chemical compound CNC(=O)OC NYXHSRNBKJIQQG-UHFFFAOYSA-N 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- ORONPIWHCJVHPQ-UHFFFAOYSA-N n'-hydroxy-3-methoxypropanimidamide Chemical compound COCCC(N)=NO ORONPIWHCJVHPQ-UHFFFAOYSA-N 0.000 description 1
- 229940078490 n,n-dimethylglycine Drugs 0.000 description 1
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 1
- TYRGLVWXHJRKMT-QMMMGPOBSA-N n-benzyloxycarbonyl-l-serine-betalactone Chemical compound OC(=O)[C@H](C)NC(=O)OCC1=CC=CC=C1 TYRGLVWXHJRKMT-QMMMGPOBSA-N 0.000 description 1
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
- WWXPJKGWWPWBTB-UHFFFAOYSA-N n-methyl-2-morpholin-4-ylethanamine Chemical compound CNCCN1CCOCC1 WWXPJKGWWPWBTB-UHFFFAOYSA-N 0.000 description 1
- 230000010807 negative regulation of binding Effects 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 229950009215 phenylbutanoic acid Drugs 0.000 description 1
- 125000005328 phosphinyl group Chemical group [PH2](=O)* 0.000 description 1
- 125000005543 phthalimide group Chemical class 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- CHWRSCGUEQEHOH-UHFFFAOYSA-N potassium oxide Chemical compound [O-2].[K+].[K+] CHWRSCGUEQEHOH-UHFFFAOYSA-N 0.000 description 1
- 229910001950 potassium oxide Inorganic materials 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- KRIOVPPHQSLHCZ-UHFFFAOYSA-N propiophenone Chemical compound CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- SGMABXRSPZLOPP-UHFFFAOYSA-N quinazolin-2-ylhydrazine Chemical compound C1=CC=CC2=NC(NN)=NC=C21 SGMABXRSPZLOPP-UHFFFAOYSA-N 0.000 description 1
- PMZDQRJGMBOQBF-UHFFFAOYSA-N quinolin-4-ol Chemical compound C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 230000004799 sedative–hypnotic effect Effects 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 150000003900 succinic acid esters Chemical class 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- UJJLJRQIPMGXEZ-UHFFFAOYSA-N tetrahydro-2-furoic acid Chemical compound OC(=O)C1CCCO1 UJJLJRQIPMGXEZ-UHFFFAOYSA-N 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 1
- YNVOMSDITJMNET-UHFFFAOYSA-N thiophene-3-carboxylic acid Chemical compound OC(=O)C=1C=CSC=1 YNVOMSDITJMNET-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 125000005023 xylyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/14—Ortho-condensed systems
-
- 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
- A61P25/18—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
- A61P25/20—Hypnotics; Sedatives
-
- 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
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/14—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Anesthesiology (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH179191 | 1991-06-17 | ||
| CH01140/92-9 | 1992-04-08 | ||
| CH01791/91-0 | 1992-04-08 | ||
| CH114092 | 1992-04-08 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH05202051A JPH05202051A (ja) | 1993-08-10 |
| JPH078869B2 true JPH078869B2 (ja) | 1995-02-01 |
Family
ID=25686778
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4179406A Expired - Lifetime JPH078869B2 (ja) | 1991-06-17 | 1992-06-12 | イミダゾジアゼピン誘導体類 |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US5387585A (enExample) |
| EP (1) | EP0519307A3 (enExample) |
| JP (1) | JPH078869B2 (enExample) |
| KR (1) | KR930000517A (enExample) |
| AU (1) | AU655472B2 (enExample) |
| CA (1) | CA2069382A1 (enExample) |
| CZ (1) | CZ185092A3 (enExample) |
| FI (1) | FI922827A7 (enExample) |
| HU (1) | HU9201929D0 (enExample) |
| IE (1) | IE921945A1 (enExample) |
| IL (1) | IL102175A0 (enExample) |
| IS (1) | IS3878A (enExample) |
| NO (1) | NO922367L (enExample) |
| NZ (1) | NZ243091A (enExample) |
| TW (1) | TW201311B (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100923393B1 (ko) * | 2004-12-14 | 2009-10-23 | 에프. 호프만-라 로슈 아게 | Ｇａｂａ 수용체 조절제로서 테트라사이클릭이미다조-벤조다이아제핀 |
| KR100923399B1 (ko) * | 2004-10-20 | 2009-10-23 | 에프. 호프만-라 로슈 아게 | 이미다조-벤조다이아제핀 유도체 |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW349100B (en) * | 1994-11-11 | 1999-01-01 | Hoffmann La Roche | Oxazolyl- and thiazolylimidazo-benzo- and thienodiazepines |
| JPH10298078A (ja) * | 1997-05-06 | 1998-11-10 | Mitsubishi Chem Corp | 抗不安薬 |
| TWI239333B (en) * | 2000-11-16 | 2005-09-11 | Hoffmann La Roche | Benzodiazepine derivatives as GABA A receptor modulators |
| US6686352B2 (en) | 2001-05-18 | 2004-02-03 | Hoffmann-La Roche Inc. | Substituted imidazo [1,5-a] pyrimido [5,4-d] [1] benzazepine derivatives |
| KR101059776B1 (ko) * | 2001-06-12 | 2011-08-26 | 웰스테트 테라퓨틱스 코포레이션 | 대사 질환의 치료용 화합물 |
| BRPI0517412A (pt) * | 2004-10-12 | 2008-10-07 | Hoffmann La Roche | derivados de benzodiazepina substituìdos |
| JP4751398B2 (ja) * | 2004-10-20 | 2011-08-17 | エフ．ホフマン−ラ ロシュ アーゲー | ハロゲン置換ベンゾジアゼピン誘導体 |
| BRPI0617204A2 (pt) | 2005-10-11 | 2011-07-19 | Hoffmann La Roche | derivados de imidazo benzodiazepina |
| AU2009300357B2 (en) * | 2008-09-23 | 2014-07-03 | The Johns Hopkins University | Fused diimidazodiazepine compounds and methods of use and manufacture thereof |
| US9322831B2 (en) | 2008-09-23 | 2016-04-26 | The Johns Hopkins University | DDX3 as a biomarker for cancer and methods related thereto |
| AU2014240289B2 (en) * | 2008-09-23 | 2015-12-03 | The Johns Hopkins University | Fused diimidazodiazepine compounds and methods of use and manufacture thereof |
| NO3034079T3 (enExample) | 2010-11-15 | 2018-06-09 | ||
| BR112016004889B1 (pt) | 2013-09-06 | 2023-10-03 | Aurigene Discovery Technologies Limited | Derivados de 1,2,4-oxadiazol como imunomoduladores |
| US10329301B2 (en) | 2013-12-20 | 2019-06-25 | Agenebio, Inc. | Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment |
| US20180044329A1 (en) * | 2015-03-10 | 2018-02-15 | Aurigene Discovery Technologies Limited | 3-substituted-1,2,4-oxadiazole and thiadiazole compounds as immunomodulators |
| EP4023645A1 (en) | 2015-03-10 | 2022-07-06 | Aurigene Discovery Technologies Limited | 1,2,4-oxadiazole and thiadiazole compounds as immunomodulators |
| CA2990004C (en) | 2015-06-19 | 2024-04-23 | Agenebio, Inc. | Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment |
| SG11201804901WA (en) | 2015-12-22 | 2018-07-30 | SHY Therapeutics LLC | Compounds for the treatment of cancer and inflammatory disease |
| US11505555B2 (en) | 2016-12-19 | 2022-11-22 | Agenebio, Inc. | Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment |
| US20180170941A1 (en) * | 2016-12-19 | 2018-06-21 | Agenebio, Inc. | Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment |
| CA3066939A1 (en) | 2017-06-21 | 2018-12-27 | SHY Therapeutics LLC | Compounds that interact with the ras superfamily for the treatment of cancers, inflammatory diseases, rasopathies, and fibrotic disease |
| WO2019061324A1 (en) | 2017-09-29 | 2019-04-04 | Curis Inc. | CRYSTALLINE FORMS OF IMMUNOMODULATORS |
| KR102838640B1 (ko) | 2017-10-11 | 2025-07-24 | 오리진 온콜로지 리미티드 | 3-치환된 1,2,4-옥사다이아졸의 결정질 형태 |
| SG11202003625VA (en) | 2017-11-03 | 2020-05-28 | Aurigene Discovery Tech Ltd | Dual inhibitors of tim-3 and pd-1 pathways |
| CN111386128A (zh) | 2017-11-06 | 2020-07-07 | 奥瑞基尼探索技术有限公司 | 用于免疫调节的联合疗法 |
| BR112020026062B1 (pt) | 2018-06-19 | 2023-04-04 | Agenebio, Inc | Compostos derivados de benzodiazepina ou um sal farmaceuticamente aceitavel, isômero ou combinação dos mesmos, composição farmacêutica compreendendo os mesmos e usos dos mesmos para o tratamento de comprometimento cognitivo, câncer cerebral e psicose da doença de parkinson |
| WO2020132071A1 (en) | 2018-12-19 | 2020-06-25 | Shy Therapeutics. Llc | Compounds that interact with the ras superfamily for the treatment of cancers, inflammatory diseases, rasopathies, and f1brotic disease |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1143728A (en) * | 1979-10-04 | 1983-03-29 | Max Gerecke | Imidazodiazepine derivatives |
| EP0150040B1 (de) * | 1984-01-19 | 1994-08-31 | F. Hoffmann-La Roche Ag | Imidazodiazepin-Derivate |
| US4897392A (en) * | 1989-07-03 | 1990-01-30 | Hoechst-Roussel Pharmaceuticals, Inc. | 4H-indolo(1,2-d)(1,2,4)triazolo(4,3-A)(1,4)benzodiazepines |
| DK443589D0 (da) * | 1989-09-08 | 1989-09-08 | Ferrosan As | Heterocykliske forbindelser, deres fremstilling og anvendelse |
| DK41191D0 (da) * | 1991-03-07 | 1991-03-07 | Novo Nordisk As | Heterocycliske forbindelser, deres fremstilling og anvendelse |
-
1992
- 1992-05-15 TW TW081103807A patent/TW201311B/zh active
- 1992-05-25 CA CA002069382A patent/CA2069382A1/en not_active Abandoned
- 1992-06-10 NZ NZ243091A patent/NZ243091A/en unknown
- 1992-06-10 EP EP19920109745 patent/EP0519307A3/de not_active Withdrawn
- 1992-06-10 HU HU9201929A patent/HU9201929D0/hu unknown
- 1992-06-11 IL IL102175A patent/IL102175A0/xx unknown
- 1992-06-12 IS IS3878A patent/IS3878A/is unknown
- 1992-06-12 JP JP4179406A patent/JPH078869B2/ja not_active Expired - Lifetime
- 1992-06-12 AU AU18234/92A patent/AU655472B2/en not_active Ceased
- 1992-06-16 NO NO92922367A patent/NO922367L/no unknown
- 1992-06-16 KR KR1019920010394A patent/KR930000517A/ko not_active Withdrawn
- 1992-06-16 CZ CS921850A patent/CZ185092A3/cs unknown
- 1992-06-17 FI FI922827A patent/FI922827A7/fi not_active Application Discontinuation
- 1992-07-01 IE IE194592A patent/IE921945A1/en not_active Application Discontinuation
-
1993
- 1993-11-15 US US08/153,234 patent/US5387585A/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100923399B1 (ko) * | 2004-10-20 | 2009-10-23 | 에프. 호프만-라 로슈 아게 | 이미다조-벤조다이아제핀 유도체 |
| KR100923393B1 (ko) * | 2004-12-14 | 2009-10-23 | 에프. 호프만-라 로슈 아게 | Ｇａｂａ 수용체 조절제로서 테트라사이클릭이미다조-벤조다이아제핀 |
Also Published As
| Publication number | Publication date |
|---|---|
| KR930000517A (ko) | 1993-01-15 |
| US5387585A (en) | 1995-02-07 |
| AU655472B2 (en) | 1994-12-22 |
| HU9201929D0 (en) | 1992-08-28 |
| FI922827A7 (fi) | 1992-12-18 |
| AU1823492A (en) | 1992-12-24 |
| FI922827A0 (fi) | 1992-06-17 |
| IS3878A (is) | 1992-12-18 |
| CZ185092A3 (en) | 1993-12-15 |
| NO922367L (no) | 1992-12-18 |
| CA2069382A1 (en) | 1992-12-18 |
| JPH05202051A (ja) | 1993-08-10 |
| NZ243091A (en) | 1994-11-25 |
| TW201311B (enExample) | 1993-03-01 |
| IL102175A0 (en) | 1993-01-14 |
| NO922367D0 (no) | 1992-06-16 |
| EP0519307A3 (en) | 1993-04-21 |
| EP0519307A2 (de) | 1992-12-23 |
| IE921945A1 (en) | 1992-12-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPH078869B2 (ja) | イミダゾジアゼピン誘導体類 | |
| AU2002217007B2 (en) | Benzodiazepine derivatives as GABA A receptor modulators | |
| DE69936998T2 (de) | Pyrazolotriazinderivate als gaba-rezeptorliganden | |
| JPH0657710B2 (ja) | イミダゾジアゼピン誘導体 | |
| JP2690282B2 (ja) | イミダゾジアゼピン | |
| JP5097696B2 (ja) | Ｖｒ１拮抗剤としての２，３−置換縮合ピリミジン−４（３ｈ）−オン | |
| KR100533406B1 (ko) | Ｇａｂａ ａ 수용체 조절제로서의이미다조[1,5-ａ]피리미도[5,4-ｄ]벤즈아제핀 유도체 | |
| JPH09506634A (ja) | 三環式ジカルボニル誘導体 | |
| AU2002217007A1 (en) | Benzodiazepine derivatives as GABA A receptor modulators | |
| WO2011012622A1 (en) | Benzoxazinone derivatives for the treatment of glytl mediated disorders | |
| JP2003516989A (ja) | Ｇａｂａ受容体リガンドとしてのピラゾロ−ピリジン誘導体 | |
| ES2319461T3 (es) | Dihidroquinazolinonas como moduladores de 5ht. | |
| DE69907923T2 (de) | Triazolopyridazinderivate zur verbesserung der kognitiven funktionen | |
| JP2003516994A (ja) | 認知能力を向上させるための置換１，２，３−トリアゾロ［１，５−ａ］キナゾリン | |
| CN105025899B (zh) | 具有A2A拮抗剂性质的杂二环取代的‑[1,2,4]三唑并[1,5‑c]喹唑啉‑5‑胺化合物 | |
| JP2003514909A (ja) | 認識能力増強用ピラゾロ〔１，５−ｄ〕〔１，２，４〕トリアジン | |
| EP0202441B1 (en) | Oxadiazolylimidazobenzodiazepines, process for their preparation and pharmaceutical compositions |