FI92203B - Förfarande för framställning av terapeutiskt aktiva 4-oxo-imidazo/1,5-a/kinoxalinderivat - Google Patents
Förfarande för framställning av terapeutiskt aktiva 4-oxo-imidazo/1,5-a/kinoxalinderivat Download PDFInfo
- Publication number
- FI92203B FI92203B FI892684A FI892684A FI92203B FI 92203 B FI92203 B FI 92203B FI 892684 A FI892684 A FI 892684A FI 892684 A FI892684 A FI 892684A FI 92203 B FI92203 B FI 92203B
- Authority
- FI
- Finland
- Prior art keywords
- cyclopropyl
- quinoxaline
- dihydro
- oxadiazol
- compound
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 12
- 238000000034 method Methods 0.000 title claims description 11
- 125000001567 quinoxalinyl group Chemical class N1=C(C=NC2=CC=CC=C12)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 45
- -1 morpholino, pyrrolidino, piperidino Chemical group 0.000 claims description 38
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 38
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 150000002367 halogens Chemical group 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 235000004431 Linum usitatissimum Nutrition 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- ASOUKPMQUOTJSJ-UHFFFAOYSA-N 5-benzyl-3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)imidazo[1,5-a]quinoxalin-4-one Chemical compound C12=CC=CC=C2N2C=NC(C=3N=C(ON=3)C3CC3)=C2C(=O)N1CC1=CC=CC=C1 ASOUKPMQUOTJSJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
- 241000208202 Linaceae Species 0.000 claims 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- SANOAHQLNAFPBJ-UHFFFAOYSA-N 3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-5-[(4-methoxyphenyl)methyl]imidazo[1,5-a]quinoxalin-4-one Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=C(C=3N=C(ON=3)C3CC3)N=CN2C2=CC=CC=C21 SANOAHQLNAFPBJ-UHFFFAOYSA-N 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
- 239000000243 solution Substances 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 239000000126 substance Substances 0.000 description 15
- 239000000203 mixture Substances 0.000 description 14
- 239000003921 oil Substances 0.000 description 14
- 230000009870 specific binding Effects 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 238000012360 testing method Methods 0.000 description 11
- 238000001914 filtration Methods 0.000 description 10
- 238000005984 hydrogenation reaction Methods 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 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 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 238000001953 recrystallisation Methods 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 102000004300 GABA-A Receptors Human genes 0.000 description 7
- 108090000839 GABA-A Receptors Proteins 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 230000029936 alkylation Effects 0.000 description 5
- 238000005804 alkylation reaction Methods 0.000 description 5
- 238000005574 benzylation reaction Methods 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- 229910004298 SiO 2 Inorganic materials 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 229960002200 flunitrazepam Drugs 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- 239000011591 potassium Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- SEPKUNXLGWMPHL-UHFFFAOYSA-N quinoxaline-2,3-dione Chemical compound C1=CC=CC2=NC(=O)C(=O)N=C21 SEPKUNXLGWMPHL-UHFFFAOYSA-N 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 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 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 208000015114 central nervous system disease Diseases 0.000 description 3
- DGBIGWXXNGSACT-UHFFFAOYSA-N clonazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1Cl DGBIGWXXNGSACT-UHFFFAOYSA-N 0.000 description 3
- 229960003120 clonazepam Drugs 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- PWKNBLFSJAVFAB-UHFFFAOYSA-N 1-fluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1F PWKNBLFSJAVFAB-UHFFFAOYSA-N 0.000 description 2
- OARGFWQSVACNCO-UHFFFAOYSA-N 1-oxidoquinoxalin-1-ium Chemical class C1=CC=C2[N+]([O-])=CC=NC2=C1 OARGFWQSVACNCO-UHFFFAOYSA-N 0.000 description 2
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 2
- MZSCYTKFLASYPJ-UHFFFAOYSA-N 4-(cyclopropylmethyl)-1h-quinoxaline-2,3-dione Chemical compound O=C1C(=O)NC2=CC=CC=C2N1CC1CC1 MZSCYTKFLASYPJ-UHFFFAOYSA-N 0.000 description 2
- ZZQRPPDUPMPUEN-UHFFFAOYSA-N 4-(pyridin-2-ylmethyl)-1h-quinoxaline-2,3-dione Chemical compound O=C1C(=O)NC2=CC=CC=C2N1CC1=CC=CC=N1 ZZQRPPDUPMPUEN-UHFFFAOYSA-N 0.000 description 2
- SIBKUTVOUINYEG-UHFFFAOYSA-N 4-benzyl-1h-quinoxaline-2,3-dione Chemical compound O=C1C(=O)NC2=CC=CC=C2N1CC1=CC=CC=C1 SIBKUTVOUINYEG-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-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
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 2
- PPTYJKAXVCCBDU-UHFFFAOYSA-N Rohypnol Chemical compound N=1CC(=O)N(C)C2=CC=C([N+]([O-])=O)C=C2C=1C1=CC=CC=C1F PPTYJKAXVCCBDU-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-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
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- 230000000949 anxiolytic effect Effects 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- IGTAQWQSTWWBIN-UHFFFAOYSA-N ethyl 2-(2-methyl-6-nitroanilino)-2-oxoacetate Chemical compound CCOC(=O)C(=O)NC1=C(C)C=CC=C1[N+]([O-])=O IGTAQWQSTWWBIN-UHFFFAOYSA-N 0.000 description 2
- YORWFQDNJTVELY-UHFFFAOYSA-N ethyl 2-(n-ethyl-2-methyl-6-nitroanilino)-2-oxoacetate Chemical compound CCOC(=O)C(=O)N(CC)C1=C(C)C=CC=C1[N+]([O-])=O YORWFQDNJTVELY-UHFFFAOYSA-N 0.000 description 2
- MYUUELKWXBKDLD-UHFFFAOYSA-N ethyl 2-[2-chloro-n-[(2-chlorophenyl)methyl]-6-nitroanilino]-2-oxoacetate Chemical compound ClC=1C=CC=C([N+]([O-])=O)C=1N(C(=O)C(=O)OCC)CC1=CC=CC=C1Cl MYUUELKWXBKDLD-UHFFFAOYSA-N 0.000 description 2
- IPARZNCOGXJAIW-UHFFFAOYSA-N ethyl 2-[2-nitro-n-(2-phenylethyl)anilino]-2-oxoacetate Chemical compound C=1C=CC=C([N+]([O-])=O)C=1N(C(=O)C(=O)OCC)CCC1=CC=CC=C1 IPARZNCOGXJAIW-UHFFFAOYSA-N 0.000 description 2
- QLQPQHXECPDHQO-UHFFFAOYSA-N ethyl 2-[4-chloro-2-nitro-6-(trifluoromethyl)anilino]-2-oxoacetate Chemical compound CCOC(=O)C(=O)NC1=C([N+]([O-])=O)C=C(Cl)C=C1C(F)(F)F QLQPQHXECPDHQO-UHFFFAOYSA-N 0.000 description 2
- UIUPBYZOZKPTQI-UHFFFAOYSA-N ethyl 2-[n-(2-morpholin-4-ylethyl)-2-nitroanilino]-2-oxoacetate Chemical compound C=1C=CC=C([N+]([O-])=O)C=1N(C(=O)C(=O)OCC)CCN1CCOCC1 UIUPBYZOZKPTQI-UHFFFAOYSA-N 0.000 description 2
- KKJAXXJNQOWTRF-UHFFFAOYSA-N ethyl 2-[n-[(2-chlorophenyl)methyl]-2-nitroanilino]-2-oxoacetate Chemical compound C=1C=CC=C([N+]([O-])=O)C=1N(C(=O)C(=O)OCC)CC1=CC=CC=C1Cl KKJAXXJNQOWTRF-UHFFFAOYSA-N 0.000 description 2
- OWZFULPEVHKEKS-UHFFFAOYSA-N ethyl 2-chloro-2-oxoacetate Chemical compound CCOC(=O)C(Cl)=O OWZFULPEVHKEKS-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000003365 glass fiber Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-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
- 239000012528 membrane Substances 0.000 description 2
- OMCUPXRCMTUDHI-UHFFFAOYSA-N n'-hydroxycyclopropanecarboximidamide Chemical compound ON=C(N)C1CC1 OMCUPXRCMTUDHI-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 150000003252 quinoxalines Chemical class 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 description 1
- CMVQZRLQEOAYSW-UHFFFAOYSA-N 1,2-dichloro-3-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC(Cl)=C1Cl CMVQZRLQEOAYSW-UHFFFAOYSA-N 0.000 description 1
- VQRBXYBBGHOGFT-UHFFFAOYSA-N 1-(chloromethyl)-2-methylbenzene Chemical compound CC1=CC=CC=C1CCl VQRBXYBBGHOGFT-UHFFFAOYSA-N 0.000 description 1
- VGISFWWEOGVMED-UHFFFAOYSA-N 1-(chloromethyl)-3-methoxybenzene Chemical compound COC1=CC=CC(CCl)=C1 VGISFWWEOGVMED-UHFFFAOYSA-N 0.000 description 1
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 1
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
- LZSYGJNFCREHMD-UHFFFAOYSA-N 1-bromo-2-(bromomethyl)benzene Chemical compound BrCC1=CC=CC=C1Br LZSYGJNFCREHMD-UHFFFAOYSA-N 0.000 description 1
- LOYZVRIHVZEDMW-UHFFFAOYSA-N 1-bromo-3-methylbut-2-ene Chemical compound CC(C)=CCBr LOYZVRIHVZEDMW-UHFFFAOYSA-N 0.000 description 1
- BASMANVIUSSIIM-UHFFFAOYSA-N 1-chloro-2-(chloromethyl)benzene Chemical compound ClCC1=CC=CC=C1Cl BASMANVIUSSIIM-UHFFFAOYSA-N 0.000 description 1
- ZVAPWJGRRUHKGP-UHFFFAOYSA-N 1h-1,5-benzodiazepine Chemical class N1C=CC=NC2=CC=CC=C12 ZVAPWJGRRUHKGP-UHFFFAOYSA-N 0.000 description 1
- YCWRFIYBUQBHJI-UHFFFAOYSA-N 2-(4-aminophenyl)acetonitrile Chemical group NC1=CC=C(CC#N)C=C1 YCWRFIYBUQBHJI-UHFFFAOYSA-N 0.000 description 1
- JLJLETOTDNHVIP-UHFFFAOYSA-N 2-[4-[[3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-4-oxoimidazo[1,5-a]quinoxalin-5-yl]methyl]phenyl]isoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C(C=C1)=CC=C1CN(C(C1=2)=O)C3=CC=CC=C3N1C=NC=2C(N=1)=NOC=1C1CC1 JLJLETOTDNHVIP-UHFFFAOYSA-N 0.000 description 1
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 1
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 1
- NPRYCHLHHVWLQZ-TURQNECASA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynylpurin-8-one Chemical compound NC1=NC=C2N(C(N(C2=N1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C NPRYCHLHHVWLQZ-TURQNECASA-N 0.000 description 1
- 125000006280 2-bromobenzyl group Chemical group [H]C1=C([H])C(Br)=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- BFUGIBOWRJBCHK-UHFFFAOYSA-N 2-chloro-n-[(2-chlorophenyl)methyl]-6-nitroaniline Chemical compound [O-][N+](=O)C1=CC=CC(Cl)=C1NCC1=CC=CC=C1Cl BFUGIBOWRJBCHK-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
- 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
- FCMRHMPITHLLLA-UHFFFAOYSA-N 2-methyl-6-nitroaniline Chemical compound CC1=CC=CC([N+]([O-])=O)=C1N FCMRHMPITHLLLA-UHFFFAOYSA-N 0.000 description 1
- ROBBUBPDMDQMGG-UHFFFAOYSA-N 2-nitro-n-(2-phenylethyl)aniline Chemical compound [O-][N+](=O)C1=CC=CC=C1NCCC1=CC=CC=C1 ROBBUBPDMDQMGG-UHFFFAOYSA-N 0.000 description 1
- BCJOYUPKFXCHHS-UHFFFAOYSA-N 2-nitro-n-(pyridin-2-ylmethyl)aniline Chemical compound [O-][N+](=O)C1=CC=CC=C1NCC1=CC=CC=N1 BCJOYUPKFXCHHS-UHFFFAOYSA-N 0.000 description 1
- JWEUQEFDYFERFJ-UHFFFAOYSA-N 3-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-5,6-dimethylimidazo[1,5-a]quinoxalin-4-one Chemical compound CC1=CC=CC(N2C=N3)=C1N(C)C(=O)C2=C3C(ON=1)=NC=1C1CC1 JWEUQEFDYFERFJ-UHFFFAOYSA-N 0.000 description 1
- RRORPQDNQAERNP-UHFFFAOYSA-N 3-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-5-(2-phenylethyl)imidazo[1,5-a]quinoxalin-4-one Chemical compound C12=CC=CC=C2N2C=NC(C=3ON=C(N=3)C3CC3)=C2C(=O)N1CCC1=CC=CC=C1 RRORPQDNQAERNP-UHFFFAOYSA-N 0.000 description 1
- ZQUHOXTXKIGMIH-UHFFFAOYSA-N 3-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-5-[(4-methoxyphenyl)methyl]imidazo[1,5-a]quinoxalin-4-one Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=C(C=3ON=C(N=3)C3CC3)N=CN2C2=CC=CC=C21 ZQUHOXTXKIGMIH-UHFFFAOYSA-N 0.000 description 1
- LOWOEMAYPORZAO-UHFFFAOYSA-N 3-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-5-methyl-6-(trifluoromethyl)imidazo[1,5-a]quinoxalin-4-one Chemical compound C=12C(=O)N(C)C3=C(C(F)(F)F)C=CC=C3N2C=NC=1C(ON=1)=NC=1C1CC1 LOWOEMAYPORZAO-UHFFFAOYSA-N 0.000 description 1
- ZDIZAPFKIXAIDV-UHFFFAOYSA-N 3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-5-(2-ethoxyethyl)imidazo[1,5-a]quinoxalin-4-one Chemical compound C=12C(=O)N(CCOCC)C3=CC=CC=C3N2C=NC=1C(N=1)=NOC=1C1CC1 ZDIZAPFKIXAIDV-UHFFFAOYSA-N 0.000 description 1
- NELMOCMSABRTBK-UHFFFAOYSA-N 3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-5-(2-oxopropyl)imidazo[1,5-a]quinoxalin-4-one Chemical compound C=12C(=O)N(CC(=O)C)C3=CC=CC=C3N2C=NC=1C(N=1)=NOC=1C1CC1 NELMOCMSABRTBK-UHFFFAOYSA-N 0.000 description 1
- PXWNYWGZRWRCSQ-UHFFFAOYSA-N 3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-5-[(2-fluorophenyl)methyl]imidazo[1,5-a]quinoxalin-4-one Chemical compound FC1=CC=CC=C1CN1C(=O)C2=C(C=3N=C(ON=3)C3CC3)N=CN2C2=CC=CC=C21 PXWNYWGZRWRCSQ-UHFFFAOYSA-N 0.000 description 1
- ZIOBFUIZUBBOOJ-UHFFFAOYSA-N 3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-5-[(2-methoxyphenyl)methyl]imidazo[1,5-a]quinoxalin-4-one Chemical compound COC1=CC=CC=C1CN1C(=O)C2=C(C=3N=C(ON=3)C3CC3)N=CN2C2=CC=CC=C21 ZIOBFUIZUBBOOJ-UHFFFAOYSA-N 0.000 description 1
- ZPWPXBHHCHKKSR-UHFFFAOYSA-N 3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-5-[(2-methylphenyl)methyl]imidazo[1,5-a]quinoxalin-4-one Chemical compound CC1=CC=CC=C1CN1C(=O)C2=C(C=3N=C(ON=3)C3CC3)N=CN2C2=CC=CC=C21 ZPWPXBHHCHKKSR-UHFFFAOYSA-N 0.000 description 1
- NXZAPMDEOFIYOF-UHFFFAOYSA-N 3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-5-phenacylimidazo[1,5-a]quinoxalin-4-one Chemical compound C=1C=CC=CC=1C(=O)CN(C(C1=2)=O)C3=CC=CC=C3N1C=NC=2C(N=1)=NOC=1C1CC1 NXZAPMDEOFIYOF-UHFFFAOYSA-N 0.000 description 1
- SVJNQVIWKIZMRC-UHFFFAOYSA-N 3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-5h-imidazo[1,5-a]quinoxalin-4-one Chemical compound C=12C(=O)NC3=CC=CC=C3N2C=NC=1C(N=1)=NOC=1C1CC1 SVJNQVIWKIZMRC-UHFFFAOYSA-N 0.000 description 1
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 1
- KFVVSDPKGPUSEL-UHFFFAOYSA-N 3-cyclopropyl-5-(isocyanomethyl)-1,2,4-oxadiazole Chemical compound O1C(C[N+]#[C-])=NC(C2CC2)=N1 KFVVSDPKGPUSEL-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
- YELMWJNXDALKFE-UHFFFAOYSA-N 3h-imidazo[4,5-f]quinoxaline Chemical class N1=CC=NC2=C(NC=N3)C3=CC=C21 YELMWJNXDALKFE-UHFFFAOYSA-N 0.000 description 1
- MSWWEVDXTOMRBH-UHFFFAOYSA-N 4-(2-morpholin-4-ylethyl)-1h-quinoxaline-2,3-dione Chemical compound O=C1C(=O)NC2=CC=CC=C2N1CCN1CCOCC1 MSWWEVDXTOMRBH-UHFFFAOYSA-N 0.000 description 1
- KXHGZQSYWAZQCY-UHFFFAOYSA-N 4-(2-phenylethyl)-1h-quinoxaline-2,3-dione Chemical compound O=C1C(=O)NC2=CC=CC=C2N1CCC1=CC=CC=C1 KXHGZQSYWAZQCY-UHFFFAOYSA-N 0.000 description 1
- GAVNQTDPNIIKJC-UHFFFAOYSA-N 4-[(2-chlorophenyl)methyl]-1h-quinoxaline-2,3-dione Chemical compound ClC1=CC=CC=C1CN1C(=O)C(=O)NC2=CC=CC=C21 GAVNQTDPNIIKJC-UHFFFAOYSA-N 0.000 description 1
- WXGHYOYBNYQPOR-UHFFFAOYSA-N 4-[(2-methoxyphenyl)methyl]-1h-quinoxaline-2,3-dione Chemical compound COC1=CC=CC=C1CN1C(=O)C(=O)NC2=CC=CC=C21 WXGHYOYBNYQPOR-UHFFFAOYSA-N 0.000 description 1
- CVINWVPRKDIGLL-UHFFFAOYSA-N 4-chloro-2-(trifluoromethyl)aniline Chemical compound NC1=CC=C(Cl)C=C1C(F)(F)F CVINWVPRKDIGLL-UHFFFAOYSA-N 0.000 description 1
- ORXQTBODCGOZSC-UHFFFAOYSA-N 4-ethyl-5-methyl-1h-quinoxaline-2,3-dione Chemical compound C1=CC=C2NC(=O)C(=O)N(CC)C2=C1C ORXQTBODCGOZSC-UHFFFAOYSA-N 0.000 description 1
- UAUQCHAJSLDYCH-UHFFFAOYSA-N 5-(cyclopropylmethyl)-3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)imidazo[1,5-a]quinoxalin-4-one Chemical compound C12=CC=CC=C2N2C=NC(C=3N=C(ON=3)C3CC3)=C2C(=O)N1CC1CC1 UAUQCHAJSLDYCH-UHFFFAOYSA-N 0.000 description 1
- XOAVJCCBDYZWTF-UHFFFAOYSA-N 5-[(2-chlorophenyl)methyl]-3-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)imidazo[1,5-a]quinoxalin-4-one Chemical compound ClC1=CC=CC=C1CN1C(=O)C2=C(C=3ON=C(N=3)C3CC3)N=CN2C2=CC=CC=C21 XOAVJCCBDYZWTF-UHFFFAOYSA-N 0.000 description 1
- JQCKWBBDICVKNM-UHFFFAOYSA-N 5-[(4-aminophenyl)methyl]-3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)imidazo[1,5-a]quinoxalin-4-one Chemical compound C1=CC(N)=CC=C1CN1C(=O)C2=C(C=3N=C(ON=3)C3CC3)N=CN2C2=CC=CC=C21 JQCKWBBDICVKNM-UHFFFAOYSA-N 0.000 description 1
- VUYCZLBYLAIZMU-UHFFFAOYSA-N 5-[(4-azidophenyl)methyl]-3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)imidazo[1,5-a]quinoxalin-4-one Chemical compound C1=CC(N=[N+]=[N-])=CC=C1CN1C(=O)C2=C(C=3N=C(ON=3)C3CC3)N=CN2C2=CC=CC=C21 VUYCZLBYLAIZMU-UHFFFAOYSA-N 0.000 description 1
- NQDZYYBPYMUOHM-UHFFFAOYSA-N 5-chloro-4-[(2-chlorophenyl)methyl]-1h-quinoxaline-2,3-dione Chemical compound ClC1=CC=CC=C1CN1C(=O)C(=O)NC2=CC=CC(Cl)=C21 NQDZYYBPYMUOHM-UHFFFAOYSA-N 0.000 description 1
- DIUSFJAUSSNMAJ-UHFFFAOYSA-N 5-methyl-6-(trifluoromethyl)imidazo[1,5-a]quinoxalin-4-one Chemical compound CN1C(C=2N(C3=CC=CC(=C13)C(F)(F)F)C=NC2)=O DIUSFJAUSSNMAJ-UHFFFAOYSA-N 0.000 description 1
- JODBJCLZSTXYON-UHFFFAOYSA-N 6-chloro-5-[(2-chlorophenyl)methyl]-3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)imidazo[1,5-a]quinoxalin-4-one Chemical compound ClC1=CC=CC=C1CN1C(=O)C2=C(C=3N=C(ON=3)C3CC3)N=CN2C2=CC=CC(Cl)=C21 JODBJCLZSTXYON-UHFFFAOYSA-N 0.000 description 1
- BMTAFVWTTFSTOG-UHFFFAOYSA-N Butylate Chemical compound CCSC(=O)N(CC(C)C)CC(C)C BMTAFVWTTFSTOG-UHFFFAOYSA-N 0.000 description 1
- CKBNKCLDEJLCPV-UHFFFAOYSA-N C1(CC1)C1=NC(=NO1)C=1N=C(N2C1C(NC1=CC=CC=C21)=O)CCN2CCOCC2 Chemical compound C1(CC1)C1=NC(=NO1)C=1N=C(N2C1C(NC1=CC=CC=C21)=O)CCN2CCOCC2 CKBNKCLDEJLCPV-UHFFFAOYSA-N 0.000 description 1
- RAXPVULHPBKCPD-UHFFFAOYSA-N C1=CC(OC)=CC=C1CN1C(=O)C(O)=[N+]([O-])C2=CC=CC=C21 Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C(O)=[N+]([O-])C2=CC=CC=C21 RAXPVULHPBKCPD-UHFFFAOYSA-N 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
- KCBAMQOKOLXLOX-BSZYMOERSA-N CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O Chemical compound CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O KCBAMQOKOLXLOX-BSZYMOERSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- GNJZTNMMXCMLHC-UHFFFAOYSA-N ClC1=C2N(C(C(=[N+](C2=CC=C1)[O-])O)=O)CC1=C(C=CC=C1)Cl.C(=O)(C(=O)OCC)N(C1=C(C=CC=C1)[N+](=O)[O-])CC1=C(C=CC=C1)OC Chemical compound ClC1=C2N(C(C(=[N+](C2=CC=C1)[O-])O)=O)CC1=C(C=CC=C1)Cl.C(=O)(C(=O)OCC)N(C1=C(C=CC=C1)[N+](=O)[O-])CC1=C(C=CC=C1)OC GNJZTNMMXCMLHC-UHFFFAOYSA-N 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- 229940126639 Compound 33 Drugs 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- 101100448208 Human herpesvirus 6B (strain Z29) U69 gene Proteins 0.000 description 1
- 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 1
- 240000006240 Linum usitatissimum Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000037482 Microtea Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- LOBXNEZEINTCAR-UHFFFAOYSA-N O=C1C(=O)N(O)C2=CC=CC=C2N1CC1=CC=CC=C1 Chemical compound O=C1C(=O)N(O)C2=CC=CC=C2N1CC1=CC=CC=C1 LOBXNEZEINTCAR-UHFFFAOYSA-N 0.000 description 1
- RHWNPBFVZBZPSL-UHFFFAOYSA-N O=C1C(O)=[N+]([O-])C2=CC=CC=C2N1CC1=CC=CC=C1 Chemical compound O=C1C(O)=[N+]([O-])C2=CC=CC=C2N1CC1=CC=CC=C1 RHWNPBFVZBZPSL-UHFFFAOYSA-N 0.000 description 1
- CHPVKBMCWLXMDG-UHFFFAOYSA-N O=C1C(O)=[N+]([O-])C2=CC=CC=C2N1CC1=CC=CC=C1Cl Chemical compound O=C1C(O)=[N+]([O-])C2=CC=CC=C2N1CC1=CC=CC=C1Cl CHPVKBMCWLXMDG-UHFFFAOYSA-N 0.000 description 1
- HTPHTTYZVUWXPC-UHFFFAOYSA-N OC1=[N+](C2=CC=CC=C2N(C1=O)CC1=C(C=CC=C1)OC)[O-].C(=O)(C(=O)OCC)N(C1=C(C=CC=C1)[N+](=O)[O-])CC1=NC=CC=C1 Chemical compound OC1=[N+](C2=CC=CC=C2N(C1=O)CC1=C(C=CC=C1)OC)[O-].C(=O)(C(=O)OCC)N(C1=C(C=CC=C1)[N+](=O)[O-])CC1=NC=CC=C1 HTPHTTYZVUWXPC-UHFFFAOYSA-N 0.000 description 1
- ODWGWWHKNCVPRL-UHFFFAOYSA-N OC1=[N+](C2=CC=CC=C2N(C1=O)CCN1CCOCC1)[O-].C(=O)(C(=O)OCC)N(C1=C(C=CC=C1)[N+](=O)[O-])CC1=CC=CC=C1 Chemical compound OC1=[N+](C2=CC=CC=C2N(C1=O)CCN1CCOCC1)[O-].C(=O)(C(=O)OCC)N(C1=C(C=CC=C1)[N+](=O)[O-])CC1=CC=CC=C1 ODWGWWHKNCVPRL-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 235000004443 Ricinus communis Nutrition 0.000 description 1
- PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 1
- XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical group [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 description 1
- SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 125000005257 alkyl acyl group Chemical group 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 229940005530 anxiolytics Drugs 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 150000001557 benzodiazepines Chemical class 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- FGNLEIGUMSBZQP-UHFFFAOYSA-N cadaverine dihydrochloride Chemical compound Cl.Cl.NCCCCCN FGNLEIGUMSBZQP-UHFFFAOYSA-N 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940125810 compound 20 Drugs 0.000 description 1
- 229940126208 compound 22 Drugs 0.000 description 1
- 229940125833 compound 23 Drugs 0.000 description 1
- 229940125961 compound 24 Drugs 0.000 description 1
- 229940125846 compound 25 Drugs 0.000 description 1
- 229940125851 compound 27 Drugs 0.000 description 1
- 229940127204 compound 29 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125877 compound 31 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- FDSGHYHRLSWSLQ-UHFFFAOYSA-N dichloromethane;propan-2-one Chemical compound ClCCl.CC(C)=O FDSGHYHRLSWSLQ-UHFFFAOYSA-N 0.000 description 1
- LGTLXDJOAJDFLR-UHFFFAOYSA-N diethyl chlorophosphate Chemical compound CCOP(Cl)(=O)OCC LGTLXDJOAJDFLR-UHFFFAOYSA-N 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- UKOOFCDBPQTEMN-UHFFFAOYSA-N ethyl 2-(2-amino-n-ethyl-6-methylanilino)-2-oxoacetate Chemical compound CCOC(=O)C(=O)N(CC)C1=C(C)C=CC=C1N UKOOFCDBPQTEMN-UHFFFAOYSA-N 0.000 description 1
- YETCHFCSGMIGCG-UHFFFAOYSA-N ethyl 2-(n,2-dimethyl-6-nitroanilino)-2-oxoacetate Chemical compound CCOC(=O)C(=O)N(C)C1=C(C)C=CC=C1[N+]([O-])=O YETCHFCSGMIGCG-UHFFFAOYSA-N 0.000 description 1
- JBNSDIIYAHXPRP-UHFFFAOYSA-N ethyl 2-(n-benzyl-2-nitroanilino)-2-oxoacetate Chemical compound C=1C=CC=C([N+]([O-])=O)C=1N(C(=O)C(=O)OCC)CC1=CC=CC=C1 JBNSDIIYAHXPRP-UHFFFAOYSA-N 0.000 description 1
- CKXVSXDELNBDJL-UHFFFAOYSA-N ethyl 2-[2-nitro-n-(pyridin-2-ylmethyl)anilino]-2-oxoacetate Chemical compound C=1C=CC=C([N+]([O-])=O)C=1N(C(=O)C(=O)OCC)CC1=CC=CC=N1 CKXVSXDELNBDJL-UHFFFAOYSA-N 0.000 description 1
- ZZAXTGDMNPOQRG-UHFFFAOYSA-N ethyl 2-[3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-4-oxoimidazo[1,5-a]quinoxalin-5-yl]acetate Chemical compound C=12C(=O)N(CC(=O)OCC)C3=CC=CC=C3N2C=NC=1C(N=1)=NOC=1C1CC1 ZZAXTGDMNPOQRG-UHFFFAOYSA-N 0.000 description 1
- SFEGNHXTMWQDDB-UHFFFAOYSA-N ethyl 2-[4-chloro-2-(trifluoromethyl)anilino]-2-oxoacetate Chemical compound CCOC(=O)C(=O)NC1=CC=C(Cl)C=C1C(F)(F)F SFEGNHXTMWQDDB-UHFFFAOYSA-N 0.000 description 1
- FMXMNHQNNVUGLQ-UHFFFAOYSA-N ethyl 2-[4-chloro-n-methyl-2-nitro-6-(trifluoromethyl)anilino]-2-oxoacetate Chemical compound CCOC(=O)C(=O)N(C)C1=C([N+]([O-])=O)C=C(Cl)C=C1C(F)(F)F FMXMNHQNNVUGLQ-UHFFFAOYSA-N 0.000 description 1
- ZUUGCWCMPFGVQW-UHFFFAOYSA-N ethyl 2-[n-(cyclopropylmethyl)-2-nitroanilino]-2-oxoacetate Chemical compound C=1C=CC=C([N+]([O-])=O)C=1N(C(=O)C(=O)OCC)CC1CC1 ZUUGCWCMPFGVQW-UHFFFAOYSA-N 0.000 description 1
- GGNPWPBNIOGCTC-UHFFFAOYSA-N ethyl 2-[n-[(2-methoxyphenyl)methyl]-2-nitroanilino]-2-oxoacetate Chemical compound C=1C=CC=C([N+]([O-])=O)C=1N(C(=O)C(=O)OCC)CC1=CC=CC=C1OC GGNPWPBNIOGCTC-UHFFFAOYSA-N 0.000 description 1
- VNYCTJDKROAOIW-UHFFFAOYSA-N ethyl 2-[n-[(4-methoxyphenyl)methyl]-2-nitroanilino]-2-oxoacetate Chemical compound C=1C=CC=C([N+]([O-])=O)C=1N(C(=O)C(=O)OCC)CC1=CC=C(OC)C=C1 VNYCTJDKROAOIW-UHFFFAOYSA-N 0.000 description 1
- GFJPZNJPGZBJOO-UHFFFAOYSA-N ethyl 5,6-dimethyl-4-oxoimidazo[1,5-a]quinoxaline-3-carboxylate Chemical compound C1=CC=C2N3C=NC(C(=O)OCC)=C3C(=O)N(C)C2=C1C GFJPZNJPGZBJOO-UHFFFAOYSA-N 0.000 description 1
- VEUUMBGHMNQHGO-UHFFFAOYSA-N ethyl chloroacetate Chemical compound CCOC(=O)CCl VEUUMBGHMNQHGO-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 235000004426 flaxseed Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- WGYMXASRWCYKQR-UHFFFAOYSA-N imidazo[1,5-a]quinoxaline Chemical class C1=CC=C2N3C=NC=C3C=NC2=C1 WGYMXASRWCYKQR-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 150000002527 isonitriles Chemical class 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- VSEAAEQOQBMPQF-UHFFFAOYSA-N morpholin-3-one Chemical compound O=C1COCCN1 VSEAAEQOQBMPQF-UHFFFAOYSA-N 0.000 description 1
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 description 1
- NSZYSZQFVBHJBA-UHFFFAOYSA-N n-(2-morpholin-4-ylethyl)-2-nitroaniline Chemical compound [O-][N+](=O)C1=CC=CC=C1NCCN1CCOCC1 NSZYSZQFVBHJBA-UHFFFAOYSA-N 0.000 description 1
- DRQPRDPGSQDAMA-UHFFFAOYSA-N n-[(2-chlorophenyl)methyl]-2-nitroaniline Chemical compound [O-][N+](=O)C1=CC=CC=C1NCC1=CC=CC=C1Cl DRQPRDPGSQDAMA-UHFFFAOYSA-N 0.000 description 1
- AYXCJSMKISRCNM-UHFFFAOYSA-N n-[(2-methoxyphenyl)methyl]-2-nitroaniline Chemical compound COC1=CC=CC=C1CNC1=CC=CC=C1[N+]([O-])=O AYXCJSMKISRCNM-UHFFFAOYSA-N 0.000 description 1
- KLPVHDQLXCJUOA-UHFFFAOYSA-N n-[(4-methoxyphenyl)methyl]-2-nitroaniline Chemical compound C1=CC(OC)=CC=C1CNC1=CC=CC=C1[N+]([O-])=O KLPVHDQLXCJUOA-UHFFFAOYSA-N 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000004866 oxadiazoles Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 1
- 229940117803 phenethylamine Drugs 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 210000004129 prosencephalon Anatomy 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- MLGCXEBRWGEOQX-UHFFFAOYSA-N tetradifon Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)C1=CC(Cl)=C(Cl)C=C1Cl MLGCXEBRWGEOQX-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 229960005486 vaccine Drugs 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
- C07D487/02—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
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Claims (6)
1. Förfarande för framställning av terapeutiskt aktiva 4-oxo-imidazo[l,5-a]kinoxalinderivat med formeln I r\ R3 ©Ci 10 *6 =H2r5 där R3 är —ά H eller — Xn^^r· N ^r· 15 där R' är cyklopropyl, R5 är väte, C^-alkoxikarbonyl, pyridyl, morfolinometyl, cyklopropyl, C2_6-alkenyl, fena-cyl, Ci.j-alkylacyl, Cj^-alkoxialkyl, ftallmldofenyl, ben-syl eller fenyl, vilka alla kan vara substituerade med 20 halogen, C1.6-alkyl, amino, azido eller en C1.6-alkoxi, och R6 är väte, C^-alkyl, halogen eller CF3, förutsatt att R5 ej är väte, dä R6 är väte eller halogen, känne-t e c k n a t därav, att a) en förening med formeln II r6 CHjR5 30 där R5 och R6 betecknar detsamma som tidigare, och Y är en avgäende grupp, s&som halogen, alkyltio, aralkyltio, N-nitrosoalkylamino, alkoxi, merkapto, -0P(0)(0R)2, där R är lägre alkyl, eller -0P(0)NR'R"), där R' och R" beteck-35 nar oberoende av varandra lägre alkyl eller fenyl eller R' och R" bildar tillsamans med kväveatomen, tili vilken • 92203 de är bundna, en heterocyklisk grupp, säsom en morfoli-no-, pyrrolidino-, piperidino- eller metylpiperazino-grupp, omsättes med en förening med formeln III
2. Förfarande enligt patentkravet 1, för fram-30 ställning av 5-bensyl-3-(5-cyklopropyl-l,2,4-oxadiazol- 3-yl)-4,5-dihydro-4-oxo-imidazo[l,5-a]kinoxalin.
3. Förfarande enligt patentkravet 1, för fram-ställning av 3-(5-cyklopropyl-l,2,4-oxadiazol-3-yl)-4,5-dihydro-5-mety1-4-oxo-6-trifluonnety1-imidazo[l,5-a]kino- 35 xalin. . . · 92203
4. Förfarande enligt patentkravet 1, för fram-ställning av 5-cyklopropylmetyl-3-(5-cyklopropyl-l,2,4-oxadiazol-3-yl)-4,5-dihydro-4-oxo-imidazo[l,5-a]kinoxa-lin. 5 5. Förfarande enligt patentkravet 1, för fram- ställning av 3-(5-cyklopropyl-l,2,4-oxadiazol-3-yl)-4,5-dihydro-5-(3,3-dimetylallyl)-4-oxo-imidazo[1,5-a]kinoxa-lin.
5 CN-CH2-R3 (III) där R3 betecknar detsamma som tidigare, för att bilda en förening med formeln I, eller b) ett reaktivt derivat av en förening med for- 10 mein IV rv ΓοΤ X ,IV) N ^0 15 r6 CH2R5 där Rs och R6 betecknar detsamma som tidigare, omsättes med en förening med formeln V
20 R’-C(-N0H)NH2 (V) där R' betecknar detsamma som tidigare, för att bilda en förening med formeln I, där R3 är . 25 /°^N N^r. där R' betecknar detsamma som tidigare.
6. Förfarande enligt patentkravet 1, för fram-10 ställning av 3-(5-cyklopropyl-l,2,4-oxadiazol-3-yl)-4,5-dihydro-5-(4-metoxibensyl)-4-oxo-imidazo[1,5-a]kinoxalin.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK297188 | 1988-06-01 | ||
| DK297188A DK297188D0 (da) | 1988-06-01 | 1988-06-01 | Imidazoquinoxalinforbindelser, deres fremstilling og anvendelse |
| DK625988A DK625988D0 (da) | 1988-11-10 | 1988-11-10 | Imidazoquinoxalinforbindelser, deres fremstilling og anvendelse |
| DK625988 | 1988-11-10 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI892684A0 FI892684A0 (sv) | 1989-06-01 |
| FI892684A FI892684A (sv) | 1989-12-02 |
| FI92203B true FI92203B (sv) | 1994-06-30 |
| FI92203C FI92203C (sv) | 1994-10-10 |
Family
ID=26066829
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI892684A FI92203C (sv) | 1988-06-01 | 1989-06-01 | Förfarande för framställning av terapeutiskt aktiva 4-oxo-imidazo/1,5-a/kinoxalinderivat |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US5075304A (sv) |
| EP (1) | EP0344943A1 (sv) |
| JP (1) | JPH0225486A (sv) |
| KR (1) | KR900018102A (sv) |
| AU (1) | AU627181B2 (sv) |
| CA (1) | CA1315786C (sv) |
| FI (1) | FI92203C (sv) |
| IL (1) | IL90315A0 (sv) |
| NO (1) | NO173185C (sv) |
| NZ (1) | NZ229346A (sv) |
| PH (1) | PH26379A (sv) |
| PT (1) | PT90721B (sv) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK155524C (da) * | 1987-03-18 | 1989-09-11 | Ferrosan As | Kondenserede imidazolderivater og farmaceutiske praeparater indeholdende disse |
| DK626288D0 (da) * | 1988-11-10 | 1988-11-10 | Ferrosan As | Kemisk proces til fremstilling af imidazoquinoxaliner og mellemprodukter til brug i processen |
| US5276028A (en) * | 1990-06-22 | 1994-01-04 | Nordisk A/S | Imidazoquinoxaline compounds |
| DK151890D0 (da) * | 1990-06-22 | 1990-06-22 | Ferrosan As | Heterocykliske forbindelser deres fremstilling og brug |
| US5371080A (en) * | 1990-06-22 | 1994-12-06 | Novo Nordisk A/S | Imidazoquinazoline compounds and their use |
| JPH06500545A (ja) * | 1990-09-04 | 1994-01-20 | ジ・アップジョン・カンパニー | 酸素化キノキサリン類 |
| KR100207360B1 (ko) * | 1991-06-14 | 1999-07-15 | 돈 더블유. 슈미츠 | 이미다조[1,5,-a]퀸옥살린 |
| US5182386A (en) * | 1991-08-27 | 1993-01-26 | Neurogen Corporation | Certain imidazoquinoxalinones; a new class of gaba brain receptor ligands |
| US5597920A (en) * | 1992-04-30 | 1997-01-28 | Neurogen Corporation | Gabaa receptor subtypes and methods for screening drug compounds using imidazoquinoxalines and pyrrolopyrimidines to bind to gabaa receptor subtypes |
| DE4228095A1 (de) * | 1992-08-24 | 1994-03-03 | Asta Medica Ag | Neue 4,5-Dihydro-4-oxo-pyrrolo[1,2-a]chinoxaline und entsprechende Aza-analoga und Verfahren zu deren Herstellung |
| IL109397A0 (en) * | 1993-04-28 | 1994-07-31 | Schering Ag | Quinoxalinedione derivatives, processes for the preparation thereof and pharmaceutical compositions containing the same |
| US5792766A (en) * | 1996-03-13 | 1998-08-11 | Neurogen Corporation | Imidazo 1,5-c! quinazolines; a new class of GABA brain receptor ligands |
| MX2021001186A (es) | 2015-11-20 | 2022-10-11 | Forma Therapeutics Inc | Purinonas como inhibidores de proteasa especifica de ubiquitina 1. |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4440929A (en) * | 1981-07-16 | 1984-04-03 | Usv Pharmaceutical Corporation | Imidazoquinoxaline compounds |
| DK476885D0 (da) * | 1985-10-17 | 1985-10-17 | Ferrosan As | Heterocycliske forbindelser og fremgangsmaader til fremstilling heraf |
| DK155524C (da) * | 1987-03-18 | 1989-09-11 | Ferrosan As | Kondenserede imidazolderivater og farmaceutiske praeparater indeholdende disse |
| DK160876C (da) * | 1987-12-08 | 1991-10-14 | Novo Nordisk As | Imidazoquinoxalinforbindelser, fremgangsmaade til deres fremstilling, anvendelse af forbindelserne og farmaceutiske praeparater, hvori forbindelserne indgaar |
-
1989
- 1989-05-16 IL IL90315A patent/IL90315A0/xx not_active IP Right Cessation
- 1989-05-17 EP EP89304982A patent/EP0344943A1/en not_active Ceased
- 1989-05-18 US US07/353,793 patent/US5075304A/en not_active Expired - Fee Related
- 1989-05-24 PH PH38687A patent/PH26379A/en unknown
- 1989-05-26 AU AU35174/89A patent/AU627181B2/en not_active Ceased
- 1989-05-30 NZ NZ229346A patent/NZ229346A/xx unknown
- 1989-05-30 CA CA000601114A patent/CA1315786C/en not_active Expired - Fee Related
- 1989-05-31 KR KR1019890007386A patent/KR900018102A/ko not_active Application Discontinuation
- 1989-05-31 NO NO892204A patent/NO173185C/no unknown
- 1989-06-01 FI FI892684A patent/FI92203C/sv not_active IP Right Cessation
- 1989-06-01 JP JP1137578A patent/JPH0225486A/ja active Pending
- 1989-06-01 PT PT90721A patent/PT90721B/pt not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| PT90721B (pt) | 1994-11-30 |
| AU627181B2 (en) | 1992-08-20 |
| PT90721A (pt) | 1989-12-29 |
| JPH0225486A (ja) | 1990-01-26 |
| NO173185B (no) | 1993-08-02 |
| KR900018102A (ko) | 1990-12-20 |
| AU3517489A (en) | 1989-12-07 |
| NO892204D0 (no) | 1989-05-31 |
| FI892684A (sv) | 1989-12-02 |
| NZ229346A (en) | 1991-11-26 |
| FI892684A0 (sv) | 1989-06-01 |
| PH26379A (en) | 1992-06-01 |
| FI92203C (sv) | 1994-10-10 |
| US5075304A (en) | 1991-12-24 |
| IL90315A0 (en) | 1989-12-15 |
| EP0344943A1 (en) | 1989-12-06 |
| NO173185C (no) | 1993-11-10 |
| NO892204L (no) | 1989-12-04 |
| CA1315786C (en) | 1993-04-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR100548853B1 (ko) | 아졸로 트리아진 및 피리미딘 | |
| KR100574313B1 (ko) | 아졸로 트리아진 및 피리미딘 | |
| JP3147902B2 (ja) | イミダゾ〔１，５−ａ〕キノキサリン | |
| JP6105578B2 (ja) | 複素環式プロテインキナーゼ阻害剤 | |
| FI82050C (sv) | Förfarande för framställning som läkemedel användbara 3-oxadiazolylder ivat av imidazol(1,5-a)kinoxaliner och 1-oxdiazolylderivat av imidazo( 1,5-a)pyrrolo(2,1-c)kinoxaliner | |
| FI92203B (sv) | Förfarande för framställning av terapeutiskt aktiva 4-oxo-imidazo/1,5-a/kinoxalinderivat | |
| KR920003981B1 (ko) | 디아제핀 항알레르기 화합물 | |
| NZ554082A (en) | Pyrazolo [1,5-alpha] pyrimidinyl derivatives useful as corticotropin-releasing factor (CRF) receptor antagonists | |
| SK2592002A3 (en) | Tricyclic inhibitors of poly(adp-ribose) polymerases | |
| MXPA02005533A (es) | Dihidropirimidinas heterociclicas como inhibidores del canal de potasio. | |
| EP0283162B1 (en) | Heterocyclic compounds and their preparation and use | |
| WO2008072779A1 (ja) | キノキサリン誘導体 | |
| EP2336122A1 (en) | 1-pyrimidinyl- or 1-pyridinyl-2-amino benzimidazole derivatives and related compounds as inhibitors of protein kinases for the treatment of cancer | |
| SK33995A3 (en) | Imidazodiazepines | |
| KR20120101721A (ko) | 야누스 키나제 억제제로서 헤테로사이클릭 화합물 | |
| EP0320136B1 (en) | Imidazoquinoxaline compounds and their preparation and use | |
| US4772599A (en) | Benzodiazepine derivatives and their preparation and use | |
| NZ246558A (en) | 5-amino (and azaheterocyclyl)-3-oxazolyl imidazoquinazoline derivatives, preparation and pharmaceutical compositions | |
| US7144887B2 (en) | Substituted 1,2,3-triazolo[1,5-a]quinazolines for enhancing cognition | |
| MXPA02005233A (es) | Pirazolo[1,5-d][1,2,4]triazinas para mejorar el conocimiento. | |
| US5100895A (en) | Heterocyclic compounds and their preparation and use | |
| TW202317577A (zh) | 新穎化合物 | |
| DK161022B (da) | Imidazoquinoxalinforbindelser, deres fremstilling og farmaceutiske praeparater, der indeholder forbindelserne | |
| ZA200702467B (en) | Pyrazolo[1,5-alpha] pyrimidinyl derivatives useful as corticotropin-releasing factor(CRF) receptor antagonists |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| BB | Publication of examined application | ||
| MM | Patent lapsed | ||
| MM | Patent lapsed |
Owner name: NOVO NORDISK A/S |