NO871867L - Fremgangsmaate for fremstilling av terapeutisk aktive heterocykliske kondenserte tricykliske forbindelser. - Google Patents
Fremgangsmaate for fremstilling av terapeutisk aktive heterocykliske kondenserte tricykliske forbindelser.Info
- Publication number
- NO871867L NO871867L NO871867A NO871867A NO871867L NO 871867 L NO871867 L NO 871867L NO 871867 A NO871867 A NO 871867A NO 871867 A NO871867 A NO 871867A NO 871867 L NO871867 L NO 871867L
- Authority
- NO
- Norway
- Prior art keywords
- formula
- alkyl
- ethyl acetate
- propyl
- compound
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 143
- 238000000034 method Methods 0.000 title claims description 80
- 238000002360 preparation method Methods 0.000 title description 7
- 230000001225 therapeutic effect Effects 0.000 title description 2
- -1 methoxy, ethoxy, propoxy Chemical group 0.000 claims description 92
- 125000000217 alkyl group Chemical group 0.000 claims description 83
- 229910052757 nitrogen Inorganic materials 0.000 claims description 75
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 63
- 238000006243 chemical reaction Methods 0.000 claims description 45
- 229910052739 hydrogen Inorganic materials 0.000 claims description 42
- 239000001257 hydrogen Substances 0.000 claims description 33
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 32
- 125000003118 aryl group Chemical group 0.000 claims description 32
- 239000000460 chlorine Substances 0.000 claims description 29
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 27
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- 125000003342 alkenyl group Chemical group 0.000 claims description 18
- 125000000304 alkynyl group Chemical group 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 18
- 229910052801 chlorine Inorganic materials 0.000 claims description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 17
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 16
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 16
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 15
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 14
- 239000003153 chemical reaction reagent Substances 0.000 claims description 13
- 239000011737 fluorine Substances 0.000 claims description 13
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- 125000001072 heteroaryl group Chemical group 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 12
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 12
- 229910052794 bromium Inorganic materials 0.000 claims description 11
- 230000008569 process Effects 0.000 claims description 11
- 239000007858 starting material Substances 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 9
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- 239000005864 Sulphur Substances 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 239000001301 oxygen Substances 0.000 claims description 8
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 8
- 238000007363 ring formation reaction Methods 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 125000006239 protecting group Chemical group 0.000 claims description 7
- 125000003107 substituted aryl group Chemical group 0.000 claims description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
- 125000001589 carboacyl group Chemical group 0.000 claims description 6
- 125000002524 organometallic group Chemical group 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 claims description 5
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 5
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- 230000027455 binding Effects 0.000 claims description 5
- 238000009739 binding Methods 0.000 claims description 5
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 5
- 239000000543 intermediate Substances 0.000 claims description 5
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 5
- 229910052723 transition metal Inorganic materials 0.000 claims description 5
- 150000003624 transition metals Chemical class 0.000 claims description 5
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 claims description 5
- 229910052725 zinc Inorganic materials 0.000 claims description 5
- 239000011701 zinc Substances 0.000 claims description 5
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 4
- 230000029936 alkylation Effects 0.000 claims description 4
- 238000005804 alkylation reaction Methods 0.000 claims description 4
- 229910052793 cadmium Inorganic materials 0.000 claims description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 4
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 239000010936 titanium Chemical group 0.000 claims description 4
- 125000006017 1-propenyl group Chemical group 0.000 claims description 3
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 3
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 3
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 claims description 3
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 3
- XXIJFHJUUXTXIX-UHFFFAOYSA-N 3-nitroso-1H-indol-2-ol Chemical compound Oc1[nH]c2ccccc2c1N=O XXIJFHJUUXTXIX-UHFFFAOYSA-N 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical group [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
- 125000000262 haloalkenyl group Chemical group 0.000 claims description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 claims description 2
- 125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
- 125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 claims description 2
- 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 claims description 2
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical group [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims description 2
- DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 230000010933 acylation Effects 0.000 claims description 2
- 238000005917 acylation reaction Methods 0.000 claims description 2
- 239000002168 alkylating agent Substances 0.000 claims description 2
- 229940100198 alkylating agent Drugs 0.000 claims description 2
- 230000002152 alkylating effect Effects 0.000 claims description 2
- 125000006242 amine protecting group Chemical group 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical group [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 230000007062 hydrolysis Effects 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 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
- 229910052719 titanium Chemical group 0.000 claims description 2
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 9
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 624
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 402
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 183
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 165
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 162
- 239000000741 silica gel Substances 0.000 description 154
- 229910002027 silica gel Inorganic materials 0.000 description 154
- 239000000047 product Substances 0.000 description 120
- 239000000203 mixture Substances 0.000 description 119
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 112
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 96
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 80
- 239000007787 solid Substances 0.000 description 71
- 239000010410 layer Substances 0.000 description 65
- 239000000243 solution Substances 0.000 description 61
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 57
- 239000003480 eluent Substances 0.000 description 56
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 56
- 239000012043 crude product Substances 0.000 description 47
- 150000002081 enamines Chemical class 0.000 description 45
- 238000004440 column chromatography Methods 0.000 description 43
- 238000003756 stirring Methods 0.000 description 41
- 239000003921 oil Substances 0.000 description 40
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
- YKYOUMDCQGMQQO-UHFFFAOYSA-L cadmium dichloride Chemical compound Cl[Cd]Cl YKYOUMDCQGMQQO-UHFFFAOYSA-L 0.000 description 38
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
- 239000012267 brine Substances 0.000 description 34
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 34
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 description 31
- 238000004458 analytical method Methods 0.000 description 29
- 229920006395 saturated elastomer Polymers 0.000 description 28
- 229910000104 sodium hydride Inorganic materials 0.000 description 26
- 238000001816 cooling Methods 0.000 description 23
- 239000011734 sodium Substances 0.000 description 23
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- 230000015572 biosynthetic process Effects 0.000 description 21
- 238000006467 substitution reaction Methods 0.000 description 21
- 239000000725 suspension Substances 0.000 description 21
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 19
- 238000002955 isolation Methods 0.000 description 18
- 238000003786 synthesis reaction Methods 0.000 description 18
- 239000008346 aqueous phase Substances 0.000 description 17
- 238000010438 heat treatment Methods 0.000 description 17
- 238000001953 recrystallisation Methods 0.000 description 17
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 14
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 14
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 14
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 13
- 239000000463 material Substances 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- 239000012312 sodium hydride Substances 0.000 description 13
- 238000012360 testing method Methods 0.000 description 12
- 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 12
- 230000003197 catalytic effect Effects 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- 239000012074 organic phase Substances 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 10
- RIOHLFAXCALWSX-UHFFFAOYSA-N 2-amino-3-pentylbenzonitrile Chemical compound CCCCCC1=CC=CC(C#N)=C1N RIOHLFAXCALWSX-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- WIBWAWQZYFHTAU-UHFFFAOYSA-N ethyl 2,4-dioxo-1-propylpyrrolidine-3-carboxylate Chemical compound CCCN1CC(=O)C(C(=O)OCC)C1=O WIBWAWQZYFHTAU-UHFFFAOYSA-N 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 9
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 238000009835 boiling Methods 0.000 description 8
- 238000001035 drying Methods 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 230000035939 shock Effects 0.000 description 8
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 8
- 229940102001 zinc bromide Drugs 0.000 description 8
- FOSJOOJRBLPLLS-UHFFFAOYSA-N 1-propylpyrrolidine-2,4-dione Chemical compound CCCN1CC(=O)CC1=O FOSJOOJRBLPLLS-UHFFFAOYSA-N 0.000 description 7
- AHUBGXJDVLADTB-UHFFFAOYSA-N 2-amino-3-(hydroxymethyl)benzonitrile Chemical compound NC1=C(CO)C=CC=C1C#N AHUBGXJDVLADTB-UHFFFAOYSA-N 0.000 description 7
- ZEHZEHAGUWIUQV-UHFFFAOYSA-N 2-amino-3-iodobenzonitrile Chemical compound NC1=C(I)C=CC=C1C#N ZEHZEHAGUWIUQV-UHFFFAOYSA-N 0.000 description 7
- ULOLIZHBYWAICY-UHFFFAOYSA-N ethyl 2-(benzylamino)acetate Chemical compound CCOC(=O)CNCC1=CC=CC=C1 ULOLIZHBYWAICY-UHFFFAOYSA-N 0.000 description 7
- 150000004795 grignard reagents Chemical class 0.000 description 7
- 229910052727 yttrium Inorganic materials 0.000 description 7
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 239000005909 Kieselgur Substances 0.000 description 6
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 6
- 239000011777 magnesium Substances 0.000 description 6
- 229910052749 magnesium Inorganic materials 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 239000002480 mineral oil Substances 0.000 description 5
- 235000010446 mineral oil Nutrition 0.000 description 5
- DEFNUDNHTUZJAL-UHFFFAOYSA-N 1-bromo-2-methylprop-1-ene Chemical compound CC(C)=CBr DEFNUDNHTUZJAL-UHFFFAOYSA-N 0.000 description 4
- 125000006020 2-methyl-1-propenyl group Chemical group 0.000 description 4
- MFMCWRUKECKAEI-UHFFFAOYSA-N 3-amino-4-pentyl-1h-pyrrole-2-carbonitrile Chemical compound CCCCCC1=CNC(C#N)=C1N MFMCWRUKECKAEI-UHFFFAOYSA-N 0.000 description 4
- 239000007818 Grignard reagent Substances 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 230000000949 anxiolytic effect Effects 0.000 description 4
- 238000011097 chromatography purification Methods 0.000 description 4
- USVZFSNDGFNNJT-UHFFFAOYSA-N cyclopenta-1,4-dien-1-yl(diphenyl)phosphane (2,3-dichlorocyclopenta-1,4-dien-1-yl)-diphenylphosphane iron(2+) Chemical compound [Fe++].c1cc[c-](c1)P(c1ccccc1)c1ccccc1.Clc1c(cc[c-]1Cl)P(c1ccccc1)c1ccccc1 USVZFSNDGFNNJT-UHFFFAOYSA-N 0.000 description 4
- 125000003963 dichloro group Chemical group Cl* 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- YSMZEMQBSONIMJ-UHFFFAOYSA-M magnesium;2-methanidylpropane;chloride Chemical compound [Mg+2].[Cl-].CC(C)[CH2-] YSMZEMQBSONIMJ-UHFFFAOYSA-M 0.000 description 4
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- DOQJUNNMZNNQAD-UHFFFAOYSA-N pyrrolidine-2,4-dione Chemical compound O=C1CNC(=O)C1 DOQJUNNMZNNQAD-UHFFFAOYSA-N 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- MIDHYAOVUFWYPU-UHFFFAOYSA-N 3-methyl-2-nitrobenzonitrile Chemical compound CC1=CC=CC(C#N)=C1[N+]([O-])=O MIDHYAOVUFWYPU-UHFFFAOYSA-N 0.000 description 3
- XYZWMVYYUIMRIZ-UHFFFAOYSA-N 4-bromo-n,n-dimethylaniline Chemical compound CN(C)C1=CC=C(Br)C=C1 XYZWMVYYUIMRIZ-UHFFFAOYSA-N 0.000 description 3
- KDUNMLRPPVCIGP-UHFFFAOYSA-N CC(C)[Zn]C(C)C Chemical compound CC(C)[Zn]C(C)C KDUNMLRPPVCIGP-UHFFFAOYSA-N 0.000 description 3
- 102000004300 GABA-A Receptors Human genes 0.000 description 3
- 108090000839 GABA-A Receptors Proteins 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 239000012300 argon atmosphere Substances 0.000 description 3
- 229940049706 benzodiazepine Drugs 0.000 description 3
- ANTSCNMPPGJYLG-UHFFFAOYSA-N chlordiazepoxide Chemical compound O=N=1CC(NC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 ANTSCNMPPGJYLG-UHFFFAOYSA-N 0.000 description 3
- 229960004782 chlordiazepoxide Drugs 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 230000035622 drinking Effects 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 3
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 3
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 3
- 238000001665 trituration Methods 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- HTDQSWDEWGSAMN-UHFFFAOYSA-N 1-bromo-2-methoxybenzene Chemical compound COC1=CC=CC=C1Br HTDQSWDEWGSAMN-UHFFFAOYSA-N 0.000 description 2
- ZBTMRBYMKUEVEU-UHFFFAOYSA-N 1-bromo-4-methylbenzene Chemical compound CC1=CC=C(Br)C=C1 ZBTMRBYMKUEVEU-UHFFFAOYSA-N 0.000 description 2
- CAGGZROVARJNDU-UHFFFAOYSA-N 1-prop-2-enylpiperidine-2,4-dione Chemical compound C=CCN1CCC(=O)CC1=O CAGGZROVARJNDU-UHFFFAOYSA-N 0.000 description 2
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 2
- DWPDSGPSDJHEQQ-UHFFFAOYSA-N 2-amino-1-pentylpyrrole-3-carbonitrile Chemical compound CCCCCN1C=CC(C#N)=C1N DWPDSGPSDJHEQQ-UHFFFAOYSA-N 0.000 description 2
- PQXGRUUJIFRFGC-UHFFFAOYSA-N 2-amino-3-methylbenzonitrile Chemical compound CC1=CC=CC(C#N)=C1N PQXGRUUJIFRFGC-UHFFFAOYSA-N 0.000 description 2
- AOPBDRUWRLBSDB-UHFFFAOYSA-N 2-bromoaniline Chemical compound NC1=CC=CC=C1Br AOPBDRUWRLBSDB-UHFFFAOYSA-N 0.000 description 2
- QKJAZPHKNWSXDF-UHFFFAOYSA-N 2-bromoquinoline Chemical compound C1=CC=CC2=NC(Br)=CC=C21 QKJAZPHKNWSXDF-UHFFFAOYSA-N 0.000 description 2
- SSPMLNWQYXPBLN-UHFFFAOYSA-N 2-formylheptanenitrile Chemical compound CCCCCC(C=O)C#N SSPMLNWQYXPBLN-UHFFFAOYSA-N 0.000 description 2
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 2
- NQEDMZWCCWWWIZ-UHFFFAOYSA-N 3-(hydroxymethyl)-2-nitrobenzonitrile Chemical compound OCC1=CC=CC(C#N)=C1[N+]([O-])=O NQEDMZWCCWWWIZ-UHFFFAOYSA-N 0.000 description 2
- HUGYRUWVKNAJOH-UHFFFAOYSA-N 3-formyl-2-nitrobenzonitrile Chemical compound [O-][N+](=O)C1=C(C=O)C=CC=C1C#N HUGYRUWVKNAJOH-UHFFFAOYSA-N 0.000 description 2
- NOONIXPOHUYFGS-UHFFFAOYSA-N 4-prop-2-enylcyclopentane-1,3-dione Chemical compound C=CCC1CC(=O)CC1=O NOONIXPOHUYFGS-UHFFFAOYSA-N 0.000 description 2
- DGDAVTPQCQXLGU-UHFFFAOYSA-N 5437-38-7 Chemical compound CC1=CC=CC(C(O)=O)=C1[N+]([O-])=O DGDAVTPQCQXLGU-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical class NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- FYVNWGDNLYCFKH-UHFFFAOYSA-N C=1C=CSC=1[Zn]C1=CC=CS1 Chemical compound C=1C=CSC=1[Zn]C1=CC=CS1 FYVNWGDNLYCFKH-UHFFFAOYSA-N 0.000 description 2
- QQTGJVBUIOTPGZ-UHFFFAOYSA-N CCC[Zn]CCC Chemical compound CCC[Zn]CCC QQTGJVBUIOTPGZ-UHFFFAOYSA-N 0.000 description 2
- 238000007445 Chromatographic isolation Methods 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 2
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-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
- 230000000049 anti-anxiety effect Effects 0.000 description 2
- 239000002249 anxiolytic agent Substances 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 150000003857 carboxamides Chemical class 0.000 description 2
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 2
- 229960002327 chloral hydrate Drugs 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- JZXVIASGAMNRDD-UHFFFAOYSA-N ethyl 2-(prop-2-enylamino)acetate Chemical compound CCOC(=O)CNCC=C JZXVIASGAMNRDD-UHFFFAOYSA-N 0.000 description 2
- RWMXNXVEIJWDFU-UHFFFAOYSA-N ethyl 2-amino-3-cyanopyrrole-1-carboxylate Chemical compound CCOC(=O)N1C=CC(C#N)=C1N RWMXNXVEIJWDFU-UHFFFAOYSA-N 0.000 description 2
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000007788 liquid Substances 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
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 125000001979 organolithium group Chemical group 0.000 description 2
- 238000005949 ozonolysis reaction Methods 0.000 description 2
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 2
- 235000010265 sodium sulphite Nutrition 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000001629 suppression Effects 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
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- NNQDMQVWOWCVEM-NSCUHMNNSA-N (e)-1-bromoprop-1-ene Chemical compound C\C=C\Br NNQDMQVWOWCVEM-NSCUHMNNSA-N 0.000 description 1
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
- QELVYIQQUJJODY-UHFFFAOYSA-N 1-benzylpyrrolidine-2,4-dione Chemical compound O=C1CC(=O)CN1CC1=CC=CC=C1 QELVYIQQUJJODY-UHFFFAOYSA-N 0.000 description 1
- PLDWAJLZAAHOGG-UHFFFAOYSA-N 1-bromo-3-methoxybenzene Chemical compound COC1=CC=CC(Br)=C1 PLDWAJLZAAHOGG-UHFFFAOYSA-N 0.000 description 1
- IUXHPSPHPKXTPA-UHFFFAOYSA-N 1-bromobut-1-ene Chemical compound CCC=CBr IUXHPSPHPKXTPA-UHFFFAOYSA-N 0.000 description 1
- YZWKKMVJZFACSU-UHFFFAOYSA-N 1-bromopentane Chemical compound CCCCCBr YZWKKMVJZFACSU-UHFFFAOYSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- IGEGCGIMFIEUTC-UHFFFAOYSA-N 1-butyl-2-[(5-oxo-1-propyl-2h-pyrrol-3-yl)amino]pyrrole-3-carbonitrile Chemical compound CCCCN1C=CC(C#N)=C1NC1=CC(=O)N(CCC)C1 IGEGCGIMFIEUTC-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- NGXLTYPELAIUHE-UHFFFAOYSA-N 2-(hydroxyamino)indol-3-one Chemical class C1=CC=C2C(=O)C(NO)=NC2=C1 NGXLTYPELAIUHE-UHFFFAOYSA-N 0.000 description 1
- UOVQICQZOOAUEX-UHFFFAOYSA-N 2-[(1-benzyl-5-oxo-2h-pyrrol-3-yl)amino]-3-(2-methylpropyl)benzonitrile Chemical compound CC(C)CC1=CC=CC(C#N)=C1NC(C1)=CC(=O)N1CC1=CC=CC=C1 UOVQICQZOOAUEX-UHFFFAOYSA-N 0.000 description 1
- BXEAPIQSHUVBNR-UHFFFAOYSA-N 2-[(1-benzyl-5-oxo-2h-pyrrol-3-yl)amino]-3-(chloromethyl)benzonitrile Chemical compound ClCC1=CC=CC(C#N)=C1NC(C1)=CC(=O)N1CC1=CC=CC=C1 BXEAPIQSHUVBNR-UHFFFAOYSA-N 0.000 description 1
- AXEIUTKBAXILEU-UHFFFAOYSA-N 2-[(1-benzyl-5-oxo-2h-pyrrol-3-yl)amino]-3-(hydroxymethyl)benzonitrile Chemical compound OCC1=CC=CC(C#N)=C1NC(C1)=CC(=O)N1CC1=CC=CC=C1 AXEIUTKBAXILEU-UHFFFAOYSA-N 0.000 description 1
- QWUXDWFPEYLAHY-UHFFFAOYSA-N 2-[(3-oxo-4-prop-2-enylcyclopenten-1-yl)amino]-3-pentylbenzonitrile Chemical compound CCCCCC1=CC=CC(C#N)=C1NC1=CC(=O)C(CC=C)C1 QWUXDWFPEYLAHY-UHFFFAOYSA-N 0.000 description 1
- QMEABEKBOXOMBG-UHFFFAOYSA-N 2-[(5-oxo-1-propyl-2h-pyrrol-3-yl)amino]-1-pentylpyrrole-3-carbonitrile Chemical compound CCCCCN1C=CC(C#N)=C1NC1=CC(=O)N(CCC)C1 QMEABEKBOXOMBG-UHFFFAOYSA-N 0.000 description 1
- SPYPVECEQWCPCL-UHFFFAOYSA-N 2-[(5-oxo-1-propyl-2h-pyrrol-3-yl)amino]-3-pentylbenzonitrile Chemical compound CCCCCC1=CC=CC(C#N)=C1NC1=CC(=O)N(CCC)C1 SPYPVECEQWCPCL-UHFFFAOYSA-N 0.000 description 1
- JETINNUNGXFHFV-UHFFFAOYSA-N 2-[(5-oxo-1-propyl-2h-pyrrol-3-yl)amino]-3-prop-2-enylbenzonitrile Chemical compound O=C1N(CCC)CC(NC=2C(=CC=CC=2CC=C)C#N)=C1 JETINNUNGXFHFV-UHFFFAOYSA-N 0.000 description 1
- UXRZDAIPRJJUSY-UHFFFAOYSA-N 2-[[1-(cyclopropylmethyl)-5-oxo-2h-pyrrol-3-yl]amino]-3-(2-methylpropyl)benzonitrile Chemical compound CC(C)CC1=CC=CC(C#N)=C1NC(C1)=CC(=O)N1CC1CC1 UXRZDAIPRJJUSY-UHFFFAOYSA-N 0.000 description 1
- WDYKKWUJWWOGHL-UHFFFAOYSA-N 2-[[1-(cyclopropylmethyl)-5-oxo-2h-pyrrol-3-yl]amino]-3-propylbenzonitrile Chemical compound CCCC1=CC=CC(C#N)=C1NC(C1)=CC(=O)N1CC1CC1 WDYKKWUJWWOGHL-UHFFFAOYSA-N 0.000 description 1
- FOEYKARRRIIPNF-UHFFFAOYSA-N 2-amino-1-butylpyrrole-3-carbonitrile Chemical compound CCCCN1C=CC(C#N)=C1N FOEYKARRRIIPNF-UHFFFAOYSA-N 0.000 description 1
- DSRMKWAJZGUISV-UHFFFAOYSA-N 2-amino-3-(2-methylprop-1-enyl)benzonitrile Chemical compound CC(C)=CC1=CC=CC(C#N)=C1N DSRMKWAJZGUISV-UHFFFAOYSA-N 0.000 description 1
- LXKUJPSTUFZRKF-UHFFFAOYSA-N 2-amino-3-(2-methylpropyl)benzonitrile Chemical compound CC(C)CC1=CC=CC(C#N)=C1N LXKUJPSTUFZRKF-UHFFFAOYSA-N 0.000 description 1
- NDRRDXQRDIFHAY-UHFFFAOYSA-N 2-amino-3-(4-methylphenyl)benzonitrile Chemical compound C1=CC(C)=CC=C1C1=CC=CC(C#N)=C1N NDRRDXQRDIFHAY-UHFFFAOYSA-N 0.000 description 1
- RTIWACSVMFUEBF-UHFFFAOYSA-N 2-amino-3-bromobenzonitrile Chemical compound NC1=C(Br)C=CC=C1C#N RTIWACSVMFUEBF-UHFFFAOYSA-N 0.000 description 1
- QMTUUULZQWPMQQ-UHFFFAOYSA-N 2-amino-3-but-1-enylbenzonitrile Chemical compound CCC=CC1=CC=CC(C#N)=C1N QMTUUULZQWPMQQ-UHFFFAOYSA-N 0.000 description 1
- SVYBOSHOMLGYLV-UHFFFAOYSA-N 2-amino-3-butylbenzonitrile Chemical compound CCCCC1=CC=CC(C#N)=C1N SVYBOSHOMLGYLV-UHFFFAOYSA-N 0.000 description 1
- WDLULBVOCYXQAH-UHFFFAOYSA-N 2-amino-3-prop-1-enylbenzonitrile Chemical compound CC=CC1=CC=CC(C#N)=C1N WDLULBVOCYXQAH-UHFFFAOYSA-N 0.000 description 1
- XQSYKXPFKWTCNV-UHFFFAOYSA-N 2-amino-3-prop-2-enylbenzonitrile Chemical compound NC1=C(CC=C)C=CC=C1C#N XQSYKXPFKWTCNV-UHFFFAOYSA-N 0.000 description 1
- FBOMPBLLNHBYLR-UHFFFAOYSA-N 2-amino-3-propylbenzonitrile Chemical compound CCCC1=CC=CC(C#N)=C1N FBOMPBLLNHBYLR-UHFFFAOYSA-N 0.000 description 1
- XFKYKTBPRBZDFG-UHFFFAOYSA-N 2-aminoacetonitrile;hydrochloride Chemical compound Cl.NCC#N XFKYKTBPRBZDFG-UHFFFAOYSA-N 0.000 description 1
- PHMRPWPDDRGGGF-UHFFFAOYSA-N 2-bromoprop-1-ene Chemical compound CC(Br)=C PHMRPWPDDRGGGF-UHFFFAOYSA-N 0.000 description 1
- OTZWITHPRWRMMX-UHFFFAOYSA-N 2-butyl-1h-pyrrole Chemical compound CCCCC1=CC=CN1 OTZWITHPRWRMMX-UHFFFAOYSA-N 0.000 description 1
- IPOVOSHRRIJKBR-UHFFFAOYSA-N 2-ethylpropanedioyl dichloride Chemical compound CCC(C(Cl)=O)C(Cl)=O IPOVOSHRRIJKBR-UHFFFAOYSA-N 0.000 description 1
- UBPDKIDWEADHPP-UHFFFAOYSA-N 2-iodoaniline Chemical compound NC1=CC=CC=C1I UBPDKIDWEADHPP-UHFFFAOYSA-N 0.000 description 1
- SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 1
- UXIWOGQMLGEQNN-UHFFFAOYSA-N 2-pentylaniline;hydrochloride Chemical compound Cl.CCCCCC1=CC=CC=C1N UXIWOGQMLGEQNN-UHFFFAOYSA-N 0.000 description 1
- JBSCONCLPFUDOO-UHFFFAOYSA-N 3-(2-methylprop-1-enyl)-2-[(5-oxo-1-propyl-2h-pyrrol-3-yl)amino]benzonitrile Chemical compound O=C1N(CCC)CC(NC=2C(=CC=CC=2C=C(C)C)C#N)=C1 JBSCONCLPFUDOO-UHFFFAOYSA-N 0.000 description 1
- OQYGOAYAHGSNAE-UHFFFAOYSA-N 3-(4-methylphenyl)-2-[(5-oxo-1-propyl-2h-pyrrol-3-yl)amino]benzonitrile Chemical compound O=C1N(CCC)CC(NC=2C(=CC=CC=2C#N)C=2C=CC(C)=CC=2)=C1 OQYGOAYAHGSNAE-UHFFFAOYSA-N 0.000 description 1
- MBDFJRKOWSWWKG-UHFFFAOYSA-N 3-(chloromethyl)-2-[(5-oxo-1-propyl-2h-pyrrol-3-yl)amino]benzonitrile Chemical compound O=C1N(CCC)CC(NC=2C(=CC=CC=2CCl)C#N)=C1 MBDFJRKOWSWWKG-UHFFFAOYSA-N 0.000 description 1
- ZKZXQXRUMFWWHR-UHFFFAOYSA-N 3-(hydroxyamino)-7-pentylindol-2-one Chemical compound CCCCCC1=CC=CC2=C1NC(=O)C2=NO ZKZXQXRUMFWWHR-UHFFFAOYSA-N 0.000 description 1
- DKKWIEUOFGXPFK-UHFFFAOYSA-N 3-[(5-oxo-1-propyl-2h-pyrrol-3-yl)amino]-4-pentyl-1h-pyrrole-2-carbonitrile Chemical compound CCCCCC1=CNC(C#N)=C1NC1=CC(=O)N(CCC)C1 DKKWIEUOFGXPFK-UHFFFAOYSA-N 0.000 description 1
- HNWGYOYCIRSRHK-UHFFFAOYSA-N 3-[2-(dimethylamino)ethenyl]-2-nitrobenzonitrile Chemical compound CN(C)C=CC1=CC=CC(C#N)=C1[N+]([O-])=O HNWGYOYCIRSRHK-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- HSLDTAUAAUGZJA-UHFFFAOYSA-N 3-bromo-2-[(3-oxo-4-prop-2-enylcyclopenten-1-yl)amino]benzonitrile Chemical compound BrC1=CC=CC(C#N)=C1NC1=CC(=O)C(CC=C)C1 HSLDTAUAAUGZJA-UHFFFAOYSA-N 0.000 description 1
- GIYUPYYBFMPGKZ-UHFFFAOYSA-N 3-bromo-2-[(5-oxo-1-propyl-2h-pyrrol-3-yl)amino]benzonitrile Chemical compound O=C1N(CCC)CC(NC=2C(=CC=CC=2Br)C#N)=C1 GIYUPYYBFMPGKZ-UHFFFAOYSA-N 0.000 description 1
- HNAAQXFBFBTAIC-UHFFFAOYSA-N 3-methyl-2-[(3-oxo-4-prop-2-enylcyclopenten-1-yl)amino]benzonitrile Chemical compound CC1=CC=CC(C#N)=C1NC1=CC(=O)C(CC=C)C1 HNAAQXFBFBTAIC-UHFFFAOYSA-N 0.000 description 1
- HTVJDAQMMNMEBZ-UHFFFAOYSA-N 3-methyl-2-nitrobenzamide Chemical compound CC1=CC=CC(C(N)=O)=C1[N+]([O-])=O HTVJDAQMMNMEBZ-UHFFFAOYSA-N 0.000 description 1
- VBBOTNFXUMPCFP-UHFFFAOYSA-N 4,4-dimethylcyclopentane-1,3-dione Chemical compound CC1(C)CC(=O)CC1=O VBBOTNFXUMPCFP-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- UBOUWYQHZBPKBQ-UHFFFAOYSA-N 4-bromo-1,1,1-trifluoro-2-methylbutane Chemical compound FC(F)(F)C(C)CCBr UBOUWYQHZBPKBQ-UHFFFAOYSA-N 0.000 description 1
- XPMQQBNUHVNWMM-UHFFFAOYSA-N 4-ethoxy-1-prop-2-enyl-2,3-dihydropyridin-6-one Chemical compound CCOC1=CC(=O)N(CC=C)CC1 XPMQQBNUHVNWMM-UHFFFAOYSA-N 0.000 description 1
- QYRCMTCDSZFQHQ-UHFFFAOYSA-N 4-prop-2-enylcyclohexane-1,3-dione Chemical compound C=CCC1CCC(=O)CC1=O QYRCMTCDSZFQHQ-UHFFFAOYSA-N 0.000 description 1
- NZORANVPNBZMRN-UHFFFAOYSA-N 5-amino-3-(2,4-dioxo-1-prop-2-enylpiperidin-3-yl)-4-pentyl-1h-pyrrole-2-carbonitrile Chemical compound CCCCCC1=C(N)NC(C#N)=C1C1C(=O)N(CC=C)CCC1=O NZORANVPNBZMRN-UHFFFAOYSA-N 0.000 description 1
- XXTLMXOGRBXMQF-UHFFFAOYSA-N 5-bromopent-2-yne Chemical compound CC#CCCBr XXTLMXOGRBXMQF-UHFFFAOYSA-N 0.000 description 1
- 150000005654 5-bromoquinolines Chemical class 0.000 description 1
- OCVKSIWBTJCXPV-UHFFFAOYSA-N 7-bromo-1h-indole-2,3-dione Chemical compound BrC1=CC=CC2=C1NC(=O)C2=O OCVKSIWBTJCXPV-UHFFFAOYSA-N 0.000 description 1
- XONKJZDHGCMRRF-UHFFFAOYSA-N 7-fluoro-1h-indole Chemical compound FC1=CC=CC2=C1NC=C2 XONKJZDHGCMRRF-UHFFFAOYSA-N 0.000 description 1
- VFKZIBQIPRCHML-UHFFFAOYSA-N 7-pentyl-1h-indole-2,3-dione Chemical compound CCCCCC1=CC=CC2=C1NC(=O)C2=O VFKZIBQIPRCHML-UHFFFAOYSA-N 0.000 description 1
- KKYXRFBDQWLNGP-UHFFFAOYSA-N 9-amino-1-oxo-2-propyl-3h-pyrrolo[3,4-b]quinoline-5-carbaldehyde Chemical compound C1=CC=C2C(N)=C(C(N(CCC)C3)=O)C3=NC2=C1C=O KKYXRFBDQWLNGP-UHFFFAOYSA-N 0.000 description 1
- GLFVJIHHVILSJB-UHFFFAOYSA-N 9-amino-2-(cyclopropylmethyl)-5-(2-methylpropyl)-3h-pyrrolo[3,4-b]quinolin-1-one Chemical compound C1C=2N=C3C(CC(C)C)=CC=CC3=C(N)C=2C(=O)N1CC1CC1 GLFVJIHHVILSJB-UHFFFAOYSA-N 0.000 description 1
- BDTXEXLXEQJCRH-UHFFFAOYSA-N 9-amino-2-(cyclopropylmethyl)-5-propyl-3h-pyrrolo[3,4-b]quinolin-1-one Chemical compound C1C=2N=C3C(CCC)=CC=CC3=C(N)C=2C(=O)N1CC1CC1 BDTXEXLXEQJCRH-UHFFFAOYSA-N 0.000 description 1
- DYNBIPVWKIQUGQ-UHFFFAOYSA-N 9-amino-2-benzyl-5-(2-methylpropyl)-3h-pyrrolo[3,4-b]quinolin-1-one Chemical compound C1C=2N=C3C(CC(C)C)=CC=CC3=C(N)C=2C(=O)N1CC1=CC=CC=C1 DYNBIPVWKIQUGQ-UHFFFAOYSA-N 0.000 description 1
- RXBJNXSKSFOCCG-UHFFFAOYSA-N 9-amino-2-propyl-5-(4,4,4-trifluoro-3-methylbutyl)-3h-pyrrolo[3,4-b]quinolin-1-one Chemical compound C1=CC=C2C(N)=C(C(N(CCC)C3)=O)C3=NC2=C1CCC(C)C(F)(F)F RXBJNXSKSFOCCG-UHFFFAOYSA-N 0.000 description 1
- LQKIHWITUKDRGC-UHFFFAOYSA-N 9-amino-5-(1-hydroxy-3-methylbutyl)-2-propyl-3h-pyrrolo[3,4-b]quinolin-1-one Chemical compound C1=CC=C2C(N)=C(C(N(CCC)C3)=O)C3=NC2=C1C(O)CC(C)C LQKIHWITUKDRGC-UHFFFAOYSA-N 0.000 description 1
- MRHHTLIXKWMDCC-UHFFFAOYSA-N 9-amino-5-(2-methylprop-1-enyl)-2-propyl-3h-pyrrolo[3,4-b]quinolin-1-one Chemical compound C1=CC=C2C(N)=C(C(N(CCC)C3)=O)C3=NC2=C1C=C(C)C MRHHTLIXKWMDCC-UHFFFAOYSA-N 0.000 description 1
- VHLAPFAYFZNLEB-UHFFFAOYSA-N 9-amino-5-(2-methylpropyl)-2,3-dihydropyrrolo[3,4-b]quinolin-1-one Chemical compound N1=C2C(CC(C)C)=CC=CC2=C(N)C2=C1CNC2=O VHLAPFAYFZNLEB-UHFFFAOYSA-N 0.000 description 1
- LMZNPVNCXYCTNA-UHFFFAOYSA-N 9-amino-5-(2-methylpropyl)-2-prop-2-enyl-2,3-dihydrocyclopenta[b]quinolin-1-one Chemical compound N1=C2C(CC(C)C)=CC=CC2=C(N)C2=C1CC(CC=C)C2=O LMZNPVNCXYCTNA-UHFFFAOYSA-N 0.000 description 1
- FEJQAVSHEXKOJG-UHFFFAOYSA-N 9-amino-5-(2-methylpropyl)-2-prop-2-ynyl-3h-pyrrolo[3,4-b]quinolin-1-one Chemical compound N1=C2C(CC(C)C)=CC=CC2=C(N)C2=C1CN(CC#C)C2=O FEJQAVSHEXKOJG-UHFFFAOYSA-N 0.000 description 1
- XHYDZDZLWRMPNC-UHFFFAOYSA-N 9-amino-5-(4-methylphenyl)-2-propyl-3h-pyrrolo[3,4-b]quinolin-1-one Chemical compound C1=CC=C2C(N)=C3C(=O)N(CCC)CC3=NC2=C1C1=CC=C(C)C=C1 XHYDZDZLWRMPNC-UHFFFAOYSA-N 0.000 description 1
- SZWDHUPWOWIJPG-UHFFFAOYSA-N 9-amino-5-bromo-2-prop-2-enyl-2,3-dihydrocyclopenta[b]quinolin-1-one Chemical compound C1=CC=C2C(N)=C(C(=O)C(CC=C)C3)C3=NC2=C1Br SZWDHUPWOWIJPG-UHFFFAOYSA-N 0.000 description 1
- WWJQTYFZFKQAQI-UHFFFAOYSA-N 9-amino-5-bromo-2-propyl-3h-pyrrolo[3,4-b]quinolin-1-one Chemical compound C1=CC=C2C(N)=C(C(N(CCC)C3)=O)C3=NC2=C1Br WWJQTYFZFKQAQI-UHFFFAOYSA-N 0.000 description 1
- XMTKYNJSZSZYOY-UHFFFAOYSA-N 9-amino-5-butyl-2-prop-2-enyl-3h-pyrrolo[3,4-b]quinolin-1-one Chemical compound N1=C2C(CCCC)=CC=CC2=C(N)C2=C1CN(CC=C)C2=O XMTKYNJSZSZYOY-UHFFFAOYSA-N 0.000 description 1
- CYGQAKFDFIUFKK-UHFFFAOYSA-N 9-amino-5-butyl-2-propyl-3h-pyrrolo[3,4-b]quinolin-1-one Chemical compound N1=C2C(CCCC)=CC=CC2=C(N)C2=C1CN(CCC)C2=O CYGQAKFDFIUFKK-UHFFFAOYSA-N 0.000 description 1
- KLOCWXJVYMETNC-UHFFFAOYSA-N 9-amino-5-iodo-2-propyl-3h-pyrrolo[3,4-b]quinolin-1-one Chemical compound C1=CC=C2C(N)=C(C(N(CCC)C3)=O)C3=NC2=C1I KLOCWXJVYMETNC-UHFFFAOYSA-N 0.000 description 1
- FXONYBGIMLDPON-UHFFFAOYSA-N 9-amino-5-methyl-2-prop-2-enyl-2,3-dihydrocyclopenta[b]quinolin-1-one Chemical compound N1=C2C(C)=CC=CC2=C(N)C2=C1CC(CC=C)C2=O FXONYBGIMLDPON-UHFFFAOYSA-N 0.000 description 1
- PWLXQNXUAJIRPX-UHFFFAOYSA-N 9-amino-5-methyl-2-propyl-3h-pyrrolo[3,4-b]quinolin-1-one Chemical compound C1=CC=C2C(N)=C(C(N(CCC)C3)=O)C3=NC2=C1C PWLXQNXUAJIRPX-UHFFFAOYSA-N 0.000 description 1
- IXFYNIYZWQGCAQ-UHFFFAOYSA-N 9-amino-5-pent-3-ynyl-2-propyl-3h-pyrrolo[3,4-b]quinolin-1-one Chemical compound C1=CC=C2C(N)=C(C(N(CCC)C3)=O)C3=NC2=C1CCC#CC IXFYNIYZWQGCAQ-UHFFFAOYSA-N 0.000 description 1
- GQVRPBWIQJPFLY-UHFFFAOYSA-N 9-amino-5-pentyl-2-prop-2-enyl-2,3-dihydrocyclopenta[b]quinolin-1-one Chemical compound N1=C2C(CCCCC)=CC=CC2=C(N)C2=C1CC(CC=C)C2=O GQVRPBWIQJPFLY-UHFFFAOYSA-N 0.000 description 1
- LBUSLCUKHFECEF-UHFFFAOYSA-N 9-amino-5-prop-2-enyl-2-propyl-3h-pyrrolo[3,4-b]quinolin-1-one Chemical compound C1=CC=C2C(N)=C(C(N(CCC)C3)=O)C3=NC2=C1CC=C LBUSLCUKHFECEF-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- ZAYNDHLMBXGBRG-UHFFFAOYSA-N C1CC1[Zn]C1CC1 Chemical compound C1CC1[Zn]C1CC1 ZAYNDHLMBXGBRG-UHFFFAOYSA-N 0.000 description 1
- LGNCSYPEFYFBDV-UHFFFAOYSA-N C1CCCC1[Zn]C1CCCC1 Chemical compound C1CCCC1[Zn]C1CCCC1 LGNCSYPEFYFBDV-UHFFFAOYSA-N 0.000 description 1
- CMEARNFQRFVRMJ-UHFFFAOYSA-N C=CCN1CCC(=O)C(C1=O)C2(C=CC=C(C2N)C#N)CO Chemical compound C=CCN1CCC(=O)C(C1=O)C2(C=CC=C(C2N)C#N)CO CMEARNFQRFVRMJ-UHFFFAOYSA-N 0.000 description 1
- DFLCBCMZFUSLNE-UHFFFAOYSA-N CC(C)C[Zn]CC(C)C Chemical compound CC(C)C[Zn]CC(C)C DFLCBCMZFUSLNE-UHFFFAOYSA-N 0.000 description 1
- ROAVDUAVBDEYPN-UHFFFAOYSA-N CCC(C)[Zn] Chemical compound CCC(C)[Zn] ROAVDUAVBDEYPN-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 241000400611 Eucalyptus deanei Species 0.000 description 1
- 101000939500 Homo sapiens UBX domain-containing protein 11 Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 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
- 241000124008 Mammalia Species 0.000 description 1
- MRQPVTORRFOOSO-UHFFFAOYSA-N N1=C2C(CC(C)(C)C)=CC=CC2=C(N)C2=C1CC(CC=C)C2=O Chemical compound N1=C2C(CC(C)(C)C)=CC=CC2=C(N)C2=C1CC(CC=C)C2=O MRQPVTORRFOOSO-UHFFFAOYSA-N 0.000 description 1
- PVUJUIUBPPWYEC-UHFFFAOYSA-N N1=C2CN(CCC)C(=O)C2=C(Cl)C2=C1C(CCCCC)SC2 Chemical compound N1=C2CN(CCC)C(=O)C2=C(Cl)C2=C1C(CCCCC)SC2 PVUJUIUBPPWYEC-UHFFFAOYSA-N 0.000 description 1
- QBNTZHSMQXRQFD-UHFFFAOYSA-N N1=C2CN(CCC)C(=O)C2=C(N)C2=C1C(CCCCC)SC2 Chemical compound N1=C2CN(CCC)C(=O)C2=C(N)C2=C1C(CCCCC)SC2 QBNTZHSMQXRQFD-UHFFFAOYSA-N 0.000 description 1
- 229910020284 Na2SO4.10H2O Inorganic materials 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- WWVWMXUVWIZNDA-UHFFFAOYSA-N O=C1C(=NO)NC2=C1C=CC=C2Br Chemical compound O=C1C(=NO)NC2=C1C=CC=C2Br WWVWMXUVWIZNDA-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 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 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 102100029645 UBX domain-containing protein 11 Human genes 0.000 description 1
- IARQYXOBHNBZDC-UHFFFAOYSA-M [Br-].CC(C)(C)C[Mg+] Chemical compound [Br-].CC(C)(C)C[Mg+] IARQYXOBHNBZDC-UHFFFAOYSA-M 0.000 description 1
- AQDPXLDQHTWRKY-UHFFFAOYSA-M [Br-].FC(F)(F)C(C)CC[Mg+] Chemical compound [Br-].FC(F)(F)C(C)CC[Mg+] AQDPXLDQHTWRKY-UHFFFAOYSA-M 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000006295 amino methylene group Chemical group [H]N(*)C([H])([H])* 0.000 description 1
- 125000005219 aminonitrile group Chemical group 0.000 description 1
- 230000001253 anti-conflict Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 229940005530 anxiolytics Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 150000001499 aryl bromides Chemical class 0.000 description 1
- 150000001557 benzodiazepines Chemical class 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 1
- 150000001661 cadmium Chemical class 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- RFKZUAOAYVHBOY-UHFFFAOYSA-M copper(1+);acetate Chemical compound [Cu+].CC([O-])=O RFKZUAOAYVHBOY-UHFFFAOYSA-M 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- GCUVBACNBHGZRS-UHFFFAOYSA-N cyclopenta-1,3-diene cyclopenta-2,4-dien-1-yl(diphenyl)phosphane iron(2+) Chemical compound [Fe++].c1cc[cH-]c1.c1cc[c-](c1)P(c1ccccc1)c1ccccc1 GCUVBACNBHGZRS-UHFFFAOYSA-N 0.000 description 1
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 1
- UVWQYWHKTZABSO-ILADVTTDSA-N de voachalotinol Chemical compound CN1C2=CC=CC=C2C(C[C@H]2[C@@H]3CO)=C1[C@H]1N2C/C(=C/C)[C@@H]3C1 UVWQYWHKTZABSO-ILADVTTDSA-N 0.000 description 1
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 1
- HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- MKRVHLWAVKJBFN-UHFFFAOYSA-N diphenylzinc Chemical compound C=1C=CC=CC=1[Zn]C1=CC=CC=C1 MKRVHLWAVKJBFN-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- FEYZMHKYJPURSF-UHFFFAOYSA-N ethyl 1-cyclopropyl-2,4-dioxopyrrolidine-3-carboxylate Chemical compound O=C1C(C(=O)OCC)C(=O)CN1C1CC1 FEYZMHKYJPURSF-UHFFFAOYSA-N 0.000 description 1
- VOZPZBSGYPGXEE-UHFFFAOYSA-N ethyl 2-(cyclopropylamino)acetate Chemical compound CCOC(=O)CNC1CC1 VOZPZBSGYPGXEE-UHFFFAOYSA-N 0.000 description 1
- BFFAICONXNLADT-UHFFFAOYSA-N ethyl 2-(cyclopropylmethylamino)acetate Chemical compound CCOC(=O)CNCC1CC1 BFFAICONXNLADT-UHFFFAOYSA-N 0.000 description 1
- HIYLMYJDQWBPLH-UHFFFAOYSA-N ethyl 2-[(2,4-dimethoxyphenyl)methylamino]acetate Chemical compound CCOC(=O)CNCC1=CC=C(OC)C=C1OC HIYLMYJDQWBPLH-UHFFFAOYSA-N 0.000 description 1
- AHXJAKSHPPOAQY-UHFFFAOYSA-N ethyl 3-[benzyl-(2-ethoxy-2-oxoethyl)amino]-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)N(CC(=O)OCC)CC1=CC=CC=C1 AHXJAKSHPPOAQY-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 229960002200 flunitrazepam Drugs 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- SDAXRHHPNYTELL-UHFFFAOYSA-N heptanenitrile Chemical compound CCCCCCC#N SDAXRHHPNYTELL-UHFFFAOYSA-N 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 210000000548 hind-foot Anatomy 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000006883 memory enhancing effect Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- AGJSNMGHAVDLRQ-IWFBPKFRSA-N methyl (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-IWFBPKFRSA-N 0.000 description 1
- LKZIONCQGYKZCF-UHFFFAOYSA-N methyl 4-[(5-oxo-1-propyl-2h-pyrrol-3-yl)amino]-5-pentylthiophene-3-carboxylate Chemical compound S1C=C(C(=O)OC)C(NC=2CN(CCC)C(=O)C=2)=C1CCCCC LKZIONCQGYKZCF-UHFFFAOYSA-N 0.000 description 1
- BRHIEGJHFVUVEI-UHFFFAOYSA-N methyl 4-amino-5-pentylthiophene-3-carboxylate Chemical compound CCCCCC=1SC=C(C(=O)OC)C=1N BRHIEGJHFVUVEI-UHFFFAOYSA-N 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- HXRAMSFGUAOAJR-UHFFFAOYSA-N n,n,n',n'-tetramethyl-1-[(2-methylpropan-2-yl)oxy]methanediamine Chemical compound CN(C)C(N(C)C)OC(C)(C)C HXRAMSFGUAOAJR-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 210000002445 nipple Anatomy 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
- 239000012285 osmium tetroxide Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- FVZVCSNXTFCBQU-UHFFFAOYSA-N phosphanyl Chemical group [PH2] FVZVCSNXTFCBQU-UHFFFAOYSA-N 0.000 description 1
- RDNZDMDLRIQQAX-UHFFFAOYSA-N piperidine-2,4-dione Chemical compound O=C1CCNC(=O)C1 RDNZDMDLRIQQAX-UHFFFAOYSA-N 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 239000013014 purified material Substances 0.000 description 1
- 150000005229 pyrazolopyridines Chemical class 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 231100000161 signs of toxicity Toxicity 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 229940080313 sodium starch Drugs 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- HLJZFARRLCQZAN-UHFFFAOYSA-I zinc titanium(3+) pentachloride Chemical compound [Cl-].[Cl-].[Cl-].[Cl-].[Cl-].[Ti+3].[Zn+2] HLJZFARRLCQZAN-UHFFFAOYSA-I 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—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
- A61P25/20—Hypnotics; Sedatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/16—Ring systems of three rings containing carbocyclic rings other than six-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—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)
- Neurosurgery (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Anesthesiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (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 And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB868610980A GB8610980D0 (en) | 1986-05-06 | 1986-05-06 | Heterocyclic fused tricyclic compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO871867D0 NO871867D0 (no) | 1987-05-05 |
| NO871867L true NO871867L (no) | 1987-11-09 |
Family
ID=10597387
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO871867A NO871867L (no) | 1986-05-06 | 1987-05-05 | Fremgangsmaate for fremstilling av terapeutisk aktive heterocykliske kondenserte tricykliske forbindelser. |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US4975435A (pt) |
| EP (1) | EP0245053B1 (pt) |
| JP (1) | JPS6327479A (pt) |
| KR (1) | KR910001283B1 (pt) |
| AU (1) | AU601975B2 (pt) |
| DD (1) | DD270913A5 (pt) |
| DK (1) | DK229987A (pt) |
| FI (1) | FI871985A (pt) |
| GB (2) | GB8610980D0 (pt) |
| HU (1) | HU196403B (pt) |
| IL (1) | IL82412A0 (pt) |
| MW (1) | MW3087A1 (pt) |
| NO (1) | NO871867L (pt) |
| NZ (1) | NZ220176A (pt) |
| PT (1) | PT84828B (pt) |
| ZA (1) | ZA873175B (pt) |
| ZM (1) | ZM3687A1 (pt) |
| ZW (1) | ZW8087A1 (pt) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0179597B1 (en) * | 1984-10-18 | 1993-02-03 | Pfizer Inc. | Spherically shaped precipitated calcium carbonate, its preparation and use |
| ES2056849T3 (es) * | 1987-04-23 | 1994-10-16 | Hoechst Roussel Pharma | Heteroalquilen-quinolinaminas condensadas, un procedimiento y productos intermedios para su preparacion y su uso como medicamentos. |
| IL87861A0 (en) * | 1987-10-05 | 1989-03-31 | Pfizer | 4-aminopyridine derivatives |
| GB8828806D0 (en) * | 1988-12-09 | 1989-01-18 | Beecham Group Plc | Novel compounds |
| JP2650533B2 (ja) * | 1991-10-04 | 1997-09-03 | 王子製紙株式会社 | 嵩高なオフセット印刷用中質紙 |
| US5243049A (en) * | 1992-01-22 | 1993-09-07 | Neurogen Corporation | Certain pyrroloquinolinones: a new class of GABA brain receptor ligands |
| US6541634B2 (en) | 1999-02-26 | 2003-04-01 | Pfizer Inc. | Process for preparing growth hormone secretagogues |
| US20030220646A1 (en) * | 2002-05-23 | 2003-11-27 | Thelen Sarah L. | Method and apparatus for reducing femoral fractures |
| US7442709B2 (en) * | 2003-08-21 | 2008-10-28 | Osi Pharmaceuticals, Inc. | N3-substituted imidazopyridine c-Kit inhibitors |
| AU2004268949A1 (en) * | 2003-08-21 | 2005-03-10 | Osi Pharmaceuticals, Inc. | N-substituted benzimidazolyl C-kit inhibitors |
| AP2006003553A0 (en) | 2003-08-21 | 2006-04-30 | Osi Pharm Inc | N-substituted pyrazolyl-amidyl-benzimidazolyl C- kit inhibitors. |
| US7419995B2 (en) * | 2004-12-01 | 2008-09-02 | Osi Pharmaceuticals, Inc. | N-substituted benzimidazoyl c-Kit inhibitors and combinatorial benzimidazole library |
| BRPI0620126A2 (pt) * | 2005-12-20 | 2011-11-01 | Astrazeneca Ab | composto, composição farmacêutica, uso de um composto, método para modular a atividade de um receptor de gabaa, e, método sintético para fabricar um composto |
| US7465795B2 (en) * | 2005-12-20 | 2008-12-16 | Astrazeneca Ab | Compounds and uses thereof |
| AR067027A1 (es) * | 2007-06-19 | 2009-09-30 | Astrazeneca Ab | Derivados de 2, 3-dihidro-1h-pirrol[3, 4b]quinolin-1-ona, una composicion farmaceutica que los comprende y su uso en la fabricacion de un medicamento para el tratamiento de enfermedades mediadas por la modulacion de la actividad del receptor gaba a. |
| TW200911760A (en) * | 2007-06-19 | 2009-03-16 | Astrazeneca Ab | Compounds and uses thereof |
| GB202016245D0 (en) * | 2020-10-13 | 2020-11-25 | Univ College Cardiff Consultants Ltd | Compounds |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3647800A (en) * | 1970-04-30 | 1972-03-07 | American Home Prod | 10-substituted - 1 2 3 4 - tetrahydrobenzo(b)(1 6)naphthyridines useful as cns depressants |
| BE790408A (fr) * | 1971-10-22 | 1973-04-20 | Rhone Poulenc Sa | Nouveaux derives de la pyrrolo (3,4-b) pyridine, leur preparation et les compositions medicinales qui les |
| US4317915A (en) * | 1976-08-23 | 1982-03-02 | Hoffmann-La Roche Inc. | Novel thiophene derivatives |
| FR2509728A1 (fr) * | 1981-07-17 | 1983-01-21 | Roussel Uclaf | Nouveaux derives de la quinoleine, leurs sels, procede de preparation, application a titre de medicaments et compositions les renfermant |
| US4511568A (en) * | 1982-05-12 | 1985-04-16 | Ici Americas Inc. | CNS-Depressant pyrazolopyridines |
| GB8329531D0 (en) * | 1983-11-04 | 1983-12-07 | Ici America Inc | Pyrazolopyridine cycloalkanones |
| GB8421116D0 (en) * | 1984-08-20 | 1984-09-26 | Ici America Inc | Alkynyl derivatives |
| ATE63903T1 (de) * | 1984-10-25 | 1991-06-15 | Hoechst Roussel Pharma | 9-amino-1,2,3,4-tetrahydroacridin-1-ol und verwandte verbindungen, verfahren zu ihrer herstellung und verwendung als arzneimittel. |
| US4631286A (en) * | 1984-10-25 | 1986-12-23 | Hoechst-Roussel Pharmaceuticals Inc. | 9-amino-1,2,3,4-tetrahydroacridin-1-ol and related compounds |
| FR2581382B1 (fr) * | 1985-05-06 | 1987-06-26 | Sanofi Sa | Derives n-(quinolyl) glycinamides, leur procede de preparation et leur application therapeutique en tant que psychotropes |
-
1986
- 1986-05-06 GB GB868610980A patent/GB8610980D0/en active Pending
-
1987
- 1987-04-29 US US07/043,873 patent/US4975435A/en not_active Expired - Fee Related
- 1987-05-01 AU AU72415/87A patent/AU601975B2/en not_active Ceased
- 1987-05-01 EP EP87303949A patent/EP0245053B1/en not_active Expired - Lifetime
- 1987-05-01 MW MW30/87A patent/MW3087A1/xx unknown
- 1987-05-01 GB GB878710384A patent/GB8710384D0/en active Pending
- 1987-05-03 IL IL82412A patent/IL82412A0/xx unknown
- 1987-05-04 HU HU871981A patent/HU196403B/hu not_active IP Right Cessation
- 1987-05-04 ZW ZW80/87A patent/ZW8087A1/xx unknown
- 1987-05-04 NZ NZ220176A patent/NZ220176A/xx unknown
- 1987-05-04 ZA ZA873175A patent/ZA873175B/xx unknown
- 1987-05-05 DD DD87302465A patent/DD270913A5/de not_active IP Right Cessation
- 1987-05-05 NO NO871867A patent/NO871867L/no unknown
- 1987-05-05 DK DK229987A patent/DK229987A/da not_active Application Discontinuation
- 1987-05-05 ZM ZM36/87A patent/ZM3687A1/xx unknown
- 1987-05-05 FI FI871985A patent/FI871985A/fi not_active Application Discontinuation
- 1987-05-06 KR KR1019870004485A patent/KR910001283B1/ko not_active IP Right Cessation
- 1987-05-06 JP JP62109073A patent/JPS6327479A/ja active Pending
- 1987-05-06 PT PT84828A patent/PT84828B/pt not_active IP Right Cessation
-
1990
- 1990-09-14 US US07/583,070 patent/US5118688A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| ZA873175B (en) | 1988-02-24 |
| EP0245053A1 (en) | 1987-11-11 |
| ZW8087A1 (en) | 1988-12-14 |
| DK229987D0 (da) | 1987-05-05 |
| NZ220176A (en) | 1990-05-28 |
| MW3087A1 (en) | 1987-12-09 |
| EP0245053B1 (en) | 1992-11-25 |
| PT84828A (en) | 1987-06-01 |
| US4975435A (en) | 1990-12-04 |
| KR910001283B1 (ko) | 1991-02-28 |
| HU196403B (en) | 1988-11-28 |
| FI871985A (fi) | 1987-11-07 |
| DK229987A (da) | 1987-11-07 |
| GB8610980D0 (en) | 1986-06-11 |
| FI871985A0 (fi) | 1987-05-05 |
| AU7241587A (en) | 1987-11-12 |
| NO871867D0 (no) | 1987-05-05 |
| KR870011136A (ko) | 1987-12-21 |
| JPS6327479A (ja) | 1988-02-05 |
| AU601975B2 (en) | 1990-09-27 |
| ZM3687A1 (en) | 1988-09-30 |
| GB8710384D0 (en) | 1987-06-03 |
| IL82412A0 (en) | 1987-11-30 |
| US5118688A (en) | 1992-06-02 |
| DD270913A5 (de) | 1989-08-16 |
| PT84828B (pt) | 1989-12-29 |
| HUT43849A (en) | 1987-12-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO871867L (no) | Fremgangsmaate for fremstilling av terapeutisk aktive heterocykliske kondenserte tricykliske forbindelser. | |
| US4563525A (en) | Process for preparing pyrazolopyridine compounds | |
| ES2273369T3 (es) | Derivados 6,5 heterobiciclicos sustituidos. | |
| SK14099A3 (en) | Substituted pyrido- or pyrimido-containing 6,6- or 6,7-bicyclic derivatives | |
| JP2008517060A (ja) | Ｃｒｆ受容体アンタゴニストおよびその製法 | |
| CZ13594A3 (en) | Quinazoline derivatives and pharmaceutical preparations based thereon | |
| JPH10512867A (ja) | 三環式ベンズアゼピンバソプレッシンアンタゴニスト | |
| US4645838A (en) | Pyrazolopyridine compounds, and intermediates, useful as anxiolytic agents | |
| CA1275100A (en) | ANTIPSYCHOTIC .gamma.-CARBOLINES | |
| WO2012175514A1 (en) | Pyridinone derivatives and pharmaceutical compositions thereof | |
| WO2011109587A1 (en) | Substituted aza-bicyclic imidazole derivatives useful as trpm8 receptor modulators | |
| JP2004530668A (ja) | バソプレッシンアゴニストとしてのｎ−ビフェニルカルボニル−およびｎ−フェニルピリジルカルボニル置換二および三環アゼピンおよびジアゼピン | |
| EP0178759B1 (en) | Alkynyl derivativesof pyrazolo-(3,4-b)-pyridine lactams | |
| NO844376L (no) | Fremgangsmaate for fremstilling av terapeutisk aktive pyrazolopyridin-cykloalkanon-derivater | |
| CZ20011480A3 (cs) | Pyranové, piperidinové a tiopyranové sloučeniny a způsoby použití | |
| EP0168350B1 (en) | Certain ring-fused pyrazolo [3,4-d]-pyridin-3-one derivatives | |
| US5317018A (en) | Benzodiazepines and compositions for treating anxiety and panic disorders, and idiopathic and psychomotor epilepsy | |
| CZ289658B6 (cs) | Deriváty 2,3-benzodiazepinu, způsob jejich výroby, meziprodukty pro jejich výrobu a farmaceutický prostředek tyto látky obsahující | |
| CA1138864A (en) | 4-phenyl-4,5,6,7-tetrahydro-pyrrolo[2,3-c] pyridines, process for the production thereof and pharmaceutical compositions | |
| Veeraraghavan et al. | Reissert compound studies. XLII. Synthesis and reactions of the 3, 4‐dihydro‐β‐carboline reissert compound and observations on α, β, and γ‐carbolines | |
| EP1086103B1 (en) | Pyrido 2,3-b]indolizine derivatives and aza analogues thereof; crf 1 specific ligands | |
| Abd El-Aal et al. | Friedel–Crafts chemistry 56*. Unprecedented construction of functionalized polycyclic quinolines via Friedel–Crafts cycliacylation and Beckmann rearrangement | |
| US3419568A (en) | Derivatives of 1,2,3,4-tetrahydro-5h-pyrido[4,3b]indoles | |
| HU193937B (en) | Process for preparing hexahydro-pyrrolo/2,1-a/isoquinoline derivatives and pharmaceutics comprising these compounds as active substance | |
| NZ234394A (en) | 5,6-dihydro (1h-indolo(3,2-c)quinoline-6,4-piperidine) derivatives, preparation and pharmaceutical compositions thereof |