SA02220709B1 - مركبات كرومان chroman علاجية - Google Patents
مركبات كرومان chroman علاجية Download PDFInfo
- Publication number
- SA02220709B1 SA02220709B1 SA02220709A SA02220709A SA02220709B1 SA 02220709 B1 SA02220709 B1 SA 02220709B1 SA 02220709 A SA02220709 A SA 02220709A SA 02220709 A SA02220709 A SA 02220709A SA 02220709 B1 SA02220709 B1 SA 02220709B1
- Authority
- SA
- Saudi Arabia
- Prior art keywords
- methyl
- chromene
- piperazin
- oxo
- phenyl
- Prior art date
Links
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical class C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 title description 3
- 230000001225 therapeutic effect Effects 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 276
- 238000000034 method Methods 0.000 claims abstract description 87
- 238000002360 preparation method Methods 0.000 claims abstract description 66
- 208000019695 Migraine disease Diseases 0.000 claims abstract description 6
- 230000008569 process Effects 0.000 claims abstract description 5
- 239000002253 acid Substances 0.000 claims description 209
- -1 aminocarbonyl carbonyl Chemical group 0.000 claims description 204
- 239000000203 mixture Substances 0.000 claims description 104
- 125000000217 alkyl group Chemical group 0.000 claims description 59
- 238000006243 chemical reaction Methods 0.000 claims description 57
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 47
- 229910052757 nitrogen Inorganic materials 0.000 claims description 44
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 41
- 125000000623 heterocyclic group Chemical group 0.000 claims description 38
- 229910052739 hydrogen Inorganic materials 0.000 claims description 38
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 37
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
- 238000012360 testing method Methods 0.000 claims description 30
- 229910052736 halogen Inorganic materials 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 29
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 28
- 150000002367 halogens Chemical class 0.000 claims description 25
- 239000003054 catalyst Substances 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 23
- 241001465754 Metazoa Species 0.000 claims description 19
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 150000007942 carboxylates Chemical group 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- 125000003118 aryl group Chemical group 0.000 claims description 16
- 229910052763 palladium Inorganic materials 0.000 claims description 15
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 10
- 238000010438 heat treatment Methods 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 230000004927 fusion Effects 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 229940079593 drug Drugs 0.000 claims description 6
- 150000002391 heterocyclic compounds Chemical class 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 5
- 125000004122 cyclic group Chemical group 0.000 claims description 5
- 125000004193 piperazinyl group Chemical group 0.000 claims description 5
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 5
- 239000003446 ligand Substances 0.000 claims description 4
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 4
- 238000006467 substitution reaction Methods 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 3
- 241000948258 Gila Species 0.000 claims description 2
- 206010019233 Headaches Diseases 0.000 claims description 2
- 231100000869 headache Toxicity 0.000 claims description 2
- 206010027599 migraine Diseases 0.000 claims description 2
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 8
- 125000000547 substituted alkyl group Chemical group 0.000 claims 3
- 150000002431 hydrogen Chemical class 0.000 claims 2
- 238000010348 incorporation Methods 0.000 claims 2
- RPAWVEMNAJPPEL-UHFFFAOYSA-N morpholine;thiomorpholine Chemical compound C1COCCN1.C1CSCCN1 RPAWVEMNAJPPEL-UHFFFAOYSA-N 0.000 claims 1
- 125000002757 morpholinyl group Chemical group 0.000 claims 1
- 206010027603 Migraine headaches Diseases 0.000 abstract description 4
- 239000000543 intermediate Substances 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 223
- 239000007787 solid Substances 0.000 description 161
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 119
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 103
- 239000000243 solution Substances 0.000 description 99
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 79
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 77
- 239000000047 product Substances 0.000 description 64
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 61
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 56
- 239000000126 substance Substances 0.000 description 56
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 52
- 239000011541 reaction mixture Substances 0.000 description 52
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 51
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 45
- 230000015572 biosynthetic process Effects 0.000 description 43
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 41
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 41
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 41
- 238000003786 synthesis reaction Methods 0.000 description 40
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 38
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 38
- 150000001408 amides Chemical class 0.000 description 37
- 235000019439 ethyl acetate Nutrition 0.000 description 35
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 33
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 31
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- 150000002500 ions Chemical class 0.000 description 30
- PHNDZBFLOPIMSM-UHFFFAOYSA-N 4-morpholin-4-ylaniline Chemical compound C1=CC(N)=CC=C1N1CCOCC1 PHNDZBFLOPIMSM-UHFFFAOYSA-N 0.000 description 28
- 238000001819 mass spectrum Methods 0.000 description 28
- 229910052799 carbon Inorganic materials 0.000 description 27
- 238000001914 filtration Methods 0.000 description 27
- 238000002844 melting Methods 0.000 description 25
- 230000008018 melting Effects 0.000 description 24
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 22
- 150000001412 amines Chemical class 0.000 description 21
- 239000000460 chlorine Substances 0.000 description 21
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 21
- 239000000725 suspension Substances 0.000 description 21
- 150000004702 methyl esters Chemical class 0.000 description 20
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 19
- 229940086542 triethylamine Drugs 0.000 description 19
- HMXJOWDZAJWLTF-UHFFFAOYSA-N 2h-chromene-2-carboxylic acid Chemical compound C1=CC=C2C=CC(C(=O)O)OC2=C1 HMXJOWDZAJWLTF-UHFFFAOYSA-N 0.000 description 18
- 238000010992 reflux Methods 0.000 description 18
- 235000017557 sodium bicarbonate Nutrition 0.000 description 18
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 18
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 16
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 16
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 15
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
- 238000004458 analytical method Methods 0.000 description 15
- 229920006395 saturated elastomer Polymers 0.000 description 15
- 229910052801 chlorine Inorganic materials 0.000 description 14
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 14
- 238000004949 mass spectrometry Methods 0.000 description 14
- RVMGXWBCQGAWBR-UHFFFAOYSA-N 4-oxo-1-benzopyran-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)=CC(=O)C2=C1 RVMGXWBCQGAWBR-UHFFFAOYSA-N 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 12
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 12
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 12
- 125000000753 cycloalkyl group Chemical group 0.000 description 12
- 239000000463 material Substances 0.000 description 12
- 239000012299 nitrogen atmosphere Substances 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- 102000005962 receptors Human genes 0.000 description 12
- 108020003175 receptors Proteins 0.000 description 12
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 238000001035 drying Methods 0.000 description 11
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 10
- ABOQBXOPVHLFEU-UHFFFAOYSA-N 5-methyl-8-(4-methylpiperazin-1-yl)-4-oxochromene-2-carboxylic acid;hydrochloride Chemical compound Cl.C1CN(C)CCN1C1=CC=C(C)C2=C1OC(C(O)=O)=CC2=O ABOQBXOPVHLFEU-UHFFFAOYSA-N 0.000 description 10
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 10
- KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 10
- 150000001721 carbon Chemical group 0.000 description 10
- 238000003818 flash chromatography Methods 0.000 description 10
- 239000000377 silicon dioxide Substances 0.000 description 10
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 9
- 239000012317 TBTU Substances 0.000 description 9
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 9
- 229910000024 caesium carbonate Inorganic materials 0.000 description 9
- 238000013375 chromatographic separation Methods 0.000 description 9
- QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 description 9
- 208000035475 disorder Diseases 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 229910052727 yttrium Inorganic materials 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- GUWNNHQLQTXJKF-UHFFFAOYSA-N 8-(4-methylpiperazin-1-yl)-4-oxochromene-2-carboxylic acid Chemical compound C1CN(C)CCN1C1=CC=CC2=C1OC(C(O)=O)=CC2=O GUWNNHQLQTXJKF-UHFFFAOYSA-N 0.000 description 8
- 125000001589 carboacyl group Chemical group 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 230000006698 induction Effects 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 7
- LJCVQZKMKTWSLM-UHFFFAOYSA-N 6-methoxy-8-(4-methylpiperazin-1-yl)-4-oxochromene-2-carboxylic acid Chemical compound C=12OC(C(O)=O)=CC(=O)C2=CC(OC)=CC=1N1CCN(C)CC1 LJCVQZKMKTWSLM-UHFFFAOYSA-N 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 7
- 229910052786 argon Inorganic materials 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 230000003197 catalytic effect Effects 0.000 description 7
- VHILMKFSCRWWIJ-UHFFFAOYSA-N dimethyl acetylenedicarboxylate Chemical compound COC(=O)C#CC(=O)OC VHILMKFSCRWWIJ-UHFFFAOYSA-N 0.000 description 7
- 125000004494 ethyl ester group Chemical group 0.000 description 7
- 239000007789 gas Substances 0.000 description 7
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- 230000035939 shock Effects 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- IBOJSHOMWQIFPZ-UHFFFAOYSA-N 8-(4-methylpiperazin-1-yl)-4-oxochromene-2-carboxylic acid;hydrochloride Chemical compound Cl.C1CN(C)CCN1C1=CC=CC2=C1OC(C(O)=O)=CC2=O IBOJSHOMWQIFPZ-UHFFFAOYSA-N 0.000 description 6
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
- 230000008878 coupling Effects 0.000 description 6
- 238000010168 coupling process Methods 0.000 description 6
- 238000005859 coupling reaction Methods 0.000 description 6
- 125000000392 cycloalkenyl group Chemical group 0.000 description 6
- 239000011737 fluorine Substances 0.000 description 6
- 229910052731 fluorine Inorganic materials 0.000 description 6
- 125000001153 fluoro group Chemical group F* 0.000 description 6
- 239000006260 foam Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- MDHBHFJQFPHMCH-UHFFFAOYSA-N methyl 8-bromo-6-methoxy-4-(2-trimethylsilylethoxymethoxy)quinoline-2-carboxylate Chemical compound C1=C(OC)C=C(Br)C2=NC(C(=O)OC)=CC(OCOCC[Si](C)(C)C)=C21 MDHBHFJQFPHMCH-UHFFFAOYSA-N 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- 239000001301 oxygen Substances 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- FQGIBHQUVCGEAC-UHFFFAOYSA-N 3-Fluoro-4-morpholinoaniline Chemical compound FC1=CC(N)=CC=C1N1CCOCC1 FQGIBHQUVCGEAC-UHFFFAOYSA-N 0.000 description 5
- ZJWLMZURLIHVHE-UHFFFAOYSA-N 3-morpholin-4-ylaniline Chemical compound NC1=CC=CC(N2CCOCC2)=C1 ZJWLMZURLIHVHE-UHFFFAOYSA-N 0.000 description 5
- 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 5
- JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
- 241000700198 Cavia Species 0.000 description 5
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 5
- 239000005909 Kieselgur Substances 0.000 description 5
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 239000007853 buffer solution Substances 0.000 description 5
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 5
- 125000001183 hydrocarbyl group Chemical group 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 5
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 239000011347 resin Substances 0.000 description 5
- 229920005989 resin Polymers 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 238000012549 training Methods 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- WEHVQIQNGXWTME-UHFFFAOYSA-N (4-aminophenyl)-morpholin-4-ylmethanone Chemical compound C1=CC(N)=CC=C1C(=O)N1CCOCC1 WEHVQIQNGXWTME-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 125000004423 acyloxy group Chemical group 0.000 description 4
- 239000012964 benzotriazole Substances 0.000 description 4
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 4
- OTAFHZMPRISVEM-UHFFFAOYSA-N chromone Chemical compound C1=CC=C2C(=O)C=COC2=C1 OTAFHZMPRISVEM-UHFFFAOYSA-N 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 235000021186 dishes Nutrition 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 210000003608 fece Anatomy 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 230000013016 learning Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000002808 molecular sieve Substances 0.000 description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 4
- 229940076279 serotonin Drugs 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 238000005507 spraying Methods 0.000 description 4
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
- HGKMBDIMUDDXFR-UHFFFAOYSA-N 1-[4-(4-aminophenyl)piperazin-1-yl]propan-1-one Chemical compound C1CN(C(=O)CC)CCN1C1=CC=C(N)C=C1 HGKMBDIMUDDXFR-UHFFFAOYSA-N 0.000 description 3
- WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 3
- SRQHYGVENNTRQB-UHFFFAOYSA-N 2-(2-bromo-4-fluorophenoxy)but-2-enedioic acid Chemical compound OC(=O)C=C(C(O)=O)OC1=CC=C(F)C=C1Br SRQHYGVENNTRQB-UHFFFAOYSA-N 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 3
- SFLFCQJQOIZMHF-UHFFFAOYSA-N 3,4-dihydro-2h-chromene-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)CCC2=C1 SFLFCQJQOIZMHF-UHFFFAOYSA-N 0.000 description 3
- QBOUWRKFJKMBRE-UHFFFAOYSA-N 6-fluoro-8-(4-methylpiperazin-1-yl)-4-oxochromene-2-carboxylic acid Chemical compound C1CN(C)CCN1C1=CC(F)=CC2=C1OC(C(O)=O)=CC2=O QBOUWRKFJKMBRE-UHFFFAOYSA-N 0.000 description 3
- OTCAWDMXJIBVTK-UHFFFAOYSA-N 6-methoxy-8-(4-methylpiperazin-1-yl)-4-oxo-n-(4-piperazin-1-ylphenyl)chromene-2-carboxamide Chemical compound C=12OC(C(=O)NC=3C=CC(=CC=3)N3CCNCC3)=CC(=O)C2=CC(OC)=CC=1N1CCN(C)CC1 OTCAWDMXJIBVTK-UHFFFAOYSA-N 0.000 description 3
- VESSYLOQFSHMQS-UHFFFAOYSA-N 8-(4-methylpiperazin-1-yl)-n-(4-morpholin-4-ylphenyl)-3,4-dihydro-2h-chromene-2-carboxamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1OC(C(=O)NC=1C=CC(=CC=1)N1CCOCC1)CC2 VESSYLOQFSHMQS-UHFFFAOYSA-N 0.000 description 3
- ARJQCAOTEZXQSD-UHFFFAOYSA-N 8-bromo-6-methoxy-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound N1C(C(O)=O)=CC(=O)C2=CC(OC)=CC(Br)=C21 ARJQCAOTEZXQSD-UHFFFAOYSA-N 0.000 description 3
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 208000019901 Anxiety disease Diseases 0.000 description 3
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 125000005236 alkanoylamino group Chemical group 0.000 description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
- 150000001450 anions Chemical class 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 230000001430 anti-depressive effect Effects 0.000 description 3
- 239000000935 antidepressant agent Substances 0.000 description 3
- 229940005513 antidepressants Drugs 0.000 description 3
- 230000036506 anxiety Effects 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- QPMLSUSACCOBDK-UHFFFAOYSA-N diazepane Chemical compound C1CCNNCC1 QPMLSUSACCOBDK-UHFFFAOYSA-N 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- RCVPYVWCNLJBMO-UHFFFAOYSA-N ethyl 8-bromo-6-methoxy-4-oxochromene-2-carboxylate Chemical compound COC1=CC(Br)=C2OC(C(=O)OCC)=CC(=O)C2=C1 RCVPYVWCNLJBMO-UHFFFAOYSA-N 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 238000007500 overflow downdraw method Methods 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 description 3
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 3
- 230000002285 radioactive effect Effects 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 239000012047 saturated solution Substances 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical compound CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 description 2
- 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 2
- UGUHFDPGDQDVGX-UHFFFAOYSA-N 1,2,3-thiadiazole Chemical compound C1=CSN=N1 UGUHFDPGDQDVGX-UHFFFAOYSA-N 0.000 description 2
- 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 2
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 2
- 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 2
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 2
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- FXHRAKUEZPSMLJ-UHFFFAOYSA-N 1-methyl-1,4-diazepane Chemical compound CN1CCCNCC1 FXHRAKUEZPSMLJ-UHFFFAOYSA-N 0.000 description 2
- ARGCQEVBJHPOGB-UHFFFAOYSA-N 2,5-dihydrofuran Chemical compound C1OCC=C1 ARGCQEVBJHPOGB-UHFFFAOYSA-N 0.000 description 2
- SFXKFYFQUSRBID-UHFFFAOYSA-N 2-amino-5-morpholin-4-ylphenol Chemical compound C1=C(O)C(N)=CC=C1N1CCOCC1 SFXKFYFQUSRBID-UHFFFAOYSA-N 0.000 description 2
- LTMSUXSPKZRMAB-UHFFFAOYSA-N 2-bromo-4-methoxyphenol Chemical compound COC1=CC=C(O)C(Br)=C1 LTMSUXSPKZRMAB-UHFFFAOYSA-N 0.000 description 2
- ZECNLXUZYQZMAL-UHFFFAOYSA-N 2-sulfonylpiperazine Chemical compound O=S(=O)=C1CNCCN1 ZECNLXUZYQZMAL-UHFFFAOYSA-N 0.000 description 2
- YWAIEVCDLAEDNO-UHFFFAOYSA-N 2h-chromene-7-carboxylic acid Chemical compound C1=CCOC2=CC(C(=O)O)=CC=C21 YWAIEVCDLAEDNO-UHFFFAOYSA-N 0.000 description 2
- BBUAXVLPFRRBQR-UHFFFAOYSA-N 3-chloro-4-morpholin-4-ylaniline Chemical compound ClC1=CC(N)=CC=C1N1CCOCC1 BBUAXVLPFRRBQR-UHFFFAOYSA-N 0.000 description 2
- ASFAFOSQXBRFMV-LJQANCHMSA-N 3-n-(2-benzyl-1,3-dihydroxypropan-2-yl)-1-n-[(1r)-1-(4-fluorophenyl)ethyl]-5-[methyl(methylsulfonyl)amino]benzene-1,3-dicarboxamide Chemical compound N([C@H](C)C=1C=CC(F)=CC=1)C(=O)C(C=1)=CC(N(C)S(C)(=O)=O)=CC=1C(=O)NC(CO)(CO)CC1=CC=CC=C1 ASFAFOSQXBRFMV-LJQANCHMSA-N 0.000 description 2
- CZFRDHLTLDECOZ-UHFFFAOYSA-N 3-oxo-4h-chromene-2-carboxylic acid Chemical compound C1=CC=C2CC(=O)C(C(=O)O)OC2=C1 CZFRDHLTLDECOZ-UHFFFAOYSA-N 0.000 description 2
- ZEQCFSSBZPZEFJ-UHFFFAOYSA-N 4-(2-fluoro-4-nitrophenyl)morpholine Chemical compound FC1=CC([N+](=O)[O-])=CC=C1N1CCOCC1 ZEQCFSSBZPZEFJ-UHFFFAOYSA-N 0.000 description 2
- SMWBBLSINLFYAB-UHFFFAOYSA-N 4-(4-fluorophenoxy)aniline Chemical compound C1=CC(N)=CC=C1OC1=CC=C(F)C=C1 SMWBBLSINLFYAB-UHFFFAOYSA-N 0.000 description 2
- DFLQDPGZILSRHW-UHFFFAOYSA-N 4-(4-methylsulfonylpiperazin-1-yl)aniline Chemical compound C1CN(S(=O)(=O)C)CCN1C1=CC=C(N)C=C1 DFLQDPGZILSRHW-UHFFFAOYSA-N 0.000 description 2
- ZZLCFHIKESPLTH-UHFFFAOYSA-N 4-Methylbiphenyl Chemical compound C1=CC(C)=CC=C1C1=CC=CC=C1 ZZLCFHIKESPLTH-UHFFFAOYSA-N 0.000 description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 description 2
- RQXQMUUSQGCLPL-UHFFFAOYSA-N 4-thiomorpholin-4-ylaniline Chemical compound C1=CC(N)=CC=C1N1CCSCC1 RQXQMUUSQGCLPL-UHFFFAOYSA-N 0.000 description 2
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 2
- WJUOUHSBDDDFDL-UHFFFAOYSA-N 5-amino-2-morpholin-4-ylbenzonitrile Chemical compound N#CC1=CC(N)=CC=C1N1CCOCC1 WJUOUHSBDDDFDL-UHFFFAOYSA-N 0.000 description 2
- MNJJTXUPEWJFRC-UHFFFAOYSA-N 5-ethoxy-1,3-benzothiazol-2-amine Chemical compound CCOC1=CC=C2SC(N)=NC2=C1 MNJJTXUPEWJFRC-UHFFFAOYSA-N 0.000 description 2
- IPQKYMYWULHWAP-UHFFFAOYSA-N 6-ethoxy-8-(4-methylpiperazin-1-yl)-4-oxochromene-2-carbonyl chloride Chemical compound C=12OC(C(Cl)=O)=CC(=O)C2=CC(OCC)=CC=1N1CCN(C)CC1 IPQKYMYWULHWAP-UHFFFAOYSA-N 0.000 description 2
- KSHNCDGHNYMUEZ-UHFFFAOYSA-N 6-fluoro-4-methoxy-8-(4-methylpiperazin-1-yl)quinoline-2-carboxylic acid Chemical compound C1=C(F)C=C2C(OC)=CC(C(O)=O)=NC2=C1N1CCN(C)CC1 KSHNCDGHNYMUEZ-UHFFFAOYSA-N 0.000 description 2
- NIKYRKCMJYEZNX-UHFFFAOYSA-N 6-methoxy-8-(4-methylpiperazin-1-yl)-n-(4-morpholin-4-ylphenyl)-4-oxochromene-2-carboxamide Chemical compound C=12OC(C(=O)NC=3C=CC(=CC=3)N3CCOCC3)=CC(=O)C2=CC(OC)=CC=1N1CCN(C)CC1 NIKYRKCMJYEZNX-UHFFFAOYSA-N 0.000 description 2
- WCFKSHDZKWZMTG-UHFFFAOYSA-N 8-(4-methylpiperazin-1-yl)-4-oxo-2,3-dihydrochromene-2-carboxylic acid Chemical compound C1CN(C)CCN1C1=CC=CC2=C1OC(C(O)=O)CC2=O WCFKSHDZKWZMTG-UHFFFAOYSA-N 0.000 description 2
- YBDJBKGYPPJOFX-UHFFFAOYSA-N 8-bromo-4-chloro-6-methoxy-n-(4-morpholin-4-ylphenyl)quinoline-2-carboxamide Chemical compound C1=C(Cl)C2=CC(OC)=CC(Br)=C2N=C1C(=O)NC(C=C1)=CC=C1N1CCOCC1 YBDJBKGYPPJOFX-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 206010012289 Dementia Diseases 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
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-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
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-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
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
- 206010047163 Vasospasm Diseases 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 125000005233 alkylalcohol group Chemical group 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- IAQRGUVFOMOMEM-UHFFFAOYSA-N butene Natural products CC=CC IAQRGUVFOMOMEM-UHFFFAOYSA-N 0.000 description 2
- 239000003990 capacitor Substances 0.000 description 2
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 150000003857 carboxamides Chemical class 0.000 description 2
- 125000005518 carboxamido group Chemical group 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 150000001805 chlorine compounds Chemical class 0.000 description 2
- QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 2
- 239000002036 chloroform fraction Substances 0.000 description 2
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 2
- 230000009615 deamination Effects 0.000 description 2
- 238000006481 deamination reaction Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- VEFJWDRGUOQLMR-UHFFFAOYSA-N ethyl 8-bromo-6-hydroxy-4-oxochromene-2-carboxylate Chemical compound OC1=CC(Br)=C2OC(C(=O)OCC)=CC(=O)C2=C1 VEFJWDRGUOQLMR-UHFFFAOYSA-N 0.000 description 2
- QMWCBNYGYPWUEO-UHFFFAOYSA-N ethyl 8-bromo-6-methyl-4-oxochromene-2-carboxylate Chemical compound CC1=CC(Br)=C2OC(C(=O)OCC)=CC(=O)C2=C1 QMWCBNYGYPWUEO-UHFFFAOYSA-N 0.000 description 2
- WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 2
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 210000003128 head Anatomy 0.000 description 2
- QKGYJVXSKCDGOK-UHFFFAOYSA-N hexane;propan-2-ol Chemical compound CC(C)O.CCCCCC QKGYJVXSKCDGOK-UHFFFAOYSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 150000002440 hydroxy compounds Chemical class 0.000 description 2
- AMWRITDGCCNYAT-UHFFFAOYSA-L hydroxy(oxo)manganese;manganese Chemical compound [Mn].O[Mn]=O.O[Mn]=O AMWRITDGCCNYAT-UHFFFAOYSA-L 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 201000001881 impotence Diseases 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 2
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 2
- SAVOWTPNSKKFIM-UHFFFAOYSA-N methyl 6-fluoro-4-methoxy-8-(4-methylpiperazin-1-yl)quinoline-2-carboxylate Chemical compound C12=NC(C(=O)OC)=CC(OC)=C2C=C(F)C=C1N1CCN(C)CC1 SAVOWTPNSKKFIM-UHFFFAOYSA-N 0.000 description 2
- AQDMZIQDJNENRB-UHFFFAOYSA-N methyl 8-bromo-6-fluoro-4-methoxyquinoline-2-carboxylate Chemical compound C1=C(F)C=C(Br)C2=NC(C(=O)OC)=CC(OC)=C21 AQDMZIQDJNENRB-UHFFFAOYSA-N 0.000 description 2
- 229940050176 methyl chloride Drugs 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- VDKZSHONJYADKP-UHFFFAOYSA-N n-phenylpiperazin-1-amine Chemical compound C1CNCCN1NC1=CC=CC=C1 VDKZSHONJYADKP-UHFFFAOYSA-N 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 150000002828 nitro derivatives Chemical class 0.000 description 2
- 125000006501 nitrophenyl group Chemical group 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 229960002195 perazine Drugs 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
- FVZVCSNXTFCBQU-UHFFFAOYSA-N phosphanyl Chemical group [PH2] FVZVCSNXTFCBQU-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 150000003248 quinolines Chemical class 0.000 description 2
- 235000008001 rakum palm Nutrition 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000009738 saturating Methods 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000006277 sulfonation reaction Methods 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 235000013616 tea Nutrition 0.000 description 2
- RXFHRKPNLPBDGE-UHFFFAOYSA-N tert-butyl 4-(4-aminophenyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C(N)C=C1 RXFHRKPNLPBDGE-UHFFFAOYSA-N 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- AVAWMINJNRAQFS-LURJTMIESA-N (3s)-n,n-dimethylpyrrolidin-3-amine Chemical compound CN(C)[C@H]1CCNC1 AVAWMINJNRAQFS-LURJTMIESA-N 0.000 description 1
- QIVUCLWGARAQIO-OLIXTKCUSA-N (3s)-n-[(3s,5s,6r)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)piperidin-3-yl]-2-oxospiro[1h-pyrrolo[2,3-b]pyridine-3,6'-5,7-dihydrocyclopenta[b]pyridine]-3'-carboxamide Chemical compound C1([C@H]2[C@H](N(C(=O)[C@@H](NC(=O)C=3C=C4C[C@]5(CC4=NC=3)C3=CC=CN=C3NC5=O)C2)CC(F)(F)F)C)=C(F)C=CC(F)=C1F QIVUCLWGARAQIO-OLIXTKCUSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- ZUKHOVWXUVAVEU-UITAMQMPSA-N (Z)-2-(2-chloro-5-methylphenoxy)but-2-enedioic acid Chemical compound CC1=CC=C(Cl)C(O\C(=C/C(O)=O)C(O)=O)=C1 ZUKHOVWXUVAVEU-UITAMQMPSA-N 0.000 description 1
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical compound C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- YGLMVCVJLXREAK-MTVMDMGHSA-N 1,1-dimethyl-3-[(1S,2R,6R,7S,8R)-8-tricyclo[5.2.1.02,6]decanyl]urea Chemical compound C([C@H]12)CC[C@@H]1[C@@H]1C[C@@H](NC(=O)N(C)C)[C@H]2C1 YGLMVCVJLXREAK-MTVMDMGHSA-N 0.000 description 1
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 1
- YGTAZGSLCXNBQL-UHFFFAOYSA-N 1,2,4-thiadiazole Chemical compound C=1N=CSN=1 YGTAZGSLCXNBQL-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- IRFSXVIRXMYULF-UHFFFAOYSA-N 1,2-dihydroquinoline Chemical compound C1=CC=C2C=CCNC2=C1 IRFSXVIRXMYULF-UHFFFAOYSA-N 0.000 description 1
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 1
- 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
- MBIZXFATKUQOOA-UHFFFAOYSA-N 1,3,4-thiadiazole Chemical compound C1=NN=CS1 MBIZXFATKUQOOA-UHFFFAOYSA-N 0.000 description 1
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 1
- CZLMRJZAHXYRIX-UHFFFAOYSA-N 1,3-dioxepane Chemical compound C1CCOCOC1 CZLMRJZAHXYRIX-UHFFFAOYSA-N 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 1
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 1
- IBXMKLPFLZYRQZ-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 IBXMKLPFLZYRQZ-UHFFFAOYSA-N 0.000 description 1
- LNRCAHQXXTWOGC-UHFFFAOYSA-N 1-(6-piperazin-1-yl-2,3-dihydroindol-1-yl)ethanone Chemical compound C1=C2N(C(=O)C)CCC2=CC=C1N1CCNCC1 LNRCAHQXXTWOGC-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- AFVUJJNEILZYJQ-UHFFFAOYSA-N 1-[4-(4-aminophenyl)-1-piperazinyl]ethanone Chemical compound C1CN(C(=O)C)CCN1C1=CC=C(N)C=C1 AFVUJJNEILZYJQ-UHFFFAOYSA-N 0.000 description 1
- RAYHCGYQIZJSKW-UHFFFAOYSA-N 1-[5-(4-benzylpiperazin-1-yl)-2,3-dihydroindol-1-yl]ethanone Chemical compound C=1C=C2N(C(=O)C)CCC2=CC=1N(CC1)CCN1CC1=CC=CC=C1 RAYHCGYQIZJSKW-UHFFFAOYSA-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
- IQXXEPZFOOTTBA-UHFFFAOYSA-N 1-benzylpiperazine Chemical compound C=1C=CC=CC=1CN1CCNCC1 IQXXEPZFOOTTBA-UHFFFAOYSA-N 0.000 description 1
- ONQBOTKLCMXPOF-UHFFFAOYSA-N 1-ethylpyrrolidine Chemical compound CCN1CCCC1 ONQBOTKLCMXPOF-UHFFFAOYSA-N 0.000 description 1
- WMASLRCNNKMRFP-UHFFFAOYSA-N 1-fluoro-3-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC(F)=C1 WMASLRCNNKMRFP-UHFFFAOYSA-N 0.000 description 1
- QUMRLXXCRQWODL-UHFFFAOYSA-N 1-methylpiperazin-1-ium;chloride Chemical compound [Cl-].C[NH+]1CCNCC1 QUMRLXXCRQWODL-UHFFFAOYSA-N 0.000 description 1
- UQCDDNDDKCZWHL-UHFFFAOYSA-N 1-methylpiperazine Chemical compound CN1CCNCC1.CN1CCNCC1 UQCDDNDDKCZWHL-UHFFFAOYSA-N 0.000 description 1
- VIIQBVNBFQUOTO-UHFFFAOYSA-N 1-methylsulfonyl-4-(4-nitrophenyl)piperazine Chemical compound C1CN(S(=O)(=O)C)CCN1C1=CC=C([N+]([O-])=O)C=C1 VIIQBVNBFQUOTO-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
- YHCUZRJTNSWYCY-UHFFFAOYSA-N 2,3,4,7-tetrahydro-1h-azepine Chemical compound C1CNCC=CC1 YHCUZRJTNSWYCY-UHFFFAOYSA-N 0.000 description 1
- OZIJESHLNXSUNE-UHFFFAOYSA-N 2,3-dihydrofuran;thiolane 1,1-dioxide Chemical compound C1CC=CO1.O=S1(=O)CCCC1 OZIJESHLNXSUNE-UHFFFAOYSA-N 0.000 description 1
- NSYDOBYFTHLPFM-UHFFFAOYSA-N 2-(2,2-dimethyl-1,3,6,2-dioxazasilocan-6-yl)ethanol Chemical compound C[Si]1(C)OCCN(CCO)CCO1 NSYDOBYFTHLPFM-UHFFFAOYSA-N 0.000 description 1
- JECYNCQXXKQDJN-UHFFFAOYSA-N 2-(2-methylhexan-2-yloxymethyl)oxirane Chemical compound CCCCC(C)(C)OCC1CO1 JECYNCQXXKQDJN-UHFFFAOYSA-N 0.000 description 1
- LXCOJLYZRDMXFG-UHFFFAOYSA-N 2-(2h-chromen-2-yl)benzamide Chemical compound NC(=O)C1=CC=CC=C1C1C=CC2=CC=CC=C2O1 LXCOJLYZRDMXFG-UHFFFAOYSA-N 0.000 description 1
- IAZJBMBBJGDCJI-UHFFFAOYSA-N 2-(4-methylpiperazin-1-yl)chromen-4-one Chemical compound C1CN(C)CCN1C1=CC(=O)C2=CC=CC=C2O1 IAZJBMBBJGDCJI-UHFFFAOYSA-N 0.000 description 1
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- XOVZYGCWFVJMOX-UHFFFAOYSA-N 2-[4-(1-acetyl-2,3-dihydroindol-6-yl)piperazine-1-carbonyl]-8-(4-methylpiperazin-1-yl)chromen-4-one Chemical compound C1CN(C)CCN1C1=CC=CC2=C1OC(C(=O)N1CCN(CC1)C=1C=C3N(C(C)=O)CCC3=CC=1)=CC2=O XOVZYGCWFVJMOX-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- RYBLOYPVMAGGRW-UHFFFAOYSA-N 2-[4-(2-methoxyphenyl)piperazine-1-carbonyl]-8-(4-methylpiperazin-1-yl)chromen-4-one Chemical compound COC1=CC=CC=C1N1CCN(C(=O)C=2OC3=C(N4CCN(C)CC4)C=CC=C3C(=O)C=2)CC1 RYBLOYPVMAGGRW-UHFFFAOYSA-N 0.000 description 1
- HCDBHFCQLBZAAZ-UHFFFAOYSA-N 2-[4-(4-aminophenyl)piperazin-1-yl]ethanol Chemical compound C1=CC(N)=CC=C1N1CCN(CCO)CC1 HCDBHFCQLBZAAZ-UHFFFAOYSA-N 0.000 description 1
- DDFYJUQMGHWQJC-UHFFFAOYSA-N 2-[4-(4-methoxyphenyl)piperazine-1-carbonyl]-8-(4-methylpiperazin-1-yl)chromen-4-one Chemical compound C1=CC(OC)=CC=C1N1CCN(C(=O)C=2OC3=C(N4CCN(C)CC4)C=CC=C3C(=O)C=2)CC1 DDFYJUQMGHWQJC-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- OIYMAXAYTGUUAO-UHFFFAOYSA-N 2-bromo-3,4-dimethylphenol Chemical compound CC1=CC=C(O)C(Br)=C1C OIYMAXAYTGUUAO-UHFFFAOYSA-N 0.000 description 1
- ZIYRDJLAJYTELF-UHFFFAOYSA-N 2-bromo-4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1Br ZIYRDJLAJYTELF-UHFFFAOYSA-N 0.000 description 1
- MEYRABVEYCFHHB-UHFFFAOYSA-N 2-bromo-4-fluorophenol Chemical compound OC1=CC=C(F)C=C1Br MEYRABVEYCFHHB-UHFFFAOYSA-N 0.000 description 1
- YBAGMTVKDRIMTB-UHFFFAOYSA-N 2-bromo-4-methoxyaniline Chemical compound COC1=CC=C(N)C(Br)=C1 YBAGMTVKDRIMTB-UHFFFAOYSA-N 0.000 description 1
- KHGMUWBYGFWGCZ-UHFFFAOYSA-N 2-bromo-5-methoxyphenol Chemical compound COC1=CC=C(Br)C(O)=C1 KHGMUWBYGFWGCZ-UHFFFAOYSA-N 0.000 description 1
- XNMQEEKYCVKGBD-UHFFFAOYSA-N 2-butyne Chemical class CC#CC XNMQEEKYCVKGBD-UHFFFAOYSA-N 0.000 description 1
- SMFHPCZZAAMJJO-UHFFFAOYSA-N 2-chloro-5-methylphenol Chemical compound CC1=CC=C(Cl)C(O)=C1 SMFHPCZZAAMJJO-UHFFFAOYSA-N 0.000 description 1
- WWWQCGABIADKJH-UHFFFAOYSA-N 2-chloro-5-piperazin-1-ylbenzonitrile Chemical compound C1=C(C#N)C(Cl)=CC=C1N1CCNCC1 WWWQCGABIADKJH-UHFFFAOYSA-N 0.000 description 1
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- YLACBMHBZVYOAP-UHFFFAOYSA-N 2-fluoro-5-nitrobenzonitrile Chemical compound [O-][N+](=O)C1=CC=C(F)C(C#N)=C1 YLACBMHBZVYOAP-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- BQTMHUUWYHEPNQ-UHFFFAOYSA-N 2-methoxy-4-morpholin-4-ylaniline Chemical compound C1=C(N)C(OC)=CC(N2CCOCC2)=C1 BQTMHUUWYHEPNQ-UHFFFAOYSA-N 0.000 description 1
- ZTQNUTNKGQGWCM-UHFFFAOYSA-N 2-methoxyquinoline Chemical compound C1=CC=CC2=NC(OC)=CC=C21 ZTQNUTNKGQGWCM-UHFFFAOYSA-N 0.000 description 1
- DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 1
- RWMGFZRJYLSGJW-UHFFFAOYSA-N 2-morpholin-4-yl-5-nitrobenzonitrile Chemical compound N#CC1=CC([N+](=O)[O-])=CC=C1N1CCOCC1 RWMGFZRJYLSGJW-UHFFFAOYSA-N 0.000 description 1
- HHAZUISNXJLXHR-UHFFFAOYSA-N 2-morpholin-4-ylbenzamide Chemical compound NC(=O)C1=CC=CC=C1N1CCOCC1 HHAZUISNXJLXHR-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- TZWRXFPFRACRLO-UHFFFAOYSA-N 2-piperazin-1-ylaniline Chemical compound NC1=CC=CC=C1N1CCNCC1 TZWRXFPFRACRLO-UHFFFAOYSA-N 0.000 description 1
- WFCSWCVEJLETKA-UHFFFAOYSA-N 2-piperazin-1-ylethanol Chemical compound OCCN1CCNCC1 WFCSWCVEJLETKA-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- HUHJIJQHHFHKQG-UHFFFAOYSA-N 2-tert-butylpiperazine-1-carboxylic acid Chemical compound CC(C)(C)C1CNCCN1C(O)=O HUHJIJQHHFHKQG-UHFFFAOYSA-N 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- UIVDCKFQBZPAEB-UHFFFAOYSA-N 2h-chromene-2-carboxylic acid;hydrochloride Chemical compound Cl.C1=CC=C2C=CC(C(=O)O)OC2=C1 UIVDCKFQBZPAEB-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
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- FTAHXMZRJCZXDL-UHFFFAOYSA-N 3-piperideine Chemical compound C1CC=CCN1 FTAHXMZRJCZXDL-UHFFFAOYSA-N 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- BAKUAUDFCNFLBX-UHFFFAOYSA-N 4,7-dihydro-1,3-dioxepine Chemical compound C1OCC=CCO1 BAKUAUDFCNFLBX-UHFFFAOYSA-N 0.000 description 1
- SMOGUURTGJUNNJ-UHFFFAOYSA-N 4-(2,6-dimethylmorpholin-4-yl)aniline Chemical compound C1C(C)OC(C)CN1C1=CC=C(N)C=C1 SMOGUURTGJUNNJ-UHFFFAOYSA-N 0.000 description 1
- DKECFAGKGYRYAT-UHFFFAOYSA-N 4-(3-nitrophenyl)morpholine Chemical compound [O-][N+](=O)C1=CC=CC(N2CCOCC2)=C1 DKECFAGKGYRYAT-UHFFFAOYSA-N 0.000 description 1
- LKEIGVIPZFBGFE-UHFFFAOYSA-N 4-(4-aminophenyl)-n,n-dimethylpiperazine-1-sulfonamide Chemical compound C1CN(S(=O)(=O)N(C)C)CCN1C1=CC=C(N)C=C1 LKEIGVIPZFBGFE-UHFFFAOYSA-N 0.000 description 1
- IRHIMRCEUXJBGP-UHFFFAOYSA-N 4-(4-nitrophenyl)thiomorpholine Chemical compound C1=CC([N+](=O)[O-])=CC=C1N1CCSCC1 IRHIMRCEUXJBGP-UHFFFAOYSA-N 0.000 description 1
- NQGWRVNXKLMQHO-UHFFFAOYSA-N 4-(4-propan-2-ylsulfonylpiperazin-1-yl)aniline Chemical compound C1CN(S(=O)(=O)C(C)C)CCN1C1=CC=C(N)C=C1 NQGWRVNXKLMQHO-UHFFFAOYSA-N 0.000 description 1
- TVVMFPCZWFJVGN-UHFFFAOYSA-N 4-(dimethylamino)-6-methoxy-8-(4-methylpiperazin-1-yl)-n-(4-morpholin-4-ylphenyl)quinoline-2-carboxamide Chemical compound C=12N=C(C(=O)NC=3C=CC(=CC=3)N3CCOCC3)C=C(N(C)C)C2=CC(OC)=CC=1N1CCN(C)CC1 TVVMFPCZWFJVGN-UHFFFAOYSA-N 0.000 description 1
- VJUKMTLBSFMMRH-UHFFFAOYSA-N 4-(thiadiazol-5-yl)aniline Chemical compound C1=CC(N)=CC=C1C1=CN=NS1 VJUKMTLBSFMMRH-UHFFFAOYSA-N 0.000 description 1
- WDFQBORIUYODSI-UHFFFAOYSA-N 4-bromoaniline Chemical compound NC1=CC=C(Br)C=C1 WDFQBORIUYODSI-UHFFFAOYSA-N 0.000 description 1
- LVOASPZGXNAHJI-UHFFFAOYSA-N 4-imidazol-1-ylaniline Chemical compound C1=CC(N)=CC=C1N1C=NC=C1 LVOASPZGXNAHJI-UHFFFAOYSA-N 0.000 description 1
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- SLOUZLINZMUENA-UHFFFAOYSA-N 4-morpholin-4-ylaniline Chemical compound Nc1ccc(cc1)N1CCOCC1.Nc1ccc(cc1)N1CCOCC1 SLOUZLINZMUENA-UHFFFAOYSA-N 0.000 description 1
- VAVOYRCCWLRTMS-UHFFFAOYSA-N 4-piperazin-1-ylaniline Chemical compound C1=CC(N)=CC=C1N1CCNCC1 VAVOYRCCWLRTMS-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- BQNJCOMADRHVEL-UHFFFAOYSA-N 4h-chromene-2-carboxamide Chemical compound C1=CC=C2OC(C(=O)N)=CCC2=C1 BQNJCOMADRHVEL-UHFFFAOYSA-N 0.000 description 1
- VEKQSHDKCBTWRO-UHFFFAOYSA-N 4h-chromene-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)=CCC2=C1 VEKQSHDKCBTWRO-UHFFFAOYSA-N 0.000 description 1
- XJNZHICOWTVWOX-UHFFFAOYSA-N 5-(furan-2-yl)-1h-pyrazol-3-amine Chemical compound N1N=C(N)C=C1C1=CC=CO1 XJNZHICOWTVWOX-UHFFFAOYSA-N 0.000 description 1
- VVDIMAMYKUTSCL-UHFFFAOYSA-N 5-amino-2-chlorobenzonitrile Chemical compound NC1=CC=C(Cl)C(C#N)=C1 VVDIMAMYKUTSCL-UHFFFAOYSA-N 0.000 description 1
- LVCHHDPHQZSQQK-UHFFFAOYSA-N 5-bromo-n-(furan-2-ylmethyl)-6-oxopyran-3-carboxamide Chemical compound O1C(=O)C(Br)=CC(C(=O)NCC=2OC=CC=2)=C1 LVCHHDPHQZSQQK-UHFFFAOYSA-N 0.000 description 1
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- ZECBLTAUELLIGI-UHFFFAOYSA-N 5-methoxy-8-(4-methylpiperazin-1-yl)-4-oxochromene-2-carboxylic acid;hydrochloride Chemical compound Cl.C1=2OC(C(O)=O)=CC(=O)C=2C(OC)=CC=C1N1CCN(C)CC1 ZECBLTAUELLIGI-UHFFFAOYSA-N 0.000 description 1
- JKPWOPNZKYPRPZ-UHFFFAOYSA-N 5-methyl-8-(4-methylpiperazin-1-yl)-n-(4-morpholin-4-ylphenyl)-4-oxochromene-2-carboxamide Chemical compound C1CN(C)CCN1C1=CC=C(C)C2=C1OC(C(=O)NC=1C=CC(=CC=1)N1CCOCC1)=CC2=O JKPWOPNZKYPRPZ-UHFFFAOYSA-N 0.000 description 1
- UOKKYJHDVFCDHJ-UHFFFAOYSA-N 6-chloro-8-(4-methylpiperazin-1-yl)-n-(4-morpholin-4-ylphenyl)-4-oxochromene-2-carboxamide Chemical compound C1CN(C)CCN1C1=CC(Cl)=CC2=C1OC(C(=O)NC=1C=CC(=CC=1)N1CCOCC1)=CC2=O UOKKYJHDVFCDHJ-UHFFFAOYSA-N 0.000 description 1
- IXZBMAVJNJWLBA-UHFFFAOYSA-N 6-fluoro-4-methoxy-8-(4-methylpiperazin-1-yl)-n-(4-morpholin-4-ylphenyl)quinoline-2-carboxamide Chemical compound C1=C(F)C=C2C(OC)=CC(C(=O)NC=3C=CC(=CC=3)N3CCOCC3)=NC2=C1N1CCN(C)CC1 IXZBMAVJNJWLBA-UHFFFAOYSA-N 0.000 description 1
- OPURFOJZTZVPMV-UHFFFAOYSA-N 6-fluoro-4-methoxy-8-(4-methylpiperazin-1-yl)quinoline-2-carboxylic acid;hydrochloride Chemical compound Cl.C1=C(F)C=C2C(OC)=CC(C(O)=O)=NC2=C1N1CCN(C)CC1 OPURFOJZTZVPMV-UHFFFAOYSA-N 0.000 description 1
- AFPJKGROIQPTID-UHFFFAOYSA-N 6-fluoro-8-(4-methylpiperazin-1-yl)-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound C1CN(C)CCN1C1=CC(F)=CC2=C1NC(C(O)=O)=CC2=O AFPJKGROIQPTID-UHFFFAOYSA-N 0.000 description 1
- PHAKLXIGVONDDJ-UHFFFAOYSA-N 6-fluoro-8-(4-methylpiperazin-1-yl)-4-oxochromene-2-carboxylic acid;hydrochloride Chemical compound Cl.C1CN(C)CCN1C1=CC(F)=CC2=C1OC(C(O)=O)=CC2=O PHAKLXIGVONDDJ-UHFFFAOYSA-N 0.000 description 1
- DCLJCEMLLBKMNJ-UHFFFAOYSA-N 6-fluoro-8-(4-methylpiperazin-1-yl)-n-(4-morpholin-4-ylphenyl)-4-oxo-1h-quinoline-2-carboxamide Chemical compound C1CN(C)CCN1C1=CC(F)=CC2=C1NC(C(=O)NC=1C=CC(=CC=1)N1CCOCC1)=CC2=O DCLJCEMLLBKMNJ-UHFFFAOYSA-N 0.000 description 1
- RVCPHLYYKMGUHA-UHFFFAOYSA-N 6-fluoro-8-(4-methylpiperazin-1-yl)-n-[4-(4-methylsulfonylpiperazin-1-yl)phenyl]-4-oxochromene-2-carboxamide Chemical compound C1CN(C)CCN1C1=CC(F)=CC2=C1OC(C(=O)NC=1C=CC(=CC=1)N1CCN(CC1)S(C)(=O)=O)=CC2=O RVCPHLYYKMGUHA-UHFFFAOYSA-N 0.000 description 1
- UNNMVNFLYJIILF-UHFFFAOYSA-N 6-fluoro-n-(3-fluoro-4-morpholin-4-ylphenyl)-8-(4-methylpiperazin-1-yl)-4-oxochromene-2-carboxamide Chemical compound C1CN(C)CCN1C1=CC(F)=CC2=C1OC(C(=O)NC=1C=C(F)C(N3CCOCC3)=CC=1)=CC2=O UNNMVNFLYJIILF-UHFFFAOYSA-N 0.000 description 1
- PAUCFXYKVZPEFT-UHFFFAOYSA-N 6-fluoro-n-(4-morpholin-4-ylphenyl)-4-oxo-8-piperazin-1-ylchromene-2-carboxamide Chemical compound C=12OC(C(=O)NC=3C=CC(=CC=3)N3CCOCC3)=CC(=O)C2=CC(F)=CC=1N1CCNCC1 PAUCFXYKVZPEFT-UHFFFAOYSA-N 0.000 description 1
- LVNIRKFAKNLJBP-UHFFFAOYSA-N 6-hydroxy-8-(4-methylpiperazin-1-yl)-4-oxochromene-2-carboxylic acid Chemical compound C1CN(C)CCN1C1=CC(O)=CC2=C1OC(C(O)=O)=CC2=O LVNIRKFAKNLJBP-UHFFFAOYSA-N 0.000 description 1
- SLPCESKZSKOAHD-UHFFFAOYSA-N 6-methoxy-4-(methylamino)-8-(4-methylpiperazin-1-yl)-n-(4-morpholin-4-ylphenyl)quinoline-2-carboxamide Chemical compound C1=C(OC)C=C2C(NC)=CC(C(=O)NC=3C=CC(=CC=3)N3CCOCC3)=NC2=C1N1CCN(C)CC1 SLPCESKZSKOAHD-UHFFFAOYSA-N 0.000 description 1
- DVPYAOAKHRABRA-UHFFFAOYSA-N 6-methoxy-8-(4-methyl-1,4-diazepan-1-yl)-4-(2-trimethylsilylethoxymethoxy)quinoline-2-carboxylic acid Chemical compound C=12N=C(C(O)=O)C=C(OCOCC[Si](C)(C)C)C2=CC(OC)=CC=1N1CCCN(C)CC1 DVPYAOAKHRABRA-UHFFFAOYSA-N 0.000 description 1
- HBXBNJCCSMPVHY-UHFFFAOYSA-N 6-methoxy-8-(4-methyl-1,4-diazepan-1-yl)-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound C=12NC(C(O)=O)=CC(=O)C2=CC(OC)=CC=1N1CCCN(C)CC1 HBXBNJCCSMPVHY-UHFFFAOYSA-N 0.000 description 1
- OQNHFDCJWMVYJK-UHFFFAOYSA-N 6-methoxy-8-(4-methyl-1,4-diazepan-1-yl)-4-oxochromene-2-carboxylic acid Chemical compound C=12OC(C(O)=O)=CC(=O)C2=CC(OC)=CC=1N1CCCN(C)CC1 OQNHFDCJWMVYJK-UHFFFAOYSA-N 0.000 description 1
- XOBHCSUAYVGWIB-UHFFFAOYSA-N 6-methoxy-8-(4-methylpiperazin-1-yl)-4-oxo-1h-quinoline-2-carboxylic acid Chemical compound C=12NC(C(O)=O)=CC(=O)C2=CC(OC)=CC=1N1CCN(C)CC1 XOBHCSUAYVGWIB-UHFFFAOYSA-N 0.000 description 1
- UWFUUJFNWZLZIA-UHFFFAOYSA-N 6-methoxy-8-(4-methylpiperazin-1-yl)-4-oxochromene-2-carboxylic acid;hydrochloride Chemical compound Cl.C=12OC(C(O)=O)=CC(=O)C2=CC(OC)=CC=1N1CCN(C)CC1 UWFUUJFNWZLZIA-UHFFFAOYSA-N 0.000 description 1
- WLYZHIQPTLDJID-UHFFFAOYSA-N 6-methoxy-8-(4-methylpiperazin-1-yl)-n-[4-[4-(2-methylpropanoyl)piperazin-1-yl]phenyl]-4-oxochromene-2-carboxamide Chemical compound C=12OC(C(=O)NC=3C=CC(=CC=3)N3CCN(CC3)C(=O)C(C)C)=CC(=O)C2=CC(OC)=CC=1N1CCN(C)CC1 WLYZHIQPTLDJID-UHFFFAOYSA-N 0.000 description 1
- CVAOIXLANSNIPO-UHFFFAOYSA-N 6-methoxy-8-(4-methylpiperazin-1-yl)-n-[4-[4-(morpholine-4-carbonyl)piperazin-1-yl]phenyl]-4-oxochromene-2-carboxamide Chemical compound C=12OC(C(=O)NC=3C=CC(=CC=3)N3CCN(CC3)C(=O)N3CCOCC3)=CC(=O)C2=CC(OC)=CC=1N1CCN(C)CC1 CVAOIXLANSNIPO-UHFFFAOYSA-N 0.000 description 1
- SIGUQEKSFHISJA-UHFFFAOYSA-N 6-methyl-8-(4-methylpiperazin-1-yl)-4-oxochromene-2-carboxylic acid Chemical compound C1CN(C)CCN1C1=CC(C)=CC2=C1OC(C(O)=O)=CC2=O SIGUQEKSFHISJA-UHFFFAOYSA-N 0.000 description 1
- YONINMPUXDRPJV-UHFFFAOYSA-N 6-methyl-8-(4-methylpiperazin-1-yl)-4-oxochromene-2-carboxylic acid;hydrochloride Chemical compound Cl.C1CN(C)CCN1C1=CC(C)=CC2=C1OC(C(O)=O)=CC2=O YONINMPUXDRPJV-UHFFFAOYSA-N 0.000 description 1
- KYARBIJYVGJZLB-UHFFFAOYSA-N 7-amino-4-hydroxy-2-naphthalenesulfonic acid Chemical compound OC1=CC(S(O)(=O)=O)=CC2=CC(N)=CC=C21 KYARBIJYVGJZLB-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- DVUPHYDVEFBQHU-UHFFFAOYSA-N 8-(4-methylpiperazin-1-yl)-2-(6-morpholin-4-yl-1,3-benzoxazol-2-yl)chromen-4-one Chemical compound C1CN(C)CCN1C1=CC=CC2=C1OC(C=1OC3=CC(=CC=C3N=1)N1CCOCC1)=CC2=O DVUPHYDVEFBQHU-UHFFFAOYSA-N 0.000 description 1
- AFLLJULIEIALKU-UHFFFAOYSA-N 8-(4-methylpiperazin-1-yl)-3,4-dihydro-2h-chromene-2-carboxylic acid Chemical compound C1CN(C)CCN1C1=CC=CC2=C1OC(C(O)=O)CC2 AFLLJULIEIALKU-UHFFFAOYSA-N 0.000 description 1
- IMTPTJSFHZIEIX-UHFFFAOYSA-N 8-(4-methylpiperazin-1-yl)-n-(4-morpholin-4-ylphenyl)-4-oxo-2,3-dihydrochromene-2-carboxamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1OC(C(=O)NC=1C=CC(=CC=1)N1CCOCC1)CC2=O IMTPTJSFHZIEIX-UHFFFAOYSA-N 0.000 description 1
- AHGUAOJIJHXBHA-UHFFFAOYSA-N 8-(4-methylpiperazin-1-yl)-n-(4-morpholin-4-ylphenyl)-4-oxochromene-2-carboxamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1OC(C(=O)NC=1C=CC(=CC=1)N1CCOCC1)=CC2=O AHGUAOJIJHXBHA-UHFFFAOYSA-N 0.000 description 1
- SHFPNPQUOGZMJD-UHFFFAOYSA-N 8-(4-methylpiperazin-1-yl)-n-[4-(morpholine-4-carbonyl)phenyl]-4-oxochromene-2-carboxamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1OC(C(=O)NC=1C=CC(=CC=1)C(=O)N1CCOCC1)=CC2=O SHFPNPQUOGZMJD-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- QGPQKWYMNWOLLI-UHFFFAOYSA-N 8-[ethyl-(1-ethylpyrrolidin-3-yl)amino]-6-methoxy-n-(4-morpholin-4-ylphenyl)-4-oxo-1h-quinoline-2-carboxamide Chemical compound C=1C(OC)=CC(C(C=C(N2)C(=O)NC=3C=CC(=CC=3)N3CCOCC3)=O)=C2C=1N(CC)C1CCN(CC)C1 QGPQKWYMNWOLLI-UHFFFAOYSA-N 0.000 description 1
- NQEIDYFNDDTEMC-UHFFFAOYSA-N 8-bromo-4-(dimethylamino)-6-methoxyquinoline-2-carboxylic acid Chemical compound N1=C(C(O)=O)C=C(N(C)C)C2=CC(OC)=CC(Br)=C21 NQEIDYFNDDTEMC-UHFFFAOYSA-N 0.000 description 1
- VIHVQAIFZPMNCA-UHFFFAOYSA-N 8-bromo-4-chloro-6-methoxyquinoline-2-carboxylic acid Chemical compound N1=C(C(O)=O)C=C(Cl)C2=CC(OC)=CC(Br)=C21 VIHVQAIFZPMNCA-UHFFFAOYSA-N 0.000 description 1
- XYQSPMMNYXJZET-UHFFFAOYSA-N 8-bromo-6-methoxy-4-(methylamino)-n-(4-morpholin-4-ylphenyl)quinoline-2-carboxamide Chemical compound N=1C2=C(Br)C=C(OC)C=C2C(NC)=CC=1C(=O)NC(C=C1)=CC=C1N1CCOCC1 XYQSPMMNYXJZET-UHFFFAOYSA-N 0.000 description 1
- 208000027559 Appetite disease Diseases 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 241000616862 Belliella Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 238000006418 Brown reaction Methods 0.000 description 1
- GEACCWZFOVROSW-UHFFFAOYSA-N CN(C1(CC=NC=C1)N(C)C)C Chemical compound CN(C1(CC=NC=C1)N(C)C)C GEACCWZFOVROSW-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- 241001643084 Cyrtanthus elatus virus A Species 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
- YIIMEMSDCNDGTB-UHFFFAOYSA-N Dimethylcarbamoyl chloride Chemical compound CN(C)C(Cl)=O YIIMEMSDCNDGTB-UHFFFAOYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical class O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 208000017701 Endocrine disease Diseases 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 208000019454 Feeding and Eating disease Diseases 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 101000939500 Homo sapiens UBX domain-containing protein 11 Proteins 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- 241001363655 Jaton Species 0.000 description 1
- 241001313288 Labia Species 0.000 description 1
- 201000010743 Lambert-Eaton myasthenic syndrome Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 241000252067 Megalops atlanticus Species 0.000 description 1
- 235000006679 Mentha X verticillata Nutrition 0.000 description 1
- 235000002899 Mentha suaveolens Nutrition 0.000 description 1
- 235000001636 Mentha x rotundifolia Nutrition 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- RLJFTICUTYVZDG-UHFFFAOYSA-N Methiothepine Chemical compound C12=CC(SC)=CC=C2SC2=CC=CC=C2CC1N1CCN(C)CC1 RLJFTICUTYVZDG-UHFFFAOYSA-N 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 241001274216 Naso Species 0.000 description 1
- 101000915175 Nicotiana tabacum 5-epi-aristolochene synthase Proteins 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical class [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Chemical class 0.000 description 1
- 235000005311 Pandanus odoratissimus Nutrition 0.000 description 1
- 240000002390 Pandanus odoratissimus Species 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 208000020584 Polyploidy Diseases 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102100038239 Protein Churchill Human genes 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 241001506137 Rapa Species 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 244000297179 Syringa vulgaris Species 0.000 description 1
- 235000004338 Syringa vulgaris Nutrition 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 102100029645 UBX domain-containing protein 11 Human genes 0.000 description 1
- SYKNUAWMBRIEKB-UHFFFAOYSA-N [Cl].[Br] Chemical compound [Cl].[Br] SYKNUAWMBRIEKB-UHFFFAOYSA-N 0.000 description 1
- QFOBEYAFRMUMDA-UHFFFAOYSA-L [Cs+].[Cs+].C([O-])(O)=O.C([O-])(O)=O Chemical compound [Cs+].[Cs+].C([O-])(O)=O.C([O-])(O)=O QFOBEYAFRMUMDA-UHFFFAOYSA-L 0.000 description 1
- GPWHDDKQSYOYBF-UHFFFAOYSA-N ac1l2u0q Chemical compound Br[Br-]Br GPWHDDKQSYOYBF-UHFFFAOYSA-N 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 1
- 125000005336 allyloxy group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- XKMRRTOUMJRJIA-UHFFFAOYSA-N ammonia nh3 Chemical compound N.N XKMRRTOUMJRJIA-UHFFFAOYSA-N 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 159000000032 aromatic acids Chemical class 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 description 1
- 235000013405 beer Nutrition 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 229940045348 brown mixture Drugs 0.000 description 1
- KDKYADYSIPSCCQ-UHFFFAOYSA-N but-1-yne Chemical class CCC#C KDKYADYSIPSCCQ-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- YTIVTFGABIZHHX-UHFFFAOYSA-N butynedioic acid Chemical compound OC(=O)C#CC(O)=O YTIVTFGABIZHHX-UHFFFAOYSA-N 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- ARQRPTNYUOLOGH-UHFFFAOYSA-N chcl3 chloroform Chemical compound ClC(Cl)Cl.ClC(Cl)Cl ARQRPTNYUOLOGH-UHFFFAOYSA-N 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 1
- WRJWRGBVPUUDLA-UHFFFAOYSA-N chlorosulfonyl isocyanate Chemical compound ClS(=O)(=O)N=C=O WRJWRGBVPUUDLA-UHFFFAOYSA-N 0.000 description 1
- 150000001843 chromanes Chemical class 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000000039 congener Substances 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000005100 correlation spectroscopy Methods 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000012045 crude solution Substances 0.000 description 1
- 150000001923 cyclic compounds Chemical class 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- KQWGXHWJMSMDJJ-UHFFFAOYSA-N cyclohexyl isocyanate Chemical compound O=C=NC1CCCCC1 KQWGXHWJMSMDJJ-UHFFFAOYSA-N 0.000 description 1
- YQAUOSVWZNDCSD-UHFFFAOYSA-N cyclohexyl-(2-phenylphenyl)phosphane Chemical group C1CCCCC1PC1=CC=CC=C1C1=CC=CC=C1 YQAUOSVWZNDCSD-UHFFFAOYSA-N 0.000 description 1
- WEPUZBYKXNKSDH-UHFFFAOYSA-N cyclopentanecarbonyl chloride Chemical compound ClC(=O)C1CCCC1 WEPUZBYKXNKSDH-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 125000005117 dialkylcarbamoyl group Chemical group 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- BNMOONUYSLLMEM-LCYFTJDESA-N diethyl (z)-2-(2-bromo-4-methoxyphenoxy)but-2-enedioate Chemical compound CCOC(=O)\C=C(C(=O)OCC)/OC1=CC=C(OC)C=C1Br BNMOONUYSLLMEM-LCYFTJDESA-N 0.000 description 1
- STRNXFOUBFLVIN-UHFFFAOYSA-N diethyl but-2-ynedioate Chemical compound CCOC(=O)C#CC(=O)OCC STRNXFOUBFLVIN-UHFFFAOYSA-N 0.000 description 1
- DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 1
- 229940008406 diethyl sulfate Drugs 0.000 description 1
- NSNHWTBQMQIDCF-UHFFFAOYSA-N dihydrate;hydrochloride Chemical compound O.O.Cl NSNHWTBQMQIDCF-UHFFFAOYSA-N 0.000 description 1
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- NHSCRWJPZDNMBU-UHFFFAOYSA-L dipotassium carbonic acid carbonate Chemical compound [K+].[K+].OC([O-])=O.OC([O-])=O NHSCRWJPZDNMBU-UHFFFAOYSA-L 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- SEACYXSIPDVVMV-UHFFFAOYSA-L eosin Y Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 SEACYXSIPDVVMV-UHFFFAOYSA-L 0.000 description 1
- FRYHCSODNHYDPU-UHFFFAOYSA-N ethanesulfonyl chloride Chemical compound CCS(Cl)(=O)=O FRYHCSODNHYDPU-UHFFFAOYSA-N 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- LBAQSKZHMLAFHH-UHFFFAOYSA-N ethoxyethane;hydron;chloride Chemical class Cl.CCOCC LBAQSKZHMLAFHH-UHFFFAOYSA-N 0.000 description 1
- OJIFHUZLFUXZLY-UHFFFAOYSA-N ethyl 3-bromo-4-oxochromene-2-carboxylate Chemical compound C1=CC=C2C(=O)C(Br)=C(C(=O)OCC)OC2=C1 OJIFHUZLFUXZLY-UHFFFAOYSA-N 0.000 description 1
- KYZBIYDKNADGMT-UHFFFAOYSA-N ethyl 4h-chromene-2-carboxylate Chemical compound C1=CC=C2OC(C(=O)OCC)=CCC2=C1 KYZBIYDKNADGMT-UHFFFAOYSA-N 0.000 description 1
- SHAFOGSEDNMVJH-UHFFFAOYSA-N ethyl 6-ethoxy-8-(4-methylpiperazin-1-yl)-4-oxochromene-2-carboxylate Chemical compound C=12OC(C(=O)OCC)=CC(=O)C2=CC(OCC)=CC=1N1CCN(C)CC1 SHAFOGSEDNMVJH-UHFFFAOYSA-N 0.000 description 1
- CTZQDUNDLLYSFG-UHFFFAOYSA-N ethyl 8-bromo-4-oxochromene-2-carboxylate Chemical compound C1=CC(Br)=C2OC(C(=O)OCC)=CC(=O)C2=C1 CTZQDUNDLLYSFG-UHFFFAOYSA-N 0.000 description 1
- AGEZXAMFKYGIMT-UHFFFAOYSA-N ethyl 8-bromo-6-chloro-4-oxochromene-2-carboxylate Chemical compound ClC1=CC(Br)=C2OC(C(=O)OCC)=CC(=O)C2=C1 AGEZXAMFKYGIMT-UHFFFAOYSA-N 0.000 description 1
- PHFGGFXZCISIIE-UHFFFAOYSA-N ethyl 8-bromo-6-ethoxy-4-oxochromene-2-carboxylate Chemical compound CCOC1=CC(Br)=C2OC(C(=O)OCC)=CC(=O)C2=C1 PHFGGFXZCISIIE-UHFFFAOYSA-N 0.000 description 1
- NIYBSDSIFPBWGM-UHFFFAOYSA-N ethyl 8-bromo-6-fluoro-4-oxochromene-2-carboxylate Chemical compound FC1=CC(Br)=C2OC(C(=O)OCC)=CC(=O)C2=C1 NIYBSDSIFPBWGM-UHFFFAOYSA-N 0.000 description 1
- UQGSGJYFGJVLJU-UHFFFAOYSA-N ethyl 8-chloro-5-methyl-4-oxochromene-2-carboxylate Chemical compound C1=CC(Cl)=C2OC(C(=O)OCC)=CC(=O)C2=C1C UQGSGJYFGJVLJU-UHFFFAOYSA-N 0.000 description 1
- 229960003750 ethyl chloride Drugs 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000011152 fibreglass Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- QEWYKACRFQMRMB-UHFFFAOYSA-N fluoroacetic acid Chemical compound OC(=O)CF QEWYKACRFQMRMB-UHFFFAOYSA-N 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000002816 gill Anatomy 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- JXYZHMPRERWTPM-UHFFFAOYSA-N hydron;morpholine;chloride Chemical compound Cl.C1COCCN1 JXYZHMPRERWTPM-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- JEGUKCSWCFPDGT-UHFFFAOYSA-M hydroxide;hydrate Chemical compound O.[OH-] JEGUKCSWCFPDGT-UHFFFAOYSA-M 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 1
- 229960004801 imipramine Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000013521 mastic Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- YXMDKSHMGZWECK-UHFFFAOYSA-N methyl 3-bromo-6-methoxy-4-(2-trimethylsilylethoxymethoxy)quinoline-2-carboxylate Chemical compound COC(=O)C1=NC2=CC=C(C=C2C(=C1Br)OCOCC[Si](C)(C)C)OC YXMDKSHMGZWECK-UHFFFAOYSA-N 0.000 description 1
- CILJSZLWPHTUIP-UHFFFAOYSA-N methyl quinoline-2-carboxylate Chemical compound C1=CC=CC2=NC(C(=O)OC)=CC=C21 CILJSZLWPHTUIP-UHFFFAOYSA-N 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- VGGZQWDRWOXJTA-UHFFFAOYSA-N morpholin-4-yl-(4-nitrophenyl)methanone Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(=O)N1CCOCC1 VGGZQWDRWOXJTA-UHFFFAOYSA-N 0.000 description 1
- AWXXNBQGZBENFO-UHFFFAOYSA-N morpholine Chemical compound C1COCCN1.C1COCCN1 AWXXNBQGZBENFO-UHFFFAOYSA-N 0.000 description 1
- ZYTYOUNYLKOKAR-UHFFFAOYSA-N morpholine;pyrrolidine Chemical compound C1CCNC1.C1COCCN1 ZYTYOUNYLKOKAR-UHFFFAOYSA-N 0.000 description 1
- CZGIEJXGCLWRPY-UHFFFAOYSA-N n,1-dimethylpyrrolidin-3-amine Chemical compound CNC1CCN(C)C1 CZGIEJXGCLWRPY-UHFFFAOYSA-N 0.000 description 1
- XHOADYKJSBCVBJ-UHFFFAOYSA-N n,n-diethylpyrrolidin-3-amine Chemical compound CCN(CC)C1CCNC1 XHOADYKJSBCVBJ-UHFFFAOYSA-N 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- DTKKDUXAKODAIE-UHFFFAOYSA-N n,n-dimethylpyrrolidin-1-amine Chemical compound CN(C)N1CCCC1 DTKKDUXAKODAIE-UHFFFAOYSA-N 0.000 description 1
- MKTATXMBNQQEPP-UHFFFAOYSA-N n-(3-chloro-4-morpholin-4-ylphenyl)-6-methoxy-8-(4-methylpiperazin-1-yl)-4-oxochromene-2-carboxamide Chemical compound C=12OC(C(=O)NC=3C=C(Cl)C(N4CCOCC4)=CC=3)=CC(=O)C2=CC(OC)=CC=1N1CCN(C)CC1 MKTATXMBNQQEPP-UHFFFAOYSA-N 0.000 description 1
- BEESXOQCOHCEIK-UHFFFAOYSA-N n-(3-chloro-4-morpholin-4-ylphenyl)-8-(4-methylpiperazin-1-yl)-4-oxochromene-2-carboxamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1OC(C(=O)NC=1C=C(Cl)C(N3CCOCC3)=CC=1)=CC2=O BEESXOQCOHCEIK-UHFFFAOYSA-N 0.000 description 1
- REDZYUKDGKRRLA-UHFFFAOYSA-N n-(3-cyano-4-morpholin-4-ylphenyl)-8-(4-methylpiperazin-1-yl)-4-oxochromene-2-carboxamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1OC(C(=O)NC=1C=C(C(N3CCOCC3)=CC=1)C#N)=CC2=O REDZYUKDGKRRLA-UHFFFAOYSA-N 0.000 description 1
- DLPXDCIRVDWTMX-UHFFFAOYSA-N n-(4-morpholin-4-ylphenyl)quinoline-2-carboxamide Chemical compound C=1C=C2C=CC=CC2=NC=1C(=O)NC(C=C1)=CC=C1N1CCOCC1 DLPXDCIRVDWTMX-UHFFFAOYSA-N 0.000 description 1
- ZRFKTUNZAWYCAC-UHFFFAOYSA-N n-[4-(4-fluorophenoxy)phenyl]-8-(4-methylpiperazin-1-yl)-4-oxochromene-2-carboxamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1OC(C(=O)NC=1C=CC(OC=3C=CC(F)=CC=3)=CC=1)=CC2=O ZRFKTUNZAWYCAC-UHFFFAOYSA-N 0.000 description 1
- SSUCGBYTVCOTHK-UHFFFAOYSA-N n-[4-[4-(2-hydroxyethyl)piperazin-1-yl]phenyl]-6-methoxy-8-(4-methylpiperazin-1-yl)-4-oxochromene-2-carboxamide Chemical compound C=12OC(C(=O)NC=3C=CC(=CC=3)N3CCN(CCO)CC3)=CC(=O)C2=CC(OC)=CC=1N1CCN(C)CC1 SSUCGBYTVCOTHK-UHFFFAOYSA-N 0.000 description 1
- DNXOUXANTOCWFK-UHFFFAOYSA-N n-[4-[4-(3-hydroxypropanoyl)piperazin-1-yl]phenyl]-6-methoxy-8-(4-methylpiperazin-1-yl)-4-oxochromene-2-carboxamide Chemical compound C=12OC(C(=O)NC=3C=CC(=CC=3)N3CCN(CC3)C(=O)CCO)=CC(=O)C2=CC(OC)=CC=1N1CCN(C)CC1 DNXOUXANTOCWFK-UHFFFAOYSA-N 0.000 description 1
- PBGGZRBOQDJSSW-UHFFFAOYSA-N n-[8-(4-methylpiperazin-1-yl)-4-oxochromen-2-yl]-4-morpholin-4-ylbenzamide Chemical compound C1CN(C)CCN1C1=CC=CC2=C1OC(NC(=O)C=1C=CC(=CC=1)N1CCOCC1)=CC2=O PBGGZRBOQDJSSW-UHFFFAOYSA-N 0.000 description 1
- GOTQULLXGZGQMK-UHFFFAOYSA-N n-benzyl-n-propan-2-ylpropan-2-amine Chemical compound CC(C)N(C(C)C)CC1=CC=CC=C1 GOTQULLXGZGQMK-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- CSFAYIHXWKUTHH-UHFFFAOYSA-N n-phenylmorpholin-4-amine Chemical compound C1COCCN1NC1=CC=CC=C1 CSFAYIHXWKUTHH-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 229910052754 neon Inorganic materials 0.000 description 1
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Substances ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 1
- UHHKSVZZTYJVEG-UHFFFAOYSA-N oxepane Chemical compound C1CCCOCC1 UHHKSVZZTYJVEG-UHFFFAOYSA-N 0.000 description 1
- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 description 1
- 238000006213 oxygenation reaction Methods 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- PIRWNASAJNPKHT-SHZATDIYSA-N pamp Chemical compound C([C@@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)N)C(C)C)C1=CC=CC=C1 PIRWNASAJNPKHT-SHZATDIYSA-N 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- WEYVCQFUGFRXOM-UHFFFAOYSA-N perazine Chemical compound C1CN(C)CCN1CCCN1C2=CC=CC=C2SC2=CC=CC=C21 WEYVCQFUGFRXOM-UHFFFAOYSA-N 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical class [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Chemical class 0.000 description 1
- RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 description 1
- RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 description 1
- 229940075559 piperine Drugs 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- GGHDAUPFEBTORZ-UHFFFAOYSA-N propane-1,1-diamine Chemical compound CCC(N)N GGHDAUPFEBTORZ-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- SBMSLRMNBSMKQC-UHFFFAOYSA-N pyrrolidin-1-amine Chemical compound NN1CCCC1 SBMSLRMNBSMKQC-UHFFFAOYSA-N 0.000 description 1
- ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000010454 slate Substances 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 208000020685 sleep-wake disease Diseases 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Substances [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- LFYCPBYLRDFURN-UHFFFAOYSA-M sodium;acetic acid;hydrogen carbonate Chemical compound [Na+].CC(O)=O.OC([O-])=O LFYCPBYLRDFURN-UHFFFAOYSA-M 0.000 description 1
- POECFFCNUXZPJT-UHFFFAOYSA-M sodium;carbonic acid;hydrogen carbonate Chemical compound [Na+].OC(O)=O.OC([O-])=O POECFFCNUXZPJT-UHFFFAOYSA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 125000004426 substituted alkynyl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- WQDSRJBTLILEEK-UHFFFAOYSA-N sulfurous acid Chemical compound OS(O)=O.OS(O)=O WQDSRJBTLILEEK-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- UOUFRTFWWBCVPV-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-1H-thieno[3,2-d]pyrimidin-3-yl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)n1c(=O)[nH]c2ccsc2c1=O UOUFRTFWWBCVPV-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229920001169 thermoplastic Polymers 0.000 description 1
- 239000004416 thermosoftening plastic Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- XSROQCDVUIHRSI-UHFFFAOYSA-N thietane Chemical compound C1CSC1 XSROQCDVUIHRSI-UHFFFAOYSA-N 0.000 description 1
- VOVUARRWDCVURC-UHFFFAOYSA-N thiirane Chemical compound C1CS1 VOVUARRWDCVURC-UHFFFAOYSA-N 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- IBBLKSWSCDAPIF-UHFFFAOYSA-N thiopyran Chemical compound S1C=CC=C=C1 IBBLKSWSCDAPIF-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 238000007492 two-way ANOVA Methods 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/50—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/24—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
- Pyrane Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US26210801P | 2001-01-16 | 2001-01-16 | |
SE0103646A SE0103646D0 (sv) | 2001-11-01 | 2001-11-01 | Therapeutic chroman compounds |
Publications (1)
Publication Number | Publication Date |
---|---|
SA02220709B1 true SA02220709B1 (ar) | 2007-01-23 |
Family
ID=26655581
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SA02220709A SA02220709B1 (ar) | 2001-01-16 | 2002-03-11 | مركبات كرومان chroman علاجية |
Country Status (15)
Country | Link |
---|---|
EP (1) | EP1353915A2 (ja) |
JP (1) | JP4280068B2 (ja) |
KR (1) | KR20030070917A (ja) |
CN (1) | CN100384833C (ja) |
AR (1) | AR036327A1 (ja) |
AU (1) | AU2002225551B8 (ja) |
BR (1) | BR0206514A (ja) |
CA (1) | CA2434015A1 (ja) |
IL (3) | IL156601A0 (ja) |
MX (1) | MXPA03006261A (ja) |
MY (1) | MY138263A (ja) |
NO (1) | NO20033205L (ja) |
NZ (1) | NZ526699A (ja) |
SA (1) | SA02220709B1 (ja) |
WO (1) | WO2002055014A2 (ja) |
Families Citing this family (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1275341C (zh) | 1996-08-08 | 2006-09-13 | 日立化成工业株式会社 | 生产用于锂二次电池的负极的方法 |
SE0103649D0 (sv) * | 2001-11-01 | 2001-11-01 | Astrazeneca Ab | Therapeutic quinoline compounds |
TWI357901B (en) * | 2004-03-12 | 2012-02-11 | Lundbeck & Co As H | Substituted morpholine and thiomorpholine derivati |
EP1807085B1 (en) | 2004-09-20 | 2013-08-21 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-coa desaturase inhibitors |
BRPI0515489A (pt) | 2004-09-20 | 2008-07-29 | Xenon Pharmaceuticals Inc | derivados heterocìclicos e sua utilização como inibidores de estearoil-coa desaturase |
JP5043668B2 (ja) | 2004-09-20 | 2012-10-10 | ゼノン・ファーマシューティカルズ・インコーポレイテッド | 複素環誘導体および治療薬としてのそれらの使用 |
CN101083992A (zh) | 2004-09-20 | 2007-12-05 | 泽农医药公司 | 抑制人硬脂酰CoA去饱和酶的哒嗪衍生物 |
US7919496B2 (en) | 2004-09-20 | 2011-04-05 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives for the treatment of diseases mediated by stearoyl-CoA desaturase enzymes |
CA2580857A1 (en) | 2004-09-20 | 2006-09-28 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-coa desaturase inhibitors |
JP5094398B2 (ja) | 2004-09-20 | 2012-12-12 | ゼノン・ファーマシューティカルズ・インコーポレイテッド | 複素環式誘導体およびステアロイル−CoAデサチュラーゼのメディエータとしてのそれらの使用 |
WO2007130075A1 (en) | 2005-06-03 | 2007-11-15 | Xenon Pharmaceuticals Inc. | Aminothiazole derivatives as human stearoyl-coa desaturase inhibitors |
UY29892A1 (es) * | 2005-11-04 | 2007-06-29 | Astrazeneca Ab | Nuevos derivados de cromano, composiciones farmaceuticas conteniendolos, procesos de preparacion y aplicaciones |
AU2006322094A1 (en) | 2005-12-08 | 2007-06-14 | Millennium Pharmaceuticals, Inc. | Bicyclic compounds with kinase inhibitory activity |
AR059356A1 (es) * | 2006-02-14 | 2008-03-26 | Astrazeneca Ab | Nuevos radioligandos |
WO2007097697A1 (en) * | 2006-02-23 | 2007-08-30 | Astrazeneca Ab | Therapeutic quinoline compounds that are 5ht1b modulators |
US7812206B2 (en) | 2006-03-21 | 2010-10-12 | Bp Corporation North America Inc. | Apparatus and process for the separation of solids and liquids |
US8530716B2 (en) | 2008-08-14 | 2013-09-10 | Bp Corporation North America Inc. | Melt-crystallization separation and purification process |
HUP0900281A2 (hu) * | 2009-05-05 | 2011-01-28 | Univ Szegedi | Kinurénsav-származékok, eljárás a vegyületek elõállítására, a vegyületeket tartalmazó gyógyászati készítmények és alkalmazásuk fejfájás kezelésére |
US9630896B2 (en) | 2013-11-22 | 2017-04-25 | Tansna Therapeutics, Inc. | 2,5-dialkyl-4-H/halo/ether-phenol compounds |
CN104262249A (zh) * | 2014-10-20 | 2015-01-07 | 云南民族大学 | 一种喹诺酮化合物的绿色高效制备方法 |
CA3026149A1 (en) | 2016-06-02 | 2017-12-07 | Cadent Therapeutics, Inc. | Potassium channel modulators |
DK3571193T3 (da) | 2017-01-23 | 2022-01-17 | Cadent Therapeutics Inc | Potassium Channel Modulators |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB8515389D0 (en) * | 1985-06-18 | 1985-07-17 | Ici Plc | Heterocyclic compounds |
US5112856A (en) * | 1986-08-15 | 1992-05-12 | Hoffmann-La Roche Inc. | Therapeutic treatment of intestinal inflammation by administration of 3,4-dihydro-2H-1-benzopyran derivatives |
SE8904361D0 (sv) * | 1989-12-22 | 1989-12-22 | Astra Ab | New chroman and thiochroman derivatives |
DE4140542A1 (de) * | 1991-12-09 | 1993-06-17 | Bayer Ag | Piperdylmethyl substituierte chormanderivate |
FR2761358B1 (fr) * | 1997-03-27 | 1999-05-07 | Adir | Nouveaux composes de n-aryl piperidine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
SE9703378D0 (sv) * | 1997-09-18 | 1997-09-18 | Astra Ab | New compounds |
FR2782515B1 (fr) * | 1998-08-21 | 2000-09-22 | Adir | NOUVEAUX DERIVES DE L'INDANE-1-Ol, LEUR PROCEDE DE PREPARATION ET LES COMPOSITIONS PHARMACEUTIQUES QUI LES CONTIENNENT |
-
2002
- 2002-01-15 CN CNB02806562XA patent/CN100384833C/zh not_active Expired - Fee Related
- 2002-01-15 KR KR10-2003-7009435A patent/KR20030070917A/ko not_active Application Discontinuation
- 2002-01-15 AU AU2002225551A patent/AU2002225551B8/en not_active Ceased
- 2002-01-15 CA CA002434015A patent/CA2434015A1/en not_active Abandoned
- 2002-01-15 EP EP02715919A patent/EP1353915A2/en not_active Withdrawn
- 2002-01-15 MX MXPA03006261A patent/MXPA03006261A/es active IP Right Grant
- 2002-01-15 IL IL15660102A patent/IL156601A0/xx unknown
- 2002-01-15 WO PCT/SE2002/000070 patent/WO2002055014A2/en active Application Filing
- 2002-01-15 JP JP2002555751A patent/JP4280068B2/ja not_active Expired - Fee Related
- 2002-01-15 BR BR0206514-2A patent/BR0206514A/pt not_active IP Right Cessation
- 2002-01-15 NZ NZ526699A patent/NZ526699A/en unknown
- 2002-01-16 MY MYPI20020159A patent/MY138263A/en unknown
- 2002-01-16 AR ARP020100142A patent/AR036327A1/es unknown
- 2002-03-11 SA SA02220709A patent/SA02220709B1/ar unknown
-
2003
- 2003-06-23 IL IL156601A patent/IL156601A/en not_active IP Right Cessation
- 2003-07-15 NO NO20033205A patent/NO20033205L/no not_active Application Discontinuation
-
2007
- 2007-05-14 IL IL183183A patent/IL183183A0/en unknown
Also Published As
Publication number | Publication date |
---|---|
AU2002225551B8 (en) | 2008-05-29 |
NO20033205L (no) | 2003-09-02 |
IL156601A (en) | 2009-06-15 |
NO20033205D0 (no) | 2003-07-15 |
CN100384833C (zh) | 2008-04-30 |
AU2002225551B2 (en) | 2008-04-03 |
NZ526699A (en) | 2005-03-24 |
MXPA03006261A (es) | 2003-09-22 |
CA2434015A1 (en) | 2002-07-18 |
KR20030070917A (ko) | 2003-09-02 |
JP2004517130A (ja) | 2004-06-10 |
CN1524077A (zh) | 2004-08-25 |
JP4280068B2 (ja) | 2009-06-17 |
AR036327A1 (es) | 2004-09-01 |
WO2002055014A2 (en) | 2002-07-18 |
BR0206514A (pt) | 2004-01-06 |
WO2002055014A3 (en) | 2002-11-14 |
IL183183A0 (en) | 2007-08-19 |
MY138263A (en) | 2009-05-29 |
IL156601A0 (en) | 2004-01-04 |
EP1353915A2 (en) | 2003-10-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
SA02220709B1 (ar) | مركبات كرومان chroman علاجية | |
JP4280067B2 (ja) | 治療用ヘテロ環式化合物 | |
CN108349981B (zh) | 新型的吡唑并[3,4-d]嘧啶化合物或其盐 | |
KR100618074B1 (ko) | 벤즈아미드 유도체 및 이것의 사이토킨 억제제로서 용도 | |
US7026314B2 (en) | Therapeutic chromone compounds | |
US20050096312A1 (en) | Therapeutic quinolone compounds with 5-ht-antagonistic properties | |
JP2005511568A (ja) | 5−ht−アンタゴニスト特性を有する治療用キノロン化合物 | |
BG108325A (bg) | Нови 4-анилинохинолин-3-карбоксамиди | |
AU2001239331A1 (en) | Derivatives of quinoline as alpha-2 antagonists | |
JP4545000B2 (ja) | テトラヒドロキノリン誘導体及びfsh受容体モジュレーターとしてのその使用 | |
AU2002225551A1 (en) | Therapeutic chroman compounds | |
DK162220B (da) | Tricykliske pyridazinderivater, som er agonister af cholinerge receptorer, fremgangsmaade til fremstilling af derivaterne, og laegemidler, hvori de er til stede | |
Yang et al. | Development of a tetrahydroindazolone-based HDAC6 inhibitor with in-vivo anti-arthritic activity | |
RU2782469C2 (ru) | Апоптоз-индуцирующие агенты | |
US20040110745A1 (en) | Therapeutic chroman compounds | |
CN1821236B (zh) | 治疗性杂环化合物 | |
CN100460402C (zh) | 用作中间体的苯并吡喃酮化合物 | |
CN100386318C (zh) | 四氢喹啉衍生物及其作为fsh受体调节剂的用途 | |
US20040082591A1 (en) | Therapeutic heterocyclic compounds | |
US20060019947A1 (en) | Therapeutic chromone compounds | |
SA515360750B1 (ar) | مركبات (ثينو]2، 3-1b][، 5 بنزوكسازبين-4-يل) بيبيرازين-1-يل في صورة مساعدات ايتش1 عكسية/مضادات ايتش تي 2 أي-5 ذات نشاط مزدوج |