CN1310706A - 磷脂酶抑制剂 - Google Patents
磷脂酶抑制剂 Download PDFInfo
- Publication number
- CN1310706A CN1310706A CN99805157A CN99805157A CN1310706A CN 1310706 A CN1310706 A CN 1310706A CN 99805157 A CN99805157 A CN 99805157A CN 99805157 A CN99805157 A CN 99805157A CN 1310706 A CN1310706 A CN 1310706A
- Authority
- CN
- China
- Prior art keywords
- alkyl
- methyl
- phenyl
- cooh
- benzyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 108010064785 Phospholipases Proteins 0.000 title description 6
- 102000015439 Phospholipases Human genes 0.000 title description 6
- 239000003112 inhibitor Substances 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 221
- 238000000034 method Methods 0.000 claims abstract description 93
- 150000003839 salts Chemical class 0.000 claims abstract description 54
- 241000124008 Mammalia Species 0.000 claims abstract description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 292
- 229910052736 halogen Inorganic materials 0.000 claims description 190
- 150000002367 halogens Chemical class 0.000 claims description 190
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 152
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 145
- -1 pyrryl Chemical group 0.000 claims description 142
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 130
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 124
- XHQZJYCNDZAGLW-UHFFFAOYSA-N 3-methoxybenzoic acid Chemical compound COC1=CC=CC(C(O)=O)=C1 XHQZJYCNDZAGLW-UHFFFAOYSA-N 0.000 claims description 100
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 85
- 125000000217 alkyl group Chemical group 0.000 claims description 84
- 125000000623 heterocyclic group Chemical group 0.000 claims description 78
- 229910052757 nitrogen Inorganic materials 0.000 claims description 75
- 229910052760 oxygen Inorganic materials 0.000 claims description 75
- 229910052717 sulfur Inorganic materials 0.000 claims description 69
- 150000002475 indoles Chemical class 0.000 claims description 67
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 65
- 229910052739 hydrogen Inorganic materials 0.000 claims description 65
- 125000003545 alkoxy group Chemical group 0.000 claims description 60
- 229910052799 carbon Inorganic materials 0.000 claims description 54
- 239000000203 mixture Substances 0.000 claims description 53
- 125000005842 heteroatom Chemical group 0.000 claims description 51
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 50
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 47
- 239000002253 acid Substances 0.000 claims description 44
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 42
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 41
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 40
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 37
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 37
- 125000004076 pyridyl group Chemical group 0.000 claims description 37
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 36
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 35
- 125000002541 furyl group Chemical group 0.000 claims description 35
- 125000001544 thienyl group Chemical group 0.000 claims description 35
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 34
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 34
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 34
- 150000003217 pyrazoles Chemical class 0.000 claims description 32
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 30
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 30
- 125000006638 cyclopentyl carbonyl group Chemical group 0.000 claims description 28
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 24
- 150000002460 imidazoles Chemical class 0.000 claims description 23
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 21
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 20
- 150000003053 piperidines Chemical class 0.000 claims description 19
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 19
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 18
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 18
- 150000002240 furans Chemical class 0.000 claims description 18
- 150000003233 pyrroles Chemical class 0.000 claims description 18
- 229930192474 thiophene Natural products 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 18
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 17
- 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 239000000126 substance Substances 0.000 claims description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 16
- 125000004429 atom Chemical group 0.000 claims description 16
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 16
- RCFKEIREOSXLET-UHFFFAOYSA-N disulfamide Chemical compound CC1=CC(Cl)=C(S(N)(=O)=O)C=C1S(N)(=O)=O RCFKEIREOSXLET-UHFFFAOYSA-N 0.000 claims description 16
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 claims description 15
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 claims description 15
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 15
- QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 claims description 15
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 15
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 14
- 125000000335 thiazolyl group Chemical group 0.000 claims description 14
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 125000001624 naphthyl group Chemical group 0.000 claims description 12
- 230000002378 acidificating effect Effects 0.000 claims description 11
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 11
- YCMLQMDWSXFTIF-UHFFFAOYSA-N 2-methylbenzenesulfonimidic acid Chemical compound CC1=CC=CC=C1S(N)(=O)=O YCMLQMDWSXFTIF-UHFFFAOYSA-N 0.000 claims description 10
- 206010061218 Inflammation Diseases 0.000 claims description 10
- 230000004054 inflammatory process Effects 0.000 claims description 10
- 125000005493 quinolyl group Chemical group 0.000 claims description 10
- 239000003937 drug carrier Substances 0.000 claims description 9
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 8
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 claims description 8
- 235000019260 propionic acid Nutrition 0.000 claims description 8
- 239000003981 vehicle Substances 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- QQVIHTHCMHWDBS-UHFFFAOYSA-N isophthalic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-N 0.000 claims description 6
- 125000001072 heteroaryl group Chemical group 0.000 claims description 5
- RFCQDOVPMUSZMN-UHFFFAOYSA-N 2-Naphthalenethiol Chemical compound C1=CC=CC2=CC(S)=CC=C21 RFCQDOVPMUSZMN-UHFFFAOYSA-N 0.000 claims description 4
- ALRHLSYJTWAHJZ-UHFFFAOYSA-N 3-hydroxypropionic acid Chemical compound OCCC(O)=O ALRHLSYJTWAHJZ-UHFFFAOYSA-N 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 125000006309 butyl amino group Chemical group 0.000 claims description 4
- PYRYOLOOOPVOHJ-UHFFFAOYSA-N cyclopentane formamide Chemical compound C(=O)N.C1CCCC1 PYRYOLOOOPVOHJ-UHFFFAOYSA-N 0.000 claims description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 229940073608 benzyl chloride Drugs 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 239000004324 sodium propionate Substances 0.000 claims description 2
- 235000010334 sodium propionate Nutrition 0.000 claims description 2
- 229960003212 sodium propionate Drugs 0.000 claims description 2
- IJFXRHURBJZNAO-UHFFFAOYSA-N 3-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=CC(O)=C1 IJFXRHURBJZNAO-UHFFFAOYSA-N 0.000 claims 2
- MTNBXMUURNBCCC-UHFFFAOYSA-N 1-benzyl-2-methyl-5-phenylmethoxyindole-3-carboxylic acid Chemical compound C=1C=C2N(CC=3C=CC=CC=3)C(C)=C(C(O)=O)C2=CC=1OCC1=CC=CC=C1 MTNBXMUURNBCCC-UHFFFAOYSA-N 0.000 claims 1
- RMDWGISNCMBXLB-UHFFFAOYSA-N 3-[[2-[1-[(4-benzylphenyl)methyl]-5-phenylmethoxyindol-3-yl]-2-oxoacetyl]amino]benzoic acid Chemical compound OC(=O)C1=CC=CC(NC(=O)C(=O)C=2C3=CC(OCC=4C=CC=CC=4)=CC=C3N(CC=3C=CC(CC=4C=CC=CC=4)=CC=3)C=2)=C1 RMDWGISNCMBXLB-UHFFFAOYSA-N 0.000 claims 1
- OVXBAOVZEWURSM-UHFFFAOYSA-N 3-[[2-[1-[(4-benzylphenyl)methyl]-5-phenylmethoxyindol-3-yl]acetyl]amino]benzoic acid Chemical compound OC(=O)C1=CC=CC(NC(=O)CC=2C3=CC(OCC=4C=CC=CC=4)=CC=C3N(CC=3C=CC(CC=4C=CC=CC=4)=CC=3)C=2)=C1 OVXBAOVZEWURSM-UHFFFAOYSA-N 0.000 claims 1
- URBXOJYDMIXMIE-UHFFFAOYSA-N 3-[[2-[1-[(4-benzylphenyl)methyl]indol-3-yl]-2-oxoacetyl]amino]benzoic acid Chemical compound OC(=O)C1=CC=CC(NC(=O)C(=O)C=2C3=CC=CC=C3N(CC=3C=CC(CC=4C=CC=CC=4)=CC=3)C=2)=C1 URBXOJYDMIXMIE-UHFFFAOYSA-N 0.000 claims 1
- XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 claims 1
- 229960001220 amsacrine Drugs 0.000 claims 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims 1
- UIUJIQZEACWQSV-UHFFFAOYSA-N succinic semialdehyde Chemical compound OC(=O)CCC=O UIUJIQZEACWQSV-UHFFFAOYSA-N 0.000 claims 1
- 230000004968 inflammatory condition Effects 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 178
- 239000000543 intermediate Substances 0.000 description 144
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 110
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 103
- 239000000047 product Substances 0.000 description 95
- 238000002360 preparation method Methods 0.000 description 78
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 68
- 235000019439 ethyl acetate Nutrition 0.000 description 66
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- 239000000243 solution Substances 0.000 description 63
- 125000004093 cyano group Chemical group *C#N 0.000 description 62
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 61
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 59
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 55
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
- 150000002148 esters Chemical class 0.000 description 51
- 239000000376 reactant Substances 0.000 description 47
- 230000007062 hydrolysis Effects 0.000 description 38
- 238000006460 hydrolysis reaction Methods 0.000 description 38
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 34
- 229940124530 sulfonamide Drugs 0.000 description 34
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 29
- 239000012141 concentrate Substances 0.000 description 29
- 238000006243 chemical reaction Methods 0.000 description 26
- 239000002904 solvent Substances 0.000 description 26
- 238000005406 washing Methods 0.000 description 26
- 239000007787 solid Substances 0.000 description 25
- 238000005804 alkylation reaction Methods 0.000 description 24
- 238000011097 chromatography purification Methods 0.000 description 23
- 238000003756 stirring Methods 0.000 description 23
- WJQWYAJTPPYORB-UHFFFAOYSA-N 5-nitro-2,3-dihydro-1h-indole Chemical compound [O-][N+](=O)C1=CC=C2NCCC2=C1 WJQWYAJTPPYORB-UHFFFAOYSA-N 0.000 description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
- 239000002168 alkylating agent Substances 0.000 description 20
- 229940100198 alkylating agent Drugs 0.000 description 20
- 230000029936 alkylation Effects 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 18
- 239000012044 organic layer Substances 0.000 description 18
- 229910000104 sodium hydride Inorganic materials 0.000 description 18
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 17
- 230000000694 effects Effects 0.000 description 17
- 150000002617 leukotrienes Chemical class 0.000 description 16
- 150000003180 prostaglandins Chemical class 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 15
- ZCBIFHNDZBSCEP-UHFFFAOYSA-N 1H-indol-5-amine Chemical compound NC1=CC=C2NC=CC2=C1 ZCBIFHNDZBSCEP-UHFFFAOYSA-N 0.000 description 14
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 14
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 14
- 150000001412 amines Chemical class 0.000 description 14
- 230000003301 hydrolyzing effect Effects 0.000 description 14
- 239000010410 layer Substances 0.000 description 14
- 239000012312 sodium hydride Substances 0.000 description 14
- 238000013459 approach Methods 0.000 description 13
- 239000003153 chemical reaction reagent Substances 0.000 description 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- 239000003513 alkali Substances 0.000 description 12
- 238000001035 drying Methods 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 238000001914 filtration Methods 0.000 description 11
- 238000001953 recrystallisation Methods 0.000 description 11
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 10
- 150000001299 aldehydes Chemical class 0.000 description 10
- 238000003818 flash chromatography Methods 0.000 description 10
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 10
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 102000004190 Enzymes Human genes 0.000 description 9
- 108090000790 Enzymes Proteins 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 150000001408 amides Chemical class 0.000 description 9
- 229940114079 arachidonic acid Drugs 0.000 description 9
- 235000021342 arachidonic acid Nutrition 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 9
- 238000000605 extraction Methods 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 239000012266 salt solution Substances 0.000 description 9
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 8
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
- 238000012545 processing Methods 0.000 description 8
- 238000010898 silica gel chromatography Methods 0.000 description 8
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 7
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 7
- 238000007126 N-alkylation reaction Methods 0.000 description 7
- 125000003118 aryl group Chemical group 0.000 description 7
- 239000013058 crude material Substances 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- MKDCJAPHKZPKOU-UHFFFAOYSA-N 1-nitro-2,3-dihydroindole Chemical compound C1=CC=C2N([N+](=O)[O-])CCC2=C1 MKDCJAPHKZPKOU-UHFFFAOYSA-N 0.000 description 6
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- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- OHOVBSAWJQSRDD-UHFFFAOYSA-N thiophen-2-yloxyboronic acid Chemical compound OB(O)OC1=CC=CS1 OHOVBSAWJQSRDD-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- HFTAFOQKODTIJY-UHFFFAOYSA-N umbelliferone Natural products Cc1cc2C=CC(=O)Oc2cc1OCC=CC(C)(C)O HFTAFOQKODTIJY-UHFFFAOYSA-N 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- MWLSOWXNZPKENC-SSDOTTSWSA-N zileuton Chemical compound C1=CC=C2SC([C@H](N(O)C(N)=O)C)=CC2=C1 MWLSOWXNZPKENC-SSDOTTSWSA-N 0.000 description 1
- 229960005332 zileuton Drugs 0.000 description 1
Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- 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
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
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- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
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- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- 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
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
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- 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
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- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07—ORGANIC CHEMISTRY
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- 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
- C07D413/12—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 chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
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- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
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US3059298A | 1998-02-25 | 1998-02-25 | |
US09/030,592 | 1998-02-25 |
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CN1310706A true CN1310706A (zh) | 2001-08-29 |
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CN99805157A Pending CN1310706A (zh) | 1998-02-25 | 1999-02-24 | 磷脂酶抑制剂 |
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EP (1) | EP1062205A2 (hu) |
JP (1) | JP2002504541A (hu) |
KR (1) | KR20010041344A (hu) |
CN (1) | CN1310706A (hu) |
AU (1) | AU765427B2 (hu) |
BG (1) | BG104779A (hu) |
BR (1) | BR9908275A (hu) |
CA (1) | CA2322162A1 (hu) |
EA (1) | EA003876B1 (hu) |
EE (1) | EE200000488A (hu) |
GE (1) | GEP20032920B (hu) |
HR (1) | HRP20000551A2 (hu) |
HU (1) | HUP0101146A3 (hu) |
ID (1) | ID26250A (hu) |
IL (1) | IL137719A0 (hu) |
NO (1) | NO20004219L (hu) |
NZ (1) | NZ506329A (hu) |
PL (1) | PL343007A1 (hu) |
SK (1) | SK12752000A3 (hu) |
TR (1) | TR200002447T2 (hu) |
WO (1) | WO1999043654A2 (hu) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102040550B (zh) * | 2005-05-27 | 2012-10-03 | 惠氏公司 | 胞质磷脂酶a2抑制剂 |
CN106810488A (zh) * | 2015-11-27 | 2017-06-09 | 中国科学院上海药物研究所 | 一类用作GPR17和CysLT1双重拮抗剂的化合物、其制备方法和用途 |
CN108530354A (zh) * | 2018-05-07 | 2018-09-14 | 青岛农业大学 | 一种含苯磺酰基喹啉类化合物的合成方法 |
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DE19917504A1 (de) * | 1999-04-17 | 2000-10-19 | Dresden Arzneimittel | Verwendung von Hydroxyindolen, die Inhibitoren der Phosphodiesterase 4 sind, zur Therapie chronisch obstruktiver Lungenerkrankungen |
HUP0102243A2 (hu) * | 1998-05-01 | 2001-10-28 | Eli Lilly And Co. | sPLA2-inhibitor vegyületek betegség kezelésére |
TWI269654B (en) * | 1999-09-28 | 2007-01-01 | Baxter Healthcare Sa | N-substituted indole-3-glyoxylamide compounds having anti-tumor action |
DE19951360A1 (de) | 1999-10-26 | 2001-05-03 | Aventis Pharma Gmbh | Substituierte Indole |
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DE19963178A1 (de) * | 1999-12-27 | 2001-07-05 | Gruenenthal Gmbh | Substituierte Indol-Mannichbasen |
DE10006139A1 (de) * | 2000-02-11 | 2001-08-16 | Merck Patent Gmbh | Indol-3-yl-Derivate |
AUPQ876400A0 (en) * | 2000-07-14 | 2000-08-03 | University Of Queensland, The | Compositions and method of using them |
ATE362468T1 (de) * | 2000-07-25 | 2007-06-15 | Merck & Co Inc | N-substituierte indole mit anwendung in der behandlung von diabetes |
DE10037310A1 (de) * | 2000-07-28 | 2002-02-07 | Asta Medica Ag | Neue Indolderivate und deren Verwendung als Arzneimittel |
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JP4399253B2 (ja) | 2001-06-20 | 2010-01-13 | ワイス | プラスミノゲンアクチベーターインヒビター−1(pai−1)のインヒビターとしての、置換されたインドール酸誘導体 |
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US7393960B2 (en) | 2002-08-29 | 2008-07-01 | Merck & Co., Inc. | Indoles having anti-diabetic activity |
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1999
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- 1999-02-24 ID IDW20001595A patent/ID26250A/id unknown
- 1999-02-24 JP JP2000533412A patent/JP2002504541A/ja not_active Withdrawn
- 1999-02-24 PL PL99343007A patent/PL343007A1/xx unknown
- 1999-02-24 WO PCT/US1999/003898 patent/WO1999043654A2/en not_active Application Discontinuation
- 1999-02-24 AU AU27825/99A patent/AU765427B2/en not_active Ceased
- 1999-02-24 CA CA002322162A patent/CA2322162A1/en not_active Abandoned
- 1999-02-24 EE EEP200000488A patent/EE200000488A/xx unknown
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- 1999-02-24 GE GEAP19995560A patent/GEP20032920B/en unknown
- 1999-02-24 CN CN99805157A patent/CN1310706A/zh active Pending
- 1999-02-24 EP EP99908378A patent/EP1062205A2/en not_active Withdrawn
- 1999-02-24 EA EA200000871A patent/EA003876B1/ru not_active IP Right Cessation
- 1999-02-24 KR KR1020007009457A patent/KR20010041344A/ko not_active Application Discontinuation
- 1999-02-24 BR BR9908275-6A patent/BR9908275A/pt not_active IP Right Cessation
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- 1999-02-24 TR TR2000/02447T patent/TR200002447T2/xx unknown
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2000
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- 2000-08-24 HR HR20000551A patent/HRP20000551A2/hr not_active Application Discontinuation
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
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CN102040550B (zh) * | 2005-05-27 | 2012-10-03 | 惠氏公司 | 胞质磷脂酶a2抑制剂 |
CN106810488A (zh) * | 2015-11-27 | 2017-06-09 | 中国科学院上海药物研究所 | 一类用作GPR17和CysLT1双重拮抗剂的化合物、其制备方法和用途 |
CN106810488B (zh) * | 2015-11-27 | 2021-02-19 | 中国科学院上海药物研究所 | 一类用作GPR17和CysLT1双重拮抗剂的化合物、其制备方法和用途 |
CN108530354A (zh) * | 2018-05-07 | 2018-09-14 | 青岛农业大学 | 一种含苯磺酰基喹啉类化合物的合成方法 |
CN108530354B (zh) * | 2018-05-07 | 2019-12-10 | 青岛农业大学 | 一种含苯磺酰基喹啉类化合物的合成方法 |
Also Published As
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WO1999043654A2 (en) | 1999-09-02 |
ID26250A (id) | 2000-12-07 |
AU2782599A (en) | 1999-09-15 |
HUP0101146A2 (hu) | 2001-08-28 |
AU765427B2 (en) | 2003-09-18 |
WO1999043654A3 (en) | 1999-10-28 |
EA003876B1 (ru) | 2003-10-30 |
BR9908275A (pt) | 2000-10-24 |
NO20004219D0 (no) | 2000-08-23 |
EP1062205A2 (en) | 2000-12-27 |
GEP20032920B (en) | 2003-03-25 |
BG104779A (en) | 2001-10-31 |
HUP0101146A3 (en) | 2001-11-28 |
KR20010041344A (ko) | 2001-05-15 |
PL343007A1 (en) | 2001-07-30 |
NZ506329A (en) | 2004-01-30 |
JP2002504541A (ja) | 2002-02-12 |
EE200000488A (et) | 2002-02-15 |
EA200000871A1 (ru) | 2001-04-23 |
CA2322162A1 (en) | 1999-09-02 |
TR200002447T2 (tr) | 2000-11-21 |
IL137719A0 (en) | 2001-10-31 |
HRP20000551A2 (en) | 2001-04-30 |
NO20004219L (no) | 2000-10-23 |
SK12752000A3 (sk) | 2001-03-12 |
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