NO310356B1 - Trisubstituerte fenylderivater, farmasöytisk preparat inneholdende slike derivater, anvendelse derav og fremgangsmåtefor deres fremstilling - Google Patents
Trisubstituerte fenylderivater, farmasöytisk preparat inneholdende slike derivater, anvendelse derav og fremgangsmåtefor deres fremstilling Download PDFInfo
- Publication number
- NO310356B1 NO310356B1 NO19974118A NO974118A NO310356B1 NO 310356 B1 NO310356 B1 NO 310356B1 NO 19974118 A NO19974118 A NO 19974118A NO 974118 A NO974118 A NO 974118A NO 310356 B1 NO310356 B1 NO 310356B1
- Authority
- NO
- Norway
- Prior art keywords
- formula
- compound
- compounds
- hydroxy
- dimethoxyphenyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 31
- 230000008569 process Effects 0.000 title claims description 24
- 238000002360 preparation method Methods 0.000 title claims description 17
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 119
- 230000002062 proliferating effect Effects 0.000 claims abstract description 9
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 8
- 208000000453 Skin Neoplasms Diseases 0.000 claims abstract description 7
- 201000000849 skin cancer Diseases 0.000 claims abstract description 7
- 208000017520 skin disease Diseases 0.000 claims abstract description 7
- 230000002265 prevention Effects 0.000 claims abstract description 6
- 125000001424 substituent group Chemical group 0.000 claims description 21
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 17
- -1 amino, diacetylamino Chemical group 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 150000003839 salts Chemical group 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000004122 cyclic group Chemical group 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 230000009467 reduction Effects 0.000 claims description 5
- PLSOFLNMARXGBD-UHFFFAOYSA-N 6-[2-(2,5-dimethoxyphenyl)ethyl]-4-ethylquinazoline Chemical group C1=C2C(CC)=NC=NC2=CC=C1CCC1=CC(OC)=CC=C1OC PLSOFLNMARXGBD-UHFFFAOYSA-N 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 230000008878 coupling Effects 0.000 claims description 4
- 238000010168 coupling process Methods 0.000 claims description 4
- 238000005859 coupling reaction Methods 0.000 claims description 4
- 125000000524 functional group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 230000010933 acylation Effects 0.000 claims description 2
- 238000005917 acylation reaction Methods 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 230000029936 alkylation Effects 0.000 claims description 2
- 238000005804 alkylation reaction Methods 0.000 claims description 2
- 229940111121 antirheumatic drug quinolines Drugs 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- ZDQWVKDDJDIVAL-UHFFFAOYSA-N catecholborane Chemical compound C1=CC=C2O[B]OC2=C1 ZDQWVKDDJDIVAL-UHFFFAOYSA-N 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 238000006114 decarboxylation reaction Methods 0.000 claims description 2
- 238000005661 deetherification reaction Methods 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 239000002243 precursor Substances 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000006239 protecting group Chemical group 0.000 claims description 2
- 150000003246 quinazolines Chemical class 0.000 claims description 2
- 150000003248 quinolines Chemical class 0.000 claims description 2
- 238000006798 ring closing metathesis reaction Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 4
- PANNVTILWOIJNS-UHFFFAOYSA-N 6-[2-(2,5-dimethoxyphenyl)ethyl]-4-ethoxyquinazoline Chemical compound C1=C2C(OCC)=NC=NC2=CC=C1CCC1=CC(OC)=CC=C1OC PANNVTILWOIJNS-UHFFFAOYSA-N 0.000 claims 1
- CTOVSSHKAQWXDM-UHFFFAOYSA-N 6-[2-(2,5-dimethoxyphenyl)ethyl]-4-methylquinazoline Chemical compound COC1=CC=C(OC)C(CCC=2C=C3C(C)=NC=NC3=CC=2)=C1 CTOVSSHKAQWXDM-UHFFFAOYSA-N 0.000 claims 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims 1
- 238000006470 amide elimination reaction Methods 0.000 claims 1
- 238000007257 deesterification reaction Methods 0.000 claims 1
- 238000011084 recovery Methods 0.000 claims 1
- 229910052720 vanadium Inorganic materials 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 120
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 38
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 239000000203 mixture Substances 0.000 description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 239000013078 crystal Substances 0.000 description 20
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 19
- 235000019341 magnesium sulphate Nutrition 0.000 description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- 238000005160 1H NMR spectroscopy Methods 0.000 description 13
- 239000002904 solvent Substances 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 238000010992 reflux Methods 0.000 description 9
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 7
- 239000007853 buffer solution Substances 0.000 description 7
- 238000010898 silica gel chromatography Methods 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- 239000003513 alkali Substances 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 239000012894 fetal calf serum Substances 0.000 description 5
- 150000002431 hydrogen Chemical group 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 230000001028 anti-proliverative effect Effects 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000002480 mineral oil Substances 0.000 description 4
- 235000010446 mineral oil Nutrition 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- IRWASZXFFDVXAA-UHFFFAOYSA-N 6-[2-(2,5-dimethoxyphenyl)ethyl]-1h-quinazolin-4-one Chemical compound COC1=CC=C(OC)C(CCC=2C=C3C(=O)NC=NC3=CC=2)=C1 IRWASZXFFDVXAA-UHFFFAOYSA-N 0.000 description 3
- YUEFBUYEPRXDBB-UHFFFAOYSA-N 6-iodoquinazolin-4-amine Chemical compound C1=C(I)C=C2C(N)=NC=NC2=C1 YUEFBUYEPRXDBB-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-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
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 210000002510 keratinocyte Anatomy 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- XBWYZWUREJXJAA-UHFFFAOYSA-N methyl 2-amino-5-[2-(2,5-dimethoxyphenyl)ethyl]benzoate Chemical compound C1=C(N)C(C(=O)OC)=CC(CCC=2C(=CC=C(OC)C=2)OC)=C1 XBWYZWUREJXJAA-UHFFFAOYSA-N 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- CZDKYDOSKNCXSM-UHFFFAOYSA-N 2-(bromomethyl)-1,4-dimethoxybenzene Chemical compound COC1=CC=C(OC)C(CBr)=C1 CZDKYDOSKNCXSM-UHFFFAOYSA-N 0.000 description 2
- IOOMXAQUNPWDLL-UHFFFAOYSA-N 2-[6-(diethylamino)-3-(diethyliminiumyl)-3h-xanthen-9-yl]-5-sulfobenzene-1-sulfonate Chemical compound C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=C(S(O)(=O)=O)C=C1S([O-])(=O)=O IOOMXAQUNPWDLL-UHFFFAOYSA-N 0.000 description 2
- XYJAHKATEAXAOA-UHFFFAOYSA-N 2-ethynyl-1,4-dimethoxybenzene Chemical group COC1=CC=C(OC)C(C#C)=C1 XYJAHKATEAXAOA-UHFFFAOYSA-N 0.000 description 2
- LFRNYDQHQSEOOO-UHFFFAOYSA-N 3-[(2,6-dimethoxyphenyl)methyl]-6-hydroxyquinazolin-4-one Chemical compound COC1=CC=CC(OC)=C1CN1C(=O)C2=CC(O)=CC=C2N=C1 LFRNYDQHQSEOOO-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- BDAIUOPDSRAOKI-UHFFFAOYSA-N 4-chloro-6-iodoquinazoline Chemical compound C1=C(I)C=C2C(Cl)=NC=NC2=C1 BDAIUOPDSRAOKI-UHFFFAOYSA-N 0.000 description 2
- DYVGZBUGKQQBDL-UHFFFAOYSA-N 5-[(2,5-dimethoxyphenyl)methoxy]-2-formamidobenzamide Chemical compound COC1=CC=C(OC)C(COC=2C=C(C(NC=O)=CC=2)C(N)=O)=C1 DYVGZBUGKQQBDL-UHFFFAOYSA-N 0.000 description 2
- KIRKUSKXZCMJJK-UHFFFAOYSA-N 6-[2-(2,5-dimethoxyphenyl)ethynyl]-n-methylquinazolin-4-amine Chemical compound C1=C2C(NC)=NC=NC2=CC=C1C#CC1=CC(OC)=CC=C1OC KIRKUSKXZCMJJK-UHFFFAOYSA-N 0.000 description 2
- QJRNXXLTDWMENM-UHFFFAOYSA-N 6-hydroxy-1h-quinazolin-4-one Chemical compound N1C=NC(=O)C2=CC(O)=CC=C21 QJRNXXLTDWMENM-UHFFFAOYSA-N 0.000 description 2
- LHMRXHSULRDCLE-UHFFFAOYSA-N 6-iodo-4-methoxyquinazoline Chemical compound C1=C(I)C=C2C(OC)=NC=NC2=C1 LHMRXHSULRDCLE-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 201000004624 Dermatitis Diseases 0.000 description 2
- 102000001301 EGF receptor Human genes 0.000 description 2
- 108060006698 EGF receptor Proteins 0.000 description 2
- 102000009024 Epidermal Growth Factor Human genes 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 201000008275 breast carcinoma Diseases 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000011097 chromatography purification Methods 0.000 description 2
- 238000007398 colorimetric assay Methods 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- 125000002534 ethynyl group Chemical class [H]C#C* 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000012737 fresh medium Substances 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- SQQDDKUFOBMLKY-UHFFFAOYSA-N methyl 2-acetamido-5-[2-(2,5-dimethoxyphenyl)ethenyl]benzoate Chemical compound C1=C(NC(C)=O)C(C(=O)OC)=CC(C=CC=2C(=CC=C(OC)C=2)OC)=C1 SQQDDKUFOBMLKY-UHFFFAOYSA-N 0.000 description 2
- YGASXVZXXXSXMH-UHFFFAOYSA-N methyl 2-acetamido-5-[2-(2,5-dimethoxyphenyl)ethyl]benzoate Chemical compound C1=C(NC(C)=O)C(C(=O)OC)=CC(CCC=2C(=CC=C(OC)C=2)OC)=C1 YGASXVZXXXSXMH-UHFFFAOYSA-N 0.000 description 2
- BCZUGNNYCCZPAA-UHFFFAOYSA-N n-acetyl-n-[6-[2-(2,5-dimethoxyphenyl)ethynyl]quinazolin-4-yl]acetamide Chemical compound COC1=CC=C(OC)C(C#CC=2C=C3C(N(C(C)=O)C(C)=O)=NC=NC3=CC=2)=C1 BCZUGNNYCCZPAA-UHFFFAOYSA-N 0.000 description 2
- BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-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
- 239000002244 precipitate Substances 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- FVUDWHPJVYTKDT-UHFFFAOYSA-M (2,5-dimethoxyphenyl)methyl-triphenylphosphanium;bromide Chemical compound [Br-].COC1=CC=C(OC)C(C[P+](C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 FVUDWHPJVYTKDT-UHFFFAOYSA-M 0.000 description 1
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 1
- AFUKNJHPZAVHGQ-UHFFFAOYSA-N 2,5-dimethoxy-Benzaldehyde Chemical compound COC1=CC=C(OC)C(C=O)=C1 AFUKNJHPZAVHGQ-UHFFFAOYSA-N 0.000 description 1
- GXAOHKNCTGIDHH-UHFFFAOYSA-N 2-(bromomethyl)-1,3-dimethoxybenzene Chemical compound COC1=CC=CC(OC)=C1CBr GXAOHKNCTGIDHH-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
- LPMKMFKURPBLSX-UHFFFAOYSA-N 2-amino-5-[2-(2,5-dimethoxyphenyl)ethynyl]benzamide Chemical compound COC1=CC=C(OC)C(C#CC=2C=C(C(N)=CC=2)C(N)=O)=C1 LPMKMFKURPBLSX-UHFFFAOYSA-N 0.000 description 1
- OZZQEKXRNJHUPY-UHFFFAOYSA-N 2-formamido-5-hydroxybenzamide Chemical compound NC(=O)C1=CC(O)=CC=C1NC=O OZZQEKXRNJHUPY-UHFFFAOYSA-N 0.000 description 1
- BLDBEYINFUSUOT-UHFFFAOYSA-N 3-[(2,5-dimethoxyphenyl)methyl]-6-hydroxyquinazolin-4-one Chemical compound COC1=CC=C(OC)C(CN2C(C3=CC(O)=CC=C3N=C2)=O)=C1 BLDBEYINFUSUOT-UHFFFAOYSA-N 0.000 description 1
- AIKJUZSASGFNQX-UHFFFAOYSA-N 4-[2-(2,5-dimethoxyphenyl)ethyl]aniline Chemical compound COC1=CC=C(OC)C(CCC=2C=CC(N)=CC=2)=C1 AIKJUZSASGFNQX-UHFFFAOYSA-N 0.000 description 1
- YLDIWAMSSPAXOZ-UHFFFAOYSA-N 4-chloro-6-[2-(2,5-dimethoxyphenyl)ethyl]quinazoline Chemical compound COC1=CC=C(OC)C(CCC=2C=C3C(Cl)=NC=NC3=CC=2)=C1 YLDIWAMSSPAXOZ-UHFFFAOYSA-N 0.000 description 1
- DLOKCBHHRDAMEH-UHFFFAOYSA-N 4-ethyl-6-iodoquinazoline Chemical compound C1=C(I)C=C2C(CC)=NC=NC2=C1 DLOKCBHHRDAMEH-UHFFFAOYSA-N 0.000 description 1
- PLQXDARCXCRUOU-UHFFFAOYSA-N 4-methoxy-3-[2-(4-methoxyquinazolin-6-yl)ethyl]phenol Chemical compound COC1=CC=C(O)C=C1CCC1=CC=C(N=CN=C2OC)C2=C1 PLQXDARCXCRUOU-UHFFFAOYSA-N 0.000 description 1
- ZDMQOOQRCQHZGE-UHFFFAOYSA-N 4-methoxy-6-[2-(5-methoxy-2-phenylmethoxyphenyl)ethynyl]quinazoline Chemical compound C=1C=C2N=CN=C(OC)C2=CC=1C#CC1=CC(OC)=CC=C1OCC1=CC=CC=C1 ZDMQOOQRCQHZGE-UHFFFAOYSA-N 0.000 description 1
- DSMQNKXNAWMIFL-UHFFFAOYSA-N 4-methoxyquinazolin-6-ol Chemical compound C1=C(O)C=C2C(OC)=NC=NC2=C1 DSMQNKXNAWMIFL-UHFFFAOYSA-N 0.000 description 1
- YXMGTAOWOGFGGL-UHFFFAOYSA-N 6-[(2,5-dimethoxyphenyl)methoxy]-1h-quinazolin-4-one Chemical compound COC1=CC=C(OC)C(COC=2C=C3C(=O)NC=NC3=CC=2)=C1 YXMGTAOWOGFGGL-UHFFFAOYSA-N 0.000 description 1
- CIYRENCMIGQQDF-UHFFFAOYSA-N 6-[(2,5-dimethoxyphenyl)methoxy]-3-[(2,6-dimethoxyphenyl)methyl]quinazolin-4-one Chemical compound COC1=CC=C(OC)C(COC=2C=C3C(=O)N(CC=4C(=CC=CC=4OC)OC)C=NC3=CC=2)=C1 CIYRENCMIGQQDF-UHFFFAOYSA-N 0.000 description 1
- ZONUMDVUXNZPOI-UHFFFAOYSA-N 6-[(2,5-dimethoxyphenyl)methylamino]-1h-quinazolin-4-one Chemical compound COC1=CC=C(OC)C(CNC=2C=C3C(=O)NC=NC3=CC=2)=C1 ZONUMDVUXNZPOI-UHFFFAOYSA-N 0.000 description 1
- RSEJBUFOAAWLGH-UHFFFAOYSA-N 6-[2-(2,5-diethoxyphenyl)ethynyl]-4-ethylquinazoline Chemical compound CCOC1=CC=C(OCC)C(C#CC=2C=C3C(CC)=NC=NC3=CC=2)=C1 RSEJBUFOAAWLGH-UHFFFAOYSA-N 0.000 description 1
- SACGAAJBBVURNE-UHFFFAOYSA-N 6-[2-(2,5-diethylphenyl)ethynyl]-4-ethylquinazoline Chemical compound CCC1=CC=C(CC)C(C#CC=2C=C3C(CC)=NC=NC3=CC=2)=C1 SACGAAJBBVURNE-UHFFFAOYSA-N 0.000 description 1
- PJWDTKSQJLBJJQ-UHFFFAOYSA-N 6-[2-(2,5-dimethoxyphenyl)ethyl]-1h-quinolin-4-one Chemical compound COC1=CC=C(OC)C(CCC=2C=C3C(O)=CC=NC3=CC=2)=C1 PJWDTKSQJLBJJQ-UHFFFAOYSA-N 0.000 description 1
- OGBQNCHGRSKYLI-UHFFFAOYSA-N 6-[2-(2,5-dimethoxyphenyl)ethyl]-2,3-dihydro-1h-quinazolin-4-one Chemical compound COC1=CC=C(OC)C(CCC=2C=C3C(=O)NCNC3=CC=2)=C1 OGBQNCHGRSKYLI-UHFFFAOYSA-N 0.000 description 1
- JGDMQTQSNLPWPU-UHFFFAOYSA-N 6-[2-(2,5-dimethoxyphenyl)ethyl]-3-methylquinazolin-4-one Chemical compound COC1=CC=C(OC)C(CCC=2C=C3C(=O)N(C)C=NC3=CC=2)=C1 JGDMQTQSNLPWPU-UHFFFAOYSA-N 0.000 description 1
- JXMHJBDGHUTCRF-UHFFFAOYSA-N 6-[2-(2,5-dimethoxyphenyl)ethyl]-4-oxo-1h-quinoline-3-carboxylic acid Chemical compound COC1=CC=C(OC)C(CCC=2C=C3C(O)=C(C(O)=O)C=NC3=CC=2)=C1 JXMHJBDGHUTCRF-UHFFFAOYSA-N 0.000 description 1
- GLEDJBNVWCCLFN-UHFFFAOYSA-N 6-[2-(2,5-dimethoxyphenyl)ethyl]-4-propan-2-yloxyquinazoline Chemical compound COC1=CC=C(OC)C(CCC=2C=C3C(OC(C)C)=NC=NC3=CC=2)=C1 GLEDJBNVWCCLFN-UHFFFAOYSA-N 0.000 description 1
- IHKKBXKQPFWXHR-UHFFFAOYSA-N 6-[2-(2,5-dimethoxyphenyl)ethyl]quinazolin-4-amine Chemical compound COC1=CC=C(OC)C(CCC=2C=C3C(N)=NC=NC3=CC=2)=C1 IHKKBXKQPFWXHR-UHFFFAOYSA-N 0.000 description 1
- JMJWSQCVKRHROB-UHFFFAOYSA-N 6-[2-(2,5-dimethoxyphenyl)ethynyl]-1h-quinazolin-4-one Chemical compound COC1=CC=C(OC)C(C#CC=2C=C3C(=O)NC=NC3=CC=2)=C1 JMJWSQCVKRHROB-UHFFFAOYSA-N 0.000 description 1
- AURSMZWPWLIWCC-UHFFFAOYSA-N 6-[2-(2,5-dimethoxyphenyl)ethynyl]-4-ethoxyquinazoline Chemical compound C1=C2C(OCC)=NC=NC2=CC=C1C#CC1=CC(OC)=CC=C1OC AURSMZWPWLIWCC-UHFFFAOYSA-N 0.000 description 1
- ZNMXHFPXUQPUIQ-UHFFFAOYSA-N 6-[2-(2,5-dimethoxyphenyl)ethynyl]-4-ethylquinazoline Chemical compound C1=C2C(CC)=NC=NC2=CC=C1C#CC1=CC(OC)=CC=C1OC ZNMXHFPXUQPUIQ-UHFFFAOYSA-N 0.000 description 1
- TXRCUOFWWYPGBS-UHFFFAOYSA-N 6-[2-(2,5-dimethoxyphenyl)ethynyl]-4-methoxyquinazoline Chemical compound COC1=CC=C(OC)C(C#CC=2C=C3C(OC)=NC=NC3=CC=2)=C1 TXRCUOFWWYPGBS-UHFFFAOYSA-N 0.000 description 1
- FUGUBPFZXQJMDJ-UHFFFAOYSA-N 6-[2-(2,5-dimethoxyphenyl)ethynyl]-4-methylquinazoline Chemical compound COC1=CC=C(OC)C(C#CC=2C=C3C(C)=NC=NC3=CC=2)=C1 FUGUBPFZXQJMDJ-UHFFFAOYSA-N 0.000 description 1
- PNBIPQFBTRMFSG-UHFFFAOYSA-N 6-[2-(2,5-dimethoxyphenyl)ethynyl]quinazoline Chemical compound COC1=CC=C(OC)C(C#CC=2C=C3C=NC=NC3=CC=2)=C1 PNBIPQFBTRMFSG-UHFFFAOYSA-N 0.000 description 1
- AREQGZMTDQZTDI-UHFFFAOYSA-N 6-[2-(2,6-dimethoxyphenyl)ethynyl]-1h-quinazolin-4-one Chemical compound COC1=CC=CC(OC)=C1C#CC1=CC=C(N=CNC2=O)C2=C1 AREQGZMTDQZTDI-UHFFFAOYSA-N 0.000 description 1
- TUSRORMIYSVZAK-UHFFFAOYSA-N 6-[2-(2,6-dimethoxyphenyl)ethynyl]-4-ethylquinazoline Chemical compound C1=C2C(CC)=NC=NC2=CC=C1C#CC1=C(OC)C=CC=C1OC TUSRORMIYSVZAK-UHFFFAOYSA-N 0.000 description 1
- DLTVSZQRKJYWFH-UHFFFAOYSA-N 6-[2-(2,6-dimethoxyphenyl)ethynyl]-4-methoxyquinazoline Chemical compound COC1=CC=CC(OC)=C1C#CC1=CC=C(N=CN=C2OC)C2=C1 DLTVSZQRKJYWFH-UHFFFAOYSA-N 0.000 description 1
- NNVINRBFHSKTDW-UHFFFAOYSA-N 6-[2-(5-hydroxy-2-methoxyphenyl)ethyl]-1h-quinazolin-4-one Chemical compound COC1=CC=C(O)C=C1CCC1=CC=C(N=CNC2=O)C2=C1 NNVINRBFHSKTDW-UHFFFAOYSA-N 0.000 description 1
- MAIZCACENPZNCN-UHFFFAOYSA-N 6-amino-1h-quinazolin-4-one Chemical compound N1=CNC(=O)C2=CC(N)=CC=C21 MAIZCACENPZNCN-UHFFFAOYSA-N 0.000 description 1
- UGMZJNQBVMUNDD-UHFFFAOYSA-N 6-iodo-n-methylquinazolin-4-amine Chemical compound C1=C(I)C=C2C(NC)=NC=NC2=C1 UGMZJNQBVMUNDD-UHFFFAOYSA-N 0.000 description 1
- 208000028185 Angioedema Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- NQXYIRJUIMPSBR-CSKARUKUSA-N C1=C(NC(C)=O)C(C(=O)OC)=CC(\C=C\C=2C(=CC=CC=2OC)OC)=C1 Chemical compound C1=C(NC(C)=O)C(C(=O)OC)=CC(\C=C\C=2C(=CC=CC=2OC)OC)=C1 NQXYIRJUIMPSBR-CSKARUKUSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- 206010014950 Eosinophilia Diseases 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 206010014989 Epidermolysis bullosa Diseases 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 238000007341 Heck reaction Methods 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 238000007126 N-alkylation reaction Methods 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010034277 Pemphigoid Diseases 0.000 description 1
- 241000721454 Pemphigus Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- 206010039793 Seborrhoeic dermatitis Diseases 0.000 description 1
- 208000012658 Skin autoimmune disease Diseases 0.000 description 1
- 101150109894 TGFA gene Proteins 0.000 description 1
- 102000009618 Transforming Growth Factors Human genes 0.000 description 1
- 108010009583 Transforming Growth Factors Proteins 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 206010047112 Vasculitides Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 208000004631 alopecia areata Diseases 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 150000001499 aryl bromides Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 150000001503 aryl iodides Chemical class 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical class BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 208000000594 bullous pemphigoid Diseases 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 0.000 description 1
- YCDZVSFQGGBKDI-UHFFFAOYSA-N diethyl 2-[[4-[2-(2,5-dimethoxyphenyl)ethyl]anilino]methylidene]propanedioate Chemical compound C1=CC(NC=C(C(=O)OCC)C(=O)OCC)=CC=C1CCC1=CC(OC)=CC=C1OC YCDZVSFQGGBKDI-UHFFFAOYSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- YTJSQSFDDWCZGW-UHFFFAOYSA-N ethenylborane Chemical class BC=C YTJSQSFDDWCZGW-UHFFFAOYSA-N 0.000 description 1
- RWMJRMPOKXSHHI-UHFFFAOYSA-N ethenylboron Chemical compound [B]C=C RWMJRMPOKXSHHI-UHFFFAOYSA-N 0.000 description 1
- BADWIIDKTXQYLW-UHFFFAOYSA-N ethenylstannane Chemical class [SnH3]C=C BADWIIDKTXQYLW-UHFFFAOYSA-N 0.000 description 1
- ZEBXKLIPIUVCII-UHFFFAOYSA-N ethyl 2-acetamido-5-[2-(2,5-dimethoxyphenyl)ethyl]benzoate Chemical compound C1=C(NC(C)=O)C(C(=O)OCC)=CC(CCC=2C(=CC=C(OC)C=2)OC)=C1 ZEBXKLIPIUVCII-UHFFFAOYSA-N 0.000 description 1
- STCFEFXRAISDCS-UHFFFAOYSA-N ethyl 6-[2-(2,5-dimethoxyphenyl)ethyl]-4-oxo-1h-quinoline-3-carboxylate Chemical compound C=1C2=C(O)C(C(=O)OCC)=CN=C2C=CC=1CCC1=CC(OC)=CC=C1OC STCFEFXRAISDCS-UHFFFAOYSA-N 0.000 description 1
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- XPYGGHVSFMUHLH-UUSULHAXSA-N falecalcitriol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(O)(C(F)(F)F)C(F)(F)F)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C XPYGGHVSFMUHLH-UUSULHAXSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 201000011486 lichen planus Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- XNVZHFYKJLGZLZ-UHFFFAOYSA-N methyl 2-acetamido-5-formylbenzoate Chemical compound COC(=O)C1=CC(C=O)=CC=C1NC(C)=O XNVZHFYKJLGZLZ-UHFFFAOYSA-N 0.000 description 1
- YBIBJZJAFKNQDE-UHFFFAOYSA-N methyl 5-[2-(2,5-dimethoxyphenyl)ethyl]-2-(methylamino)benzoate Chemical compound C1=C(C(=O)OC)C(NC)=CC=C1CCC1=CC(OC)=CC=C1OC YBIBJZJAFKNQDE-UHFFFAOYSA-N 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- LAGYNCSCIYGAIL-UHFFFAOYSA-N n-acetyl-n-(6-iodoquinazolin-4-yl)acetamide Chemical compound C1=C(I)C=C2C(N(C(C)=O)C(=O)C)=NC=NC2=C1 LAGYNCSCIYGAIL-UHFFFAOYSA-N 0.000 description 1
- LVIPOXCRHJGSQD-UHFFFAOYSA-N n-acetyl-n-[6-[2-(2,5-dimethoxyphenyl)ethyl]quinazolin-4-yl]acetamide Chemical compound COC1=CC=C(OC)C(CCC=2C=C3C(N(C(C)=O)C(C)=O)=NC=NC3=CC=2)=C1 LVIPOXCRHJGSQD-UHFFFAOYSA-N 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 231100001221 nontumorigenic Toxicity 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 208000008742 seborrheic dermatitis Diseases 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- WBQTXTBONIWRGK-UHFFFAOYSA-N sodium;propan-2-olate Chemical compound [Na+].CC(C)[O-] WBQTXTBONIWRGK-UHFFFAOYSA-N 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C233/53—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
- C07C233/54—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of a saturated carbon skeleton
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C229/56—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino and carboxyl groups bound in ortho-position
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C229/64—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring the carbon skeleton being further substituted by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/26—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring
- C07C271/28—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring to a carbon atom of a non-condensed six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/74—Quinazolines; Hydrogenated quinazolines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to ring carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/88—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Quinoline Compounds (AREA)
- Photoreceptors In Electrophotography (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9505080.3A GB9505080D0 (en) | 1995-03-14 | 1995-03-14 | Organic compounds |
| GBGB9505858.2A GB9505858D0 (en) | 1995-03-23 | 1995-03-23 | Organic Compounds |
| GBGB9526593.0A GB9526593D0 (en) | 1995-12-28 | 1995-12-28 | Organic compounds |
| PCT/EP1996/001116 WO1996028430A1 (en) | 1995-03-14 | 1996-03-14 | Trisubstituted phenyl derivatives |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO974118D0 NO974118D0 (no) | 1997-09-08 |
| NO974118L NO974118L (no) | 1997-09-08 |
| NO310356B1 true NO310356B1 (no) | 2001-06-25 |
Family
ID=27267624
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19974118A NO310356B1 (no) | 1995-03-14 | 1997-09-08 | Trisubstituerte fenylderivater, farmasöytisk preparat inneholdende slike derivater, anvendelse derav og fremgangsmåtefor deres fremstilling |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US5990116A (de) |
| EP (1) | EP0815087B1 (de) |
| JP (1) | JP3194963B2 (de) |
| KR (1) | KR100437580B1 (de) |
| CN (1) | CN1101386C (de) |
| AT (1) | ATE208763T1 (de) |
| AU (1) | AU704544B2 (de) |
| BR (1) | BR9607240A (de) |
| CA (1) | CA2214131C (de) |
| CZ (1) | CZ289944B6 (de) |
| DE (1) | DE69616993T2 (de) |
| DK (1) | DK0815087T3 (de) |
| ES (1) | ES2168463T3 (de) |
| FI (1) | FI120537B (de) |
| HU (1) | HUP9801828A3 (de) |
| MX (1) | MX9707022A (de) |
| NO (1) | NO310356B1 (de) |
| NZ (1) | NZ304291A (de) |
| PL (1) | PL185875B1 (de) |
| PT (1) | PT815087E (de) |
| RU (1) | RU2164224C2 (de) |
| SK (1) | SK282155B6 (de) |
| WO (1) | WO1996028430A1 (de) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5747498A (en) | 1996-05-28 | 1998-05-05 | Pfizer Inc. | Alkynyl and azido-substituted 4-anilinoquinazolines |
| US6706721B1 (en) | 1998-04-29 | 2004-03-16 | Osi Pharmaceuticals, Inc. | N-(3-ethynylphenylamino)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine mesylate anhydrate and monohydrate |
| UA71945C2 (en) | 1999-01-27 | 2005-01-17 | Pfizer Prod Inc | Substituted bicyclic derivatives being used as anticancer agents |
| JP3270834B2 (ja) | 1999-01-27 | 2002-04-02 | ファイザー・プロダクツ・インク | 抗がん剤として有用なヘテロ芳香族二環式誘導体 |
| US6545004B1 (en) | 1999-10-27 | 2003-04-08 | Cytokinetics, Inc. | Methods and compositions utilizing quinazolinones |
| US7230000B1 (en) | 1999-10-27 | 2007-06-12 | Cytokinetics, Incorporated | Methods and compositions utilizing quinazolinones |
| UA74803C2 (uk) | 1999-11-11 | 2006-02-15 | Осі Фармасьютікалз, Інк. | Стійкий поліморф гідрохлориду n-(3-етинілфеніл)-6,7-біс(2-метоксіетокси)-4-хіназолінаміну, спосіб його одержання (варіанти) та фармацевтичне застосування |
| US7087613B2 (en) | 1999-11-11 | 2006-08-08 | Osi Pharmaceuticals, Inc. | Treating abnormal cell growth with a stable polymorph of N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine hydrochloride |
| KR100819716B1 (ko) * | 2000-04-07 | 2008-04-07 | 칫소가부시키가이샤 | 신규한 디아미노 화합물, 당해 디아미노 화합물을사용하여 합성된 중합체, 및 당해 중합체를 사용하는니스, 배향막 및 액정 표시소자 |
| EP1434585A1 (de) * | 2001-10-12 | 2004-07-07 | Warner-Lambert Company LLC | Alkine als inhibitoren von metalloproteinasen |
| US7053216B2 (en) | 2001-11-19 | 2006-05-30 | Iconix Pharmaceuticals, Inc. | Modulators of Rho C activity |
| EP1553931A4 (de) | 2002-05-09 | 2006-08-30 | Cytokinetics Inc | Verbindungen, zusammensetzungen und verfahren |
| EP1513820A4 (de) | 2002-05-23 | 2006-09-13 | Cytokinetics Inc | Verbindungen, zusammensetzungen und verfahren |
| MXPA05000638A (es) * | 2002-07-17 | 2005-03-31 | Warner Lambert Co | Combinacion de un inhibidor alquino alosterico de metaloproteinasa-13 de matriz con un inhibidor selectivo de ciclooxigenasa-2 que no es celecoxib o valdecoxib. |
| BR0312708A (pt) * | 2002-07-17 | 2005-04-26 | Warner Lambert Co | Combinação de um inibidor alcina alostérico de metaloproteinase-13 de matriz com celecoxib ou valdecoxib |
| EP1537089A4 (de) | 2002-07-23 | 2008-04-16 | Cytokinetics Inc | Verbindungen, zusammenstellungen und verfahren |
| AU2003249539A1 (en) * | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | Cyclic compounds containing zinc binding groups as matrix metalloproteinase inhibitors |
| WO2004034972A2 (en) | 2002-09-30 | 2004-04-29 | Cytokinetics, Inc. | Compounds, compositions, and methods |
| JP4384053B2 (ja) * | 2002-12-13 | 2009-12-16 | エフ．ホフマン−ラ ロシュ アーゲー | ３ｈ−キナゾリン−４−オン誘導体 |
| GB0319497D0 (en) * | 2003-08-19 | 2003-09-17 | Novartis Ag | Organic compounds |
| SE0400234D0 (sv) * | 2004-02-06 | 2004-02-06 | Active Biotech Ab | New compounds, methods for their preparation and use thereof |
| AU2005227192A1 (en) * | 2004-03-11 | 2005-10-06 | Kythera Biopharmaceuticals, Inc. | Compositions and methods for preventing and treating skin and hair conditions |
| US20080031898A1 (en) * | 2004-03-26 | 2008-02-07 | David Nathaniel E | Compositions and methods to increase the effect of a neurotoxin treatment |
| GB0412769D0 (en) * | 2004-06-08 | 2004-07-07 | Novartis Ag | Organic compounds |
| ES2407813T3 (es) * | 2004-08-04 | 2013-06-14 | Meiji Seika Pharma Co., Ltd. | Derivados de quinolina e insecticida que contienen los mismos como constituyente activo |
| WO2008044688A1 (en) * | 2006-10-11 | 2008-04-17 | Daiichi Sankyo Company, Limited | Urea derivative |
| JP5349332B2 (ja) * | 2007-02-06 | 2013-11-20 | チェルシー・セラピューティクス，インコーポレイテッド | 新規化合物、その調製方法、およびその使用 |
| EP3762379A1 (de) | 2018-03-07 | 2021-01-13 | Bayer Aktiengesellschaft | Identifizierung und verwendung von erk5-inhibitoren |
| WO2021026672A1 (en) * | 2019-08-09 | 2021-02-18 | Novartis Ag | Heterocyclic wdr5 inhibitors as anti-cancer compounds |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0028305B1 (de) * | 1979-09-13 | 1984-02-01 | The Wellcome Foundation Limited | Diarylverbindungen und diese enthaltende pharmazeutische Zusammensetzungen |
| CA1219587A (en) * | 1981-12-14 | 1987-03-24 | Norman P. Jensen | Hydroxybenzylaminobenzenes as anti-inflammatory agents |
| NZ213986A (en) * | 1984-10-30 | 1989-07-27 | Usv Pharma Corp | Heterocyclic or aromatic compounds, and pharmaceutical compositions containing such |
| CH661687A5 (fr) * | 1984-12-19 | 1987-08-14 | Battelle Memorial Institute | Imprimante matricielle a aiguilles. |
| GB8607683D0 (en) * | 1986-03-27 | 1986-04-30 | Ici Plc | Anti-tumor agents |
| KR890700023A (ko) * | 1986-11-19 | 1989-03-02 | 케맥스 파마슈우티칼스 인코포레이티드 | 리폭시게나제 저해제 |
| WO1988003806A1 (en) * | 1986-11-19 | 1988-06-02 | Chemex Pharmaceuticals, Inc. | Pharmacologically active compositions of catecholic butanes with zinc |
| US5272167A (en) * | 1986-12-10 | 1993-12-21 | Schering Corporation | Pharmaceutically active compounds |
| US4851423A (en) * | 1986-12-10 | 1989-07-25 | Schering Corporation | Pharmaceutically active compounds |
| WO1991000858A1 (en) * | 1989-07-07 | 1991-01-24 | Schering Corporation | Pharmaceutically active compounds |
| RU2025473C1 (ru) * | 1990-07-27 | 1994-12-30 | Исихара Сангио Кайся Лтд. | Производные бензоилмочевины или их фармацевтически приемлемые соли, обладающие противоопухолевой активностью |
| HUT60458A (en) * | 1991-02-01 | 1992-09-28 | Sandoz Ag | Process for producing benzyloxyphenyl derivatives and pharmaceutical compositions comprising same |
| SG64322A1 (en) * | 1991-05-10 | 1999-04-27 | Rhone Poulenc Rorer Int | Bis mono and bicyclic aryl and heteroaryl compounds which inhibit egf and/or pdgf receptor tyrosine kinase |
| US5480883A (en) * | 1991-05-10 | 1996-01-02 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Bis mono- and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| GB9121943D0 (en) * | 1991-10-16 | 1991-11-27 | Sandoz Ltd | Organic compounds,processes for their production and their use |
| US5656643A (en) * | 1993-11-08 | 1997-08-12 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Bis mono-and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
-
1996
- 1996-03-14 RU RU97117169/04A patent/RU2164224C2/ru not_active IP Right Cessation
- 1996-03-14 HU HU9801828A patent/HUP9801828A3/hu unknown
- 1996-03-14 SK SK1245-97A patent/SK282155B6/sk not_active IP Right Cessation
- 1996-03-14 CZ CZ19972869A patent/CZ289944B6/cs not_active IP Right Cessation
- 1996-03-14 PL PL96322134A patent/PL185875B1/pl not_active IP Right Cessation
- 1996-03-14 JP JP52729096A patent/JP3194963B2/ja not_active Expired - Fee Related
- 1996-03-14 EP EP96908043A patent/EP0815087B1/de not_active Expired - Lifetime
- 1996-03-14 DK DK96908043T patent/DK0815087T3/da active
- 1996-03-14 US US08/913,597 patent/US5990116A/en not_active Expired - Fee Related
- 1996-03-14 AU AU51443/96A patent/AU704544B2/en not_active Ceased
- 1996-03-14 KR KR1019970706458A patent/KR100437580B1/ko not_active Expired - Fee Related
- 1996-03-14 BR BR9607240A patent/BR9607240A/pt not_active IP Right Cessation
- 1996-03-14 NZ NZ304291A patent/NZ304291A/xx not_active IP Right Cessation
- 1996-03-14 ES ES96908043T patent/ES2168463T3/es not_active Expired - Lifetime
- 1996-03-14 DE DE69616993T patent/DE69616993T2/de not_active Expired - Fee Related
- 1996-03-14 WO PCT/EP1996/001116 patent/WO1996028430A1/en not_active Ceased
- 1996-03-14 CA CA002214131A patent/CA2214131C/en not_active Expired - Fee Related
- 1996-03-14 AT AT96908043T patent/ATE208763T1/de not_active IP Right Cessation
- 1996-03-14 PT PT96908043T patent/PT815087E/pt unknown
- 1996-03-14 CN CN96193716A patent/CN1101386C/zh not_active Expired - Fee Related
-
1997
- 1997-08-21 FI FI973440A patent/FI120537B/fi not_active IP Right Cessation
- 1997-09-08 NO NO19974118A patent/NO310356B1/no not_active IP Right Cessation
- 1997-09-12 MX MX9707022A patent/MX9707022A/es not_active IP Right Cessation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO310356B1 (no) | Trisubstituerte fenylderivater, farmasöytisk preparat inneholdende slike derivater, anvendelse derav og fremgangsmåtefor deres fremstilling | |
| JP6715357B2 (ja) | イミダゾピリジンアミンフェニル誘導体およびその使用 | |
| AU635593B2 (en) | Azaoxindole derivatives | |
| WO2008008059A1 (en) | Anti-cancer agents ans uses thereof | |
| AU2017237362A1 (en) | Naphthyridines as integrin antagonists | |
| KR20140144696A (ko) | ２환성 화합물 | |
| CA2929562A1 (en) | Dimethylbenzoic acid compounds | |
| EP1992622B1 (de) | 4-(3-benzoylaminophenyl)-6,7-dimethoxy-2-methylaminochinazolinderivat | |
| JPH04210946A (ja) | 新規なアリールビニルアミド誘導体およびその製造方法 | |
| Zhang et al. | Synthesis and biological evaluation of novel 5-alkyl-2-arylthio-6-((3, 4-dihydroquinolin-1 (2H)-yl) methyl) pyrimidin-4 (3H)-ones as potent non-nucleoside HIV-1 reverse transcriptase inhibitors | |
| EP1436293B1 (de) | Polycyclische verbindungen mit antitumor-wirkung | |
| NO178540B (no) | Bisfenyletanderivater, farmasöytisk preparat derav samt anvendelse | |
| BRPI0708098A2 (pt) | derivados de 4-benzoilaminofenil)-6,7-dimetóxi-2-metilaminoquinaz olina | |
| Ju et al. | Novel 2, 4-Diarylaminopyrimidine Derivatives Containing Pyridine Moiety: Design, Synthesis, Crystal Structure and Biological Evaluation① | |
| HK40079172A (en) | Immunosuppressant, and preparation method therefor and use thereof | |
| US20030229098A1 (en) | Polycyclic compounds exhibiting anti-tumor activities | |
| CA2892658A1 (en) | Substituted amino-arylcarboxamides as kcnq2/3 modulators | |
| HK1014440B (en) | Trisubstituted phenyl derivatives | |
| HK1122025B (en) | 4-(3-benzoylaminophenyl)-6,7-dimethoxy-2- methylaminoquinazoline derivative | |
| HK1146046A (en) | Derivatives of n-phenyl-imidazo[1,2-a]pyridine-2-carboxamides, preparation thereof and therapeutic application thereof | |
| CA2892652A1 (en) | Heteroquinoline-3-carboxamides as kcnq2/3 modulators |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |