PH26046A - Dihydropyridine PAF antagonists - Google Patents
Dihydropyridine PAF antagonists Download PDFInfo
- Publication number
- PH26046A PH26046A PH37617A PH37617A PH26046A PH 26046 A PH26046 A PH 26046A PH 37617 A PH37617 A PH 37617A PH 37617 A PH37617 A PH 37617A PH 26046 A PH26046 A PH 26046A
- Authority
- PH
- Philippines
- Prior art keywords
- alkyl
- pyridyl
- mmol
- substituted
- methylimidazo
- Prior art date
Links
- 239000005557 antagonist Substances 0.000 title description 3
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 110
- -1 cyano, 1, 3-benzodioxolanyl Chemical group 0.000 claims description 71
- 125000000217 alkyl group Chemical group 0.000 claims description 59
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 41
- 229910052799 carbon Inorganic materials 0.000 claims description 36
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
- 125000003545 alkoxy group Chemical group 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 22
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 125000003118 aryl group Chemical group 0.000 claims description 17
- 125000004076 pyridyl group Chemical group 0.000 claims description 16
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 125000000335 thiazolyl group Chemical group 0.000 claims description 9
- 125000002883 imidazolyl group Chemical group 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 125000004193 piperazinyl group Chemical group 0.000 claims description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 6
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
- 125000002971 oxazolyl group Chemical group 0.000 claims description 5
- 230000003287 optical effect Effects 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 2
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 3
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical group C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 claims 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims 2
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims 2
- 125000001425 triazolyl group Chemical group 0.000 claims 2
- 125000004463 2,4-dimethyl-thiazol-5-yl group Chemical group CC=1SC(=C(N1)C)* 0.000 claims 1
- 238000009933 burial Methods 0.000 claims 1
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 123
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 105
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 91
- 239000000203 mixture Substances 0.000 description 65
- 239000000243 solution Substances 0.000 description 51
- 239000007787 solid Substances 0.000 description 43
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- 235000019439 ethyl acetate Nutrition 0.000 description 42
- 238000002360 preparation method Methods 0.000 description 42
- 229940093499 ethyl acetate Drugs 0.000 description 40
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 description 33
- 108010003541 Platelet Activating Factor Proteins 0.000 description 33
- 238000000034 method Methods 0.000 description 32
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
- 238000010992 reflux Methods 0.000 description 31
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 239000000047 product Substances 0.000 description 26
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- 239000002904 solvent Substances 0.000 description 24
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 23
- 238000003818 flash chromatography Methods 0.000 description 22
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 16
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- 239000000284 extract Substances 0.000 description 13
- HXUIDZOMTRMIOE-UHFFFAOYSA-M 3-oxo-3-phenylpropionate Chemical compound [O-]C(=O)CC(=O)C1=CC=CC=C1 HXUIDZOMTRMIOE-UHFFFAOYSA-M 0.000 description 12
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- 125000005843 halogen group Chemical group 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 description 10
- 239000012267 brine Substances 0.000 description 9
- 125000001072 heteroaryl group Chemical group 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 235000019341 magnesium sulphate Nutrition 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- 238000001816 cooling Methods 0.000 description 8
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- VFHUVFGXZCUGTA-UHFFFAOYSA-N 4-(1-bromo-2-oxopropyl)benzonitrile Chemical compound CC(=O)C(Br)C1=CC=C(C#N)C=C1 VFHUVFGXZCUGTA-UHFFFAOYSA-N 0.000 description 6
- YUSNIYMLRWTCCC-UHFFFAOYSA-N 4-[(3-aminopyridin-4-yl)amino]benzonitrile Chemical compound NC1=CN=CC=C1NC1=CC=C(C#N)C=C1 YUSNIYMLRWTCCC-UHFFFAOYSA-N 0.000 description 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- 150000001299 aldehydes Chemical class 0.000 description 6
- 230000000172 allergic effect Effects 0.000 description 6
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 6
- 208000010668 atopic eczema Diseases 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 125000000753 cycloalkyl group Chemical group 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- FPYUJUBAXZAQNL-UHFFFAOYSA-N 2-chlorobenzaldehyde Chemical compound ClC1=CC=CC=C1C=O FPYUJUBAXZAQNL-UHFFFAOYSA-N 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 238000010828 elution Methods 0.000 description 5
- 125000000623 heterocyclic group Chemical group 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 125000000468 ketone group Chemical group 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 4
- ZXRGQOWZKLFSQY-UHFFFAOYSA-N 4-(2-methylbenzimidazol-1-yl)benzonitrile Chemical compound CC1=NC2=CC=CC=C2N1C1=CC=C(C#N)C=C1 ZXRGQOWZKLFSQY-UHFFFAOYSA-N 0.000 description 4
- YBAZINRZQSAIAY-UHFFFAOYSA-N 4-aminobenzonitrile Chemical compound NC1=CC=C(C#N)C=C1 YBAZINRZQSAIAY-UHFFFAOYSA-N 0.000 description 4
- XLSZMDLNRCVEIJ-UHFFFAOYSA-N 4-methylimidazole Chemical compound CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 description 4
- 238000003445 Hantzsch reaction Methods 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 125000004093 cyano group Chemical group *C#N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 230000002757 inflammatory effect Effects 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 238000001665 trituration Methods 0.000 description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- GUKKGBSNKJVHDK-IHWYPQMZSA-N (z)-2-aminobut-2-enamide Chemical compound C\C=C(/N)C(N)=O GUKKGBSNKJVHDK-IHWYPQMZSA-N 0.000 description 3
- WYECURVXVYPVAT-UHFFFAOYSA-N 1-(4-bromophenyl)ethanone Chemical compound CC(=O)C1=CC=C(Br)C=C1 WYECURVXVYPVAT-UHFFFAOYSA-N 0.000 description 3
- QUJQOWRVTLABIP-UHFFFAOYSA-N 1-[4-(benzimidazol-1-yl)phenyl]ethanone Chemical compound C1=CC(C(=O)C)=CC=C1N1C2=CC=CC=C2N=C1 QUJQOWRVTLABIP-UHFFFAOYSA-N 0.000 description 3
- JWQVOMJORQXNME-UHFFFAOYSA-N 2-methyl-3h-imidazo[4,5-c]pyridine Chemical compound C1=NC=C2NC(C)=NC2=C1 JWQVOMJORQXNME-UHFFFAOYSA-N 0.000 description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- KWZFAXCYTKJXLM-UHFFFAOYSA-N 4-(2-methylimidazo[4,5-b]pyridin-3-yl)benzonitrile Chemical compound CC1=NC2=CC=CN=C2N1C1=CC=C(C#N)C=C1 KWZFAXCYTKJXLM-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 206010006482 Bronchospasm Diseases 0.000 description 3
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 3
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 3
- 241000282414 Homo sapiens Species 0.000 description 3
- 229930194542 Keto Natural products 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 230000004931 aggregating effect Effects 0.000 description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 3
- 125000004414 alkyl thio group Chemical group 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 206010003246 arthritis Diseases 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 230000007885 bronchoconstriction Effects 0.000 description 3
- 239000007853 buffer solution Substances 0.000 description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 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 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- NDQXKKFRNOPRDW-UHFFFAOYSA-N 1,1,1-triethoxyethane Chemical compound CCOC(C)(OCC)OCC NDQXKKFRNOPRDW-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- KAMRUSGFSRDFFH-UHFFFAOYSA-N 1-(4-iodophenyl)-2-methylbenzimidazole Chemical compound CC1=NC2=CC=CC=C2N1C1=CC=C(I)C=C1 KAMRUSGFSRDFFH-UHFFFAOYSA-N 0.000 description 2
- 125000004173 1-benzimidazolyl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N1* 0.000 description 2
- HPYNZHMRTTWQTB-UHFFFAOYSA-N 2,3-dimethylpyridine Chemical compound CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 2
- VEOGZFDBTMWPDV-UHFFFAOYSA-N 2,4-dimethyl-1h-imidazol-1-ium;chloride Chemical compound Cl.CC1=CNC(C)=N1 VEOGZFDBTMWPDV-UHFFFAOYSA-N 0.000 description 2
- QTKRICXKOUIGOK-WAYWQWQTSA-N 2-cyanoethyl (z)-3-aminobut-2-enoate Chemical compound C\C(N)=C\C(=O)OCCC#N QTKRICXKOUIGOK-WAYWQWQTSA-N 0.000 description 2
- HIADXXVQRNYRGG-UHFFFAOYSA-N 2-n-(4-iodophenyl)benzene-1,2-diamine Chemical compound NC1=CC=CC=C1NC1=CC=C(I)C=C1 HIADXXVQRNYRGG-UHFFFAOYSA-N 0.000 description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
- QRNLZDKAPOJMQB-UHFFFAOYSA-N 4-(2,4-dichlorophenyl)-2-hydroxy-5,5-dimethyl-1,3,2$l^{5}-dioxaphosphinane 2-oxide Chemical compound CC1(C)COP(O)(=O)OC1C1=CC=C(Cl)C=C1Cl QRNLZDKAPOJMQB-UHFFFAOYSA-N 0.000 description 2
- FLZZNCMRFDMVDR-UHFFFAOYSA-N 4-(2-methylimidazo[4,5-c]pyridin-1-yl)benzonitrile Chemical compound CC1=NC2=CN=CC=C2N1C1=CC=C(C#N)C=C1 FLZZNCMRFDMVDR-UHFFFAOYSA-N 0.000 description 2
- DVGPNOLTLLGBJC-UHFFFAOYSA-N 4-(4-amino-3-nitro-2h-pyridin-1-yl)benzonitrile Chemical compound C1=CC(N)=C([N+]([O-])=O)CN1C1=CC=C(C#N)C=C1 DVGPNOLTLLGBJC-UHFFFAOYSA-N 0.000 description 2
- REUDLMVWBUGLDA-UHFFFAOYSA-N 4-(4-methyl-1,3-thiazol-5-yl)benzonitrile Chemical compound N1=CSC(C=2C=CC(=CC=2)C#N)=C1C REUDLMVWBUGLDA-UHFFFAOYSA-N 0.000 description 2
- QRPXRCHWNQTBDM-UHFFFAOYSA-N 4-(6-chloro-8-methylpurin-9-yl)benzonitrile Chemical compound CC1=NC2=C(Cl)N=CN=C2N1C1=CC=C(C#N)C=C1 QRPXRCHWNQTBDM-UHFFFAOYSA-N 0.000 description 2
- RVQVLVKTZGPNJB-UHFFFAOYSA-N 4-(6-methoxy-8-methylpurin-9-yl)benzonitrile Chemical compound CC1=NC=2C(OC)=NC=NC=2N1C1=CC=C(C#N)C=C1 RVQVLVKTZGPNJB-UHFFFAOYSA-N 0.000 description 2
- HQSCPPCMBMFJJN-UHFFFAOYSA-N 4-bromobenzonitrile Chemical compound BrC1=CC=C(C#N)C=C1 HQSCPPCMBMFJJN-UHFFFAOYSA-N 0.000 description 2
- PSBGFLWVQDGETK-UHFFFAOYSA-N 4-chloro-2,6-dimethyl-3-nitropyridine Chemical compound CC1=CC(Cl)=C([N+]([O-])=O)C(C)=N1 PSBGFLWVQDGETK-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/82—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- C07D417/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
- Pyridine Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB878722977A GB8722977D0 (en) | 1987-09-30 | 1987-09-30 | Therapeutic agents |
| GB888804441A GB8804441D0 (en) | 1988-02-25 | 1988-02-25 | Therapeutic agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PH26046A true PH26046A (en) | 1992-01-29 |
Family
ID=26292797
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PH37617A PH26046A (en) | 1987-09-30 | 1988-09-30 | Dihydropyridine PAF antagonists |
Country Status (26)
| Country | Link |
|---|---|
| US (3) | US4935430A (el) |
| EP (1) | EP0310386B1 (el) |
| JP (2) | JP2660016B2 (el) |
| KR (1) | KR900008318B1 (el) |
| CN (1) | CN1032648C (el) |
| AU (2) | AU597190B2 (el) |
| CA (1) | CA1340785C (el) |
| CY (1) | CY1722A (el) |
| DE (1) | DE3866077D1 (el) |
| DK (1) | DK170376B1 (el) |
| EG (1) | EG18563A (el) |
| ES (1) | ES2038766T3 (el) |
| FI (1) | FI93444C (el) |
| GR (1) | GR3003468T3 (el) |
| HK (1) | HK66093A (el) |
| HU (1) | HU201061B (el) |
| IE (1) | IE61045B1 (el) |
| IL (1) | IL101332A0 (el) |
| MY (1) | MY104933A (el) |
| NO (1) | NO168107C (el) |
| NZ (1) | NZ226397A (el) |
| PH (1) | PH26046A (el) |
| PL (1) | PL157186B1 (el) |
| PT (1) | PT88614B (el) |
| SG (1) | SG49393G (el) |
| YU (1) | YU46698B (el) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8906324D0 (en) * | 1989-03-20 | 1989-05-04 | Pfizer Ltd | 1,4-dihydropyridines |
| US4990518A (en) * | 1989-09-13 | 1991-02-05 | G. D. Searle & Co. | Pharmacologically active heteroaryl substituted imidazo (4,5-c) pyridines |
| GB9010404D0 (en) * | 1990-05-09 | 1990-06-27 | Pfizer Ltd | Therapeutic agents |
| GB9015524D0 (en) * | 1990-07-13 | 1990-08-29 | Pfizer Ltd | Therapeutic agents |
| GB9019409D0 (en) * | 1990-09-05 | 1990-10-17 | Pfizer Ltd | Therapeutic agents |
| ES2245660T3 (es) | 1990-11-30 | 2006-01-16 | Otsuka Pharmaceutical Co., Ltd. | Derivados de azol y su utilizacion como inhibidores de los radicales superoxidos. |
| US5288866A (en) * | 1991-12-20 | 1994-02-22 | American Cyanamid Company | 5,6-disubstituted-3-pyridylmethyl ammonium halide compounds useful for the preparation of 5- (substituted methyl)-2,3-pyridinedicarboxylic acids |
| DK40192D0 (da) * | 1992-03-26 | 1992-03-26 | Neurosearch As | Imidazolforbindelser, deres fremstilling og anvendelse |
| MY128323A (en) | 1996-09-30 | 2007-01-31 | Otsuka Pharma Co Ltd | Thiazole derivatives for inhibition of cytokine production and of cell adhesion |
| US6232320B1 (en) | 1998-06-04 | 2001-05-15 | Abbott Laboratories | Cell adhesion-inhibiting antiinflammatory compounds |
| JP2002517396A (ja) * | 1998-06-04 | 2002-06-18 | アボット・ラボラトリーズ | 細胞接着阻害抗炎症性化合物 |
| WO2000075145A1 (en) * | 1999-06-03 | 2000-12-14 | Abbott Laboratories | Cell adhesion-inhibiting antiinflammatory compounds |
| CA2774959C (en) * | 2000-08-04 | 2016-05-31 | Dmi Biosciences, Inc. | Method of using diketopiperazines and composition containing them |
| CN103191409A (zh) | 2003-05-15 | 2013-07-10 | Dmi生物科学公司 | T-细胞介导的疾病的治疗 |
| CN113999167B (zh) * | 2021-10-18 | 2023-09-29 | 蚌埠中实化学技术有限公司 | 一种4-氯-2,6-二甲基-3-硝基吡啶的制备方法 |
| CN117568743B (zh) * | 2024-01-15 | 2024-03-19 | 江苏普坦科金属科技有限公司 | 一种铁基材料的表面耐腐蚀耐磨处理工艺 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3971791A (en) * | 1972-03-06 | 1976-07-27 | Bayer Aktiengesellschaft | 2-Amino-1,4-dihydropyridine derivatives |
| DE2738153A1 (de) * | 1977-08-24 | 1979-03-08 | Bayer Ag | 2-pyridyl-1,4-dihydropyridine, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
| DE2752820A1 (de) * | 1977-11-26 | 1979-05-31 | Bayer Ag | Neue nitrosubstituierte 1,4-dihydropyridine, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
| US4285955A (en) * | 1978-10-31 | 1981-08-25 | Bayer Aktiengesellschaft | 1,4-Dihydropyridinecarboxylic acids |
| US4317909A (en) * | 1980-03-24 | 1982-03-02 | Sterling Drug Inc. | Preparation of 1,3-dihydro-5-(pyridinyl)-2H-imidazo[4,5-b]pyridin-2-ones |
| US4353905A (en) | 1981-09-17 | 1982-10-12 | Warner-Lambert Company | Substituted 4,5-dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinones and 6-[4-(1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinones |
| US4414213A (en) * | 1982-03-22 | 1983-11-08 | Mead Johnson & Company | Dihydropyridyl cyclic imidate esters and their pharmaceutical use |
| DE3363743D1 (en) | 1982-07-22 | 1986-07-03 | Pfizer Ltd | Dihydropyridine anti-ischaemic and antihypertensive agents |
| EP0125803A3 (en) * | 1983-04-27 | 1987-01-21 | FISONS plc | Pharmaceutically active dihydropyridines |
| JPS60120861A (ja) * | 1983-12-02 | 1985-06-28 | Otsuka Pharmaceut Co Ltd | ジヒドロピリジン誘導体 |
| GB8620880D0 (en) | 1986-08-29 | 1986-10-08 | Pfizer Ltd | Therapeutic agents |
| US4871745A (en) * | 1986-09-22 | 1989-10-03 | Ortho Pharmaceutical Corporation | 2- or 3-aryl substituted imidazo(1,2-A)pyridines and their use as antisecretory agents |
| NO874194L (no) | 1986-11-07 | 1988-05-09 | Pfizer Ltd | Fremgangsmaate ved fremstilling av dihydro-pyridinderivater |
| US4820842A (en) * | 1986-11-19 | 1989-04-11 | Warner-Lambert Company | 2-substituted-1,4-dihydropyridines |
| GB8712747D0 (en) * | 1987-05-30 | 1987-07-01 | Pfizer Ltd | Therapeutic agents |
| GB8803963D0 (en) * | 1988-02-19 | 1988-03-23 | Pfizer Ltd | Therapeutic agents |
-
1988
- 1988-09-26 MY MYPI88001070A patent/MY104933A/en unknown
- 1988-09-28 PT PT88614A patent/PT88614B/pt active IP Right Grant
- 1988-09-28 CA CA000578630A patent/CA1340785C/en not_active Expired - Fee Related
- 1988-09-29 PL PL1988274977A patent/PL157186B1/pl unknown
- 1988-09-29 ES ES198888309039T patent/ES2038766T3/es not_active Expired - Lifetime
- 1988-09-29 EG EG499/88A patent/EG18563A/xx active
- 1988-09-29 AU AU22973/88A patent/AU597190B2/en not_active Ceased
- 1988-09-29 US US07/251,413 patent/US4935430A/en not_active Expired - Lifetime
- 1988-09-29 EP EP88309039A patent/EP0310386B1/en not_active Expired - Lifetime
- 1988-09-29 YU YU182088A patent/YU46698B/sh unknown
- 1988-09-29 DE DE8888309039T patent/DE3866077D1/de not_active Expired - Lifetime
- 1988-09-29 FI FI884471A patent/FI93444C/fi not_active IP Right Cessation
- 1988-09-29 NZ NZ226397A patent/NZ226397A/en unknown
- 1988-09-29 DK DK544588A patent/DK170376B1/da not_active IP Right Cessation
- 1988-09-29 HU HU885063A patent/HU201061B/hu not_active IP Right Cessation
- 1988-09-29 IE IE294488A patent/IE61045B1/en not_active IP Right Cessation
- 1988-09-29 NO NO884333A patent/NO168107C/no unknown
- 1988-09-30 KR KR1019880012718A patent/KR900008318B1/ko not_active IP Right Cessation
- 1988-09-30 PH PH37617A patent/PH26046A/en unknown
- 1988-09-30 JP JP63247281A patent/JP2660016B2/ja not_active Expired - Fee Related
- 1988-10-04 CN CN88109031A patent/CN1032648C/zh not_active Expired - Fee Related
-
1990
- 1990-05-01 US US07/517,116 patent/US5063237A/en not_active Expired - Lifetime
- 1990-05-01 US US07/517,115 patent/US5120747A/en not_active Expired - Lifetime
- 1990-08-23 AU AU61261/90A patent/AU617256B2/en not_active Ceased
-
1991
- 1991-12-30 GR GR91402199T patent/GR3003468T3/el unknown
-
1992
- 1992-03-22 IL IL101332A patent/IL101332A0/xx not_active IP Right Cessation
-
1993
- 1993-04-17 SG SG493/93A patent/SG49393G/en unknown
- 1993-07-08 HK HK660/93A patent/HK66093A/xx not_active IP Right Cessation
-
1994
- 1994-05-06 CY CY172294A patent/CY1722A/xx unknown
-
1997
- 1997-01-31 JP JP9018645A patent/JP2898256B2/ja not_active Expired - Fee Related
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