FI108229B - Menetelmä farmaseuttisesti käyttökelpoisten pyridopyridatsinoni- ja -pyridatsiinitioniyhdisteiden valmistamiseksi - Google Patents
Menetelmä farmaseuttisesti käyttökelpoisten pyridopyridatsinoni- ja -pyridatsiinitioniyhdisteiden valmistamiseksi Download PDFInfo
- Publication number
- FI108229B FI108229B FI941567A FI941567A FI108229B FI 108229 B FI108229 B FI 108229B FI 941567 A FI941567 A FI 941567A FI 941567 A FI941567 A FI 941567A FI 108229 B FI108229 B FI 108229B
- Authority
- FI
- Finland
- Prior art keywords
- alkyl
- formula
- hydrogen
- nitro
- compound
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims description 165
- 238000002360 preparation method Methods 0.000 title claims description 108
- 238000000034 method Methods 0.000 title claims description 60
- 230000008569 process Effects 0.000 title claims description 15
- DYHGFTMEUMYPOC-UHFFFAOYSA-N 8-(3-nitrophenyl)-6-(pyridin-4-ylmethyl)pyrido[2,3-d]pyridazin-5-one Chemical compound [O-][N+](=O)C1=CC=CC(C=2C3=NC=CC=C3C(=O)N(CC=3C=CN=CC=3)N=2)=C1 DYHGFTMEUMYPOC-UHFFFAOYSA-N 0.000 title description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 203
- 239000001257 hydrogen Substances 0.000 claims abstract description 203
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 120
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 117
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 111
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 107
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 64
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 64
- 239000001301 oxygen Substances 0.000 claims abstract description 64
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 51
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 16
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 13
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 11
- 239000011593 sulfur Substances 0.000 claims abstract description 11
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 8
- 125000001475 halogen functional group Chemical group 0.000 claims abstract 4
- -1 1,2- (methylenedioxy) Chemical class 0.000 claims description 108
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 93
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 54
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 30
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 30
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- 150000002367 halogens Chemical class 0.000 claims description 21
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 239000003153 chemical reaction reagent Substances 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 7
- SFNYPXFZPRSDTB-UHFFFAOYSA-N 7h-pyrido[2,3-d]pyridazin-8-one Chemical compound C1=CN=C2C(O)=NN=CC2=C1 SFNYPXFZPRSDTB-UHFFFAOYSA-N 0.000 claims description 7
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- 229960004738 nicotinyl alcohol Drugs 0.000 claims description 6
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
- 125000004122 cyclic group Chemical group 0.000 claims description 5
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 claims description 5
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- JBMKAUGHUNFTOL-UHFFFAOYSA-N Aldoclor Chemical class C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC=NS2(=O)=O JBMKAUGHUNFTOL-UHFFFAOYSA-N 0.000 claims description 3
- 125000004423 acyloxy group Chemical group 0.000 claims description 3
- 150000001350 alkyl halides Chemical class 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 239000012458 free base Substances 0.000 claims description 3
- 239000003451 thiazide diuretic agent Substances 0.000 claims description 3
- JZTWPAAGZLBARZ-UHFFFAOYSA-N 5-phenyl-7h-pyrido[2,3-d]pyridazin-8-one Chemical compound C12=CC=CN=C2C(O)=NN=C1C1=CC=CC=C1 JZTWPAAGZLBARZ-UHFFFAOYSA-N 0.000 claims description 2
- LVQDSZBWRMLCLQ-UHFFFAOYSA-N 8-phenyl-6h-pyrido[2,3-d]pyridazin-5-one Chemical compound C12=NC=CC=C2C(=O)NN=C1C1=CC=CC=C1 LVQDSZBWRMLCLQ-UHFFFAOYSA-N 0.000 claims description 2
- 229910000102 alkali metal hydride Inorganic materials 0.000 claims description 2
- 150000008046 alkali metal hydrides Chemical class 0.000 claims description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 2
- 241001061127 Thione Species 0.000 claims 2
- 239000003086 colorant Substances 0.000 claims 2
- 238000004040 coloring Methods 0.000 claims 2
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims 1
- 238000009432 framing Methods 0.000 claims 1
- 210000005036 nerve Anatomy 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 abstract description 91
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 90
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract description 33
- 125000001072 heteroaryl group Chemical group 0.000 abstract description 19
- 125000003118 aryl group Chemical group 0.000 abstract description 13
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 13
- 150000002148 esters Chemical class 0.000 abstract description 11
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 7
- 230000001506 immunosuppresive effect Effects 0.000 abstract description 7
- KMUUDIJYIRNGRO-UHFFFAOYSA-N 2h-pyrido[3,2-c]pyridazin-3-one Chemical class N1=CC=CC2=NNC(=O)C=C21 KMUUDIJYIRNGRO-UHFFFAOYSA-N 0.000 abstract description 6
- 208000023275 Autoimmune disease Diseases 0.000 abstract description 3
- 150000001266 acyl halides Chemical class 0.000 abstract description 3
- 239000000730 antalgic agent Substances 0.000 abstract description 3
- 239000000924 antiasthmatic agent Substances 0.000 abstract description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 abstract description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 3
- 125000002252 acyl group Chemical group 0.000 abstract description 2
- 230000001088 anti-asthma Effects 0.000 abstract description 2
- YQQSRZSUGBETRS-UHFFFAOYSA-N 1h-pyridazine-6-thione Chemical class SC1=CC=CN=N1 YQQSRZSUGBETRS-UHFFFAOYSA-N 0.000 abstract 1
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 abstract 1
- 125000002947 alkylene group Chemical group 0.000 abstract 1
- 125000005605 benzo group Chemical group 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 141
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 123
- 239000000243 solution Substances 0.000 description 79
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 70
- 125000001309 chloro group Chemical group Cl* 0.000 description 70
- 239000000203 mixture Substances 0.000 description 61
- 238000006243 chemical reaction Methods 0.000 description 57
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 56
- 239000002904 solvent Substances 0.000 description 56
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 46
- 239000000047 product Substances 0.000 description 43
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 32
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 27
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 239000000725 suspension Substances 0.000 description 23
- DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 description 22
- 239000000460 chlorine Substances 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 229910052801 chlorine Inorganic materials 0.000 description 21
- 238000007792 addition Methods 0.000 description 20
- 238000004587 chromatography analysis Methods 0.000 description 20
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 19
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 239000002253 acid Substances 0.000 description 18
- DWHIRSWNWDXFMQ-UHFFFAOYSA-N 4h-pyridazin-5-one Chemical compound O=C1CC=NN=C1 DWHIRSWNWDXFMQ-UHFFFAOYSA-N 0.000 description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 16
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- DHLCTHXZKHGREA-UHFFFAOYSA-N 6h-pyrido[2,3-d]pyridazin-5-one Chemical class C1=CC=C2C(=O)NN=CC2=N1 DHLCTHXZKHGREA-UHFFFAOYSA-N 0.000 description 14
- 238000002425 crystallisation Methods 0.000 description 14
- 230000008025 crystallization Effects 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 13
- 239000007818 Grignard reagent Substances 0.000 description 13
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 13
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 13
- 238000001914 filtration Methods 0.000 description 13
- 150000004795 grignard reagents Chemical class 0.000 description 13
- 238000003556 assay Methods 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- 239000012298 atmosphere Substances 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 150000001336 alkenes Chemical class 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 description 10
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 9
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 9
- 150000008064 anhydrides Chemical class 0.000 description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 9
- 210000000265 leukocyte Anatomy 0.000 description 9
- WYJZAOJIEFJLSR-UHFFFAOYSA-N methyl 2-(3-nitrobenzoyl)pyridine-3-carboxylate Chemical compound COC(=O)C1=CC=CN=C1C(=O)C1=CC=CC([N+]([O-])=O)=C1 WYJZAOJIEFJLSR-UHFFFAOYSA-N 0.000 description 9
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 9
- 229910017604 nitric acid Inorganic materials 0.000 description 9
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
- 239000012312 sodium hydride Substances 0.000 description 9
- 229910000104 sodium hydride Inorganic materials 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- ROIBSGBAPNGMQB-UHFFFAOYSA-N 2-(3-chlorobenzoyl)pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1C(=O)C1=CC=CC(Cl)=C1 ROIBSGBAPNGMQB-UHFFFAOYSA-N 0.000 description 7
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 230000004048 modification Effects 0.000 description 7
- 238000012986 modification Methods 0.000 description 7
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 6
- AHBXARCBESHFJQ-UHFFFAOYSA-N 8-(3-nitrophenyl)-6h-pyrido[2,3-d]pyridazin-5-one Chemical compound [O-][N+](=O)C1=CC=CC(C=2C3=NC=CC=C3C(=O)NN=2)=C1 AHBXARCBESHFJQ-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 6
- 238000006751 Mitsunobu reaction Methods 0.000 description 6
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical class O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 6
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- MOJUSWWYZQYKIN-UHFFFAOYSA-N methyl 2-(3-chlorobenzoyl)pyridine-3-carboxylate Chemical compound COC(=O)C1=CC=CN=C1C(=O)C1=CC=CC(Cl)=C1 MOJUSWWYZQYKIN-UHFFFAOYSA-N 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 5
- UNGQAOLERFZXSF-UHFFFAOYSA-N 8-(3-chlorophenyl)-6h-pyrido[2,3-d]pyridazin-5-one Chemical compound ClC1=CC=CC(C=2C3=NC=CC=C3C(=O)NN=2)=C1 UNGQAOLERFZXSF-UHFFFAOYSA-N 0.000 description 5
- 229940121363 anti-inflammatory agent Drugs 0.000 description 5
- 239000002260 anti-inflammatory agent Substances 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 210000004698 lymphocyte Anatomy 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- MCRVVYSQNADFRB-UHFFFAOYSA-N methyl 3-(3-chlorobenzoyl)pyridine-2-carboxylate Chemical compound COC(=O)C1=NC=CC=C1C(=O)C1=CC=CC(Cl)=C1 MCRVVYSQNADFRB-UHFFFAOYSA-N 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- IVOMOUWHDPKRLL-KQYNXXCUSA-M 3',5'-cyclic AMP(1-) Chemical compound C([C@H]1O2)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-M 0.000 description 4
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
- WZIYCIBURCPKAR-UHFFFAOYSA-N 4-(chloromethyl)pyridine Chemical compound ClCC1=CC=NC=C1 WZIYCIBURCPKAR-UHFFFAOYSA-N 0.000 description 4
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 208000009329 Graft vs Host Disease Diseases 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 150000001450 anions Chemical class 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 150000001768 cations Chemical class 0.000 description 4
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 125000001153 fluoro group Chemical group F* 0.000 description 4
- 208000024908 graft versus host disease Diseases 0.000 description 4
- RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 4
- 239000003018 immunosuppressive agent Substances 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 239000003226 mitogen Substances 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 125000001979 organolithium group Chemical group 0.000 description 4
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- RPGWZZNNEUHDAQ-UHFFFAOYSA-N phenylphosphine Chemical compound PC1=CC=CC=C1 RPGWZZNNEUHDAQ-UHFFFAOYSA-N 0.000 description 1
- 150000003003 phosphines Chemical class 0.000 description 1
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- 230000035790 physiological processes and functions Effects 0.000 description 1
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- UDJFFSGCRRMVFH-UHFFFAOYSA-N pyrido[2,3-d]pyrimidine Chemical compound N1=CN=CC2=CC=CN=C21 UDJFFSGCRRMVFH-UHFFFAOYSA-N 0.000 description 1
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- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- 229960004889 salicylic acid Drugs 0.000 description 1
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- 239000003998 snake venom Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
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- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000012134 supernatant fraction Substances 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- 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
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/30—Phthalazines
- C07D237/32—Phthalazines with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Rheumatology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US77567991A | 1991-10-09 | 1991-10-09 | |
| US77567991 | 1991-10-09 | ||
| PCT/US1992/008398 WO1993007146A1 (en) | 1991-10-09 | 1992-10-08 | Benzo and pyrido pyridazinone and pyridazinthione compounds with pde iv inhibiting activity |
| US9208398 | 1992-10-08 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI941567L FI941567L (fi) | 1994-04-06 |
| FI941567A0 FI941567A0 (fi) | 1994-04-06 |
| FI108229B true FI108229B (fi) | 2001-12-14 |
Family
ID=25105161
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI941567A FI108229B (fi) | 1991-10-09 | 1994-04-06 | Menetelmä farmaseuttisesti käyttökelpoisten pyridopyridatsinoni- ja -pyridatsiinitioniyhdisteiden valmistamiseksi |
Country Status (20)
| Country | Link |
|---|---|
| EP (1) | EP0612321B1 (da) |
| JP (1) | JP3245165B2 (da) |
| KR (1) | KR100263494B1 (da) |
| AT (1) | ATE183745T1 (da) |
| AU (1) | AU670544B2 (da) |
| CA (1) | CA2117059C (da) |
| DE (1) | DE69229874T2 (da) |
| DK (1) | DK0612321T3 (da) |
| ES (2) | ES2105920B1 (da) |
| FI (1) | FI108229B (da) |
| GR (1) | GR3030969T3 (da) |
| HU (2) | HUT66969A (da) |
| IL (1) | IL103388A (da) |
| MX (1) | MX9205794A (da) |
| NO (1) | NO302888B1 (da) |
| NZ (1) | NZ244660A (da) |
| PT (1) | PT100938B (da) |
| TW (1) | TW365606B (da) |
| WO (1) | WO1993007146A1 (da) |
| ZA (1) | ZA927755B (da) |
Families Citing this family (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9200689D0 (en) * | 1992-01-14 | 1992-03-11 | Rhone Poulenc Agriculture | New compositions of matter |
| GB9314412D0 (en) * | 1993-07-13 | 1993-08-25 | Rhone Poulenc Agriculture | New compositions of matter |
| US5665754A (en) * | 1993-09-20 | 1997-09-09 | Glaxo Wellcome Inc. | Substituted pyrrolidines |
| US5466697A (en) * | 1994-07-13 | 1995-11-14 | Syntex (U.S.A.) Inc. | 8-phenyl-1,6-naphthyridin-5-ones |
| US5817670A (en) * | 1994-08-29 | 1998-10-06 | Yamanouchi Pharmaceutical Co., Ltd. | Naphthyridine derivatives and pharmaceutical compositions thereof |
| US6069151A (en) * | 1996-11-06 | 2000-05-30 | Darwin Discovery, Ltd. | Quinolines and their therapeutic use |
| GB9712761D0 (en) * | 1997-06-17 | 1997-08-20 | Chiroscience Ltd | Quinolines and their therapeutic use |
| ES2137113B1 (es) * | 1997-07-29 | 2000-09-16 | Almirall Prodesfarma Sa | Nuevos derivados de triazolo-piridazinas heterociclicos. |
| ATE258930T1 (de) | 1997-12-15 | 2004-02-15 | Altana Pharma Ag | Dihydrobenzifurane |
| EP0934933A1 (en) * | 1998-02-06 | 1999-08-11 | Byk Gulden Lomberg Chemische Fabrik GmbH | Phthalazinones |
| IT1303272B1 (it) * | 1998-10-29 | 2000-11-06 | Zambon Spa | Derivati triciclici inibitori della fosfodiesterasi 4 |
| 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 |
| CA2715683A1 (en) | 1999-08-21 | 2001-03-01 | Nycomed Gmbh | Synergistic combination |
| HRP20030636B1 (en) | 2001-02-15 | 2012-05-31 | Nycomed Gmbh | Phthalayinone-piperidino-derivatives as pde4 inhibitors |
| EE200300514A (et) * | 2001-04-25 | 2004-02-16 | Altana Pharma Ag | Ftalasinoonid, nende kasutamine hingamisteede haigusnähte leevendavate ravimite valmistamiseks ningneid sisaldavad ravimid |
| JP4021329B2 (ja) | 2001-04-25 | 2007-12-12 | ニコメッド ゲゼルシャフト ミット ベシュレンクテル ハフツング | ピペラジノ誘導体およびｐｄｅ４阻害剤としてのその使用 |
| ES2195785B1 (es) | 2002-05-16 | 2005-03-16 | Almirall Prodesfarma, S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| JP2005538140A (ja) | 2002-08-10 | 2005-12-15 | アルタナ ファルマ アクチエンゲゼルシャフト | Ｐｄｅ４インヒビターとしてのピペリジン−ピリダゾン及びフタラゾン |
| HRP20050197A2 (en) * | 2002-08-10 | 2006-06-30 | Altana Pharma Ag | Piperidine-n-oxide-derivatives |
| ES2211344B1 (es) | 2002-12-26 | 2005-10-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| EA200501548A1 (ru) | 2003-04-01 | 2006-02-24 | Апплайд Резеч Системз Арс Холдинг Н.В. | Ингибиторы фосфодиэстераз при бесплодии |
| AU2005210042B2 (en) | 2004-02-04 | 2011-04-21 | Takeda Gmbh | 2-(piperidin-4-yl) -4, 5-dihydro-2H-pyridazin-3-one derivatives as PDE4 inhibitors |
| ES2251866B1 (es) | 2004-06-18 | 2007-06-16 | Laboratorios Almirall S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| MX2009013293A (es) | 2007-06-04 | 2010-02-15 | Synergy Pharmaceuticals Inc | Agonistas de guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros trastornos. |
| PL383550A1 (pl) * | 2007-10-15 | 2009-04-27 | Uniwersytet Łódzki | Nowe pochodne benzeno- i pirydopirydazynonów |
| EP2810951B1 (en) | 2008-06-04 | 2017-03-15 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| CA2730603C (en) | 2008-07-16 | 2019-09-24 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| CA3100941C (en) | 2011-03-01 | 2024-03-05 | Synergy Pharmaceuticals Inc. | Process of preparing guanylate cyclase c agonists |
| US20130116241A1 (en) | 2011-11-09 | 2013-05-09 | Abbvie Inc. | Novel inhibitor compounds of phosphodiesterase type 10a |
| WO2013097052A1 (en) | 2011-12-30 | 2013-07-04 | Abbott Laboratories | Bromodomain inhibitors |
| EP3718557A3 (en) | 2013-02-25 | 2020-10-21 | Bausch Health Ireland Limited | Guanylate cyclase receptor agonist sp-333 for use in colonic cleansing |
| CN105307655B (zh) | 2013-03-13 | 2019-05-03 | 弗拉特利发现实验室有限责任公司 | 哒嗪酮化合物及其用于制备治疗囊肿状纤维化的药物的应用 |
| JP2016514671A (ja) | 2013-03-15 | 2016-05-23 | シナジー ファーマシューティカルズ インコーポレイテッド | グアニル酸シクラーゼのアゴニストおよびその使用 |
| JP2016514670A (ja) | 2013-03-15 | 2016-05-23 | シナジー ファーマシューティカルズ インコーポレイテッド | 他の薬物と組み合わせたグアニル酸シクラーゼ受容体アゴニスト |
| EA201592263A1 (ru) | 2013-06-05 | 2016-05-31 | Синерджи Фармасьютикалз, Инк. | Ультрачистые агонисты гуанилатциклазы c, способ их получения и использования |
| KR20160042039A (ko) | 2013-08-09 | 2016-04-18 | 알데릭스, 인코포레이티드 | 인산염 수송을 억제하기 위한 화합물 및 방법 |
| US11319318B2 (en) * | 2015-03-05 | 2022-05-03 | Boehringer Ingelheim International Gmbh | Pyridinones and isoquinolinones as inhibitors of the bromodomain BRD9 |
| JP6837052B2 (ja) * | 2016-03-09 | 2021-03-03 | 日本曹達株式会社 | ピリジン化合物およびその用途 |
| ES2793239T3 (es) | 2016-04-15 | 2020-11-13 | Abbvie Inc | Inhibidores del bromodominio |
| WO2020237096A1 (en) | 2019-05-21 | 2020-11-26 | Ardelyx, Inc. | Combination for lowering serum phosphate in a patient |
| FR3105254B1 (fr) | 2019-12-19 | 2022-08-12 | Syctom Lagence Metropolitaine Des Dechets Menagers | Installation et procédé de gazéification hydrothermale de biomasse |
| AR127621A1 (es) * | 2021-11-09 | 2024-02-14 | Vigil Neuroscience Inc | Compuestos heterocíclicos como agonistas del receptor activador expresado en células mieloides 2 y métodos de uso |
| WO2025046523A1 (ko) * | 2023-08-31 | 2025-03-06 | 삼진제약주식회사 | 신규한 피리도 피리다진온 유도체 화합물 및 이를 포함하는 약학적 조성물 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2805344B2 (ja) * | 1989-07-11 | 1998-09-30 | 昭和電工株式会社 | オレフィン重合触媒の製造方法およびオレフィンの重合方法 |
| JP3120857B2 (ja) * | 1990-02-19 | 2000-12-25 | 中外製薬株式会社 | 新規な縮合複素環化合物とこれを用いた抗喘息剤 |
-
1992
- 1992-10-08 JP JP50707893A patent/JP3245165B2/ja not_active Expired - Fee Related
- 1992-10-08 IL IL103388A patent/IL103388A/xx not_active IP Right Cessation
- 1992-10-08 MX MX9205794A patent/MX9205794A/es not_active IP Right Cessation
- 1992-10-08 NZ NZ244660A patent/NZ244660A/en unknown
- 1992-10-08 ES ES09201998A patent/ES2105920B1/es not_active Expired - Fee Related
- 1992-10-08 CA CA002117059A patent/CA2117059C/en not_active Expired - Fee Related
- 1992-10-08 TW TW081108015A patent/TW365606B/zh active
- 1992-10-08 HU HU9400949A patent/HUT66969A/hu unknown
- 1992-10-08 DK DK92922090T patent/DK0612321T3/da active
- 1992-10-08 WO PCT/US1992/008398 patent/WO1993007146A1/en not_active Ceased
- 1992-10-08 ZA ZA927755A patent/ZA927755B/xx unknown
- 1992-10-08 ES ES92922090T patent/ES2135416T3/es not_active Expired - Lifetime
- 1992-10-08 PT PT100938A patent/PT100938B/pt not_active IP Right Cessation
- 1992-10-08 AT AT92922090T patent/ATE183745T1/de not_active IP Right Cessation
- 1992-10-08 DE DE69229874T patent/DE69229874T2/de not_active Expired - Fee Related
- 1992-10-08 EP EP92922090A patent/EP0612321B1/en not_active Expired - Lifetime
- 1992-10-08 KR KR1019940701129A patent/KR100263494B1/ko not_active Expired - Fee Related
- 1992-10-08 AU AU27815/92A patent/AU670544B2/en not_active Ceased
-
1994
- 1994-04-05 NO NO941210A patent/NO302888B1/no not_active IP Right Cessation
- 1994-04-06 FI FI941567A patent/FI108229B/fi active
-
1995
- 1995-04-24 HU HU95P/P00113P patent/HU210814A9/hu unknown
-
1999
- 1999-08-26 GR GR990401632T patent/GR3030969T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ES2105920B1 (es) | 1998-07-01 |
| DK0612321T3 (da) | 1999-12-13 |
| NO941210L (no) | 1994-04-05 |
| IL103388A (en) | 1997-09-30 |
| KR100263494B1 (ko) | 2000-08-01 |
| WO1993007146A1 (en) | 1993-04-15 |
| DE69229874D1 (de) | 1999-09-30 |
| DE69229874T2 (de) | 1999-12-09 |
| NO941210D0 (no) | 1994-04-05 |
| HU9400949D0 (en) | 1994-06-28 |
| MX9205794A (es) | 1993-04-01 |
| HUT66969A (en) | 1995-01-30 |
| EP0612321A1 (en) | 1994-08-31 |
| CA2117059C (en) | 2003-05-20 |
| ES2135416T3 (es) | 1999-11-01 |
| JP3245165B2 (ja) | 2002-01-07 |
| PT100938B (pt) | 1999-10-29 |
| ATE183745T1 (de) | 1999-09-15 |
| TW365606B (en) | 1999-08-01 |
| AU2781592A (en) | 1993-05-03 |
| PT100938A (pt) | 1993-10-29 |
| EP0612321B1 (en) | 1999-08-25 |
| AU670544B2 (en) | 1996-07-25 |
| FI941567L (fi) | 1994-04-06 |
| NZ244660A (en) | 1995-05-26 |
| ES2105920A1 (es) | 1997-10-16 |
| IL103388A0 (en) | 1993-03-15 |
| FI941567A0 (fi) | 1994-04-06 |
| JPH07500321A (ja) | 1995-01-12 |
| GR3030969T3 (en) | 1999-11-30 |
| NO302888B1 (no) | 1998-05-04 |
| ZA927755B (en) | 1994-04-08 |
| HU210814A9 (en) | 1995-08-28 |
| KR940702868A (ko) | 1994-09-17 |
| CA2117059A1 (en) | 1993-04-15 |
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