CA2578858A1 - Arylpyridazinones inhibitrices de la biosynthese de la prostaglandine endoperoxyde h synthase - Google Patents
Arylpyridazinones inhibitrices de la biosynthese de la prostaglandine endoperoxyde h synthase Download PDFInfo
- Publication number
- CA2578858A1 CA2578858A1 CA002578858A CA2578858A CA2578858A1 CA 2578858 A1 CA2578858 A1 CA 2578858A1 CA 002578858 A CA002578858 A CA 002578858A CA 2578858 A CA2578858 A CA 2578858A CA 2578858 A1 CA2578858 A1 CA 2578858A1
- Authority
- CA
- Canada
- Prior art keywords
- heterocyclic
- alkyl
- group
- cycloalkyl
- aryl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 230000015572 biosynthetic process Effects 0.000 title claims description 15
- 150000003180 prostaglandins Chemical class 0.000 title claims description 14
- 239000003112 inhibitor Substances 0.000 title abstract description 7
- -1 cycloalkenylalkyl Chemical group 0.000 claims abstract description 371
- 150000001875 compounds Chemical class 0.000 claims abstract description 306
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 166
- 125000003118 aryl group Chemical group 0.000 claims abstract description 139
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 134
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 130
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 114
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 100
- 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 99
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 88
- 239000001257 hydrogen Substances 0.000 claims abstract description 86
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims abstract description 78
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 73
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 66
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 60
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 50
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims abstract description 47
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 42
- 150000002148 esters Chemical class 0.000 claims abstract description 41
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 39
- 150000003839 salts Chemical class 0.000 claims abstract description 39
- AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical class OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 claims abstract description 36
- 150000002367 halogens Chemical group 0.000 claims abstract description 35
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 35
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 34
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 31
- 229940002612 prodrug Drugs 0.000 claims abstract description 31
- 239000000651 prodrug Substances 0.000 claims abstract description 31
- 125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 29
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract description 26
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 26
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 25
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 19
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims abstract description 17
- 125000006239 protecting group Chemical group 0.000 claims abstract description 17
- 125000004450 alkenylene group Chemical group 0.000 claims abstract description 15
- 125000003302 alkenyloxy group Chemical group 0.000 claims abstract description 15
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims abstract description 15
- 125000005015 aryl alkynyl group Chemical group 0.000 claims abstract description 15
- 125000000262 haloalkenyl group Chemical group 0.000 claims abstract description 14
- 125000005018 aryl alkenyl group Chemical group 0.000 claims abstract description 13
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims abstract description 13
- 125000000232 haloalkynyl group Chemical group 0.000 claims abstract description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 13
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims abstract description 12
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims abstract description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 12
- 125000005191 hydroxyalkylamino group Chemical group 0.000 claims abstract description 12
- 125000004688 alkyl sulfonyl alkyl group Chemical group 0.000 claims abstract description 11
- 125000004181 carboxyalkyl group Chemical group 0.000 claims abstract description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 11
- 125000003368 amide group Chemical group 0.000 claims abstract description 10
- 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims abstract description 10
- 125000001769 aryl amino group Chemical group 0.000 claims abstract description 10
- 125000004966 cyanoalkyl group Chemical group 0.000 claims abstract description 10
- 125000004986 diarylamino group Chemical group 0.000 claims abstract description 10
- 125000004438 haloalkoxy group Chemical group 0.000 claims abstract description 10
- 206010061218 Inflammation Diseases 0.000 claims abstract description 9
- 125000005093 alkyl carbonyl alkyl group Chemical group 0.000 claims abstract description 9
- 125000001691 aryl alkyl amino group Chemical group 0.000 claims abstract description 9
- 230000004054 inflammatory process Effects 0.000 claims abstract description 9
- 150000003573 thiols Chemical class 0.000 claims abstract description 9
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 8
- 125000006213 aryl hydroxyalkyl group Chemical group 0.000 claims abstract description 8
- 125000006212 aryloxy hydroxyalkyl group Chemical group 0.000 claims abstract description 8
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 8
- 125000002431 aminoalkoxy group Chemical group 0.000 claims abstract description 7
- 125000000000 cycloalkoxy group Chemical group 0.000 claims abstract description 7
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims abstract description 7
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 7
- 150000001356 alkyl thiols Chemical class 0.000 claims abstract description 6
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims abstract description 6
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims abstract description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims abstract description 5
- 125000004429 atom Chemical group 0.000 claims abstract description 4
- 125000005291 haloalkenyloxy group Chemical group 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 328
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 8
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 208000002193 Pain Diseases 0.000 claims description 5
- 206010037660 Pyrexia Diseases 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 201000008482 osteoarthritis Diseases 0.000 claims description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
- 239000002841 Lewis acid Substances 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 150000007517 lewis acids Chemical class 0.000 claims description 3
- 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 5
- 206010028980 Neoplasm Diseases 0.000 claims 4
- 201000011510 cancer Diseases 0.000 claims 4
- 238000004519 manufacturing process Methods 0.000 claims 4
- 239000003937 drug carrier Substances 0.000 claims 2
- 230000000269 nucleophilic effect Effects 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 abstract description 18
- 108010037462 Cyclooxygenase 2 Proteins 0.000 abstract description 16
- 102100038277 Prostaglandin G/H synthase 1 Human genes 0.000 abstract description 9
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 abstract description 7
- 108010037464 Cyclooxygenase 1 Proteins 0.000 abstract description 5
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 abstract description 5
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 abstract description 5
- 229940124639 Selective inhibitor Drugs 0.000 abstract description 5
- 102000004190 Enzymes Human genes 0.000 abstract description 4
- 108090000790 Enzymes Proteins 0.000 abstract description 4
- 108010029485 Protein Isoforms Proteins 0.000 abstract description 4
- 102000001708 Protein Isoforms Human genes 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 4
- 230000002496 gastric effect Effects 0.000 abstract description 4
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract description 2
- 230000001939 inductive effect Effects 0.000 abstract description 2
- 210000003734 kidney Anatomy 0.000 abstract description 2
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 abstract 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 365
- 238000005481 NMR spectroscopy Methods 0.000 description 281
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 257
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 174
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 171
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 139
- 239000000243 solution Substances 0.000 description 122
- 235000019439 ethyl acetate Nutrition 0.000 description 118
- 229910001868 water Inorganic materials 0.000 description 111
- 239000000047 product Substances 0.000 description 98
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 84
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 84
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 77
- 239000000203 mixture Substances 0.000 description 74
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 63
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 58
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 57
- 238000006243 chemical reaction Methods 0.000 description 57
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 53
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
- 239000000741 silica gel Substances 0.000 description 51
- 229910002027 silica gel Inorganic materials 0.000 description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 49
- NVNPLEPBDPJYRZ-UHFFFAOYSA-N 1-(bromomethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CBr)C=C1 NVNPLEPBDPJYRZ-UHFFFAOYSA-N 0.000 description 48
- 239000011541 reaction mixture Substances 0.000 description 47
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 45
- 230000002829 reductive effect Effects 0.000 description 45
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 44
- 239000012267 brine Substances 0.000 description 43
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 43
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 42
- 235000019341 magnesium sulphate Nutrition 0.000 description 42
- 150000002431 hydrogen Chemical group 0.000 description 41
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 38
- 238000010992 reflux Methods 0.000 description 37
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
- 101150041968 CDC13 gene Proteins 0.000 description 33
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 33
- 239000007787 solid Substances 0.000 description 30
- 239000000706 filtrate Substances 0.000 description 25
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 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 24
- YEUYZNNBXLMFCW-UHFFFAOYSA-N 1-bromo-4-methylsulfanylbenzene Chemical compound CSC1=CC=C(Br)C=C1 YEUYZNNBXLMFCW-UHFFFAOYSA-N 0.000 description 22
- 238000004440 column chromatography Methods 0.000 description 22
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 22
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- 239000003921 oil Substances 0.000 description 21
- 235000019198 oils Nutrition 0.000 description 21
- LZMJNVRJMFMYQS-UHFFFAOYSA-N poseltinib Chemical group C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC(OC=2C=C(NC(=O)C=C)C=CC=2)=C(OC=C2)C2=N1 LZMJNVRJMFMYQS-UHFFFAOYSA-N 0.000 description 21
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
- IVUHTLFKBDDICS-UHFFFAOYSA-N (4-methylsulfanylphenyl)boronic acid Chemical compound CSC1=CC=C(B(O)O)C=C1 IVUHTLFKBDDICS-UHFFFAOYSA-N 0.000 description 18
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- 239000012044 organic layer Substances 0.000 description 18
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 17
- 239000002585 base Substances 0.000 description 17
- 125000005843 halogen group Chemical group 0.000 description 17
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 16
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- 229910000027 potassium carbonate Inorganic materials 0.000 description 16
- AITNMTXHTIIIBB-UHFFFAOYSA-N 1-bromo-4-fluorobenzene Chemical compound FC1=CC=C(Br)C=C1 AITNMTXHTIIIBB-UHFFFAOYSA-N 0.000 description 15
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- XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 14
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- JJIFTOPVKWDHJI-UHFFFAOYSA-N 4-(bromomethyl)-1,2-difluorobenzene Chemical group FC1=CC=C(CBr)C=C1F JJIFTOPVKWDHJI-UHFFFAOYSA-N 0.000 description 13
- ZMCKLPPZCCJCBA-UHFFFAOYSA-N 5-(4-fluorophenyl)-4-(4-methylsulfonylphenyl)-1h-pyridazin-6-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC(F)=CC=2)C(=O)NN=C1 ZMCKLPPZCCJCBA-UHFFFAOYSA-N 0.000 description 13
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- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 12
- 238000004587 chromatography analysis Methods 0.000 description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
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- RKOUFQLNMRAACI-UHFFFAOYSA-N 1,1,1-trifluoro-2-iodoethane Chemical group FC(F)(F)CI RKOUFQLNMRAACI-UHFFFAOYSA-N 0.000 description 9
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- 239000007858 starting material Substances 0.000 description 8
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- KNMCZSNDSSMJRZ-UHFFFAOYSA-N 4-chloro-5-(4-methylsulfonylphenyl)-2-(2,2,2-trifluoroethyl)pyridazin-3-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(Cl)C(=O)N(CC(F)(F)F)N=C1 KNMCZSNDSSMJRZ-UHFFFAOYSA-N 0.000 description 7
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- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
- 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 7
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 7
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 7
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 7
- 229910052731 fluorine Inorganic materials 0.000 description 7
- 239000000463 material Substances 0.000 description 7
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- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 3
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- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 238000011160 research Methods 0.000 description 1
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 1
- 229910001958 silver carbonate Inorganic materials 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
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- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
- GRONZTPUWOOUFQ-UHFFFAOYSA-M sodium;methanol;hydroxide Chemical compound [OH-].[Na+].OC GRONZTPUWOOUFQ-UHFFFAOYSA-M 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 230000004206 stomach function Effects 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
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- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 150000003555 thioacetals Chemical class 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- CIWZUQUKZAMSIZ-UHFFFAOYSA-N trimethoxy borate Chemical compound COOB(OOC)OOC CIWZUQUKZAMSIZ-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US91702397A | 1997-08-22 | 1997-08-22 | |
US08/917,023 | 1997-08-22 | ||
CA002299300A CA2299300C (fr) | 1997-08-22 | 1998-08-10 | Arylpyridazinones inhibitrices de la biosynthese de la prostaglandine endoperoxyde h synthase |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002299300A Division CA2299300C (fr) | 1997-08-22 | 1998-08-10 | Arylpyridazinones inhibitrices de la biosynthese de la prostaglandine endoperoxyde h synthase |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2578858A1 true CA2578858A1 (fr) | 1999-03-04 |
Family
ID=38024523
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002578858A Abandoned CA2578858A1 (fr) | 1997-08-22 | 1998-08-10 | Arylpyridazinones inhibitrices de la biosynthese de la prostaglandine endoperoxyde h synthase |
Country Status (1)
Country | Link |
---|---|
CA (1) | CA2578858A1 (fr) |
-
1998
- 1998-08-10 CA CA002578858A patent/CA2578858A1/fr not_active Abandoned
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