CA2431023A1 - Substituted benzoindoles as spla2 inhibitors - Google Patents
Substituted benzoindoles as spla2 inhibitors Download PDFInfo
- Publication number
- CA2431023A1 CA2431023A1 CA002431023A CA2431023A CA2431023A1 CA 2431023 A1 CA2431023 A1 CA 2431023A1 CA 002431023 A CA002431023 A CA 002431023A CA 2431023 A CA2431023 A CA 2431023A CA 2431023 A1 CA2431023 A1 CA 2431023A1
- Authority
- CA
- Canada
- Prior art keywords
- group
- hydrogen
- compound
- alkyl
- acid
- 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
- 239000003112 inhibitor Substances 0.000 title claims description 10
- HIYWOHBEPVGIQN-UHFFFAOYSA-N 1h-benzo[g]indole Chemical class C1=CC=CC2=C(NC=C3)C3=CC=C21 HIYWOHBEPVGIQN-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 123
- 102000005473 Secretory Phospholipases A2 Human genes 0.000 claims abstract description 23
- 108010031873 Secretory Phospholipases A2 Proteins 0.000 claims abstract description 23
- 238000011282 treatment Methods 0.000 claims abstract description 16
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 14
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 10
- 239000000194 fatty acid Substances 0.000 claims abstract description 10
- 229930195729 fatty acid Natural products 0.000 claims abstract description 10
- 150000004665 fatty acids Chemical class 0.000 claims abstract description 10
- 230000001404 mediated effect Effects 0.000 claims abstract description 9
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 6
- -1 indole compound Chemical class 0.000 claims description 101
- 239000002253 acid Substances 0.000 claims description 93
- 229910052739 hydrogen Inorganic materials 0.000 claims description 78
- 239000001257 hydrogen Substances 0.000 claims description 69
- 239000000203 mixture Substances 0.000 claims description 64
- 125000005647 linker group Chemical group 0.000 claims description 61
- 150000002431 hydrogen Chemical class 0.000 claims description 36
- 125000001424 substituent group Chemical group 0.000 claims description 35
- 125000003118 aryl group Chemical group 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 30
- 125000004442 acylamino group Chemical group 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 25
- 229910052760 oxygen Inorganic materials 0.000 claims description 24
- 150000001413 amino acids Chemical class 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 23
- 229910052717 sulfur Inorganic materials 0.000 claims description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 21
- 239000001301 oxygen Substances 0.000 claims description 21
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 20
- 125000003368 amide group Chemical group 0.000 claims description 20
- 125000004429 atom Chemical group 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 20
- 239000011593 sulfur Substances 0.000 claims description 20
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 20
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 19
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 19
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 18
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 18
- 230000002452 interceptive effect Effects 0.000 claims description 18
- 239000000651 prodrug Substances 0.000 claims description 18
- 229940002612 prodrug Drugs 0.000 claims description 18
- 230000002378 acidificating effect Effects 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 14
- 150000001408 amides Chemical group 0.000 claims description 14
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 14
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 14
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 125000005843 halogen group Chemical group 0.000 claims description 13
- 125000000539 amino acid group Chemical group 0.000 claims description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 239000012453 solvate Substances 0.000 claims description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 8
- 125000003277 amino group Chemical group 0.000 claims description 8
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 8
- 125000001188 haloalkyl group Chemical group 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000004104 aryloxy group Chemical group 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- RLJUIKVXQJUBAN-UHFFFAOYSA-N 2-(1-benzyl-2-ethyl-3-oxamoylbenzo[f]indol-4-yl)oxyacetic acid Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)C3=CC=CC=C3C=C2N1CC1=CC=CC=C1 RLJUIKVXQJUBAN-UHFFFAOYSA-N 0.000 claims description 4
- ZKYVBSXZRJFJRC-UHFFFAOYSA-N benzyl 2-(1-benzyl-2-ethyl-3-oxamoylbenzo[f]indol-4-yl)oxyacetate Chemical compound C12=CC=CC=C2C=C2N(CC=3C=CC=CC=3)C(CC)=C(C(=O)C(N)=O)C2=C1OCC(=O)OCC1=CC=CC=C1 ZKYVBSXZRJFJRC-UHFFFAOYSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 239000004305 biphenyl Substances 0.000 claims description 4
- 235000010290 biphenyl Nutrition 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000005425 toluyl group Chemical group 0.000 claims description 4
- 125000002256 xylenyl group Chemical group C1(C(C=CC=C1)C)(C)* 0.000 claims description 4
- 125000003358 C2-C20 alkenyl group Chemical group 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 2
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 2
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 2
- 125000000033 alkoxyamino group Chemical group 0.000 claims description 2
- 125000004694 alkoxyaminocarbonyl group Chemical group 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 2
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 125000004691 alkyl thio carbonyl group Chemical group 0.000 claims description 2
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 2
- GQBNRKIHKLCHTG-UHFFFAOYSA-N ethyl 2-(1-benzyl-2-ethyl-3-oxamoylbenzo[f]indol-4-yl)oxyacetate Chemical compound C12=CC3=CC=CC=C3C(OCC(=O)OCC)=C2C(C(=O)C(N)=O)=C(CC)N1CC1=CC=CC=C1 GQBNRKIHKLCHTG-UHFFFAOYSA-N 0.000 claims description 2
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 2
- 125000004441 haloalkylsulfonyl group Chemical group 0.000 claims description 2
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 150000003555 thioacetals Chemical class 0.000 claims description 2
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 11
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 3
- 125000006755 (C2-C20) alkyl group Chemical group 0.000 claims 2
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims 1
- 125000006553 (C3-C8) cycloalkenyl group Chemical group 0.000 claims 1
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims 1
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims 1
- 229910006069 SO3H Inorganic materials 0.000 claims 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
- 230000001575 pathological effect Effects 0.000 claims 1
- FLJIWUNZRZLSME-UHFFFAOYSA-N 1h-benzo[f]indole Chemical class C1=CC=C2C=C(NC=C3)C3=CC2=C1 FLJIWUNZRZLSME-UHFFFAOYSA-N 0.000 abstract description 3
- 206010040070 Septic Shock Diseases 0.000 abstract description 3
- 230000036303 septic shock Effects 0.000 abstract description 3
- HOKDBMAJZXIPGC-UHFFFAOYSA-N Mequitazine Chemical compound C12=CC=CC=C2SC2=CC=CC=C2N1CC1C(CC2)CCN2C1 HOKDBMAJZXIPGC-UHFFFAOYSA-N 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 69
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 43
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 32
- 125000000217 alkyl group Chemical group 0.000 description 32
- 239000000243 solution Substances 0.000 description 32
- 238000006243 chemical reaction Methods 0.000 description 30
- 239000004480 active ingredient Substances 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 23
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 22
- 150000002475 indoles Chemical class 0.000 description 22
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- 150000002148 esters Chemical class 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- 235000001014 amino acid Nutrition 0.000 description 17
- 229940024606 amino acid Drugs 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 238000002360 preparation method Methods 0.000 description 16
- 239000000047 product Substances 0.000 description 16
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical group CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
- 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 14
- 238000009472 formulation Methods 0.000 description 14
- 239000000543 intermediate Substances 0.000 description 14
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
- 150000003254 radicals Chemical class 0.000 description 14
- 239000002585 base Substances 0.000 description 13
- 239000003826 tablet Substances 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- 101150041968 CDC13 gene Proteins 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 229920002472 Starch Polymers 0.000 description 10
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 239000008107 starch Substances 0.000 description 10
- 235000019698 starch Nutrition 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 9
- 125000000753 cycloalkyl group Chemical group 0.000 description 9
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 8
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 8
- 229940114079 arachidonic acid Drugs 0.000 description 7
- 235000021342 arachidonic acid Nutrition 0.000 description 7
- 206010003246 arthritis Diseases 0.000 description 7
- 235000019359 magnesium stearate Nutrition 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 125000002837 carbocyclic group Chemical group 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- AMANDCZTVNQSNB-UHFFFAOYSA-N glyoxamide Chemical compound NC(=O)C=O AMANDCZTVNQSNB-UHFFFAOYSA-N 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 6
- 238000010626 work up procedure Methods 0.000 description 6
- 150000003869 acetamides Chemical class 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 229910000024 caesium carbonate Inorganic materials 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- ZOAMBXDOGPRZLP-UHFFFAOYSA-N indole-3-acetamide Chemical compound C1=CC=C2C(CC(=O)N)=CNC2=C1 ZOAMBXDOGPRZLP-UHFFFAOYSA-N 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 4
- SFKZPTYRENGBTJ-UHFFFAOYSA-N 4-methoxynaphthalen-2-amine Chemical compound C1=CC=C2C(OC)=CC(N)=CC2=C1 SFKZPTYRENGBTJ-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-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
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 4
- 125000003342 alkenyl group Chemical group 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 208000006673 asthma Diseases 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 description 4
- 125000001309 chloro group Chemical group Cl* 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 4
- 239000012634 fragment Substances 0.000 description 4
- AWMLDBKLOPNOAR-UHFFFAOYSA-N indole-3-glyoxylamide Natural products C1=CC=C2C(C(=O)C(=O)N)=CNC2=C1 AWMLDBKLOPNOAR-UHFFFAOYSA-N 0.000 description 4
- 150000007529 inorganic bases Chemical class 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000006138 lithiation reaction Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 150000007530 organic bases Chemical class 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 150000002923 oximes Chemical group 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 4
- 229910052705 radium Inorganic materials 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 4
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- 235000012222 talc Nutrition 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- RBACIKXCRWGCBB-UHFFFAOYSA-N 1,2-Epoxybutane Chemical compound CCC1CO1 RBACIKXCRWGCBB-UHFFFAOYSA-N 0.000 description 3
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- 102000006447 Phospholipases A2 Human genes 0.000 description 3
- 108010058864 Phospholipases A2 Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
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Classifications
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Landscapes
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25628100P | 2000-12-18 | 2000-12-18 | |
| US60/256,281 | 2000-12-18 | ||
| PCT/US2001/043184 WO2002050028A2 (en) | 2000-12-18 | 2001-12-06 | Substituted benzoindoles as spla2 inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2431023A1 true CA2431023A1 (en) | 2002-06-27 |
Family
ID=22971644
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002431023A Abandoned CA2431023A1 (en) | 2000-12-18 | 2001-12-06 | Substituted benzoindoles as spla2 inhibitors |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US6930123B2 (enExample) |
| EP (1) | EP1349832A2 (enExample) |
| JP (1) | JP2004518657A (enExample) |
| AU (1) | AU2002237655A1 (enExample) |
| CA (1) | CA2431023A1 (enExample) |
| WO (1) | WO2002050028A2 (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101499882B (zh) | 2008-11-05 | 2011-05-04 | 华为技术有限公司 | 半静态调度数据包的应答信息的反馈、接收方法及其装置 |
| CN107233337A (zh) | 2009-04-29 | 2017-10-10 | 阿马里纳药物爱尔兰有限公司 | 含有epa和心血管剂的药物组合物以及使用其的方法 |
| KR101213495B1 (ko) * | 2010-06-03 | 2013-01-14 | 삼성디스플레이 주식회사 | 유기 발광 소자 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU163443B (enExample) * | 1970-08-26 | 1973-08-28 | ||
| WO2000010568A1 (en) * | 1998-08-24 | 2000-03-02 | Draheim Susan E | Methods and compositions for treating periodontal disease with an inhibitor of secretory phospholipase a¿2? |
| WO2000037358A1 (en) * | 1998-12-22 | 2000-06-29 | Eli Lilly And Company | NOVEL sPLA2 INHIBITORS |
| DE60032774D1 (de) * | 1999-07-19 | 2007-02-15 | Lilly Co Eli | Spla2 inhibitoren |
| WO2001021587A2 (en) * | 1999-09-20 | 2001-03-29 | Eli Lilly And Company | Hydroxyfunctional amide 1h-indole derivatives active as spla2 inhibitors |
-
2001
- 2001-12-06 EP EP01986459A patent/EP1349832A2/en not_active Withdrawn
- 2001-12-06 WO PCT/US2001/043184 patent/WO2002050028A2/en not_active Ceased
- 2001-12-06 AU AU2002237655A patent/AU2002237655A1/en not_active Abandoned
- 2001-12-06 JP JP2002551525A patent/JP2004518657A/ja active Pending
- 2001-12-06 US US10/450,929 patent/US6930123B2/en not_active Expired - Fee Related
- 2001-12-06 CA CA002431023A patent/CA2431023A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2002050028A8 (en) | 2005-03-17 |
| WO2002050028A3 (en) | 2002-09-19 |
| AU2002237655A1 (en) | 2002-07-01 |
| US6930123B2 (en) | 2005-08-16 |
| EP1349832A2 (en) | 2003-10-08 |
| WO2002050028A2 (en) | 2002-06-27 |
| JP2004518657A (ja) | 2004-06-24 |
| US20040059130A1 (en) | 2004-03-25 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |