SK12782000A3 - Inhibítory fosfolipázových enzýmov, farmaceutický prostriedok s ich obsahom a ich použitie - Google Patents
Inhibítory fosfolipázových enzýmov, farmaceutický prostriedok s ich obsahom a ich použitie Download PDFInfo
- Publication number
- SK12782000A3 SK12782000A3 SK1278-2000A SK12782000A SK12782000A3 SK 12782000 A3 SK12782000 A3 SK 12782000A3 SK 12782000 A SK12782000 A SK 12782000A SK 12782000 A3 SK12782000 A3 SK 12782000A3
- Authority
- SK
- Slovakia
- Prior art keywords
- alkyl
- cooh
- benzyl
- alkoxy
- phenyl
- Prior art date
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- 239000003112 inhibitor Substances 0.000 title claims abstract description 15
- 102100037611 Lysophospholipase Human genes 0.000 title 1
- 108010058864 Phospholipases A2 Proteins 0.000 title 1
- 230000000694 effects Effects 0.000 claims abstract description 17
- 239000000126 substance Substances 0.000 claims abstract description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 283
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 171
- 150000001875 compounds Chemical class 0.000 claims description 168
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 143
- -1 -CHO Chemical group 0.000 claims description 140
- 125000003545 alkoxy group Chemical group 0.000 claims description 132
- 229910052736 halogen Inorganic materials 0.000 claims description 101
- 150000002367 halogens Chemical class 0.000 claims description 99
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 91
- 102000015439 Phospholipases Human genes 0.000 claims description 91
- 108010064785 Phospholipases Proteins 0.000 claims description 91
- 150000003839 salts Chemical class 0.000 claims description 76
- ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 claims description 75
- 239000002532 enzyme inhibitor Substances 0.000 claims description 70
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 67
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 61
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 60
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 57
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 51
- 125000001424 substituent group Chemical group 0.000 claims description 50
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 42
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 42
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 37
- 229910052757 nitrogen Inorganic materials 0.000 claims description 37
- 239000002253 acid Substances 0.000 claims description 35
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 34
- 150000003536 tetrazoles Chemical class 0.000 claims description 33
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 30
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 29
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 29
- 229910052760 oxygen Inorganic materials 0.000 claims description 29
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 28
- 229910052717 sulfur Inorganic materials 0.000 claims description 28
- 125000000623 heterocyclic group Chemical group 0.000 claims description 27
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 26
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims description 23
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 22
- 125000005842 heteroatom Chemical group 0.000 claims description 22
- 125000003107 substituted aryl group Chemical group 0.000 claims description 22
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 21
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 21
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 20
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 20
- 125000003342 alkenyl group Chemical group 0.000 claims description 19
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 19
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 17
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 16
- 125000002619 bicyclic group Chemical group 0.000 claims description 16
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 16
- 102000004190 Enzymes Human genes 0.000 claims description 15
- 108090000790 Enzymes Proteins 0.000 claims description 15
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 15
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 14
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 14
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 14
- 150000001732 carboxylic acid derivatives Chemical group 0.000 claims description 14
- 125000001041 indolyl group Chemical group 0.000 claims description 14
- 229930192474 thiophene Natural products 0.000 claims description 14
- 125000000304 alkynyl group Chemical group 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 12
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 11
- 239000005711 Benzoic acid Substances 0.000 claims description 10
- 235000010233 benzoic acid Nutrition 0.000 claims description 10
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 10
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 8
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 claims description 8
- GDRVFDDBLLKWRI-UHFFFAOYSA-N 4H-quinolizine Chemical compound C1=CC=CN2CC=CC=C21 GDRVFDDBLLKWRI-UHFFFAOYSA-N 0.000 claims description 8
- 230000002378 acidificating effect Effects 0.000 claims description 8
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 8
- QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 claims description 8
- 125000002541 furyl group Chemical group 0.000 claims description 8
- HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 claims description 8
- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 claims description 8
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 claims description 8
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 8
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 claims description 7
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 claims description 7
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 claims description 7
- KWIVRAVCZJXOQC-UHFFFAOYSA-N 3h-oxathiazole Chemical compound N1SOC=C1 KWIVRAVCZJXOQC-UHFFFAOYSA-N 0.000 claims description 7
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 claims description 7
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 7
- DPOPAJRDYZGTIR-UHFFFAOYSA-N Tetrazine Chemical compound C1=CN=NN=N1 DPOPAJRDYZGTIR-UHFFFAOYSA-N 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 7
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 7
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 claims description 7
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 claims description 7
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 7
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 4
- 230000004968 inflammatory condition Effects 0.000 claims description 4
- 125000006413 ring segment Chemical group 0.000 claims description 4
- ADUQNJRBRWUMHN-ZMOGYAJESA-N (5e)-5-[[1-[[2,4-bis(trifluoromethyl)phenyl]methyl]-5-phenylmethoxyindol-2-yl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC=C1CN1C2=CC=C(OCC=3C=CC=CC=3)C=C2C=C1\C=C\1C(=O)NC(=O)S/1 ADUQNJRBRWUMHN-ZMOGYAJESA-N 0.000 claims description 3
- KRNPKCSYCMJBTQ-UHFFFAOYSA-N 1-benzhydryl-5-bromoindole-2-carboxylic acid Chemical compound OC(=O)C1=CC2=CC(Br)=CC=C2N1C(C=1C=CC=CC=1)C1=CC=CC=C1 KRNPKCSYCMJBTQ-UHFFFAOYSA-N 0.000 claims description 3
- 241000124008 Mammalia Species 0.000 claims description 3
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 claims description 3
- 125000004122 cyclic group Chemical group 0.000 claims description 3
- QQVIHTHCMHWDBS-UHFFFAOYSA-N isophthalic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 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
- ISSHANURJKHZRG-OGLMXYFKSA-N (5e)-5-[[1-(naphthalen-2-ylmethyl)-5-phenylmethoxyindol-2-yl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)\C1=C/C1=CC2=CC(OCC=3C=CC=CC=3)=CC=C2N1CC1=CC=C(C=CC=C2)C2=C1 ISSHANURJKHZRG-OGLMXYFKSA-N 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- BNKKKTZQQXNCGR-NTCAYCPXSA-N (e)-3-[1-(naphthalen-2-ylmethyl)-5-phenylmethoxyindol-2-yl]prop-2-enoic acid Chemical compound C=1C=C2N(CC=3C=C4C=CC=CC4=CC=3)C(/C=C/C(=O)O)=CC2=CC=1OCC1=CC=CC=C1 BNKKKTZQQXNCGR-NTCAYCPXSA-N 0.000 claims description 2
- NFNQMVOXPQKBGZ-UHFFFAOYSA-N 1-[[2,4-bis(trifluoromethyl)phenyl]methyl]-5-phenylmethoxyindole-2-carboxylic acid Chemical compound C=1C=C2N(CC=3C(=CC(=CC=3)C(F)(F)F)C(F)(F)F)C(C(=O)O)=CC2=CC=1OCC1=CC=CC=C1 NFNQMVOXPQKBGZ-UHFFFAOYSA-N 0.000 claims description 2
- WHCAURSNEMNDOM-UHFFFAOYSA-N 1-benzhydryl-5-thiophen-2-ylindole-2-carboxylic acid Chemical compound OC(=O)C1=CC2=CC(C=3SC=CC=3)=CC=C2N1C(C=1C=CC=CC=1)C1=CC=CC=C1 WHCAURSNEMNDOM-UHFFFAOYSA-N 0.000 claims description 2
- JJLZPNRRWPACDZ-UHFFFAOYSA-N 1-benzyl-5-(4-fluorophenyl)indole-2-carboxylic acid Chemical compound OC(=O)C1=CC2=CC(C=3C=CC(F)=CC=3)=CC=C2N1CC1=CC=CC=C1 JJLZPNRRWPACDZ-UHFFFAOYSA-N 0.000 claims description 2
- DANPCKAHXFNYDT-UHFFFAOYSA-N 1-benzyl-5-phenylindole-2-carboxylic acid Chemical compound OC(=O)C1=CC2=CC(C=3C=CC=CC=3)=CC=C2N1CC1=CC=CC=C1 DANPCKAHXFNYDT-UHFFFAOYSA-N 0.000 claims description 2
- KCJOYERDJPJBOI-UHFFFAOYSA-N 1-benzyl-5-thiophen-2-ylindole-2-carboxylic acid Chemical compound OC(=O)C1=CC2=CC(C=3SC=CC=3)=CC=C2N1CC1=CC=CC=C1 KCJOYERDJPJBOI-UHFFFAOYSA-N 0.000 claims description 2
- 125000004398 2-methyl-2-butyl group Chemical group CC(C)(CC)* 0.000 claims description 2
- CWTFOVSWHLNBJT-UHFFFAOYSA-N 5-(1-benzofuran-2-yl)-1-benzylindole-2-carboxylic acid Chemical compound OC(=O)C1=CC2=CC(C=3OC4=CC=CC=C4C=3)=CC=C2N1CC1=CC=CC=C1 CWTFOVSWHLNBJT-UHFFFAOYSA-N 0.000 claims description 2
- ARDPQCDUFUIKMH-UHFFFAOYSA-N 5-(3-acetamidophenyl)-1-benzhydrylindole-2-carboxylic acid Chemical compound CC(=O)NC1=CC=CC(C=2C=C3C=C(N(C(C=4C=CC=CC=4)C=4C=CC=CC=4)C3=CC=2)C(O)=O)=C1 ARDPQCDUFUIKMH-UHFFFAOYSA-N 0.000 claims description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 229940125532 enzyme inhibitor Drugs 0.000 claims 58
- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 claims 3
- UZMKYCSFFAEDNI-UHFFFAOYSA-N 2-(5-chloropyridin-3-yl)oxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1OC1=CN=CC(Cl)=C1 UZMKYCSFFAEDNI-UHFFFAOYSA-N 0.000 claims 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 2
- 150000001413 amino acids Chemical class 0.000 claims 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
- AXOUYTDWPLMZNO-OGLMXYFKSA-N (5e)-5-[[1-(naphthalen-2-ylmethyl)-5-phenylmethoxyindol-2-yl]methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one Chemical compound O=C1NC(=S)S\C1=C\C1=CC2=CC(OCC=3C=CC=CC=3)=CC=C2N1CC1=CC=C(C=CC=C2)C2=C1 AXOUYTDWPLMZNO-OGLMXYFKSA-N 0.000 claims 1
- LNSOOGNRKWDVBC-JLHYYAGUSA-N (e)-3-[1-[(4-chlorophenyl)methyl]-5-phenylmethoxyindol-2-yl]prop-2-enoic acid Chemical compound C=1C=C2N(CC=3C=CC(Cl)=CC=3)C(/C=C/C(=O)O)=CC2=CC=1OCC1=CC=CC=C1 LNSOOGNRKWDVBC-JLHYYAGUSA-N 0.000 claims 1
- JGJGATZSBDRWIU-UHFFFAOYSA-N 1-(3-methoxyphenyl)indole-2-carboxylic acid Chemical compound COC1=CC=CC(N2C3=CC=CC=C3C=C2C(O)=O)=C1 JGJGATZSBDRWIU-UHFFFAOYSA-N 0.000 claims 1
- OGFBPSUSECTQIE-UHFFFAOYSA-N 1-[[4-[[3,5-bis(trifluoromethyl)phenoxy]methyl]phenyl]methyl]indole-2-carboxylic acid Chemical compound OC(=O)C1=CC2=CC=CC=C2N1CC(C=C1)=CC=C1COC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 OGFBPSUSECTQIE-UHFFFAOYSA-N 0.000 claims 1
- WHBNKGILKCASDH-UHFFFAOYSA-N 2-(2,4-dioxo-1,3-thiazolidin-3-yl)acetic acid Chemical compound OC(=O)CN1C(=O)CSC1=O WHBNKGILKCASDH-UHFFFAOYSA-N 0.000 claims 1
- AIVXYYVZURTCJQ-STBIYBPSSA-N 2-[(5e)-5-[[1-(naphthalen-2-ylmethyl)-5-phenylmethoxyindol-2-yl]methylidene]-2,4-dioxo-1,3-thiazolidin-3-yl]acetic acid Chemical compound O=C1N(CC(=O)O)C(=O)S\C1=C\C1=CC2=CC(OCC=3C=CC=CC=3)=CC=C2N1CC1=CC=C(C=CC=C2)C2=C1 AIVXYYVZURTCJQ-STBIYBPSSA-N 0.000 claims 1
- ZEYHEAKUIGZSGI-UHFFFAOYSA-N 4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1 ZEYHEAKUIGZSGI-UHFFFAOYSA-N 0.000 claims 1
- CBPXNKUWVDUJAZ-UHFFFAOYSA-N CC(C(C1=C2)=C(COC(C=CC=C3)=C3C(O)=O)N(CC3=CC4=CC=CC=C4C=C3)C1=CC=C2OCC1=CC=CC=C1)=O Chemical compound CC(C(C1=C2)=C(COC(C=CC=C3)=C3C(O)=O)N(CC3=CC4=CC=CC=C4C=C3)C1=CC=C2OCC1=CC=CC=C1)=O CBPXNKUWVDUJAZ-UHFFFAOYSA-N 0.000 claims 1
- YKZLXAHIQGBSPD-UHFFFAOYSA-N OC(C(C=CC=C1)=C1OCC1=C(C(C(F)(F)F)=O)C2=CC(OCC3=CC=CC=C3)=CC=C2N1CC1=CC2=CC=CC=C2C=C1)=O Chemical compound OC(C(C=CC=C1)=C1OCC1=C(C(C(F)(F)F)=O)C2=CC(OCC3=CC=CC=C3)=CC=C2N1CC1=CC2=CC=CC=C2C=C1)=O YKZLXAHIQGBSPD-UHFFFAOYSA-N 0.000 claims 1
- 238000002591 computed tomography Methods 0.000 claims 1
- 125000001188 haloalkyl group Chemical group 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- ILUJQPXNXACGAN-UHFFFAOYSA-N ortho-methoxybenzoic acid Natural products COC1=CC=CC=C1C(O)=O ILUJQPXNXACGAN-UHFFFAOYSA-N 0.000 claims 1
- 102100022893 Histone acetyltransferase KAT5 Human genes 0.000 abstract 1
- 108020002496 Lysophospholipase Proteins 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 507
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 223
- 235000019439 ethyl acetate Nutrition 0.000 description 172
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 157
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- DEKPYXUDJRABNK-UHFFFAOYSA-N dimethyl 5-aminobenzene-1,3-dicarboxylate Chemical compound COC(=O)C1=CC(N)=CC(C(=O)OC)=C1 DEKPYXUDJRABNK-UHFFFAOYSA-N 0.000 description 1
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- STCDDNDGEFVYKE-UHFFFAOYSA-N diphenylphosphane;propane Chemical compound CCC.C=1C=CC=CC=1PC1=CC=CC=C1.C=1C=CC=CC=1PC1=CC=CC=C1 STCDDNDGEFVYKE-UHFFFAOYSA-N 0.000 description 1
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- NPIUAXNFAUGNHP-UHFFFAOYSA-N ethyl 5-methoxy-1h-indole-2-carboxylate Chemical compound COC1=CC=C2NC(C(=O)OCC)=CC2=C1 NPIUAXNFAUGNHP-UHFFFAOYSA-N 0.000 description 1
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- 125000001072 heteroaryl group Chemical group 0.000 description 1
- VBZWSGALLODQNC-UHFFFAOYSA-N hexafluoroacetone Chemical compound FC(F)(F)C(=O)C(F)(F)F VBZWSGALLODQNC-UHFFFAOYSA-N 0.000 description 1
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- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
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- HAFCSCBORMDMFL-UHFFFAOYSA-N methyl 2-(4-methoxy-3-nitrophenyl)acetate Chemical compound COC(=O)CC1=CC=C(OC)C([N+]([O-])=O)=C1 HAFCSCBORMDMFL-UHFFFAOYSA-N 0.000 description 1
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- PKYQHJVAKJQNSM-UHFFFAOYSA-N methyl 4-methoxy-3-[3-[1-(2-naphthalen-2-yloxyacetyl)-5-phenylmethoxy-2,3-dihydroindol-2-yl]propanethioylamino]benzoate Chemical compound COC(=O)C1=CC=C(OC)C(NC(=S)CCC2N(C3=CC=C(OCC=4C=CC=CC=4)C=C3C2)C(=O)COC=2C=C3C=CC=CC3=CC=2)=C1 PKYQHJVAKJQNSM-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D209/32—Oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D209/12—Radicals substituted by oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/22—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an aralkyl radical attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3010298A | 1998-02-25 | 1998-02-25 | |
| PCT/US1999/003388 WO1999043672A1 (en) | 1998-02-25 | 1999-02-17 | Inhibitors of phospholipase a2 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK12782000A3 true SK12782000A3 (sk) | 2001-04-09 |
Family
ID=21852517
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1278-2000A SK12782000A3 (sk) | 1998-02-25 | 1999-02-17 | Inhibítory fosfolipázových enzýmov, farmaceutický prostriedok s ich obsahom a ich použitie |
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| BG (1) | BG104781A (id) |
| BR (1) | BR9909242A (id) |
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| EE (1) | EE200000522A (id) |
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| SK (1) | SK12782000A3 (id) |
| TR (1) | TR200002445T2 (id) |
| WO (1) | WO1999043672A1 (id) |
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Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL109311A0 (en) * | 1993-04-16 | 1994-07-31 | Lilly Co Eli | 1H-indole-3-acetamide sPla2 inhibitors |
| DE4338770A1 (de) * | 1993-11-12 | 1995-05-18 | Matthias Dr Lehr | Indol-2-alkansäuren und ihre Derivate als Hemmstoffe der Phospholipase A¶2¶ |
| JP3923079B2 (ja) * | 1995-07-31 | 2007-05-30 | 塩野義製薬株式会社 | ホスホリパーゼa2阻害活性を有するピロリジン誘導体 |
| ATE255090T1 (de) * | 1996-08-01 | 2003-12-15 | Merckle Gmbh | Acylpyrroldicarbonsäuren und acylindoldicarbonsäuren sowie ihre derivate als hemmstoffe der cytosolischen phospholipase a2 |
| JP2000516958A (ja) * | 1996-08-26 | 2000-12-19 | ジェネティックス・インスチチュート・インコーポレーテッド | ホスホリパーゼ酵素の阻害剤 |
-
1999
- 1999-02-17 HU HU0100156A patent/HUP0100156A3/hu unknown
- 1999-02-17 SK SK1278-2000A patent/SK12782000A3/sk unknown
- 1999-02-17 TR TR2000/02445T patent/TR200002445T2/xx unknown
- 1999-02-17 JP JP2000533428A patent/JP2002504551A/ja not_active Withdrawn
- 1999-02-17 EE EEP200000522A patent/EE200000522A/xx unknown
- 1999-02-17 BR BR9909242-5A patent/BR9909242A/pt not_active IP Right Cessation
- 1999-02-17 AU AU32970/99A patent/AU3297099A/en not_active Abandoned
- 1999-02-17 CN CN99805379A patent/CN1298404A/zh active Pending
- 1999-02-17 KR KR1020007009459A patent/KR20010041346A/ko not_active Withdrawn
- 1999-02-17 ID IDW20001568A patent/ID26123A/id unknown
- 1999-02-17 CA CA002322163A patent/CA2322163A1/en not_active Abandoned
- 1999-02-17 IL IL13754099A patent/IL137540A0/xx unknown
- 1999-02-17 WO PCT/US1999/003388 patent/WO1999043672A1/en not_active Ceased
- 1999-02-17 HR HR20000513A patent/HRP20000513A2/hr not_active Application Discontinuation
- 1999-02-17 PL PL99342516A patent/PL342516A1/xx unknown
- 1999-02-17 EP EP99936073A patent/EP1062216A1/en not_active Withdrawn
- 1999-02-17 EA EA200000873A patent/EA200000873A1/ru unknown
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2000
- 2000-08-23 NO NO20004217A patent/NO20004217L/no not_active Application Discontinuation
- 2000-09-19 BG BG104781A patent/BG104781A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP2002504551A (ja) | 2002-02-12 |
| KR20010041346A (ko) | 2001-05-15 |
| EE200000522A (et) | 2002-02-15 |
| HUP0100156A2 (hu) | 2001-07-30 |
| NO20004217L (no) | 2000-10-23 |
| NO20004217D0 (no) | 2000-08-23 |
| IL137540A0 (en) | 2001-07-24 |
| HUP0100156A3 (en) | 2002-12-28 |
| HRP20000513A2 (en) | 2001-12-31 |
| PL342516A1 (en) | 2001-06-18 |
| WO1999043672A9 (en) | 2000-05-04 |
| WO1999043672A1 (en) | 1999-09-02 |
| BR9909242A (pt) | 2000-11-14 |
| EA200000873A1 (ru) | 2001-04-23 |
| CN1298404A (zh) | 2001-06-06 |
| TR200002445T2 (tr) | 2000-12-21 |
| ID26123A (id) | 2000-11-23 |
| EP1062216A1 (en) | 2000-12-27 |
| CA2322163A1 (en) | 1999-09-02 |
| BG104781A (en) | 2001-10-31 |
| AU3297099A (en) | 1999-09-15 |
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