CA2335448A1 - Bicyclic spla2 inhibitors - Google Patents
Bicyclic spla2 inhibitors Download PDFInfo
- Publication number
- CA2335448A1 CA2335448A1 CA002335448A CA2335448A CA2335448A1 CA 2335448 A1 CA2335448 A1 CA 2335448A1 CA 002335448 A CA002335448 A CA 002335448A CA 2335448 A CA2335448 A CA 2335448A CA 2335448 A1 CA2335448 A1 CA 2335448A1
- Authority
- CA
- Canada
- Prior art keywords
- pyrrolo
- ethyl
- pyrimidin
- oxy
- acetic 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 8
- 125000002619 bicyclic group Chemical group 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 100
- 102000005473 Secretory Phospholipases A2 Human genes 0.000 claims abstract description 26
- 108010031873 Secretory Phospholipases A2 Proteins 0.000 claims abstract description 26
- 150000004943 pyrrolo[2,3-d]pyrimidines Chemical class 0.000 claims abstract description 17
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 9
- 230000001404 mediated effect Effects 0.000 claims abstract description 9
- 238000011282 treatment Methods 0.000 claims abstract description 7
- 239000000203 mixture Substances 0.000 claims description 71
- -1 pyrrolo[2,3-d]pyrimidine compound Chemical class 0.000 claims description 67
- 229910052739 hydrogen Inorganic materials 0.000 claims description 38
- 239000001257 hydrogen Substances 0.000 claims description 38
- 125000005647 linker group Chemical group 0.000 claims description 28
- 239000004480 active ingredient Substances 0.000 claims description 27
- 150000002431 hydrogen Chemical group 0.000 claims description 24
- 239000002253 acid Substances 0.000 claims description 23
- 125000001424 substituent group Chemical group 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 22
- 230000002378 acidificating effect Effects 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
- 239000000651 prodrug Chemical class 0.000 claims description 19
- 229940002612 prodrug Drugs 0.000 claims description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- 125000001188 haloalkyl group Chemical group 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 230000002452 interceptive effect Effects 0.000 claims description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
- 239000001301 oxygen Substances 0.000 claims description 11
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 10
- 239000000194 fatty acid Substances 0.000 claims description 10
- 229930195729 fatty acid Natural products 0.000 claims description 10
- 150000004665 fatty acids Chemical class 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 229910052717 sulfur Chemical group 0.000 claims description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
- 125000004429 atom Chemical group 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 239000011593 sulfur Chemical group 0.000 claims description 9
- 241000124008 Mammalia Species 0.000 claims description 8
- 208000027866 inflammatory disease Diseases 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 239000004305 biphenyl Substances 0.000 claims description 7
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
- 150000002148 esters Chemical class 0.000 claims description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
- 239000012453 solvate Chemical class 0.000 claims description 7
- 235000010290 biphenyl Nutrition 0.000 claims description 6
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- UTXVGTYLJHXCFV-UHFFFAOYSA-N methyl 2-(7-benzyl-6-ethyl-2-methylsulfanyl-5-oxamoylpyrrolo[2,3-d]pyrimidin-4-yl)oxyacetate Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(=O)OC)N=C(SC)N=C2N1CC1=CC=CC=C1 UTXVGTYLJHXCFV-UHFFFAOYSA-N 0.000 claims description 6
- MJXZAPRPPVABHR-UHFFFAOYSA-N 2-[6-ethyl-2-methylsulfanyl-5-oxamoyl-7-[(2-phenylphenyl)methyl]pyrrolo[2,3-d]pyrimidin-4-yl]oxyacetic acid Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)N=C(SC)N=C2N1CC1=CC=CC=C1C1=CC=CC=C1 MJXZAPRPPVABHR-UHFFFAOYSA-N 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- UIWQNCFJKCMNQC-UHFFFAOYSA-N methyl 2-(7-benzyl-6-ethyl-5-oxamoyl-2-phenylsulfanylpyrrolo[2,3-d]pyrimidin-4-yl)oxyacetate Chemical compound N1=C2N(CC=3C=CC=CC=3)C(CC)=C(C(=O)C(N)=O)C2=C(OCC(=O)OC)N=C1SC1=CC=CC=C1 UIWQNCFJKCMNQC-UHFFFAOYSA-N 0.000 claims description 5
- FPDGJKOVFVDIQT-UHFFFAOYSA-N methyl 2-[6-ethyl-2-methylsulfanyl-5-oxamoyl-7-[[2-(trifluoromethyl)phenyl]methyl]pyrrolo[2,3-d]pyrimidin-4-yl]oxyacetate Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(=O)OC)N=C(SC)N=C2N1CC1=CC=CC=C1C(F)(F)F FPDGJKOVFVDIQT-UHFFFAOYSA-N 0.000 claims description 5
- WLRNRNFXAKBHGW-UHFFFAOYSA-N methyl 2-[6-ethyl-5-oxamoyl-7-[[3-(trifluoromethyl)phenyl]methyl]pyrrolo[2,3-d]pyrimidin-4-yl]oxyacetate Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(=O)OC)N=CN=C2N1CC1=CC=CC(C(F)(F)F)=C1 WLRNRNFXAKBHGW-UHFFFAOYSA-N 0.000 claims description 5
- QJXHLLIMLWFJFE-UHFFFAOYSA-N methyl 2-[6-ethyl-7-[(3-fluorophenyl)methyl]-2-methylsulfanyl-5-oxamoylpyrrolo[2,3-d]pyrimidin-4-yl]oxyacetate Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(=O)OC)N=C(SC)N=C2N1CC1=CC=CC(F)=C1 QJXHLLIMLWFJFE-UHFFFAOYSA-N 0.000 claims description 5
- RRKYFHSYPHNTJP-UHFFFAOYSA-N methyl 2-[6-ethyl-7-[(3-fluorophenyl)methyl]-5-oxamoylpyrrolo[2,3-d]pyrimidin-4-yl]oxyacetate Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(=O)OC)N=CN=C2N1CC1=CC=CC(F)=C1 RRKYFHSYPHNTJP-UHFFFAOYSA-N 0.000 claims description 5
- GACWKGUHYXUDJG-UHFFFAOYSA-N methyl 2-[7-[(3-chlorophenyl)methyl]-6-ethyl-2-methylsulfanyl-5-oxamoylpyrrolo[2,3-d]pyrimidin-4-yl]oxyacetate Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(=O)OC)N=C(SC)N=C2N1CC1=CC=CC(Cl)=C1 GACWKGUHYXUDJG-UHFFFAOYSA-N 0.000 claims description 5
- MVWAFQKBFWWTGK-UHFFFAOYSA-N methyl 2-[7-[(3-chlorophenyl)methyl]-6-ethyl-5-oxamoylpyrrolo[2,3-d]pyrimidin-4-yl]oxyacetate Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(=O)OC)N=CN=C2N1CC1=CC=CC(Cl)=C1 MVWAFQKBFWWTGK-UHFFFAOYSA-N 0.000 claims description 5
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 4
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 4
- WPEVNKWGKHIBOA-UHFFFAOYSA-N 2-(7-benzyl-6-ethyl-2-methoxy-5-oxamoylpyrrolo[2,3-d]pyrimidin-4-yl)oxyacetic acid Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)N=C(OC)N=C2N1CC1=CC=CC=C1 WPEVNKWGKHIBOA-UHFFFAOYSA-N 0.000 claims description 4
- CDQYBTDSVYJQCA-UHFFFAOYSA-N 2-[6-ethyl-2-methylsulfanyl-5-oxamoyl-7-[[3-(trifluoromethyl)phenyl]methyl]pyrrolo[2,3-d]pyrimidin-4-yl]oxyacetic acid Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)N=C(SC)N=C2N1CC1=CC=CC(C(F)(F)F)=C1 CDQYBTDSVYJQCA-UHFFFAOYSA-N 0.000 claims description 4
- SRAPMULSNIDCQT-UHFFFAOYSA-N 2-[6-ethyl-7-[(3-fluorophenyl)methyl]-2-methylsulfanyl-5-oxamoylpyrrolo[2,3-d]pyrimidin-4-yl]oxyacetic acid Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)N=C(SC)N=C2N1CC1=CC=CC(F)=C1 SRAPMULSNIDCQT-UHFFFAOYSA-N 0.000 claims description 4
- YURRGXLFZZKHEH-UHFFFAOYSA-N 2-[6-ethyl-7-[(3-fluorophenyl)methyl]-5-oxamoylpyrrolo[2,3-d]pyrimidin-4-yl]oxyacetic acid Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)N=CN=C2N1CC1=CC=CC(F)=C1 YURRGXLFZZKHEH-UHFFFAOYSA-N 0.000 claims description 4
- SWMZZGWHRAEFBN-UHFFFAOYSA-N 2-[7-[(3-chlorophenyl)methyl]-6-ethyl-2-methylsulfanyl-5-oxamoylpyrrolo[2,3-d]pyrimidin-4-yl]oxyacetic acid Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)N=C(SC)N=C2N1CC1=CC=CC(Cl)=C1 SWMZZGWHRAEFBN-UHFFFAOYSA-N 0.000 claims description 4
- KAXAMNGVKFDQEN-UHFFFAOYSA-N 2-[7-[(3-chlorophenyl)methyl]-6-ethyl-5-oxamoylpyrrolo[2,3-d]pyrimidin-4-yl]oxyacetic acid Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)N=CN=C2N1CC1=CC=CC(Cl)=C1 KAXAMNGVKFDQEN-UHFFFAOYSA-N 0.000 claims description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- SQVKJRUWCAGTQT-UHFFFAOYSA-N methyl 2-(7-benzyl-6-ethyl-2-methoxy-5-oxamoylpyrrolo[2,3-d]pyrimidin-4-yl)oxyacetate Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(=O)OC)N=C(OC)N=C2N1CC1=CC=CC=C1 SQVKJRUWCAGTQT-UHFFFAOYSA-N 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
- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims description 3
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 3
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 3
- RHYKRHXRPOKXIN-UHFFFAOYSA-N 2-[6-ethyl-2-methylsulfanyl-5-oxamoyl-7-[[2-(trifluoromethyl)phenyl]methyl]pyrrolo[2,3-d]pyrimidin-4-yl]oxyacetic acid Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)N=C(SC)N=C2N1CC1=CC=CC=C1C(F)(F)F RHYKRHXRPOKXIN-UHFFFAOYSA-N 0.000 claims description 3
- RSSFXDQLFYNXKQ-UHFFFAOYSA-N 2-[6-ethyl-5-oxamoyl-7-[(2-phenylphenyl)methyl]pyrrolo[2,3-d]pyrimidin-4-yl]oxyacetic acid Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)N=CN=C2N1CC1=CC=CC=C1C1=CC=CC=C1 RSSFXDQLFYNXKQ-UHFFFAOYSA-N 0.000 claims description 3
- VQESUOQWWMOUFN-UHFFFAOYSA-N 2-[6-ethyl-5-oxamoyl-7-[[3-(trifluoromethyl)phenyl]methyl]pyrrolo[2,3-d]pyrimidin-4-yl]oxyacetic acid Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)N=CN=C2N1CC1=CC=CC(C(F)(F)F)=C1 VQESUOQWWMOUFN-UHFFFAOYSA-N 0.000 claims description 3
- 125000004054 acenaphthylenyl group Chemical group C1(=CC2=CC=CC3=CC=CC1=C23)* 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 claims description 3
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- CIBVUOKJGYZYGA-UHFFFAOYSA-N methyl 2-[6-ethyl-5-oxamoyl-7-[(2-phenylphenyl)methyl]pyrrolo[2,3-d]pyrimidin-4-yl]oxyacetate Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(=O)OC)N=CN=C2N1CC1=CC=CC=C1C1=CC=CC=C1 CIBVUOKJGYZYGA-UHFFFAOYSA-N 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 125000005593 norbornanyl group Chemical group 0.000 claims description 3
- 159000000000 sodium salts Chemical class 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 2
- WENVYWUWPIAIIR-UHFFFAOYSA-N 2-(7-benzyl-6-ethyl-5-oxamoyl-2-phenylsulfanylpyrrolo[2,3-d]pyrimidin-4-yl)oxyacetic acid Chemical compound N1=C2N(CC=3C=CC=CC=3)C(CC)=C(C(=O)C(N)=O)C2=C(OCC(O)=O)N=C1SC1=CC=CC=C1 WENVYWUWPIAIIR-UHFFFAOYSA-N 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 125000006125 ethylsulfonyl group Chemical group 0.000 claims description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
- 125000004001 thioalkyl group Chemical group 0.000 claims description 2
- 230000001575 pathological effect Effects 0.000 claims 2
- 125000006699 (C1-C3) hydroxyalkyl group Chemical group 0.000 claims 1
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims 1
- 229910006069 SO3H Inorganic materials 0.000 claims 1
- 125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 claims 1
- 201000010099 disease Diseases 0.000 abstract description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
- 206010040070 Septic Shock Diseases 0.000 abstract description 3
- 230000036303 septic shock Effects 0.000 abstract description 3
- 239000007787 solid Substances 0.000 description 122
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 105
- 238000006243 chemical reaction Methods 0.000 description 89
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 74
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
- 238000002360 preparation method Methods 0.000 description 56
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
- 239000000243 solution Substances 0.000 description 52
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 40
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- 239000000047 product Substances 0.000 description 36
- 239000000377 silicon dioxide Substances 0.000 description 35
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 32
- 101150041968 CDC13 gene Proteins 0.000 description 31
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 31
- 238000003818 flash chromatography Methods 0.000 description 30
- 239000012074 organic phase Substances 0.000 description 30
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 29
- 229910052938 sodium sulfate Inorganic materials 0.000 description 29
- 235000011152 sodium sulphate Nutrition 0.000 description 29
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
- 238000001914 filtration Methods 0.000 description 25
- 229910000104 sodium hydride Inorganic materials 0.000 description 23
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 22
- 239000012312 sodium hydride Substances 0.000 description 22
- 239000003921 oil Substances 0.000 description 19
- 239000000725 suspension Substances 0.000 description 19
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 16
- 125000000217 alkyl group Chemical group 0.000 description 15
- 238000010992 reflux Methods 0.000 description 15
- 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
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 13
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 13
- 239000000908 ammonium hydroxide Substances 0.000 description 13
- 238000009472 formulation Methods 0.000 description 13
- 239000003826 tablet Substances 0.000 description 13
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 11
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 11
- 229920002472 Starch Polymers 0.000 description 10
- 239000008107 starch Substances 0.000 description 10
- 235000019698 starch Nutrition 0.000 description 10
- 229960000583 acetic acid Drugs 0.000 description 9
- 239000002002 slurry Substances 0.000 description 9
- 238000004809 thin layer chromatography Methods 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
- 238000003556 assay Methods 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 235000019359 magnesium stearate Nutrition 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 150000003254 radicals Chemical class 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- RLQFPFJRWAPOQL-UHFFFAOYSA-N 4-chloro-6-ethyl-2-methylsulfanyl-7h-pyrrolo[2,3-d]pyrimidine Chemical compound N1=C(SC)NC2=NC(CC)=CC2=C1Cl RLQFPFJRWAPOQL-UHFFFAOYSA-N 0.000 description 5
- JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical class N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 description 5
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- IIJREXIVDSIOFR-UHFFFAOYSA-N dichloromethane;heptane Chemical compound ClCCl.CCCCCCC IIJREXIVDSIOFR-UHFFFAOYSA-N 0.000 description 5
- AMANDCZTVNQSNB-UHFFFAOYSA-N glyoxamide Chemical compound NC(=O)C=O AMANDCZTVNQSNB-UHFFFAOYSA-N 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- FDPLWOXXZQDXRQ-UHFFFAOYSA-N 4-chloro-6-ethyl-2-methylsulfanyl-7-[(2-phenylphenyl)methyl]pyrrolo[2,3-d]pyrimidine Chemical compound CCC1=CC2=C(Cl)N=C(SC)N=C2N1CC1=CC=CC=C1C1=CC=CC=C1 FDPLWOXXZQDXRQ-UHFFFAOYSA-N 0.000 description 4
- MGLOHGYZKNLKIX-UHFFFAOYSA-N 4-chloro-6-ethyl-7h-pyrrolo[2,3-d]pyrimidine Chemical compound N1=CNC2=NC(CC)=CC2=C1Cl MGLOHGYZKNLKIX-UHFFFAOYSA-N 0.000 description 4
- BNMISLNPEGIRLA-UHFFFAOYSA-N 6-amino-5-[(2-ethyl-1,3-dioxolan-2-yl)methyl]-2-methyl-1h-pyrimidin-4-one Chemical compound NC=1N=C(C)N=C(O)C=1CC1(CC)OCCO1 BNMISLNPEGIRLA-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 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
- 239000007864 aqueous solution Substances 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 4
- KLOMROGGKUPJKQ-UHFFFAOYSA-N ethyl 2-cyano-3-(2-ethyl-1,3-dioxolan-2-yl)propanoate Chemical compound CCOC(=O)C(C#N)CC1(CC)OCCO1 KLOMROGGKUPJKQ-UHFFFAOYSA-N 0.000 description 4
- DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 4
- UWGHGOTZHCZNOP-UHFFFAOYSA-N methyl 2-(7-benzyl-6-ethyl-2-methylsulfonyl-5-oxamoylpyrrolo[2,3-d]pyrimidin-4-yl)oxyacetate Chemical class CCC1=C(C(=O)C(N)=O)C2=C(OCC(=O)OC)N=C(S(C)(=O)=O)N=C2N1CC1=CC=CC=C1 UWGHGOTZHCZNOP-UHFFFAOYSA-N 0.000 description 4
- QBBYSNHHXRMCAW-UHFFFAOYSA-N methyl 2-(7-benzyl-6-ethylpyrrolo[2,3-d]pyrimidin-4-yl)oxyacetate Chemical compound CCC1=CC2=C(OCC(=O)OC)N=CN=C2N1CC1=CC=CC=C1 QBBYSNHHXRMCAW-UHFFFAOYSA-N 0.000 description 4
- FYCIHLAQTWFKNK-UHFFFAOYSA-N methyl 2-[6-ethyl-2-methylsulfanyl-5-oxamoyl-7-[[3-(trifluoromethyl)phenyl]methyl]pyrrolo[2,3-d]pyrimidin-4-yl]oxyacetate Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(=O)OC)N=C(SC)N=C2N1CC1=CC=CC(C(F)(F)F)=C1 FYCIHLAQTWFKNK-UHFFFAOYSA-N 0.000 description 4
- QEXRYLKDCIBNRD-UHFFFAOYSA-N methyl 2-[6-ethyl-2-methylsulfanyl-7-[(2-phenylphenyl)methyl]pyrrolo[2,3-d]pyrimidin-4-yl]oxyacetate Chemical compound CCC1=CC2=C(OCC(=O)OC)N=C(SC)N=C2N1CC1=CC=CC=C1C1=CC=CC=C1 QEXRYLKDCIBNRD-UHFFFAOYSA-N 0.000 description 4
- HUUBZFPZWHTCAB-UHFFFAOYSA-N methyl 2-[6-ethyl-2-methylsulfanyl-7-[[3-(trifluoromethyl)phenyl]methyl]pyrrolo[2,3-d]pyrimidin-4-yl]oxyacetate Chemical compound CCC1=CC2=C(OCC(=O)OC)N=C(SC)N=C2N1CC1=CC=CC(C(F)(F)F)=C1 HUUBZFPZWHTCAB-UHFFFAOYSA-N 0.000 description 4
- FWQBZADWNMUHMF-UHFFFAOYSA-N methyl 2-[7-[(3-chlorophenyl)methyl]-6-ethyl-2-methylsulfanylpyrrolo[2,3-d]pyrimidin-4-yl]oxyacetate Chemical compound CCC1=CC2=C(OCC(=O)OC)N=C(SC)N=C2N1CC1=CC=CC(Cl)=C1 FWQBZADWNMUHMF-UHFFFAOYSA-N 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 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
- 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
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
- CCXQVBSQUQCEEO-UHFFFAOYSA-N 1-bromobutan-2-one Chemical compound CCC(=O)CBr CCXQVBSQUQCEEO-UHFFFAOYSA-N 0.000 description 3
- GBZDXRUTTBTZMQ-UHFFFAOYSA-N 4-chloro-6-ethyl-2-methylsulfanyl-7-[[3-(trifluoromethyl)phenyl]methyl]pyrrolo[2,3-d]pyrimidine Chemical compound CCC1=CC2=C(Cl)N=C(SC)N=C2N1CC1=CC=CC(C(F)(F)F)=C1 GBZDXRUTTBTZMQ-UHFFFAOYSA-N 0.000 description 3
- YHDIZEIBZLFQRN-UHFFFAOYSA-N 4-chloro-6-ethyl-7-[(3-fluorophenyl)methyl]-2-methylsulfanylpyrrolo[2,3-d]pyrimidine Chemical compound CCC1=CC2=C(Cl)N=C(SC)N=C2N1CC1=CC=CC(F)=C1 YHDIZEIBZLFQRN-UHFFFAOYSA-N 0.000 description 3
- GIQJBODAWOWOEV-UHFFFAOYSA-N 4-chloro-7-[(3-chlorophenyl)methyl]-6-ethyl-2-methylsulfanylpyrrolo[2,3-d]pyrimidine Chemical compound CCC1=CC2=C(Cl)N=C(SC)N=C2N1CC1=CC=CC(Cl)=C1 GIQJBODAWOWOEV-UHFFFAOYSA-N 0.000 description 3
- IHIHAMGWZKGJAE-UHFFFAOYSA-N 6-amino-5-[(2-ethyl-1,3-dioxolan-2-yl)methyl]-2-methylsulfanyl-1h-pyrimidin-4-one Chemical compound NC=1N=C(SC)N=C(O)C=1CC1(CC)OCCO1 IHIHAMGWZKGJAE-UHFFFAOYSA-N 0.000 description 3
- REVOBEIKPMZITI-UHFFFAOYSA-N 6-amino-5-[(2-ethyl-1,3-dioxolan-2-yl)methyl]-2-sulfanylidene-1h-pyrimidin-4-one Chemical compound NC=1NC(=S)NC(=O)C=1CC1(CC)OCCO1 REVOBEIKPMZITI-UHFFFAOYSA-N 0.000 description 3
- UNNXDYKEIOTBHR-UHFFFAOYSA-N 6-ethyl-1,7-dihydropyrrolo[2,3-d]pyrimidin-4-one Chemical compound N1C=NC(=O)C2=C1NC(CC)=C2 UNNXDYKEIOTBHR-UHFFFAOYSA-N 0.000 description 3
- KXUDDNNSSBGXHS-UHFFFAOYSA-N 6-ethyl-2-methyl-1,7-dihydropyrrolo[2,3-d]pyrimidin-4-one Chemical compound N1C(C)=NC(=O)C2=C1NC(CC)=C2 KXUDDNNSSBGXHS-UHFFFAOYSA-N 0.000 description 3
- SREOBKUIHCOLBN-UHFFFAOYSA-N 7-benzyl-4-chloro-6-ethyl-2-methylpyrrolo[2,3-d]pyrimidine Chemical compound CCC1=CC2=C(Cl)N=C(C)N=C2N1CC1=CC=CC=C1 SREOBKUIHCOLBN-UHFFFAOYSA-N 0.000 description 3
- NTXFQLIHVJDNHY-UHFFFAOYSA-N 7-benzyl-4-chloro-6-ethyl-2-methylsulfanylpyrrolo[2,3-d]pyrimidine Chemical compound CCC1=CC2=C(Cl)N=C(SC)N=C2N1CC1=CC=CC=C1 NTXFQLIHVJDNHY-UHFFFAOYSA-N 0.000 description 3
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-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
- 239000000443 aerosol Substances 0.000 description 3
- 125000003342 alkenyl group Chemical group 0.000 description 3
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- BCUVAIQXNYBCMA-UHFFFAOYSA-N ethyl 2-cyano-4-oxohexanoate Chemical compound CCOC(=O)C(C#N)CC(=O)CC BCUVAIQXNYBCMA-UHFFFAOYSA-N 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- POBSAJHIMRRRPG-UHFFFAOYSA-N methyl 2-(7-benzyl-6-ethyl-2-methyl-5-oxamoylpyrrolo[2,3-d]pyrimidin-4-yl)oxyacetate Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(=O)OC)N=C(C)N=C2N1CC1=CC=CC=C1 POBSAJHIMRRRPG-UHFFFAOYSA-N 0.000 description 3
- LCVWGSYLRZNXSI-UHFFFAOYSA-N methyl 2-(7-benzyl-6-ethyl-2-methylpyrrolo[2,3-d]pyrimidin-4-yl)oxyacetate Chemical compound CCC1=CC2=C(OCC(=O)OC)N=C(C)N=C2N1CC1=CC=CC=C1 LCVWGSYLRZNXSI-UHFFFAOYSA-N 0.000 description 3
- CDUBCARTFWSPQS-UHFFFAOYSA-N methyl 2-(7-benzyl-6-ethyl-2-methylsulfanylpyrrolo[2,3-d]pyrimidin-4-yl)oxyacetate Chemical compound CCC1=CC2=C(OCC(=O)OC)N=C(SC)N=C2N1CC1=CC=CC=C1 CDUBCARTFWSPQS-UHFFFAOYSA-N 0.000 description 3
- UISCPYYXHAJPON-UHFFFAOYSA-N methyl 2-(7-benzyl-6-ethyl-5-oxamoylpyrrolo[2,3-d]pyrimidin-4-yl)oxyacetate Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(=O)OC)N=CN=C2N1CC1=CC=CC=C1 UISCPYYXHAJPON-UHFFFAOYSA-N 0.000 description 3
- CPTHFHBRTPXMRM-UHFFFAOYSA-N methyl 2-[6-ethyl-7-[(3-fluorophenyl)methyl]-2-methylsulfanylpyrrolo[2,3-d]pyrimidin-4-yl]oxyacetate Chemical compound CCC1=CC2=C(OCC(=O)OC)N=C(SC)N=C2N1CC1=CC=CC(F)=C1 CPTHFHBRTPXMRM-UHFFFAOYSA-N 0.000 description 3
- CHXKEHLHUMXNBR-UHFFFAOYSA-N methyl 2-[6-ethyl-7-[(3-fluorophenyl)methyl]pyrrolo[2,3-d]pyrimidin-4-yl]oxyacetate Chemical compound CCC1=CC2=C(OCC(=O)OC)N=CN=C2N1CC1=CC=CC(F)=C1 CHXKEHLHUMXNBR-UHFFFAOYSA-N 0.000 description 3
- RRDIEWAKRLQWMG-UHFFFAOYSA-N methyl 2-[6-ethyl-7-[[3-(trifluoromethyl)phenyl]methyl]pyrrolo[2,3-d]pyrimidin-4-yl]oxyacetate Chemical compound CCC1=CC2=C(OCC(=O)OC)N=CN=C2N1CC1=CC=CC(C(F)(F)F)=C1 RRDIEWAKRLQWMG-UHFFFAOYSA-N 0.000 description 3
- QTBFIWHZKCUTSO-UHFFFAOYSA-N methyl 2-[7-[(3-chlorophenyl)methyl]-6-ethylpyrrolo[2,3-d]pyrimidin-4-yl]oxyacetate Chemical compound CCC1=CC2=C(OCC(=O)OC)N=CN=C2N1CC1=CC=CC(Cl)=C1 QTBFIWHZKCUTSO-UHFFFAOYSA-N 0.000 description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 3
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 3
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 3
- 239000011535 reaction buffer Substances 0.000 description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 3
- WIHWTSLNPNPLRN-UHFFFAOYSA-N 2-(7-benzyl-6-ethyl-2-methyl-5-oxamoylpyrrolo[2,3-d]pyrimidin-4-yl)oxyacetic acid Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)N=C(C)N=C2N1CC1=CC=CC=C1 WIHWTSLNPNPLRN-UHFFFAOYSA-N 0.000 description 2
- MGBNYWSLEJOBNU-UHFFFAOYSA-N 2-(7-benzyl-6-ethyl-2-methylsulfanyl-5-oxamoylpyrrolo[2,3-d]pyrimidin-4-yl)oxyacetic acid Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)N=C(SC)N=C2N1CC1=CC=CC=C1 MGBNYWSLEJOBNU-UHFFFAOYSA-N 0.000 description 2
- VORJJXJVVBBNBR-UHFFFAOYSA-N 2-(7-benzyl-6-ethyl-5-oxamoylpyrrolo[2,3-d]pyrimidin-4-yl)oxyacetic acid Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(O)=O)N=CN=C2N1CC1=CC=CC=C1 VORJJXJVVBBNBR-UHFFFAOYSA-N 0.000 description 2
- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 2
- WPSZGBCZDALODF-UHFFFAOYSA-N 4-chloro-6-ethyl-2-methyl-7h-pyrrolo[2,3-d]pyrimidine Chemical compound N1=C(C)NC2=NC(CC)=CC2=C1Cl WPSZGBCZDALODF-UHFFFAOYSA-N 0.000 description 2
- QALVGBIRXIRGOL-UHFFFAOYSA-N 6-amino-5-[(2-ethyl-1,3-dioxolan-2-yl)methyl]-1h-pyrimidin-4-one Chemical compound NC=1N=CN=C(O)C=1CC1(CC)OCCO1 QALVGBIRXIRGOL-UHFFFAOYSA-N 0.000 description 2
- ITXBRIYDDOZUTD-UHFFFAOYSA-N 6-ethyl-2-methylsulfanyl-1,7-dihydropyrrolo[2,3-d]pyrimidin-4-one Chemical compound N1C(SC)=NC(=O)C2=C1NC(CC)=C2 ITXBRIYDDOZUTD-UHFFFAOYSA-N 0.000 description 2
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- 206010006448 Bronchiolitis Diseases 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 208000004575 Infectious Arthritis Diseases 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- 208000012659 Joint disease Diseases 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 2
- 206010039085 Rhinitis allergic Diseases 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- JFIRWDCBJXNJFI-SANMLTNESA-N [(2s)-2,3-bis(decanoylsulfanyl)propyl] 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCC(=O)SC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)SC(=O)CCCCCCCCC JFIRWDCBJXNJFI-SANMLTNESA-N 0.000 description 2
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 201000010105 allergic rhinitis Diseases 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- 206010006451 bronchitis Diseases 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 239000010779 crude oil Substances 0.000 description 2
- 230000002939 deleterious effect Effects 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 2
- 229940093476 ethylene glycol Drugs 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- HOOQFNAKLQAFPR-UHFFFAOYSA-N methyl 2-[6-ethyl-2-methylsulfanyl-5-oxamoyl-7-[(2-phenylphenyl)methyl]pyrrolo[2,3-d]pyrimidin-4-yl]oxyacetate Chemical compound CCC1=C(C(=O)C(N)=O)C2=C(OCC(=O)OC)N=C(SC)N=C2N1CC1=CC=CC=C1C1=CC=CC=C1 HOOQFNAKLQAFPR-UHFFFAOYSA-N 0.000 description 2
- CMYRKWYILVUVOJ-UHFFFAOYSA-N methyl 2-[6-ethyl-7-[(2-phenylphenyl)methyl]pyrrolo[2,3-d]pyrimidin-4-yl]oxyacetate Chemical compound CCC1=CC2=C(OCC(=O)OC)N=CN=C2N1CC1=CC=CC=C1C1=CC=CC=C1 CMYRKWYILVUVOJ-UHFFFAOYSA-N 0.000 description 2
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 125000000962 organic group Chemical group 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 208000002574 reactive arthritis Diseases 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 210000001179 synovial fluid Anatomy 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 description 1
- IGERFAHWSHDDHX-UHFFFAOYSA-N 1,3-dioxanyl Chemical group [CH]1OCCCO1 IGERFAHWSHDDHX-UHFFFAOYSA-N 0.000 description 1
- JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
- ILWJAOPQHOZXAN-UHFFFAOYSA-N 1,3-dithianyl Chemical group [CH]1SCCCS1 ILWJAOPQHOZXAN-UHFFFAOYSA-N 0.000 description 1
- 125000005940 1,4-dioxanyl group Chemical group 0.000 description 1
- HKDFRDIIELOLTJ-UHFFFAOYSA-N 1,4-dithianyl Chemical group [CH]1CSCCS1 HKDFRDIIELOLTJ-UHFFFAOYSA-N 0.000 description 1
- SEXZHJJUKFXNDY-UHFFFAOYSA-N 1-(bromomethyl)-2-phenylbenzene Chemical compound BrCC1=CC=CC=C1C1=CC=CC=C1 SEXZHJJUKFXNDY-UHFFFAOYSA-N 0.000 description 1
- MYYYZNVAUZVXBO-UHFFFAOYSA-N 1-(bromomethyl)-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(CBr)=C1 MYYYZNVAUZVXBO-UHFFFAOYSA-N 0.000 description 1
- LZIYAIRGDHSVED-UHFFFAOYSA-N 1-(bromomethyl)-3-chlorobenzene Chemical compound ClC1=CC=CC(CBr)=C1 LZIYAIRGDHSVED-UHFFFAOYSA-N 0.000 description 1
- SCBZBMXPJYMXRC-UHFFFAOYSA-N 1-(bromomethyl)-3-fluorobenzene Chemical compound FC1=CC=CC(CBr)=C1 SCBZBMXPJYMXRC-UHFFFAOYSA-N 0.000 description 1
- CQQUWTMMFMJEFE-UHFFFAOYSA-N 2-chloro-n,n-diethylacetamide Chemical compound CCN(CC)C(=O)CCl CQQUWTMMFMJEFE-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
- NBJHDLKSWUDGJG-UHFFFAOYSA-N 4-(2-chloroethyl)morpholin-4-ium;chloride Chemical compound Cl.ClCCN1CCOCC1 NBJHDLKSWUDGJG-UHFFFAOYSA-N 0.000 description 1
- KDOPAZIWBAHVJB-UHFFFAOYSA-N 5h-pyrrolo[3,2-d]pyrimidine Chemical compound C1=NC=C2NC=CC2=N1 KDOPAZIWBAHVJB-UHFFFAOYSA-N 0.000 description 1
- GUBSLMPLVZFMHF-UHFFFAOYSA-N 6-amino-5-[(2-methyl-1,3-dioxolan-2-yl)methyl]-2-sulfanylidene-1h-pyrimidin-4-one Chemical compound NC=1NC(=S)NC(=O)C=1CC1(C)OCCO1 GUBSLMPLVZFMHF-UHFFFAOYSA-N 0.000 description 1
- MEGQODXNAQDLEH-UHFFFAOYSA-N 7-benzyl-4-chloro-6-ethylpyrrolo[2,3-d]pyrimidine Chemical compound CCC1=CC2=C(Cl)N=CN=C2N1CC1=CC=CC=C1 MEGQODXNAQDLEH-UHFFFAOYSA-N 0.000 description 1
- OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010000599 Acromegaly Diseases 0.000 description 1
- 208000008190 Agammaglobulinemia Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 102000001381 Arachidonate 5-Lipoxygenase Human genes 0.000 description 1
- 108010093579 Arachidonate 5-lipoxygenase Proteins 0.000 description 1
- 206010003267 Arthritis reactive Diseases 0.000 description 1
- 206010003274 Arthritis viral Diseases 0.000 description 1
- 208000036487 Arthropathies Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- 206010006811 Bursitis Diseases 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
- 206010008690 Chondrocalcinosis pyrophosphate Diseases 0.000 description 1
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 201000011275 Epicondylitis Diseases 0.000 description 1
- 206010016207 Familial Mediterranean fever Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 102000019054 Group II Phospholipases A2 Human genes 0.000 description 1
- 108010026929 Group II Phospholipases A2 Proteins 0.000 description 1
- 208000018565 Hemochromatosis Diseases 0.000 description 1
- 201000004331 Henoch-Schoenlein purpura Diseases 0.000 description 1
- 206010019617 Henoch-Schonlein purpura Diseases 0.000 description 1
- 201000002980 Hyperparathyroidism Diseases 0.000 description 1
- 206010020877 Hypertrophic osteoarthropathy Diseases 0.000 description 1
- 206010020983 Hypogammaglobulinaemia Diseases 0.000 description 1
- 208000031814 IgA Vasculitis Diseases 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 208000034624 Leukocytoclastic Cutaneous Vasculitis Diseases 0.000 description 1
- 208000032514 Leukocytoclastic vasculitis Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 208000016604 Lyme disease Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- FIWILGQIZHDAQG-UHFFFAOYSA-N NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F Chemical compound NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F FIWILGQIZHDAQG-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 206010065159 Polychondritis Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 208000033464 Reiter syndrome Diseases 0.000 description 1
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 1
- 201000002661 Spondylitis Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 229920002253 Tannate Polymers 0.000 description 1
- 208000002240 Tennis Elbow Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- LFFIJRJGKBSELO-FQEVSTJZSA-N [(2s)-2,3-bis(heptanoylsulfanyl)propyl] 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCC(=O)SC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)SC(=O)CCCCCC LFFIJRJGKBSELO-FQEVSTJZSA-N 0.000 description 1
- ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 208000021240 acute bronchiolitis Diseases 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 125000003302 alkenyloxy group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
- 125000005133 alkynyloxy group Chemical group 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 206010003230 arteritis Diseases 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000005418 aryl aryl group Chemical group 0.000 description 1
- 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 1
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 208000003295 carpal tunnel syndrome Diseases 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 208000002849 chondrocalcinosis Diseases 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229940090805 clavulanate Drugs 0.000 description 1
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 125000005509 dibenzothiophenyl group Chemical group 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- SPCNPOWOBZQWJK-UHFFFAOYSA-N dimethoxy-(2-propan-2-ylsulfanylethylsulfanyl)-sulfanylidene-$l^{5}-phosphane Chemical compound COP(=S)(OC)SCCSC(C)C SPCNPOWOBZQWJK-UHFFFAOYSA-N 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 229940009662 edetate Drugs 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 229950000206 estolate Drugs 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- WCQOBLXWLRDEQA-UHFFFAOYSA-N ethanimidamide;hydrochloride Chemical compound Cl.CC(N)=N WCQOBLXWLRDEQA-UHFFFAOYSA-N 0.000 description 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 229940091249 fluoride supplement Drugs 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 229940050411 fumarate Drugs 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
- 229960001731 gluceptate Drugs 0.000 description 1
- KWMLJOLKUYYJFJ-VFUOTHLCSA-N glucoheptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(O)=O KWMLJOLKUYYJFJ-VFUOTHLCSA-N 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 229940049906 glutamate Drugs 0.000 description 1
- 125000004438 haloalkoxy group Chemical group 0.000 description 1
- 125000004441 haloalkylsulfonyl group Chemical group 0.000 description 1
- 208000002085 hemarthrosis Diseases 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 201000006362 hypersensitivity vasculitis Diseases 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 208000015446 immunoglobulin a vasculitis Diseases 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 201000004990 juvenile ankylosing spondylitis Diseases 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 239000011344 liquid material Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000009973 maize Nutrition 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- ISABMMMDMMFPSD-UHFFFAOYSA-N methyl 2-[6-ethyl-2-methylsulfanyl-7-[[2-(trifluoromethyl)phenyl]methyl]pyrrolo[2,3-d]pyrimidin-4-yl]oxyacetate Chemical compound CCC1=CC2=C(OCC(=O)OC)N=C(SC)N=C2N1CC1=CC=CC=C1C(F)(F)F ISABMMMDMMFPSD-UHFFFAOYSA-N 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical compound CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 125000006203 morpholinoethyl group Chemical group [H]C([H])(*)C([H])([H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 description 1
- 201000011201 multicentric reticulohistiocytosis Diseases 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 229940014662 pantothenate Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 150000008318 pyrimidones Chemical class 0.000 description 1
- 150000004944 pyrrolopyrimidines Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 208000009169 relapsing polychondritis Diseases 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000012056 semi-solid material Substances 0.000 description 1
- 201000001223 septic arthritis Diseases 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000000526 short-path distillation Methods 0.000 description 1
- 208000007056 sickle cell anemia Diseases 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 125000004354 sulfur functional group Chemical group 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl 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
- 125000004149 thio group Chemical group *S* 0.000 description 1
- 150000003555 thioacetals Chemical class 0.000 description 1
- YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- SFBUZLPJTDBGAC-UHFFFAOYSA-N thiopyran-2-imine Chemical compound N=C1C=CC=CS1 SFBUZLPJTDBGAC-UHFFFAOYSA-N 0.000 description 1
- 150000003585 thioureas Chemical class 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 230000003156 vasculitic effect Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Biochemistry (AREA)
- Pulmonology (AREA)
- Endocrinology (AREA)
- Pain & Pain Management (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US9124898P | 1998-06-30 | 1998-06-30 | |
| US60/091,248 | 1998-06-30 | ||
| PCT/US1999/014213 WO2000000201A1 (en) | 1998-06-30 | 1999-06-23 | BICYCLIC sPLA2 INHIBITORS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2335448A1 true CA2335448A1 (en) | 2000-01-06 |
Family
ID=22226793
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002335448A Abandoned CA2335448A1 (en) | 1998-06-30 | 1999-06-23 | Bicyclic spla2 inhibitors |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US6384041B1 (enExample) |
| EP (1) | EP1091738B1 (enExample) |
| JP (1) | JP2002519325A (enExample) |
| AT (1) | ATE347362T1 (enExample) |
| AU (1) | AU4710699A (enExample) |
| CA (1) | CA2335448A1 (enExample) |
| DE (1) | DE69934311D1 (enExample) |
| WO (1) | WO2000000201A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107915738A (zh) * | 2017-11-14 | 2018-04-17 | 厦门海乐景生化有限公司 | 用于合成巴瑞替尼的关键中间体2的制备方法 |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2001267823A1 (en) * | 2000-06-29 | 2002-01-08 | Shionogi And Co., Ltd. | Compounds exhibiting x-type spla2 inhibiting effect |
| AU2001280461A1 (en) * | 2000-08-04 | 2002-02-18 | Eli Lilly And Company | Substituted pyrrole compounds and their use as spla2 inhibitors |
| US6730694B1 (en) | 2001-07-20 | 2004-05-04 | Eli Lilly And Company | sPLA2 inhibitors |
| GB0121033D0 (en) * | 2001-08-30 | 2001-10-24 | Novartis Ag | Organic compounds |
| AUPS282602A0 (en) | 2002-06-07 | 2002-06-27 | Garvan Institute Of Medical Research | Method of inhibiting cell proliferation |
| AR043692A1 (es) * | 2003-02-06 | 2005-08-10 | Novartis Ag | 2-cianopirrolopirimidinas y sus usos farmaceuticos |
| GB0302748D0 (en) * | 2003-02-06 | 2003-03-12 | Novartis Ag | Organic compounds |
| US20050124623A1 (en) | 2003-11-26 | 2005-06-09 | Bender John A. | Diazaindole-dicarbonyl-piperazinyl antiviral agents |
| US20060100432A1 (en) | 2004-11-09 | 2006-05-11 | Matiskella John D | Crystalline materials of 1-(4-benzoyl-piperazin-1-yl)-2-[4-methoxy-7-(3-methyl-[1,2,4]triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-ethane-1,2-dione |
| US7851476B2 (en) | 2005-12-14 | 2010-12-14 | Bristol-Myers Squibb Company | Crystalline forms of 1-benzoyl-4-[2-[4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-YL)-1-[(phosphonooxy)methyl]-1H-pyrrolo[2,3-C]pyridin-3-YL]-1,2-dioxoethyl]-piperazine |
| US7807671B2 (en) | 2006-04-25 | 2010-10-05 | Bristol-Myers Squibb Company | Diketo-piperazine and piperidine derivatives as antiviral agents |
| NZ595789A (en) | 2009-04-29 | 2014-05-30 | Amarin Pharmaceuticals Ie Ltd | Pharmaceutical compositions comprising epa and a cardiovascular agent and methods of using the same |
| EP2890980B1 (en) | 2012-08-30 | 2018-12-19 | Qiagen GmbH | A method for obtaining blood plasma from a whole blood sample |
| DE102012215957A1 (de) | 2012-09-10 | 2014-05-15 | Schaeffler Technologies Gmbh & Co. Kg | Resolverlager |
| DE102012023252B4 (de) | 2012-11-29 | 2016-11-10 | Selux Ag | Leuchte mit Elektroladestation für Elektrofahrzeuge |
| DE102013101611B3 (de) | 2013-02-19 | 2014-07-10 | HvS-Consulting AG | Verschlüsselungsverfahren für e-mails |
| DE102013022275A1 (de) | 2013-03-28 | 2014-10-02 | Elmos Semiconductor Ag | Straßenbeleuchtung |
| CN103204857A (zh) * | 2013-05-08 | 2013-07-17 | 兰州聚成生物科技有限公司 | 一种4-氯-2-(甲硫基)-7h-吡咯并[2,3-d]嘧啶的合成方法 |
| DE102013215468A1 (de) | 2013-08-06 | 2015-02-12 | Schaeffler Technologies Gmbh & Co. Kg | Tauchlageranordnung und Verfahren zur Abdichtung derselben |
| EP2902692B1 (de) | 2013-12-06 | 2017-10-25 | MAGNA STEYR Engineering AG & Co KG | Bauteil eines Tanksystems |
| WO2015158361A1 (en) | 2014-04-14 | 2015-10-22 | Shanghai Amphenol Airwave Communication Electronics Co., Ltd. | Windshield antenna |
| EP3396430B1 (en) | 2017-04-27 | 2023-08-16 | Euroimmun Medizinische Labordiagnostika AG | Optical scanning arrangement and method |
| WO2019050890A1 (en) * | 2017-09-05 | 2019-03-14 | President And Fellows Of Harvard College | METHODS AND COMPOSITIONS FOR THE TREATMENT OF TUBERCULOSIS |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3867386A (en) | 1969-11-04 | 1975-02-18 | American Home Prod | 5-amino-2,6-substituted-7h-pyrrolo(2,3-d)pyrimidines and related compounds |
| US5916922A (en) | 1996-12-03 | 1999-06-29 | Eli Lilly And Company | Phenyl glyoxamides as SPLA2 inhibitors |
-
1999
- 1999-06-23 EP EP99930602A patent/EP1091738B1/en not_active Expired - Lifetime
- 1999-06-23 DE DE69934311T patent/DE69934311D1/de not_active Expired - Lifetime
- 1999-06-23 CA CA002335448A patent/CA2335448A1/en not_active Abandoned
- 1999-06-23 JP JP2000556786A patent/JP2002519325A/ja not_active Withdrawn
- 1999-06-23 WO PCT/US1999/014213 patent/WO2000000201A1/en not_active Ceased
- 1999-06-23 AT AT99930602T patent/ATE347362T1/de not_active IP Right Cessation
- 1999-06-23 US US09/719,318 patent/US6384041B1/en not_active Expired - Fee Related
- 1999-06-23 AU AU47106/99A patent/AU4710699A/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107915738A (zh) * | 2017-11-14 | 2018-04-17 | 厦门海乐景生化有限公司 | 用于合成巴瑞替尼的关键中间体2的制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| ATE347362T1 (de) | 2006-12-15 |
| EP1091738B1 (en) | 2006-12-06 |
| AU4710699A (en) | 2000-01-17 |
| WO2000000201A1 (en) | 2000-01-06 |
| EP1091738A4 (en) | 2003-03-05 |
| US6384041B1 (en) | 2002-05-07 |
| EP1091738A1 (en) | 2001-04-18 |
| JP2002519325A (ja) | 2002-07-02 |
| DE69934311D1 (de) | 2007-01-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6384041B1 (en) | Bicyclic sPLA2 inhibitors | |
| US6787545B1 (en) | Pyrrolotriazine derivatives having spla2-inhibitory activities | |
| US6608099B1 (en) | Indole sPLA2 inhibitors | |
| US20040077704A1 (en) | Novel spla2 inhibitors | |
| US6451839B1 (en) | Indole sPLA2 inhibitors | |
| EP1156050B1 (en) | Substituted tricyclics useful in sPLA2 induced diseases | |
| WO2003014082A1 (en) | Cyclopenta ` b ! indole derivatives as spla2 inhibitors | |
| US6831095B1 (en) | Hydroxyfunctional amide 1h-indole derivatives active as sPLA2 inhibitors | |
| US20040198801A1 (en) | Cyclohept'b!indole derivatives as spla2 inhibitors | |
| US6730694B1 (en) | sPLA2 inhibitors | |
| US6391908B1 (en) | Oxime amide indole type sPLA2 inhibitors | |
| EP1140943B1 (en) | Substituted pyrroloindoles | |
| US20040087796A1 (en) | Substituted carbazoles as inhibitors of spla2 | |
| WO2002012249A2 (en) | Substituted pyrrole compounds and their use as spla2 inhibitors | |
| EP1220839B1 (en) | Hydroxyfunctional amide 1h-indole derivatives active as spla2 inhibitors | |
| US6930123B2 (en) | sPLA2 inhibitors | |
| US20040063967A1 (en) | Novel spla2 inhibitors | |
| HK1025091A (en) | Substituted tricyclics useful in spla2 induced diseases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |