CA2480452C - Thioxanthine derivatives as myeloperoxidase inhibitors - Google Patents
Thioxanthine derivatives as myeloperoxidase inhibitors Download PDFInfo
- Publication number
- CA2480452C CA2480452C CA2480452A CA2480452A CA2480452C CA 2480452 C CA2480452 C CA 2480452C CA 2480452 A CA2480452 A CA 2480452A CA 2480452 A CA2480452 A CA 2480452A CA 2480452 C CA2480452 C CA 2480452C
- Authority
- CA
- Canada
- Prior art keywords
- thioxanthine
- mmol
- compound
- methyl
- thioxo
- 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.)
- Expired - Fee Related
Links
- PQJUJGAVDBINPI-UHFFFAOYSA-N 9H-thioxanthene Chemical class C1=CC=C2CC3=CC=CC=C3SC2=C1 PQJUJGAVDBINPI-UHFFFAOYSA-N 0.000 title description 5
- 229940122159 Myeloperoxidase inhibitor Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 117
- 150000003839 salts Chemical class 0.000 claims abstract description 34
- 238000011282 treatment Methods 0.000 claims abstract description 24
- 239000003814 drug Substances 0.000 claims abstract description 12
- 238000004519 manufacturing process Methods 0.000 claims abstract description 10
- 208000036110 Neuroinflammatory disease Diseases 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 40
- 125000003545 alkoxy group Chemical group 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- RSPDBEVKURKEII-UHFFFAOYSA-N 3-(oxolan-2-ylmethyl)-2-sulfanylidene-7h-purin-6-one Chemical compound C1=2N=CNC=2C(=O)NC(=S)N1CC1CCCO1 RSPDBEVKURKEII-UHFFFAOYSA-N 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 239000002671 adjuvant Substances 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- QTXZVSXYBGMMAU-UHFFFAOYSA-N 3-(cyclohexylmethyl)-2-sulfanylidene-7h-purin-6-one Chemical compound C1=2N=CNC=2C(=O)NC(=S)N1CC1CCCCC1 QTXZVSXYBGMMAU-UHFFFAOYSA-N 0.000 claims description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
- 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 4
- 125000002757 morpholinyl group Chemical group 0.000 claims description 4
- KULKOCNEGWFYNO-UHFFFAOYSA-N 3-(cyclopropylmethyl)-2-sulfanylidene-7h-purin-6-one Chemical compound C1=2N=CNC=2C(=O)NC(=S)N1CC1CC1 KULKOCNEGWFYNO-UHFFFAOYSA-N 0.000 claims description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims description 3
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 3
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 3
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 claims description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 2
- 102000003896 Myeloperoxidases Human genes 0.000 abstract description 31
- 108090000235 Myeloperoxidases Proteins 0.000 abstract description 31
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 18
- 238000000034 method Methods 0.000 abstract description 17
- 201000010099 disease Diseases 0.000 abstract description 15
- 238000011321 prophylaxis Methods 0.000 abstract description 10
- 230000005764 inhibitory process Effects 0.000 abstract description 7
- 230000009286 beneficial effect Effects 0.000 abstract description 6
- 238000002360 preparation method Methods 0.000 abstract description 6
- 239000003112 inhibitor Substances 0.000 abstract description 5
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 136
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 81
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 69
- 239000007787 solid Substances 0.000 description 55
- 239000000243 solution Substances 0.000 description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 36
- 239000011541 reaction mixture Substances 0.000 description 34
- 238000005481 NMR spectroscopy Methods 0.000 description 32
- 239000000047 product Substances 0.000 description 28
- 239000000203 mixture Substances 0.000 description 26
- 238000001914 filtration Methods 0.000 description 24
- 239000002904 solvent Substances 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- 238000007429 general method Methods 0.000 description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 19
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 18
- 235000019253 formic acid Nutrition 0.000 description 18
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 18
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 17
- 238000005160 1H NMR spectroscopy Methods 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- 239000002244 precipitate Substances 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 238000000746 purification Methods 0.000 description 14
- 229910052717 sulfur Inorganic materials 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 235000010288 sodium nitrite Nutrition 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 239000013078 crystal Substances 0.000 description 7
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 7
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 230000035484 reaction time Effects 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 150000004985 diamines Chemical class 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 125000005842 heteroatom Chemical group 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- -1 aromatic amino acids Chemical class 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 210000000224 granular leucocyte Anatomy 0.000 description 5
- 238000006386 neutralization reaction Methods 0.000 description 5
- SWTXSGKQNZRCQK-UHFFFAOYSA-N 1-methyl-3-(2-methylpropyl)-2-sulfanylidene-7h-purin-6-one Chemical compound O=C1N(C)C(=S)N(CC(C)C)C2=C1NC=N2 SWTXSGKQNZRCQK-UHFFFAOYSA-N 0.000 description 4
- QYMIGFAAZFXYSQ-UHFFFAOYSA-N 3-(2-phenylethyl)-2-sulfanylidene-7h-purin-6-one Chemical compound C1=2N=CNC=2C(=O)NC(=S)N1CCC1=CC=CC=C1 QYMIGFAAZFXYSQ-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 4
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 4
- SGKJJXCTYVZODW-UHFFFAOYSA-N 1,8-dimethyl-3-(2-methylpropyl)-6-sulfanylidene-7h-purin-2-one Chemical compound S=C1N(C)C(=O)N(CC(C)C)C2=C1NC(C)=N2 SGKJJXCTYVZODW-UHFFFAOYSA-N 0.000 description 3
- VXTADZREIUKIHH-UHFFFAOYSA-N 3-(2-methoxyethyl)-2-sulfanylidene-7h-purin-6-one Chemical compound O=C1NC(=S)N(CCOC)C2=C1NC=N2 VXTADZREIUKIHH-UHFFFAOYSA-N 0.000 description 3
- YWXBNZQTOMKSGH-UHFFFAOYSA-N 3-(2-methylbutyl)-6-sulfanylidene-7h-purin-2-one Chemical compound S=C1NC(=O)N(CC(C)CC)C2=C1NC=N2 YWXBNZQTOMKSGH-UHFFFAOYSA-N 0.000 description 3
- BYEFLNKUKSUKMO-UHFFFAOYSA-N 3-(3-methoxypropyl)-2-sulfanylidene-7h-purin-6-one Chemical compound O=C1NC(=S)N(CCCOC)C2=C1NC=N2 BYEFLNKUKSUKMO-UHFFFAOYSA-N 0.000 description 3
- HZXVQEUOCFTRDT-UHFFFAOYSA-N 3-[(4-methoxyphenyl)methyl]-2-sulfanylidene-7h-purin-6-one Chemical compound C1=CC(OC)=CC=C1CN1C(=S)NC(=O)C2=C1N=CN2 HZXVQEUOCFTRDT-UHFFFAOYSA-N 0.000 description 3
- PMCJHNWKVBFKTN-UHFFFAOYSA-N 3-butyl-2-sulfanylidene-7h-purin-6-one Chemical compound O=C1NC(=S)N(CCCC)C2=C1NC=N2 PMCJHNWKVBFKTN-UHFFFAOYSA-N 0.000 description 3
- WLSCEYDWCKJQSG-UHFFFAOYSA-N 8-methyl-3-(2-methylpropyl)-2-sulfanylidene-7h-purin-6-one Chemical compound O=C1NC(=S)N(CC(C)C)C2=C1NC(C)=N2 WLSCEYDWCKJQSG-UHFFFAOYSA-N 0.000 description 3
- IXHYELJKKHRULV-UHFFFAOYSA-N 8-methyl-3-(2-methylpropyl)-6-sulfanylidene-7h-purin-2-one Chemical compound S=C1NC(=O)N(CC(C)C)C2=C1NC(C)=N2 IXHYELJKKHRULV-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 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 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 239000012131 assay buffer Substances 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- 125000002541 furyl group Chemical group 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 210000000680 phagosome Anatomy 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 125000001544 thienyl group Chemical group 0.000 description 3
- 239000003643 water by type Substances 0.000 description 3
- NDQXKKFRNOPRDW-UHFFFAOYSA-N 1,1,1-triethoxyethane Chemical compound CCOC(C)(OCC)OCC NDQXKKFRNOPRDW-UHFFFAOYSA-N 0.000 description 2
- BZKMVNIULPWSQZ-UHFFFAOYSA-N 1,3-dibutyl-8-methyl-6-sulfanylidene-7h-purin-2-one Chemical compound S=C1N(CCCC)C(=O)N(CCCC)C2=C1NC(C)=N2 BZKMVNIULPWSQZ-UHFFFAOYSA-N 0.000 description 2
- NSDDRJXKROCWRZ-UHFFFAOYSA-N 1-isothiocyanato-2-methylpropane Chemical compound CC(C)CN=C=S NSDDRJXKROCWRZ-UHFFFAOYSA-N 0.000 description 2
- XNHFAGRBSMMFKL-UHFFFAOYSA-N 2-sulfanylidene-3,7-dihydropurin-6-one Chemical compound O=C1NC(=S)NC2=C1NC=N2 XNHFAGRBSMMFKL-UHFFFAOYSA-N 0.000 description 2
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 2
- HWSAZERBFFRQGX-UHFFFAOYSA-N 3-(2-methylpropyl)-2-sulfanylidene-7h-purin-6-one Chemical compound O=C1NC(=S)N(CC(C)C)C2=C1NC=N2 HWSAZERBFFRQGX-UHFFFAOYSA-N 0.000 description 2
- PJTMMMDNGKWSPK-UHFFFAOYSA-N 3-(2-methylpropyl)-6-sulfanylidene-7h-purin-2-one Chemical compound S=C1NC(=O)N(CC(C)C)C2=C1NC=N2 PJTMMMDNGKWSPK-UHFFFAOYSA-N 0.000 description 2
- KDGNPNTWFNHLSX-UHFFFAOYSA-N 3-(2-methylpropyl)-7h-purine-2,6-dithione Chemical compound S=C1NC(=S)N(CC(C)C)C2=C1NC=N2 KDGNPNTWFNHLSX-UHFFFAOYSA-N 0.000 description 2
- XGZKFMGVJXEFAS-UHFFFAOYSA-N 3-(furan-2-ylmethyl)-2-sulfanylidene-7h-purin-6-one Chemical compound C1=2N=CNC=2C(=O)NC(=S)N1CC1=CC=CO1 XGZKFMGVJXEFAS-UHFFFAOYSA-N 0.000 description 2
- GMNQNGTVFNOHLD-UHFFFAOYSA-N 3-[(4-fluorophenyl)methyl]-2-sulfanylidene-7h-purin-6-one Chemical compound C1=CC(F)=CC=C1CN1C(=S)NC(=O)C2=C1N=CN2 GMNQNGTVFNOHLD-UHFFFAOYSA-N 0.000 description 2
- VKDUMIUFSCZHIE-UHFFFAOYSA-N 3-propyl-2-sulfanylidene-7h-purin-6-one Chemical compound O=C1NC(=S)N(CCC)C2=C1NC=N2 VKDUMIUFSCZHIE-UHFFFAOYSA-N 0.000 description 2
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 2
- NVUOISMYEXJTLN-UHFFFAOYSA-N 5,6-diamino-1-[(4-fluorophenyl)methyl]-2-sulfanylidenepyrimidin-4-one Chemical compound NC1=C(N)C(=O)NC(=S)N1CC1=CC=C(F)C=C1 NVUOISMYEXJTLN-UHFFFAOYSA-N 0.000 description 2
- QNHGIMKLMXYDRR-UHFFFAOYSA-N 6-amino-1-(cyclohexylmethyl)-2-sulfanylidenepyrimidin-4-one Chemical compound NC1=CC(=O)NC(=S)N1CC1CCCCC1 QNHGIMKLMXYDRR-UHFFFAOYSA-N 0.000 description 2
- NNTDSLSGJNLIBT-UHFFFAOYSA-N 6-amino-1-(cyclopropylmethyl)-2-sulfanylidenepyrimidin-4-one Chemical compound NC1=CC(=O)NC(=S)N1CC1CC1 NNTDSLSGJNLIBT-UHFFFAOYSA-N 0.000 description 2
- BCFFDFRKPXYIEA-UHFFFAOYSA-N 6-amino-1-(furan-2-ylmethyl)-2-sulfanylidenepyrimidin-4-one Chemical compound NC1=CC(=O)NC(=S)N1CC1=CC=CO1 BCFFDFRKPXYIEA-UHFFFAOYSA-N 0.000 description 2
- GKBJWLMSFGUGFH-UHFFFAOYSA-N 6-amino-1-(furan-2-ylmethyl)-5-nitroso-2-sulfanylidenepyrimidin-4-one Chemical compound NC1=C(N=O)C(=O)NC(=S)N1CC1=CC=CO1 GKBJWLMSFGUGFH-UHFFFAOYSA-N 0.000 description 2
- MOFDFCKZIKYFPL-UHFFFAOYSA-N 6-amino-1-[(4-fluorophenyl)methyl]-2-sulfanylidenepyrimidin-4-one Chemical compound NC1=CC(=O)NC(=S)N1CC1=CC=C(F)C=C1 MOFDFCKZIKYFPL-UHFFFAOYSA-N 0.000 description 2
- HXGPQRKBKJHVID-UHFFFAOYSA-N 6-amino-1-[(4-fluorophenyl)methyl]-5-nitroso-2-sulfanylidenepyrimidin-4-one Chemical compound NC1=C(N=O)C(=O)NC(=S)N1CC1=CC=C(F)C=C1 HXGPQRKBKJHVID-UHFFFAOYSA-N 0.000 description 2
- DNSSALHMKAOQTH-UHFFFAOYSA-N 6-amino-1-[(4-methoxyphenyl)methyl]-5-nitroso-2-sulfanylidenepyrimidin-4-one Chemical compound C1=CC(OC)=CC=C1CN1C(=S)NC(=O)C(N=O)=C1N DNSSALHMKAOQTH-UHFFFAOYSA-N 0.000 description 2
- HLNCAJLLNMQPQT-UHFFFAOYSA-N 6-amino-3-methyl-1-(2-methylpropyl)-5-nitroso-2-sulfanylidenepyrimidin-4-one Chemical compound CC(C)CN1C(N)=C(N=O)C(=O)N(C)C1=S HLNCAJLLNMQPQT-UHFFFAOYSA-N 0.000 description 2
- NKEZZQHUMGOMGY-UHFFFAOYSA-N 8-methyl-1,3-bis(2-methylpropyl)-6-sulfanylidene-7h-purin-2-one Chemical compound S=C1N(CC(C)C)C(=O)N(CC(C)C)C2=C1NC(C)=N2 NKEZZQHUMGOMGY-UHFFFAOYSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 201000003883 Cystic fibrosis Diseases 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- 102100038609 Lactoperoxidase Human genes 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 239000008351 acetate buffer Substances 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 229910000085 borane Inorganic materials 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
- 230000001434 glomerular Effects 0.000 description 2
- 150000003278 haem Chemical class 0.000 description 2
- 125000001841 imino group Chemical group [H]N=* 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 150000002905 orthoesters Chemical class 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 230000003595 spectral effect Effects 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- UZJXXZZIIAZHAL-UHFFFAOYSA-N (4-fluorophenyl)methylthiourea Chemical compound NC(=S)NCC1=CC=C(F)C=C1 UZJXXZZIIAZHAL-UHFFFAOYSA-N 0.000 description 1
- KCPZCBGTVXMSPQ-UHFFFAOYSA-N (4-methoxyphenyl)methylthiourea Chemical compound COC1=CC=C(CNC(N)=S)C=C1 KCPZCBGTVXMSPQ-UHFFFAOYSA-N 0.000 description 1
- FGWYWKIOMUZSQF-UHFFFAOYSA-N 1,1,1-triethoxypropane Chemical compound CCOC(CC)(OCC)OCC FGWYWKIOMUZSQF-UHFFFAOYSA-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
- JTRRTBLKLLLCJO-UHFFFAOYSA-N 1,3-dibutyl-8-methyl-7H-purine-2,6-dione 1,3-dibutyl-8-methyl-6-sulfanylidene-7H-purin-2-one Chemical compound C(CCC)N1C(=O)N(C=2N=C(NC2C1=O)C)CCCC.C(CCC)N1C(=O)N(C=2N=C(NC2C1=S)C)CCCC JTRRTBLKLLLCJO-UHFFFAOYSA-N 0.000 description 1
- SGJBIFUEFLWXJY-UHFFFAOYSA-N 1-(dibutoxymethoxy)butane Chemical compound CCCCOC(OCCCC)OCCCC SGJBIFUEFLWXJY-UHFFFAOYSA-N 0.000 description 1
- RWNXXQFJBALKAX-UHFFFAOYSA-N 1-(dipropoxymethoxy)propane Chemical compound CCCOC(OCCC)OCCC RWNXXQFJBALKAX-UHFFFAOYSA-N 0.000 description 1
- IDLVQYYJEKHMSE-UHFFFAOYSA-N 1-(furan-2-yl)-1-methylthiourea Chemical compound NC(=S)N(C)C1=CC=CO1 IDLVQYYJEKHMSE-UHFFFAOYSA-N 0.000 description 1
- CXBDYQVECUFKRK-UHFFFAOYSA-N 1-methoxybutane Chemical compound CCCCOC CXBDYQVECUFKRK-UHFFFAOYSA-N 0.000 description 1
- KQBNKAIIHJFCFB-UHFFFAOYSA-N 1-methyl-1-(oxolan-2-yl)thiourea Chemical compound NC(=S)N(C)C1CCCO1 KQBNKAIIHJFCFB-UHFFFAOYSA-N 0.000 description 1
- VYXKZXCLFLKQPF-UHFFFAOYSA-N 1-methyl-3-(2-methylpropyl)thiourea Chemical compound CNC(=S)NCC(C)C VYXKZXCLFLKQPF-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- FPIVAWNGRDHRSQ-UHFFFAOYSA-N 2-[di(propan-2-yloxy)methoxy]propane Chemical compound CC(C)OC(OC(C)C)OC(C)C FPIVAWNGRDHRSQ-UHFFFAOYSA-N 0.000 description 1
- XLJXJKHWLMYXBE-UHFFFAOYSA-N 2-methoxyethylthiourea Chemical compound COCCNC(N)=S XLJXJKHWLMYXBE-UHFFFAOYSA-N 0.000 description 1
- OFVGPHQYOCKLLM-UHFFFAOYSA-N 2-phenylethylthiourea Chemical compound NC(=S)NCCC1=CC=CC=C1 OFVGPHQYOCKLLM-UHFFFAOYSA-N 0.000 description 1
- FDWYDCXQLVOMPE-UHFFFAOYSA-N 3-methoxypropylthiourea Chemical compound COCCCNC(N)=S FDWYDCXQLVOMPE-UHFFFAOYSA-N 0.000 description 1
- WYRHXGZNMSZCJX-UHFFFAOYSA-N 5,6-diamino-1-(2-methoxyethyl)-2-sulfanylidenepyrimidin-4-one Chemical compound COCCN1C(N)=C(N)C(=O)NC1=S WYRHXGZNMSZCJX-UHFFFAOYSA-N 0.000 description 1
- YUMMJRDPNNJVEX-UHFFFAOYSA-N 5,6-diamino-1-(2-methylpropyl)-2-sulfanylidenepyrimidin-4-one Chemical compound CC(C)CN1C(N)=C(N)C(=O)NC1=S YUMMJRDPNNJVEX-UHFFFAOYSA-N 0.000 description 1
- PRDFCVJMYONNEA-UHFFFAOYSA-N 5,6-diamino-1-(cyclohexylmethyl)-2-sulfanylidenepyrimidin-4-one Chemical compound NC1=C(N)C(=O)NC(=S)N1CC1CCCCC1 PRDFCVJMYONNEA-UHFFFAOYSA-N 0.000 description 1
- GLXRHWDWLPRNMQ-UHFFFAOYSA-N 5,6-diamino-1-(furan-2-ylmethyl)-2-sulfanylidenepyrimidin-4-one Chemical compound NC1=C(N)C(=O)NC(=S)N1CC1=CC=CO1 GLXRHWDWLPRNMQ-UHFFFAOYSA-N 0.000 description 1
- FQUKTEMFZKKAEZ-UHFFFAOYSA-N 5,6-diamino-1-[(4-methoxyphenyl)methyl]-2-sulfanylidenepyrimidin-4-one Chemical compound C1=CC(OC)=CC=C1CN1C(=S)NC(=O)C(N)=C1N FQUKTEMFZKKAEZ-UHFFFAOYSA-N 0.000 description 1
- JJGAMWNEQHQICU-UHFFFAOYSA-N 6-amino-1-(1-phenylethyl)-2-sulfanylidenepyrimidin-4-one Chemical compound NC1=CC(=O)NC(=S)N1C(C)C1=CC=CC=C1 JJGAMWNEQHQICU-UHFFFAOYSA-N 0.000 description 1
- VOXCAUCNNZPGTD-UHFFFAOYSA-N 6-amino-1-(2-methoxyethyl)-2-sulfanylidenepyrimidin-4-one Chemical compound COCCN1C(N)=CC(=O)NC1=S VOXCAUCNNZPGTD-UHFFFAOYSA-N 0.000 description 1
- NZQXUEJETLYCSR-UHFFFAOYSA-N 6-amino-1-(2-methoxyethyl)-5-nitroso-2-sulfanylidenepyrimidin-4-one Chemical compound COCCN1C(N)=C(N=O)C(=O)NC1=S NZQXUEJETLYCSR-UHFFFAOYSA-N 0.000 description 1
- UERIGJUNZSHWIJ-UHFFFAOYSA-N 6-amino-1-(3-methoxypropyl)-2-sulfanylidenepyrimidin-4-one Chemical compound COCCCN1C(N)=CC(=O)NC1=S UERIGJUNZSHWIJ-UHFFFAOYSA-N 0.000 description 1
- WMIUWSWAXVYJSV-UHFFFAOYSA-N 6-amino-1-(3-methoxypropyl)-5-nitroso-2-sulfanylidenepyrimidin-4-one Chemical compound COCCCN1C(N)=C(N=O)C(=O)NC1=S WMIUWSWAXVYJSV-UHFFFAOYSA-N 0.000 description 1
- GWUVZWRPYGCLBS-UHFFFAOYSA-N 6-amino-1-(cyclohexylmethyl)-5-nitroso-2-sulfanylidenepyrimidin-4-one Chemical compound NC1=C(N=O)C(=O)NC(=S)N1CC1CCCCC1 GWUVZWRPYGCLBS-UHFFFAOYSA-N 0.000 description 1
- QRZMDYTVUIWYQP-UHFFFAOYSA-N 6-amino-1-(cyclopropylmethyl)-5-nitroso-2-sulfanylidenepyrimidin-4-one Chemical compound NC1=C(N=O)C(=O)NC(=S)N1CC1CC1 QRZMDYTVUIWYQP-UHFFFAOYSA-N 0.000 description 1
- OGEPSVQJSNQNNE-UHFFFAOYSA-N 6-amino-1-(oxolan-2-ylmethyl)-2-sulfanylidenepyrimidin-4-one Chemical compound NC1=CC(=O)NC(=S)N1CC1OCCC1 OGEPSVQJSNQNNE-UHFFFAOYSA-N 0.000 description 1
- KZPGCCDZASOPSP-UHFFFAOYSA-N 6-amino-1-[(4-methoxyphenyl)methyl]-2-sulfanylidenepyrimidin-4-one Chemical compound C1=CC(OC)=CC=C1CN1C(=S)NC(=O)C=C1N KZPGCCDZASOPSP-UHFFFAOYSA-N 0.000 description 1
- ODYNJZRHNNANKQ-UHFFFAOYSA-N 6-amino-5-nitroso-1-(1-phenylethyl)-2-sulfanylidenepyrimidin-4-one Chemical compound NC1=C(C(NC(N1C(C)C1=CC=CC=C1)=S)=O)N=O ODYNJZRHNNANKQ-UHFFFAOYSA-N 0.000 description 1
- OPZUKVWMKYAGPB-UHFFFAOYSA-N 7-methyl-3-(2-methylpropyl)-2-sulfanylidenepurin-6-one Chemical compound O=C1NC(=S)N(CC(C)C)C2=C1N(C)C=N2 OPZUKVWMKYAGPB-UHFFFAOYSA-N 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- AWASJLRLODFZMS-UHFFFAOYSA-N C(C(C)C)N1C(NC(C=2NC=NC12)=O)=S.C(C(C)C)N1C(NC(C=2NC=NC12)=S)=S Chemical compound C(C(C)C)N1C(NC(C=2NC=NC12)=O)=S.C(C(C)C)N1C(NC(C=2NC=NC12)=S)=S AWASJLRLODFZMS-UHFFFAOYSA-N 0.000 description 1
- JQZZKCZURQENNG-UHFFFAOYSA-N CC(O)=O.COCCCn1c2nc[nH]c2c(=O)[nH]c1=S Chemical compound CC(O)=O.COCCCn1c2nc[nH]c2c(=O)[nH]c1=S JQZZKCZURQENNG-UHFFFAOYSA-N 0.000 description 1
- SWDPAQLBIQUXQD-UHFFFAOYSA-N CN.CNC(=S)NCC(C)C Chemical compound CN.CNC(=S)NCC(C)C SWDPAQLBIQUXQD-UHFFFAOYSA-N 0.000 description 1
- 102000016938 Catalase Human genes 0.000 description 1
- 108010053835 Catalase Proteins 0.000 description 1
- QDHHCQZDFGDHMP-UHFFFAOYSA-N Chloramine Chemical class ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 1
- 108010092408 Eosinophil Peroxidase Proteins 0.000 description 1
- 102100028471 Eosinophil peroxidase Human genes 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 101001099464 Homo sapiens Lactoperoxidase Proteins 0.000 description 1
- 101001099460 Homo sapiens Myeloperoxidase Proteins 0.000 description 1
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 108010036012 Iodide peroxidase Proteins 0.000 description 1
- 102000011845 Iodide peroxidase Human genes 0.000 description 1
- 108010023244 Lactoperoxidase Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- FGTBZFNDBYAMDQ-UHFFFAOYSA-N NC1=C(C(NC(N1CC(C)C)=S)=O)N=O.NC=1C(NC(N(C1N)CC(C)C)=S)=O Chemical compound NC1=C(C(NC(N1CC(C)C)=S)=O)N=O.NC=1C(NC(N(C1N)CC(C)C)=S)=O FGTBZFNDBYAMDQ-UHFFFAOYSA-N 0.000 description 1
- TWNUDNHTCCKNJB-UHFFFAOYSA-N NC1=C(C(NC(N1CC(C)C)=S)=O)NC.C(C(C)C)N1C(NC(C=2N(C=NC12)C)=O)=S Chemical compound NC1=C(C(NC(N1CC(C)C)=S)=O)NC.C(C(C)C)N1C(NC(C=2N(C=NC12)C)=O)=S TWNUDNHTCCKNJB-UHFFFAOYSA-N 0.000 description 1
- VZFPYECKOSMDHI-UHFFFAOYSA-N NC1=C(C(NC(N1CC(C)C)=S)=O)NC=O.NC1=C(C(NC(N1CC(C)C)=S)=O)NC Chemical compound NC1=C(C(NC(N1CC(C)C)=S)=O)NC=O.NC1=C(C(NC(N1CC(C)C)=S)=O)NC VZFPYECKOSMDHI-UHFFFAOYSA-N 0.000 description 1
- YKKWLTHMIHUFNG-UHFFFAOYSA-N NC1=CC(NC(N1CC(C)C)=S)=O.NC1=C(C(NC(N1CC(C)C)=S)=O)N=O Chemical compound NC1=CC(NC(N1CC(C)C)=S)=O.NC1=C(C(NC(N1CC(C)C)=S)=O)N=O YKKWLTHMIHUFNG-UHFFFAOYSA-N 0.000 description 1
- IWMSFSUGPSOUJO-UHFFFAOYSA-N NC1=CC(NC(N1CC1CC1)=S)=O.C1(CC1)CN1C(NC(C=2NC=NC12)=O)=S Chemical compound NC1=CC(NC(N1CC1CC1)=S)=O.C1(CC1)CN1C(NC(C=2NC=NC12)=O)=S IWMSFSUGPSOUJO-UHFFFAOYSA-N 0.000 description 1
- LUPBLCGHOIQVGA-UHFFFAOYSA-N NC1=CC(NC(N1CC1OCCC1)=S)=O.NC1=C(C(NC(N1CC1OCCC1)=S)=O)N=O Chemical compound NC1=CC(NC(N1CC1OCCC1)=S)=O.NC1=C(C(NC(N1CC1OCCC1)=S)=O)N=O LUPBLCGHOIQVGA-UHFFFAOYSA-N 0.000 description 1
- HZJIUARKESFFJP-UHFFFAOYSA-N NC1=CC(NC(N1CCOC)=S)=O.NC1=C(C(NC(N1CCOC)=S)=O)N=O Chemical compound NC1=CC(NC(N1CCOC)=S)=O.NC1=C(C(NC(N1CCOC)=S)=O)N=O HZJIUARKESFFJP-UHFFFAOYSA-N 0.000 description 1
- PXPCYMUTKCHZTD-UHFFFAOYSA-N NC=1C(NC(N(C1N)CC(C)C)=S)=O.C(C(C)C)N1C(NC(C=2NC=NC12)=O)=S Chemical compound NC=1C(NC(N(C1N)CC(C)C)=S)=O.C(C(C)C)N1C(NC(C=2NC=NC12)=O)=S PXPCYMUTKCHZTD-UHFFFAOYSA-N 0.000 description 1
- UWAOYDQJJWOZLG-UHFFFAOYSA-N NC=1C(NC(N(C1N)CC(C)C)=S)=O.NC1=C(C(NC(N1CC(C)C)=S)=O)NC=O Chemical compound NC=1C(NC(N(C1N)CC(C)C)=S)=O.NC1=C(C(NC(N1CC(C)C)=S)=O)NC=O UWAOYDQJJWOZLG-UHFFFAOYSA-N 0.000 description 1
- XJVYSJFGPAVDOL-UHFFFAOYSA-N NC=1C(NC(N(C1N)CC1=CC=C(C=C1)OC)=S)=O.COC1=CC=C(CN2C(NC(C=3NC=NC23)=O)=S)C=C1 Chemical compound NC=1C(NC(N(C1N)CC1=CC=C(C=C1)OC)=S)=O.COC1=CC=C(CN2C(NC(C=3NC=NC23)=O)=S)C=C1 XJVYSJFGPAVDOL-UHFFFAOYSA-N 0.000 description 1
- MDKHQQDZFFHVIT-UHFFFAOYSA-N NC=1C(NC(N(C1N)CC1CCCCC1)=S)=O.C1(CCCCC1)CN1C(NC(C=2NC=NC12)=O)=S Chemical compound NC=1C(NC(N(C1N)CC1CCCCC1)=S)=O.C1(CCCCC1)CN1C(NC(C=2NC=NC12)=O)=S MDKHQQDZFFHVIT-UHFFFAOYSA-N 0.000 description 1
- FEUUKGBCXBCMBT-UHFFFAOYSA-N NC=1C(NC(N(C1N)CC1OCCC1)=S)=O.O1C(CCC1)CN1C(NC(C=2NC=NC12)=O)=S Chemical compound NC=1C(NC(N(C1N)CC1OCCC1)=S)=O.O1C(CCC1)CN1C(NC(C=2NC=NC12)=O)=S FEUUKGBCXBCMBT-UHFFFAOYSA-N 0.000 description 1
- RTBALDBLCMRWIC-UHFFFAOYSA-N NC=1C(NC(N(C1N)CC=1OC=CC1)=S)=O.O1C(=CC=C1)CN1C(NC(C=2NC=NC12)=O)=S Chemical compound NC=1C(NC(N(C1N)CC=1OC=CC1)=S)=O.O1C(=CC=C1)CN1C(NC(C=2NC=NC12)=O)=S RTBALDBLCMRWIC-UHFFFAOYSA-N 0.000 description 1
- AQIAUERHOCSNNK-UHFFFAOYSA-N NC=1C(NC(N(C1N)CCOC)=S)=O.COCCN1C(NC(C=2NC=NC12)=O)=S Chemical compound NC=1C(NC(N(C1N)CCOC)=S)=O.COCCN1C(NC(C=2NC=NC12)=O)=S AQIAUERHOCSNNK-UHFFFAOYSA-N 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 108700020962 Peroxidase Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 206010036774 Proctitis Diseases 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- 150000008107 benzenesulfonic acids Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 229940045348 brown mixture Drugs 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000010549 co-Evaporation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- BHJTYNJTDMRWOT-UHFFFAOYSA-N cyclopropylmethylthiourea Chemical compound NC(=S)NCC1CC1 BHJTYNJTDMRWOT-UHFFFAOYSA-N 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- GRWZHXKQBITJKP-UHFFFAOYSA-L dithionite(2-) Chemical compound [O-]S(=O)S([O-])=O GRWZHXKQBITJKP-UHFFFAOYSA-L 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 208000007565 gingivitis Diseases 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 102000051251 human MPO Human genes 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 1
- 238000001990 intravenous administration 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
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 229940057428 lactoperoxidase Drugs 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000003641 microbiacidal effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000004108 n-butyl group Chemical group [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
- 230000002314 neuroinflammatory effect Effects 0.000 description 1
- 230000003962 neuroinflammatory response Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000004262 preparative liquid chromatography Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000002577 pseudohalo group Chemical group 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 208000033610 salivary peroxidase Diseases 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 201000009890 sinusitis Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- HNKDNKZBNPSTEW-UHFFFAOYSA-N sodium;6-amino-1-(3-methoxypropyl)-2-sulfanylidenepyrimidin-4-one;methanolate Chemical compound [Na+].[O-]C.COCCCN1C(N)=CC(=O)NC1=S HNKDNKZBNPSTEW-UHFFFAOYSA-N 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 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
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 210000003934 vacuole Anatomy 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/20—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two sulfur atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- 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
- A61P35/00—Antineoplastic agents
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/22—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one sulfur atom
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA2752132A CA2752132A1 (en) | 2002-04-19 | 2003-04-15 | Thioxanthine derivatives as myeloperoxidase inhibitors |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0201193A SE0201193D0 (sv) | 2002-04-19 | 2002-04-19 | Novel use |
| SE0201193-0 | 2002-04-19 | ||
| SE0202239-0 | 2002-07-17 | ||
| SE0202239A SE0202239D0 (sv) | 2002-07-17 | 2002-07-17 | Novel use |
| PCT/SE2003/000617 WO2003089430A1 (en) | 2002-04-19 | 2003-04-15 | Thioxanthine derivatives as myeloperoxidase inhibitors |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2752132A Division CA2752132A1 (en) | 2002-04-19 | 2003-04-15 | Thioxanthine derivatives as myeloperoxidase inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2480452A1 CA2480452A1 (en) | 2003-10-30 |
| CA2480452C true CA2480452C (en) | 2011-11-22 |
Family
ID=29253791
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2480452A Expired - Fee Related CA2480452C (en) | 2002-04-19 | 2003-04-15 | Thioxanthine derivatives as myeloperoxidase inhibitors |
| CA2752132A Abandoned CA2752132A1 (en) | 2002-04-19 | 2003-04-15 | Thioxanthine derivatives as myeloperoxidase inhibitors |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2752132A Abandoned CA2752132A1 (en) | 2002-04-19 | 2003-04-15 | Thioxanthine derivatives as myeloperoxidase inhibitors |
Country Status (21)
| Country | Link |
|---|---|
| US (2) | US7425560B2 (enExample) |
| EP (2) | EP1499613B1 (enExample) |
| JP (2) | JP4649112B2 (enExample) |
| KR (3) | KR101064092B1 (enExample) |
| CN (1) | CN100379737C (enExample) |
| AR (1) | AR039385A1 (enExample) |
| AT (1) | ATE529428T1 (enExample) |
| AU (2) | AU2003224548B2 (enExample) |
| BR (1) | BR0309012A (enExample) |
| CA (2) | CA2480452C (enExample) |
| ES (1) | ES2373224T3 (enExample) |
| IL (1) | IL164315A0 (enExample) |
| IS (1) | IS7509A (enExample) |
| MX (1) | MXPA04010055A (enExample) |
| MY (1) | MY157949A (enExample) |
| NO (2) | NO331002B1 (enExample) |
| NZ (1) | NZ535406A (enExample) |
| PL (1) | PL373197A1 (enExample) |
| RU (2) | RU2323219C2 (enExample) |
| TW (1) | TWI335918B (enExample) |
| WO (1) | WO2003089430A1 (enExample) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR039385A1 (es) * | 2002-04-19 | 2005-02-16 | Astrazeneca Ab | Derivados de tioxantina como inhibidores de la mieloperoxidasa |
| SE0302756D0 (sv) * | 2003-10-17 | 2003-10-17 | Astrazeneca Ab | Novel Compounds |
| SE0402591D0 (sv) * | 2004-10-25 | 2004-10-25 | Astrazeneca Ab | Novel use |
| MY140748A (en) * | 2004-12-06 | 2010-01-15 | Astrazeneca Ab | Novel pyrrolo [3,2-d] pyrimidin-4-one derivatives and their use in therapy |
| CN101472926A (zh) * | 2006-04-13 | 2009-07-01 | 阿斯利康(瑞典)有限公司 | 硫代黄嘌呤衍生物以及它们作为髓过氧化物酶抑制剂的用途 |
| UY30267A1 (es) * | 2006-04-13 | 2007-11-30 | Astrazeneca Ab | Nuevos derivados de la tioxantina , composiciones farmacéuticas que los contienen, procedimientos de preparacion y aplicaciones |
| WO2007142577A1 (en) * | 2006-06-05 | 2007-12-13 | Astrazeneca Ab | Pyrrolo[3,2-d]pyrimidin-4-one derivative as myeloperoxidase inhibitor |
| TW200804383A (en) * | 2006-06-05 | 2008-01-16 | Astrazeneca Ab | New compounds |
| AR066936A1 (es) * | 2007-06-13 | 2009-09-23 | Astrazeneca Ab | 3 - (2r - tetrahidrofuril - metil) - 2 - tioxantina. composiciones farmaceuticas. |
| US20090053176A1 (en) * | 2007-08-23 | 2009-02-26 | Astrazeneca Ab | New Combination 937 |
| US20090054468A1 (en) * | 2007-08-23 | 2009-02-26 | Astrazeneca Ab | New Use 938 |
| US20100081159A1 (en) * | 2008-09-26 | 2010-04-01 | Lebedeva Irina V | Profiling reactive oxygen, nitrogen and halogen species |
| WO2010062787A1 (en) * | 2008-11-03 | 2010-06-03 | Washington University | Bioluminescence imaging of myeloperoxidase activity in vivo, methods, compositions and apparatuses therefor |
| WO2010068171A1 (en) * | 2008-12-12 | 2010-06-17 | Astrazeneca Ab | A process for the preparation of 3- [ (2r) tetrahydrofuran-2- ylmethyl] -2-thioxo-l, 2, 3, 7-tetrahydro-6h-purin-6-one |
| AU2010251930A1 (en) * | 2009-05-27 | 2011-11-24 | Universite Libre De Bruxelles | 3-alkyl-5-fluoroindole derivatives as myeloperoxidase inhibitors |
| GB0913345D0 (en) | 2009-07-31 | 2009-09-16 | Astrazeneca Ab | New combination 802 |
| WO2011061527A1 (en) | 2009-11-17 | 2011-05-26 | Astrazeneca Ab | Combinations comprising a glucocorticoid receptor modulator for the treatment of respiratory diseases |
| WO2011133581A1 (en) | 2010-04-19 | 2011-10-27 | General Atomics | Methods and compositions for assaying enzymatic activity of myeloperoxidase in blood samples |
| GB201021992D0 (en) | 2010-12-23 | 2011-02-02 | Astrazeneca Ab | Compound |
| GB201021979D0 (en) | 2010-12-23 | 2011-02-02 | Astrazeneca Ab | New compound |
| WO2012151576A1 (en) * | 2011-05-05 | 2012-11-08 | Robert Sackstein | Methods of treating complications and disorders associated with g-csf administration |
| AU2012335220B2 (en) | 2011-11-11 | 2017-06-01 | Pfizer Inc. | 2-thiopyrimidinones |
| US9616063B2 (en) | 2014-12-01 | 2017-04-11 | Astrazeneca Ab | 1-[2-(aminomethyl)benzyl]-2-thioxo-1,2,3,5-tetrahydro-4H-pyrrolo[3,2-d]pyrimidin-4-ones as inhibitors of myeloperoxidase |
| SG11201708407TA (en) | 2015-05-05 | 2017-11-29 | Pfizer | 2-thiopyrimidinones |
| EP3397640B1 (en) * | 2015-12-29 | 2021-08-04 | INSERM - Institut National de la Santé et de la Recherche Médicale | Xanthine derivative inhibitors of bet proteins |
| WO2020021300A1 (en) | 2018-07-24 | 2020-01-30 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of myeloperoxidase (mpo) inhibitors for the treatment of chemoresistant acute myeloid leukemia (aml) |
| WO2021013942A1 (en) | 2019-07-24 | 2021-01-28 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of myeloperoxidase inhibitors for the treatment of cardiovascular diseases in patients suffering from myeloproliferative neoplasms |
| TW202426450A (zh) | 2022-08-18 | 2024-07-01 | 瑞典商阿斯特捷利康公司 | 髓過氧化物酶抑制劑 |
| WO2025172474A1 (en) | 2024-02-15 | 2025-08-21 | Astrazeneca Ab | Inhibitors of myeloperoxidase |
| WO2025190901A1 (en) | 2024-03-13 | 2025-09-18 | Institut National de la Santé et de la Recherche Médicale | Use of myeloperoxidase (mpo) inhibitors for promoting cd8+ t cell responses |
| CN121378265B (zh) * | 2025-10-30 | 2026-07-24 | 乐平市康鑫医药化工有限公司 | 一种吡唑类化合物及其制备方法和用途 |
Family Cites Families (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3135753A (en) * | 1961-05-10 | 1964-06-02 | Burroughs Wellcome Co | Alkylthiopurines and method |
| SE7810947L (sv) | 1978-10-20 | 1980-04-21 | Draco Ab | 3-alkylxanthines |
| US4710503A (en) * | 1985-02-07 | 1987-12-01 | Euroceltique S.A. | 6-thioxanthine derivatives |
| AU2948189A (en) | 1987-12-31 | 1989-08-01 | Smithkline Beckman Corporation | 4-aralkyl-5-substituted-1,2,4-triazole-5-thiols |
| DK440989A (da) | 1988-09-12 | 1990-03-13 | Smithkline Beecham Corp | Dopamin-beta-hydroxylase inhibitorer |
| JPH02160235A (ja) | 1988-12-13 | 1990-06-20 | Konica Corp | ハロゲン化銀カラー写真画像の形成方法 |
| WO1990012797A1 (en) * | 1989-04-19 | 1990-11-01 | The United States Of America, As Represented By The Secretary, U.S. Department Of Commerce | Sulfer-containing xanthine derivatives as adenosin antagonists |
| GB8918297D0 (en) * | 1989-08-10 | 1989-09-20 | Beecham Group Plc | Novel treatment |
| EP0430300A3 (en) | 1989-12-01 | 1992-03-25 | Takeda Chemical Industries, Ltd. | Xanthine derivatives, their production and use |
| US5100906A (en) | 1990-04-19 | 1992-03-31 | Merrell Dow Pharmaceuticals Inc. | 5-aryl-4-alkyl-3h-1,2,4-triazole-3-thiones useful as memory enhancers |
| FR2665636B1 (fr) * | 1990-08-10 | 1994-10-07 | Adir | Utilisation d'un derive de la trimethyl-1,3,7 xanthine pour le traitement des troubles de la memoire, des troubles intellectuels de la senescence et de la maladie d'alzheimer. |
| US6046019A (en) * | 1991-07-09 | 2000-04-04 | Goumeniouk; Alexander P. | Diagnostic kits and methods for making granulocyte cell counts |
| US6469017B1 (en) | 1998-01-16 | 2002-10-22 | Cell Therapeutics, Inc. | Method of inhibiting interleukin-12 signaling |
| GB9312853D0 (en) | 1993-06-22 | 1993-08-04 | Euro Celtique Sa | Chemical compounds |
| CZ283564B6 (cs) * | 1993-11-26 | 1998-05-13 | Pfizer Inc. | 3-Aryl-2-isoxazolin-5-hydroxamové kyseliny a farmaceutické prostředky na jejich bázi |
| US5489598A (en) * | 1994-06-08 | 1996-02-06 | Warner-Lambert Company | Cytoprotection utilizing aryltriazol-3-thiones |
| EP0799040B1 (en) * | 1994-12-13 | 2003-08-20 | Euroceltique S.A. | Trisubstituted thioxanthines |
| WO1996018400A1 (en) * | 1994-12-13 | 1996-06-20 | Euro-Celtique, S.A. | Trisubstituted thioxanthines |
| US6025361A (en) * | 1994-12-13 | 2000-02-15 | Euro-Celtique, S.A. | Trisubstituted thioxanthines |
| JPH10508032A (ja) * | 1994-12-13 | 1998-08-04 | ユーロ−セルティーク，エス．エイ． | アリールチオキサンチン類 |
| US5756511A (en) * | 1995-04-03 | 1998-05-26 | Cell Therapeutics, Inc. | Method for treating symptoms of a neurodegenerative condition |
| US6294541B1 (en) * | 1996-06-06 | 2001-09-25 | Euro-Celtique S.A. | Purine derivatives having phosphodiesterase IV inhibition activity |
| DE19707655A1 (de) * | 1997-02-26 | 1998-08-27 | Hoechst Ag | Kombinationspräparat zur Anwendung bei Demenz |
| US5976823A (en) * | 1997-03-19 | 1999-11-02 | Integrated Biomedical Technology, Inc. | Low range total available chlorine test strip |
| ES2264210T3 (es) * | 1997-09-05 | 2006-12-16 | Kyowa Hakko Kogyo Co., Ltd. | Derivados de xantina para el tratamiento de la isquemia cerebral. |
| WO1999014204A1 (en) | 1997-09-16 | 1999-03-25 | G.D. Searle & Co. | Substituted 1,2,4-triazoles useful for inhibiting cholesteryl ester transfer protein activity |
| AR013669A1 (es) | 1997-10-07 | 2001-01-10 | Smithkline Beecham Corp | Compuestos y metodos |
| US6187777B1 (en) | 1998-02-06 | 2001-02-13 | Amgen Inc. | Compounds and methods which modulate feeding behavior and related diseases |
| US6319928B1 (en) * | 1998-11-30 | 2001-11-20 | Euro-Celtique, S.A. | Purine derivatives having phosphodiesterase IV inhibition activity |
| DZ3019A1 (fr) | 1999-03-01 | 2005-05-20 | Smithkline Beecham Corp | Utilisation d'un inhibiteur de pde4 dans la préparation d'un médicament contre la copd. |
| EP1169321A4 (en) | 1999-04-02 | 2002-10-30 | Euro Celtique Sa | PURINE DERIVATIVES WITH PHOSPHODIESTERASE INHIBITOR ACTIVITY |
| WO2001011967A1 (en) | 1999-08-12 | 2001-02-22 | Euro-Celtique S.A. | Novel hypoxanthine and thiohypoxanthine compounds |
| GB2362101A (en) | 2000-05-12 | 2001-11-14 | Astrazeneca Ab | Treatment of chronic obstructive pulmonary disease |
| FR2811989A1 (fr) | 2000-07-18 | 2002-01-25 | Sanofi Synthelabo | Derives de polyfluoroalkytriazole, leur preparation et leur application en therapeutique |
| AU2001276023A1 (en) | 2000-07-21 | 2002-02-05 | Mark B Lyles | Materials and methods for binding nucleic acids to surfaces |
| FR2819723B1 (fr) * | 2001-01-23 | 2006-11-17 | Arnaud Mainnemare | Composition halogene, son procede de preparation et ses utilisations |
| WO2002066447A1 (en) | 2001-02-21 | 2002-08-29 | Ono Pharmaceutical Co., Ltd. | 4h-1,2,4-triazole-3(2h)-thione deratives as sphingomyelinase inhibitors |
| SE0103766D0 (sv) * | 2001-11-09 | 2001-11-09 | Astrazeneca Ab | Novel assay |
| CA2446039A1 (en) | 2001-05-08 | 2002-11-14 | Astrazeneca Ab | An assay for detecting inhibitors of the enzyme mueloperokidase |
| ES2193839B1 (es) * | 2001-06-22 | 2005-02-16 | Almirall Prodesfarma, S.A. | Nuevos derivados de 6-fenildihidropirrolpirimidindiona. |
| ES2208063B1 (es) | 2002-04-01 | 2005-10-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de la 4-(pirrolopirimidin-6-il)bencenosulfonamida. |
| AR039385A1 (es) * | 2002-04-19 | 2005-02-16 | Astrazeneca Ab | Derivados de tioxantina como inhibidores de la mieloperoxidasa |
| SE0301232D0 (sv) | 2003-04-25 | 2003-04-25 | Astrazeneca Ab | Novel use |
| SE0302756D0 (sv) | 2003-10-17 | 2003-10-17 | Astrazeneca Ab | Novel Compounds |
| US7449473B2 (en) | 2003-10-31 | 2008-11-11 | Cv Therapeutics, Inc. | Substituted pyrrolo[3,2-d]pyrimidin-2,4-diones as A2b adenosine receptor antagonists |
| CA2556073C (en) | 2004-02-14 | 2012-01-10 | Smithkline Beecham Corporation | 8-chloro-1,3-disubstituted xanthine derivatives as hm74a receptor modulators |
| WO2006045564A1 (en) | 2004-10-22 | 2006-05-04 | Smithkline Beecham Corporation | Xanthine derivatives with hm74a receptor activity |
| SE0402591D0 (sv) | 2004-10-25 | 2004-10-25 | Astrazeneca Ab | Novel use |
| MY140748A (en) | 2004-12-06 | 2010-01-15 | Astrazeneca Ab | Novel pyrrolo [3,2-d] pyrimidin-4-one derivatives and their use in therapy |
| UY30267A1 (es) * | 2006-04-13 | 2007-11-30 | Astrazeneca Ab | Nuevos derivados de la tioxantina , composiciones farmacéuticas que los contienen, procedimientos de preparacion y aplicaciones |
| TW200804383A (en) | 2006-06-05 | 2008-01-16 | Astrazeneca Ab | New compounds |
| AR066936A1 (es) * | 2007-06-13 | 2009-09-23 | Astrazeneca Ab | 3 - (2r - tetrahidrofuril - metil) - 2 - tioxantina. composiciones farmaceuticas. |
| US20090054468A1 (en) * | 2007-08-23 | 2009-02-26 | Astrazeneca Ab | New Use 938 |
-
2003
- 2003-04-07 AR ARP030101208A patent/AR039385A1/es unknown
- 2003-04-14 TW TW092108547A patent/TWI335918B/zh not_active IP Right Cessation
- 2003-04-15 AT AT03721211T patent/ATE529428T1/de not_active IP Right Cessation
- 2003-04-15 BR BR0309012-4A patent/BR0309012A/pt not_active IP Right Cessation
- 2003-04-15 WO PCT/SE2003/000617 patent/WO2003089430A1/en not_active Ceased
- 2003-04-15 RU RU2004128389/04A patent/RU2323219C2/ru not_active IP Right Cessation
- 2003-04-15 KR KR1020047016709A patent/KR101064092B1/ko not_active Expired - Fee Related
- 2003-04-15 KR KR1020117027657A patent/KR20110132635A/ko not_active Ceased
- 2003-04-15 MX MXPA04010055A patent/MXPA04010055A/es active IP Right Grant
- 2003-04-15 CA CA2480452A patent/CA2480452C/en not_active Expired - Fee Related
- 2003-04-15 CN CNB038083558A patent/CN100379737C/zh not_active Expired - Fee Related
- 2003-04-15 PL PL03373197A patent/PL373197A1/xx not_active Application Discontinuation
- 2003-04-15 AU AU2003224548A patent/AU2003224548B2/en not_active Ceased
- 2003-04-15 CA CA2752132A patent/CA2752132A1/en not_active Abandoned
- 2003-04-15 EP EP03721211A patent/EP1499613B1/en not_active Expired - Lifetime
- 2003-04-15 NZ NZ535406A patent/NZ535406A/en not_active IP Right Cessation
- 2003-04-15 JP JP2003586151A patent/JP4649112B2/ja not_active Expired - Fee Related
- 2003-04-15 EP EP10170768A patent/EP2332541A1/en not_active Withdrawn
- 2003-04-15 US US10/511,537 patent/US7425560B2/en not_active Expired - Fee Related
- 2003-04-15 KR KR1020117007364A patent/KR20110036871A/ko not_active Withdrawn
- 2003-04-15 ES ES03721211T patent/ES2373224T3/es not_active Expired - Lifetime
- 2003-04-17 MY MYPI20031447A patent/MY157949A/en unknown
-
2004
- 2004-09-27 IL IL16431504A patent/IL164315A0/xx unknown
- 2004-10-15 IS IS7509A patent/IS7509A/is unknown
- 2004-11-17 NO NO20044998A patent/NO331002B1/no not_active IP Right Cessation
-
2007
- 2007-11-16 RU RU2007142328/04A patent/RU2007142328A/ru not_active Application Discontinuation
-
2008
- 2008-08-04 US US12/185,158 patent/US8236951B2/en not_active Expired - Fee Related
-
2010
- 2010-01-29 AU AU2010200345A patent/AU2010200345B2/en not_active Ceased
- 2010-03-08 JP JP2010049998A patent/JP2010138190A/ja active Pending
- 2010-06-28 NO NO20100939A patent/NO20100939L/no not_active Application Discontinuation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8236951B2 (en) | Thioxanthine derivatives as myeloperoxidase inhibitors | |
| US4564616A (en) | Anti-cancer quinazoline derivatives | |
| US20070032468A1 (en) | Novel thioxanthine derivatives for use as inhibitors of mpo | |
| US20070093483A1 (en) | Use of derivatives of 2, 4-dihydro-[1,2,4] triazole-3-thione as inhibitors of the enzyme myeloperoxidase (mpo) | |
| JP2009533426A (ja) | チオキサンチン誘導体およびそれらのｍｐｏ阻害剤としての用途 | |
| Jacobson et al. | Sulfur-containing 1, 3-dialkylxanthine derivatives as selective antagonists at A1-adenosine receptors | |
| US6187780B1 (en) | Assymetrically substituted xanthine derivatives having adenosine A1 antagonistic activity | |
| US5453426A (en) | Sulfur-containing xanthine derivatives as adenosine antagonists | |
| US20080096929A1 (en) | Novel Use | |
| HK1158940A (en) | Use of thioxanthine derivatives as mpo inhibitors | |
| HK1071568B (en) | Thioxanthine derivatives as myeloperoxidase inhibitors | |
| CN101062037B (zh) | 作为髓过氧化物酶抑制剂的硫代黄嘌呤衍生物的制法及其应用 | |
| US20180148451A1 (en) | Hydroxyl purine compounds and use thereof | |
| HK1114500B (en) | Method for producing thioxanthine derivatives as myeloperoxidase inhibitors, and use of said thioxanthine derivatives | |
| EP0269841B1 (fr) | 1-Hydroxyalkylxanthines, leurs procédés de préparation et médicament les contenant | |
| JPWO1998035968A1 (ja) | 呼吸器疾患治療・予防用医薬 | |
| CN121591709A (zh) | 一种4-氨基-2,6-二羟基嘧啶衍生物及其应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20150415 |