KR20150082194A - 피리딘 유도체 - Google Patents
피리딘 유도체 Download PDFInfo
- Publication number
- KR20150082194A KR20150082194A KR1020157008457A KR20157008457A KR20150082194A KR 20150082194 A KR20150082194 A KR 20150082194A KR 1020157008457 A KR1020157008457 A KR 1020157008457A KR 20157008457 A KR20157008457 A KR 20157008457A KR 20150082194 A KR20150082194 A KR 20150082194A
- Authority
- KR
- South Korea
- Prior art keywords
- group
- methyl
- dichlorobenzyl
- imidazole
- pyridin
- 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.)
- Withdrawn
Links
- 150000003222 pyridines Chemical class 0.000 title claims description 39
- 150000003839 salts Chemical class 0.000 claims abstract description 46
- 239000012453 solvate Substances 0.000 claims abstract description 36
- 208000031226 Hyperlipidaemia Diseases 0.000 claims abstract description 8
- 238000011282 treatment Methods 0.000 claims abstract description 5
- 208000011580 syndromic disease Diseases 0.000 claims abstract description 3
- -1 2-hydroxypropan-2-yl group Chemical group 0.000 claims description 557
- 125000004432 carbon atom Chemical group C* 0.000 claims description 298
- 150000001875 compounds Chemical class 0.000 claims description 233
- 125000000217 alkyl group Chemical group 0.000 claims description 157
- 125000005843 halogen group Chemical group 0.000 claims description 108
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 85
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 84
- 239000000203 mixture Substances 0.000 claims description 82
- 238000003786 synthesis reaction Methods 0.000 claims description 65
- 125000003545 alkoxy group Chemical group 0.000 claims description 64
- 230000015572 biosynthetic process Effects 0.000 claims description 64
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 61
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 50
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 48
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 43
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 42
- 229910052757 nitrogen Inorganic materials 0.000 claims description 39
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 38
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 37
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 34
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 31
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 30
- 239000000126 substance Substances 0.000 claims description 29
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 27
- 125000005605 benzo group Chemical group 0.000 claims description 26
- 125000006184 2,5-dimethyl benzyl group Chemical group [H]C1=C(C([H])=C(C(=C1[H])C([H])([H])[H])C([H])([H])*)C([H])([H])[H] 0.000 claims description 20
- 125000003277 amino group Chemical group 0.000 claims description 20
- 229940002612 prodrug Drugs 0.000 claims description 20
- 239000000651 prodrug Substances 0.000 claims description 20
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 19
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 18
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 18
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 17
- 229910052801 chlorine Inorganic materials 0.000 claims description 16
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 16
- 125000002883 imidazolyl group Chemical group 0.000 claims description 16
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 15
- 125000004414 alkyl thio group Chemical group 0.000 claims description 15
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 15
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 15
- 201000005569 Gout Diseases 0.000 claims description 14
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 14
- 150000002596 lactones Chemical group 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- 125000004434 sulfur atom Chemical group 0.000 claims description 14
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 12
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
- 229910052740 iodine Inorganic materials 0.000 claims description 12
- 125000004193 piperazinyl group Chemical group 0.000 claims description 12
- 238000006467 substitution reaction Methods 0.000 claims description 12
- 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 11
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 11
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 7
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 7
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 7
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 claims description 6
- AQSGVSNQROMBSI-UHFFFAOYSA-N 1-(naphthalen-1-ylmethyl)-5-pyridin-3-ylpyrrole-2-carboxylic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CN1C(C(=O)O)=CC=C1C1=CC=CN=C1 AQSGVSNQROMBSI-UHFFFAOYSA-N 0.000 claims description 5
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 5
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 5
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 4
- 125000004149 thio group Chemical group *S* 0.000 claims description 4
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- LYHHVUJPNBEXJU-UHFFFAOYSA-N COC(=O)c1nc(Br)n(Cc2ccccc2Cl)c1C(=O)OC Chemical compound COC(=O)c1nc(Br)n(Cc2ccccc2Cl)c1C(=O)OC LYHHVUJPNBEXJU-UHFFFAOYSA-N 0.000 claims description 3
- CKUWZBFLDVYZPD-UHFFFAOYSA-N ClC=1N(C(=CC1)C=O)CC=1SC=CC1 Chemical compound ClC=1N(C(=CC1)C=O)CC=1SC=CC1 CKUWZBFLDVYZPD-UHFFFAOYSA-N 0.000 claims description 3
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 claims description 3
- 239000001630 malic acid Substances 0.000 claims description 3
- 235000011090 malic acid Nutrition 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- 229910052721 tungsten Inorganic materials 0.000 claims description 3
- 229910052727 yttrium Inorganic materials 0.000 claims description 3
- ASUMVAPLXCRBMA-UHFFFAOYSA-N (3,5-dichloro-4-hydroxyphenyl)-(2,3-dihydro-1,4-benzoxazin-4-yl)methanone Chemical compound C1=C(Cl)C(O)=C(Cl)C=C1C(=O)N1C2=CC=CC=C2OCC1 ASUMVAPLXCRBMA-UHFFFAOYSA-N 0.000 claims description 2
- IQHSSYROJYPFDV-UHFFFAOYSA-N 2-bromo-1,3-dichloro-5-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC(Cl)=C(Br)C(Cl)=C1 IQHSSYROJYPFDV-UHFFFAOYSA-N 0.000 claims description 2
- JRLTTZUODKEYDH-UHFFFAOYSA-N 8-methylquinoline Chemical group C1=CN=C2C(C)=CC=CC2=C1 JRLTTZUODKEYDH-UHFFFAOYSA-N 0.000 claims description 2
- 229940083914 URAT1 inhibitor Drugs 0.000 claims description 2
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000006125 ethylsulfonyl group Chemical group 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- GJLOKYIYZIOIPN-UHFFFAOYSA-N 5-chloropyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(Cl)C=N1 GJLOKYIYZIOIPN-UHFFFAOYSA-N 0.000 claims 4
- VFMUXIRJRXFVAD-UHFFFAOYSA-N 1-[(2,5-dichlorophenyl)methyl]-5-(5-fluoropyridin-3-yl)-n-methylsulfonylpyrrole-2-carboxamide Chemical compound C=1C(Cl)=CC=C(Cl)C=1CN1C(C(=O)NS(=O)(=O)C)=CC=C1C1=CN=CC(F)=C1 VFMUXIRJRXFVAD-UHFFFAOYSA-N 0.000 claims 2
- QTWFANLICQFIDK-UHFFFAOYSA-N 1-[(2,5-dichlorophenyl)methyl]-5-(5-fluoropyridin-3-yl)pyrrole-2-carboxylic acid Chemical compound C=1C(Cl)=CC=C(Cl)C=1CN1C(C(=O)O)=CC=C1C1=CN=CC(F)=C1 QTWFANLICQFIDK-UHFFFAOYSA-N 0.000 claims 2
- UKWQCATXJHTCEL-UHFFFAOYSA-N 1-[(2,5-dichlorophenyl)methyl]-5-(5-methylpyridin-3-yl)pyrrole-2-carboxylic acid Chemical compound CC1=CN=CC(C=2N(C(C(O)=O)=CC=2)CC=2C(=CC=C(Cl)C=2)Cl)=C1 UKWQCATXJHTCEL-UHFFFAOYSA-N 0.000 claims 2
- JEDRULCJYVMJIL-UHFFFAOYSA-N 1-[(2,5-dichlorophenyl)methyl]-5-pyridin-3-ylpyrrole-2-carboxylic acid Chemical compound C=1C(Cl)=CC=C(Cl)C=1CN1C(C(=O)O)=CC=C1C1=CC=CN=C1 JEDRULCJYVMJIL-UHFFFAOYSA-N 0.000 claims 2
- OYWSAUWBAMKMHQ-UHFFFAOYSA-N 1-[(2,5-dichlorophenyl)methyl]-n-methylsulfonyl-5-pyridin-3-ylpyrrole-2-carboxamide Chemical compound C=1C(Cl)=CC=C(Cl)C=1CN1C(C(=O)NS(=O)(=O)C)=CC=C1C1=CC=CN=C1 OYWSAUWBAMKMHQ-UHFFFAOYSA-N 0.000 claims 2
- SPYLPSQENGZXMM-UHFFFAOYSA-N 1-[(2,5-dimethylphenyl)methyl]-5-pyridin-3-ylpyrrole-2-carboxylic acid Chemical compound CC1=CC=C(C)C(CN2C(=CC=C2C(O)=O)C=2C=NC=CC=2)=C1 SPYLPSQENGZXMM-UHFFFAOYSA-N 0.000 claims 2
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims 2
- ANVCNSSMSMUJDJ-UHFFFAOYSA-N 1-methyl-5-pyridin-3-ylpyrrole-2-carboxylic acid Chemical compound CN1C(C(O)=O)=CC=C1C1=CC=CN=C1 ANVCNSSMSMUJDJ-UHFFFAOYSA-N 0.000 claims 2
- BVVNCWBGCFGVAU-UHFFFAOYSA-N 4-(trifluoromethyl)-1-benzothiophene-2-carboxylic acid Chemical compound C1=CC=C2SC(C(=O)O)=CC2=C1C(F)(F)F BVVNCWBGCFGVAU-UHFFFAOYSA-N 0.000 claims 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 2
- XEHZMRPYICCAOB-UHFFFAOYSA-N 5-(5-chloropyridin-3-yl)-1-[(2,5-dichlorophenyl)methyl]-n-methylsulfonylpyrrole-2-carboxamide Chemical compound C=1C(Cl)=CC=C(Cl)C=1CN1C(C(=O)NS(=O)(=O)C)=CC=C1C1=CN=CC(Cl)=C1 XEHZMRPYICCAOB-UHFFFAOYSA-N 0.000 claims 2
- CPZDKJXBLKNJOB-UHFFFAOYSA-N 5-(5-chloropyridin-3-yl)-n-cyclopropylsulfonyl-1-[(2,5-dichlorophenyl)methyl]pyrrole-2-carboxamide Chemical compound ClC1=CC=C(Cl)C(CN2C(=CC=C2C(=O)NS(=O)(=O)C2CC2)C=2C=C(Cl)C=NC=2)=C1 CPZDKJXBLKNJOB-UHFFFAOYSA-N 0.000 claims 2
- WOBBVYCMKRJMFS-UHFFFAOYSA-N ClC=1C=C(C=NC1)C=1N(C(=C(N1)C(=O)O)C(=O)O)CC1=C(C=CC(=C1)Cl)Cl Chemical compound ClC=1C=C(C=NC1)C=1N(C(=C(N1)C(=O)O)C(=O)O)CC1=C(C=CC(=C1)Cl)Cl WOBBVYCMKRJMFS-UHFFFAOYSA-N 0.000 claims 2
- QKICVGWLUYRTCB-UHFFFAOYSA-N ClC=1C=C(C=NC1)C=1N(C(=CC1)C(=O)O)CC1=C(C=CC(=C1)Cl)Cl Chemical compound ClC=1C=C(C=NC1)C=1N(C(=CC1)C(=O)O)CC1=C(C=CC(=C1)Cl)Cl QKICVGWLUYRTCB-UHFFFAOYSA-N 0.000 claims 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 2
- TXWOGHSRPAYOML-UHFFFAOYSA-N cyclobutanecarboxylic acid Chemical compound OC(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-N 0.000 claims 2
- LIALEJLYIDSXQD-UHFFFAOYSA-N n-cyclopropylsulfonyl-1-[(2,5-dichlorophenyl)methyl]-5-(5-fluoropyridin-3-yl)pyrrole-2-carboxamide Chemical compound FC1=CN=CC(C=2N(C(C(=O)NS(=O)(=O)C3CC3)=CC=2)CC=2C(=CC=C(Cl)C=2)Cl)=C1 LIALEJLYIDSXQD-UHFFFAOYSA-N 0.000 claims 2
- AHYQPYJVNDSRFG-UHFFFAOYSA-N n-cyclopropylsulfonyl-1-[(2,5-dichlorophenyl)methyl]-5-pyridin-3-ylpyrrole-2-carboxamide Chemical compound ClC1=CC=C(Cl)C(CN2C(=CC=C2C(=O)NS(=O)(=O)C2CC2)C=2C=NC=CC=2)=C1 AHYQPYJVNDSRFG-UHFFFAOYSA-N 0.000 claims 2
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 claims 2
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 claims 1
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims 1
- 125000006280 2-bromobenzyl group Chemical group [H]C1=C([H])C(Br)=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000006512 3,4-dichlorobenzyl group Chemical group [H]C1=C(Cl)C(Cl)=C([H])C(=C1[H])C([H])([H])* 0.000 claims 1
- 125000006279 3-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Br)=C1[H])C([H])([H])* 0.000 claims 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims 1
- ZZLCFHIKESPLTH-UHFFFAOYSA-N 4-Methylbiphenyl Chemical compound C1=CC(C)=CC=C1C1=CC=CC=C1 ZZLCFHIKESPLTH-UHFFFAOYSA-N 0.000 claims 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
- 201000001320 Atherosclerosis Diseases 0.000 claims 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims 1
- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 claims 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims 1
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims 1
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims 1
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 claims 1
- 150000003230 pyrimidines Chemical class 0.000 claims 1
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims 1
- 101000821903 Homo sapiens Solute carrier family 22 member 12 Proteins 0.000 abstract description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 14
- 102100021495 Solute carrier family 22 member 12 Human genes 0.000 abstract description 13
- 201000010099 disease Diseases 0.000 abstract description 10
- 206010003210 Arteriosclerosis Diseases 0.000 abstract description 6
- 206010020772 Hypertension Diseases 0.000 abstract description 6
- 208000011775 arteriosclerosis disease Diseases 0.000 abstract description 6
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 5
- 201000006334 interstitial nephritis Diseases 0.000 abstract description 5
- 230000002265 prevention Effects 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 138
- 238000006243 chemical reaction Methods 0.000 description 105
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 88
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- 239000000243 solution Substances 0.000 description 59
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 56
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 56
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 53
- 239000012044 organic layer Substances 0.000 description 52
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 48
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 46
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 45
- 239000002904 solvent Substances 0.000 description 41
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 32
- 238000004440 column chromatography Methods 0.000 description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 30
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 28
- 229940116269 uric acid Drugs 0.000 description 28
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 27
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 27
- 239000012046 mixed solvent Substances 0.000 description 26
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 25
- 239000002585 base Substances 0.000 description 23
- 238000000746 purification Methods 0.000 description 21
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- 238000004128 high performance liquid chromatography Methods 0.000 description 20
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- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 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
- 238000005708 tetrahydropyranylation reaction Methods 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 125000000101 thioether group Chemical group 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
- GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 1
- IIHPVYJPDKJYOU-UHFFFAOYSA-N triphenylcarbethoxymethylenephosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OCC)C1=CC=CC=C1 IIHPVYJPDKJYOU-UHFFFAOYSA-N 0.000 description 1
- 108010078530 urate transporter Proteins 0.000 description 1
- 208000008281 urolithiasis Diseases 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D233/58—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- 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
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Beans For Foods Or Fodder (AREA)
- Heat Sensitive Colour Forming Recording (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JPJP-P-2012-250661 | 2012-11-14 | ||
| JP2012250661 | 2012-11-14 | ||
| PCT/JP2013/080706 WO2014077285A1 (ja) | 2012-11-14 | 2013-11-13 | ピリジン誘導体 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20150082194A true KR20150082194A (ko) | 2015-07-15 |
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| KR1020157008457A Withdrawn KR20150082194A (ko) | 2012-11-14 | 2013-11-13 | 피리딘 유도체 |
Country Status (36)
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| Publication number | Priority date | Publication date | Assignee | Title |
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| KR20170003569A (ko) * | 2014-05-13 | 2017-01-09 | 데이진 화-마 가부시키가이샤 | 피리딘 유도체의 신규 결정 다형체 및 그 제조 방법 |
| NO3144306T3 (enExample) * | 2014-05-13 | 2018-04-14 | ||
| US20200288710A1 (en) | 2016-03-15 | 2020-09-17 | Bayer Cropscience Aktiengesellschaft | Substituted sulphonamides for controlling animal pests |
| CN107286156A (zh) * | 2016-04-05 | 2017-10-24 | 江苏新元素医药科技有限公司 | 新型urat1抑制剂及其在医药上的应用 |
| CN106008488B (zh) * | 2016-05-20 | 2018-10-30 | 广东东阳光药业有限公司 | 氰基吲哚类衍生物及其制备方法和用途 |
| CA3025078C (en) * | 2016-05-23 | 2021-04-13 | Cstone Pharmaceutical (Suzhou) Co., Ltd. | Thiophene, manufacturing method thereof, and pharmaceutical application of same |
| TW201822637A (zh) | 2016-11-07 | 2018-07-01 | 德商拜耳廠股份有限公司 | 用於控制動物害蟲的經取代磺醯胺類 |
| UY37557A (es) | 2017-01-10 | 2018-07-31 | Bayer Ag | Derivados heterocíclicos como pesticidas |
| AU2018207776B2 (en) | 2017-01-10 | 2021-06-17 | Bayer Aktiengesellschaft | Heterocyclene derivatives as pest control agents |
| CN108658879A (zh) * | 2017-03-29 | 2018-10-16 | 天津药物研究院有限公司 | 一种urat1抑制剂及其制备方法和用途 |
| CN109251184B (zh) * | 2017-07-13 | 2021-06-15 | 浙江海正药业股份有限公司 | 一种2-三氟甲基苯磺酰胺类衍生物的医药用途 |
| WO2019226213A2 (en) | 2018-03-08 | 2019-11-28 | Incyte Corporation | AMINOPYRAZINE DIOL COMPOUNDS AS PI3K-y INHIBITORS |
| WO2020010003A1 (en) | 2018-07-02 | 2020-01-09 | Incyte Corporation | AMINOPYRAZINE DERIVATIVES AS PI3K-γ INHIBITORS |
| TWI820231B (zh) | 2018-10-11 | 2023-11-01 | 德商拜耳廠股份有限公司 | 用於製備經取代咪唑衍生物之方法 |
| CN111943957B (zh) * | 2019-05-17 | 2023-01-06 | 中国医学科学院药物研究所 | 喹啉甲酰胺类化合物及其制备方法和用途 |
| JP2023501978A (ja) | 2019-11-07 | 2023-01-20 | バイエル・アクチエンゲゼルシヤフト | 動物害虫駆除用の置換スルホニルアミド |
| KR20230039665A (ko) | 2020-07-02 | 2023-03-21 | 바이엘 악티엔게젤샤프트 | 해충 방제제로서의 헤테로사이클 유도체 |
| CN114315729B (zh) * | 2021-12-09 | 2024-01-26 | 大连理工大学 | 1-苄基-2，4-二芳基咪唑类化合物、合成方法及其在抗肿瘤上的应用 |
| WO2025026738A1 (en) | 2023-07-31 | 2025-02-06 | Bayer Aktiengesellschaft | 6-[5-(ethylsulfonyl)-1-methyl-1h-imidazol-4-yl]-7-methyl-3-(pentafluoroethyl)-7h-imidazo[4,5-c]pyridazine derivatives as pesticides |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1599032A (en) | 1977-03-04 | 1981-09-30 | May & Baker Ltd | Imidazole derivatives having herbicidal activity |
| JPS5671073A (en) | 1979-11-12 | 1981-06-13 | Takeda Chem Ind Ltd | Imidazole derivative |
| US4770689A (en) | 1986-03-10 | 1988-09-13 | Janssen Pharmaceutica N.V. | Herbicidal imidazole-5-carboxylic acid derivatives |
| PL149675B1 (pl) * | 1986-03-10 | 1990-03-31 | Sposób wytwarzania nowych pochodnych kwasu 1-metyl0-1h-imidaz0l0karb0ksyl0weg0-5 | |
| US4851424A (en) | 1986-06-06 | 1989-07-25 | Ciba-Geigy Corporation | 1-Phenyl-lower alkyl-imidazole 4- or 5-carboxamide compounds which are useful in the treatment of epilepsy |
| DD260928A5 (de) * | 1986-06-06 | 1988-10-12 | Ciba-Geigy Ag,Ch | Verfahren zur herstellung neuer aralkylimidizolderivate |
| JPH08119936A (ja) | 1994-10-18 | 1996-05-14 | Fujisawa Pharmaceut Co Ltd | 複素環式誘導体 |
| IT1295405B1 (it) * | 1997-09-30 | 1999-05-12 | Merck Sharp & Dohme Italia S P | Uso di un antagonista recettoriale di angiotensina ii per la preparazione di farmaci per aumentare il tasso di sopravvivenza di |
| CA2416946A1 (en) * | 2000-07-28 | 2003-01-22 | Sumitomo Pharmaceuticals Co., Ltd. | Pyrrole derivatives |
| JP3999128B2 (ja) | 2001-02-22 | 2007-10-31 | 帝人株式会社 | ベンゾ［ｂ］チオフェン誘導体、およびその製造方法 |
| AU2003902828A0 (en) * | 2003-06-05 | 2003-06-26 | Fujisawa Pharmaceutical Co., Ltd. | Dpp-iv inhibitor |
| MX2010005776A (es) * | 2007-11-27 | 2010-08-31 | Ardea Biosciences Inc | Nuevos compuestos y composiciones y metodos de uso. |
| WO2009148599A1 (en) * | 2008-06-04 | 2009-12-10 | Synta Pharmaceuticals Corp. | Pyrrole compunds that modulate hsp90 activity |
| CN103819419B (zh) * | 2008-09-04 | 2016-12-07 | 亚德生化公司 | 调节尿酸含量的化合物、组合物及其使用方法 |
| JP2010202575A (ja) * | 2009-03-03 | 2010-09-16 | Takeda Chem Ind Ltd | 複素環化合物 |
| BR112012000606A2 (pt) * | 2009-07-10 | 2016-11-22 | Brigham & Womens Hospital | análogos de etomidato que não inibem a síntese de esteróides adrenocorticais |
| CN102035579B (zh) * | 2009-09-28 | 2014-09-03 | 夏普株式会社 | 信息反馈方法和用户设备 |
| AR081930A1 (es) * | 2010-06-16 | 2012-10-31 | Ardea Biosciences Inc | Compuestos de tioacetato |
| JP5485811B2 (ja) * | 2010-06-23 | 2014-05-07 | 株式会社ジャパンディスプレイ | 双方向シフトレジスタ、及びこれを用いた画像表示装置 |
| UY33554A (es) | 2010-08-11 | 2012-02-29 | Millennium Pharm Inc | Heteroarilos y usos de los mismos |
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2013
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- 2013-11-13 CN CN201710933918.5A patent/CN107721931A/zh active Pending
- 2013-11-13 UA UAA201505767A patent/UA117359C2/uk unknown
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2015
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2017
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2018
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