NO325206B1 - N-substituerte hydroksypyrimidinonkarboksamidinhibitorer for HIV-integrase, farmasoytiske preparater som omfatter slike forbindelser, og anvendelse av forbindelsene ved fremstilling av medikamenter mot HIV og AIDS. - Google Patents
N-substituerte hydroksypyrimidinonkarboksamidinhibitorer for HIV-integrase, farmasoytiske preparater som omfatter slike forbindelser, og anvendelse av forbindelsene ved fremstilling av medikamenter mot HIV og AIDS. Download PDFInfo
- Publication number
- NO325206B1 NO325206B1 NO20042165A NO20042165A NO325206B1 NO 325206 B1 NO325206 B1 NO 325206B1 NO 20042165 A NO20042165 A NO 20042165A NO 20042165 A NO20042165 A NO 20042165A NO 325206 B1 NO325206 B1 NO 325206B1
- Authority
- NO
- Norway
- Prior art keywords
- methyl
- oxo
- hydroxy
- carboxamide
- alkyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims description 168
- -1 N-substituted hydroxypyrimidinone carboxamide Chemical class 0.000 title claims description 46
- 208000030507 AIDS Diseases 0.000 title claims description 16
- 239000003814 drug Substances 0.000 title claims description 6
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- 229940079593 drug Drugs 0.000 title claims description 3
- 239000003112 inhibitor Substances 0.000 title description 5
- 108010002459 HIV Integrase Proteins 0.000 title description 4
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 125000001424 substituent group Chemical group 0.000 claims description 171
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 96
- 125000005842 heteroatom Chemical group 0.000 claims description 82
- 125000000623 heterocyclic group Chemical group 0.000 claims description 78
- 229910052736 halogen Inorganic materials 0.000 claims description 73
- 150000002367 halogens Chemical class 0.000 claims description 72
- 229920006395 saturated elastomer Polymers 0.000 claims description 67
- 125000001072 heteroaryl group Chemical group 0.000 claims description 56
- 125000000217 alkyl group Chemical group 0.000 claims description 55
- 150000003839 salts Chemical class 0.000 claims description 51
- 125000003118 aryl group Chemical group 0.000 claims description 48
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 44
- 125000004043 oxo group Chemical group O=* 0.000 claims description 42
- 125000004432 carbon atom Chemical group C* 0.000 claims description 36
- 229910052757 nitrogen Inorganic materials 0.000 claims description 28
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 28
- 125000002619 bicyclic group Chemical group 0.000 claims description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- 125000002950 monocyclic group Chemical group 0.000 claims description 24
- 239000000460 chlorine Substances 0.000 claims description 23
- 229910052794 bromium Inorganic materials 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 18
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 17
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 17
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 17
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 17
- 125000002837 carbocyclic group Chemical group 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 229910052801 chlorine Inorganic materials 0.000 claims description 17
- 239000011737 fluorine Substances 0.000 claims description 17
- 229910052731 fluorine Inorganic materials 0.000 claims description 17
- 229910052760 oxygen Inorganic materials 0.000 claims description 17
- 229910052717 sulfur Inorganic materials 0.000 claims description 17
- 125000004122 cyclic group Chemical group 0.000 claims description 16
- 125000001624 naphthyl group Chemical group 0.000 claims description 13
- 238000011321 prophylaxis Methods 0.000 claims description 13
- MMPZNODECHHWIW-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-2-(4-methylmorpholin-3-yl)-6-oxopyrimidine-4-carboxamide Chemical compound CN1CCOCC1C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N1C MMPZNODECHHWIW-UHFFFAOYSA-N 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 10
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 9
- MAUMSNABMVEOGP-UHFFFAOYSA-N (methyl-$l^{2}-azanyl)methane Chemical compound C[N]C MAUMSNABMVEOGP-UHFFFAOYSA-N 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 208000015181 infectious disease Diseases 0.000 claims description 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 5
- KICKGPQKASOONE-UHFFFAOYSA-N 2-(4-ethyl-1-methylpiperazin-2-yl)-n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxopyrimidine-4-carboxamide Chemical compound C1N(CC)CCN(C)C1C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N1C KICKGPQKASOONE-UHFFFAOYSA-N 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 125000002527 bicyclic carbocyclic group Chemical group 0.000 claims description 5
- KHJBWBNIGQBOFA-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxo-2-[1-(pyridine-2-carbonyl)-3,4-dihydro-2h-quinolin-2-yl]pyrimidine-4-carboxamide Chemical compound OC=1C(=O)N(C)C(C2N(C3=CC=CC=C3CC2)C(=O)C=2N=CC=CC=2)=NC=1C(=O)NCC1=CC=C(F)C=C1 KHJBWBNIGQBOFA-UHFFFAOYSA-N 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- SXBRRPCHWCRBGM-UHFFFAOYSA-N 2-(1-acetylpyrrolidin-2-yl)-n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxopyrimidine-4-carboxamide Chemical compound CC(=O)N1CCCC1C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N1C SXBRRPCHWCRBGM-UHFFFAOYSA-N 0.000 claims description 4
- ALTIACWYHGENDH-ZDUSSCGKSA-N 2-[(2s)-1-[2-(dimethylamino)-2-oxoacetyl]-4,4-difluoropyrrolidin-2-yl]-n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxopyrimidine-4-carboxamide Chemical compound CN(C)C(=O)C(=O)N1CC(F)(F)C[C@H]1C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N1C ALTIACWYHGENDH-ZDUSSCGKSA-N 0.000 claims description 4
- XWCKLKLAVPVPPD-MSOLQXFVSA-N 2-[(2s,4r)-1-benzoyl-4-hydroxypyrrolidin-2-yl]-n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxopyrimidine-4-carboxamide Chemical compound OC=1C(=O)N(C)C([C@H]2N(C[C@H](O)C2)C(=O)C=2C=CC=CC=2)=NC=1C(=O)NCC1=CC=C(F)C=C1 XWCKLKLAVPVPPD-MSOLQXFVSA-N 0.000 claims description 4
- MMUHCXFDVPIMLD-RPBOFIJWSA-N 2-[(2s,4r)-1-benzoyl-4-phenylmethoxypyrrolidin-2-yl]-n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxopyrimidine-4-carboxamide Chemical compound OC=1C(=O)N(C)C([C@H]2N(C[C@@H](C2)OCC=2C=CC=CC=2)C(=O)C=2C=CC=CC=2)=NC=1C(=O)NCC1=CC=C(F)C=C1 MMUHCXFDVPIMLD-RPBOFIJWSA-N 0.000 claims description 4
- NBBLWTOHJFZTMU-KBPBESRZSA-N 2-[(2s,4s)-1-acetyl-4-fluoropyrrolidin-2-yl]-n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxopyrimidine-4-carboxamide Chemical compound CC(=O)N1C[C@@H](F)C[C@H]1C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N1C NBBLWTOHJFZTMU-KBPBESRZSA-N 0.000 claims description 4
- UTJPUNPSZAIQOP-UHFFFAOYSA-N 2-[2-(4-benzoylpiperazin-1-yl)ethyl]-n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxopyrimidine-4-carboxamide Chemical compound N=1C(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N(C)C=1CCN(CC1)CCN1C(=O)C1=CC=CC=C1 UTJPUNPSZAIQOP-UHFFFAOYSA-N 0.000 claims description 4
- 150000001204 N-oxides Chemical class 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- OVRFHKWFMGUJFC-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxopyrimidine-4-carboxamide Chemical compound O=C1N(C)C=NC(C(=O)NCC=2C=CC(F)=CC=2)=C1O OVRFHKWFMGUJFC-UHFFFAOYSA-N 0.000 claims description 4
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 3
- ZUEYJJHLMMKJSS-UHFFFAOYSA-N 2-(1,2-dimethyl-4-methylsulfonylpiperazin-2-yl)-n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxopyrimidine-4-carboxamide Chemical compound CN1CCN(S(C)(=O)=O)CC1(C)C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N1C ZUEYJJHLMMKJSS-UHFFFAOYSA-N 0.000 claims description 3
- HTUOQGFZWIWCSK-UHFFFAOYSA-N 2-(1,4-dimethylpiperazin-2-yl)-n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxopyrimidine-4-carboxamide Chemical compound C1N(C)CCN(C)C1C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N1C HTUOQGFZWIWCSK-UHFFFAOYSA-N 0.000 claims description 3
- GVTUUPQFRYGXMA-UHFFFAOYSA-N 2-(1-benzoyl-2,3-dihydroindol-2-yl)-n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxopyrimidine-4-carboxamide Chemical compound OC=1C(=O)N(C)C(C2N(C3=CC=CC=C3C2)C(=O)C=2C=CC=CC=2)=NC=1C(=O)NCC1=CC=C(F)C=C1 GVTUUPQFRYGXMA-UHFFFAOYSA-N 0.000 claims description 3
- QRIHGCAEXUHLOW-UHFFFAOYSA-N 2-(1-benzoylpyrrolidin-2-yl)-n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxopyrimidine-4-carboxamide Chemical compound OC=1C(=O)N(C)C(C2N(CCC2)C(=O)C=2C=CC=CC=2)=NC=1C(=O)NCC1=CC=C(F)C=C1 QRIHGCAEXUHLOW-UHFFFAOYSA-N 0.000 claims description 3
- FOSNNBJCOZOKQS-RTWAWAEBSA-N 2-[(2s,4r)-1-acetyl-4-phenylmethoxypyrrolidin-2-yl]-n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxopyrimidine-4-carboxamide Chemical compound OC=1C(=O)N(C)C([C@@H]2C[C@H](CN2C(=O)C)OCC=2C=CC=CC=2)=NC=1C(=O)NCC1=CC=C(F)C=C1 FOSNNBJCOZOKQS-RTWAWAEBSA-N 0.000 claims description 3
- MPSJYOCYFDZSFL-ZDUSSCGKSA-N 2-[(4r)-3-acetyl-1,3-thiazolidin-4-yl]-n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxopyrimidine-4-carboxamide Chemical compound CC(=O)N1CSC[C@H]1C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N1C MPSJYOCYFDZSFL-ZDUSSCGKSA-N 0.000 claims description 3
- NGPNFONVUNXVEL-UHFFFAOYSA-N 2-[1-(dimethylamino)-2-phenylethyl]-n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxopyrimidine-4-carboxamide Chemical compound N=1C(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N(C)C=1C(N(C)C)CC1=CC=CC=C1 NGPNFONVUNXVEL-UHFFFAOYSA-N 0.000 claims description 3
- RFJKJXDRFILWJW-UHFFFAOYSA-N 2-[1-(ethylcarbamoyl)pyrrolidin-2-yl]-n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxopyrimidine-4-carboxamide Chemical compound CCNC(=O)N1CCCC1C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N1C RFJKJXDRFILWJW-UHFFFAOYSA-N 0.000 claims description 3
- KNIHLZWBFJLOPD-UHFFFAOYSA-N 2-[dimethylamino(phenyl)methyl]-n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxopyrimidine-4-carboxamide Chemical compound N=1C(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N(C)C=1C(N(C)C)C1=CC=CC=C1 KNIHLZWBFJLOPD-UHFFFAOYSA-N 0.000 claims description 3
- JQIPHXBYCSUSNI-UHFFFAOYSA-N 4-n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxo-2-n-(pyridin-2-ylmethyl)pyrimidine-2,4-dicarboxamide Chemical compound OC=1C(=O)N(C)C(C(=O)NCC=2N=CC=CC=2)=NC=1C(=O)NCC1=CC=C(F)C=C1 JQIPHXBYCSUSNI-UHFFFAOYSA-N 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 125000001188 haloalkyl group Chemical group 0.000 claims description 3
- QYJBDRMUCWAECJ-UHFFFAOYSA-N n-[(2,3-dimethoxyphenyl)methyl]-5-hydroxy-1-methyl-2-[4-(morpholin-4-ylmethyl)phenyl]-6-oxopyrimidine-4-carboxamide Chemical compound COC1=CC=CC(CNC(=O)C2=C(C(=O)N(C)C(C=3C=CC(CN4CCOCC4)=CC=3)=N2)O)=C1OC QYJBDRMUCWAECJ-UHFFFAOYSA-N 0.000 claims description 3
- VZCYYKRGROYDTL-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-5-hydroxy-1-(2-hydroxy-3-morpholin-4-ylpropyl)-6-oxopyrimidine-4-carboxamide Chemical compound C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N1CC(O)CN1CCOCC1 VZCYYKRGROYDTL-UHFFFAOYSA-N 0.000 claims description 3
- JDCVYDDPFWSXIY-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-2-(1-methyl-3,4-dihydro-2h-quinolin-2-yl)-6-oxopyrimidine-4-carboxamide Chemical compound C1CC2=CC=CC=C2N(C)C1C(N(C(=O)C=1O)C)=NC=1C(=O)NCC1=CC=C(F)C=C1 JDCVYDDPFWSXIY-UHFFFAOYSA-N 0.000 claims description 3
- SCQMBPMJBXEQHB-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-2-(1-methyl-4-propan-2-ylsulfonylpiperazin-2-yl)-6-oxopyrimidine-4-carboxamide Chemical compound C1N(S(=O)(=O)C(C)C)CCN(C)C1C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N1C SCQMBPMJBXEQHB-UHFFFAOYSA-N 0.000 claims description 3
- AHOZQSJDGWQTGZ-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-2-(1-methylpiperazin-2-yl)-6-oxopyrimidine-4-carboxamide Chemical compound CN1CCNCC1C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N1C AHOZQSJDGWQTGZ-UHFFFAOYSA-N 0.000 claims description 3
- HGPPRMHXEAZMCS-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-2-(1-methylpiperidin-2-yl)-6-oxopyrimidine-4-carboxamide Chemical compound CN1CCCCC1C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N1C HGPPRMHXEAZMCS-UHFFFAOYSA-N 0.000 claims description 3
- VKPSGRZTOPVKNO-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-2-(1-methylsulfonylpyrrolidin-2-yl)-6-oxopyrimidine-4-carboxamide Chemical compound OC=1C(=O)N(C)C(C2N(CCC2)S(C)(=O)=O)=NC=1C(=O)NCC1=CC=C(F)C=C1 VKPSGRZTOPVKNO-UHFFFAOYSA-N 0.000 claims description 3
- XELOXWAFQQJLHA-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-2-(2-methyl-3,4-dihydro-1h-isoquinolin-3-yl)-6-oxopyrimidine-4-carboxamide Chemical compound CN1CC2=CC=CC=C2CC1C(N(C(=O)C=1O)C)=NC=1C(=O)NCC1=CC=C(F)C=C1 XELOXWAFQQJLHA-UHFFFAOYSA-N 0.000 claims description 3
- WHVOMNUJJHPZEB-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-2-(4-methylphenyl)-6-oxopyrimidine-4-carboxamide Chemical compound C1=CC(C)=CC=C1C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N1C WHVOMNUJJHPZEB-UHFFFAOYSA-N 0.000 claims description 3
- IEKQWIQTLCCVDM-UXHICEINSA-N n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-2-[(2s,4r)-1-methyl-4-phenylmethoxypyrrolidin-2-yl]-6-oxopyrimidine-4-carboxamide Chemical compound OC=1C(=O)N(C)C([C@@H]2C[C@H](CN2C)OCC=2C=CC=CC=2)=NC=1C(=O)NCC1=CC=C(F)C=C1 IEKQWIQTLCCVDM-UXHICEINSA-N 0.000 claims description 3
- DXFBOOODWPDDKU-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-2-[1-(1-methylimidazole-2-carbonyl)pyrrolidin-2-yl]-6-oxopyrimidine-4-carboxamide Chemical compound CN1C=CN=C1C(=O)N1C(C=2N(C(=O)C(O)=C(C(=O)NCC=3C=CC(F)=CC=3)N=2)C)CCC1 DXFBOOODWPDDKU-UHFFFAOYSA-N 0.000 claims description 3
- IPNOUNCILQRZJN-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-2-[1-(1-oxidopyridin-1-ium-2-carbonyl)pyrrolidin-2-yl]-6-oxopyrimidine-4-carboxamide Chemical compound OC=1C(=O)N(C)C(C2N(CCC2)C(=O)C=2[N+](=CC=CC=2)[O-])=NC=1C(=O)NCC1=CC=C(F)C=C1 IPNOUNCILQRZJN-UHFFFAOYSA-N 0.000 claims description 3
- DTHZLIPXZZDEAW-VWNXMTODSA-N n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxo-2-[(2s,4r)-4-phenylmethoxy-1-(pyridine-2-carbonyl)pyrrolidin-2-yl]pyrimidine-4-carboxamide Chemical compound OC=1C(=O)N(C)C([C@H]2N(C[C@@H](C2)OCC=2C=CC=CC=2)C(=O)C=2N=CC=CC=2)=NC=1C(=O)NCC1=CC=C(F)C=C1 DTHZLIPXZZDEAW-VWNXMTODSA-N 0.000 claims description 3
- FMLGYBYNMDDGBV-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxo-2-[1-(pyridine-2-carbonyl)-2,3-dihydroindol-2-yl]pyrimidine-4-carboxamide Chemical compound OC=1C(=O)N(C)C(C2N(C3=CC=CC=C3C2)C(=O)C=2N=CC=CC=2)=NC=1C(=O)NCC1=CC=C(F)C=C1 FMLGYBYNMDDGBV-UHFFFAOYSA-N 0.000 claims description 3
- BCCKQMVHHMROSZ-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxo-2-[1-(pyridine-2-carbonyl)pyrrolidin-2-yl]pyrimidine-4-carboxamide Chemical compound OC=1C(=O)N(C)C(C2N(CCC2)C(=O)C=2N=CC=CC=2)=NC=1C(=O)NCC1=CC=C(F)C=C1 BCCKQMVHHMROSZ-UHFFFAOYSA-N 0.000 claims description 3
- DKAPDWBJGOHKGB-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxo-2-[1-(pyridine-3-carbonyl)pyrrolidin-2-yl]pyrimidine-4-carboxamide Chemical compound OC=1C(=O)N(C)C(C2N(CCC2)C(=O)C=2C=NC=CC=2)=NC=1C(=O)NCC1=CC=C(F)C=C1 DKAPDWBJGOHKGB-UHFFFAOYSA-N 0.000 claims description 3
- ROOWWHJTOPZXFJ-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxo-2-[1-(pyridine-4-carbonyl)pyrrolidin-2-yl]pyrimidine-4-carboxamide Chemical compound OC=1C(=O)N(C)C(C2N(CCC2)C(=O)C=2C=CN=CC=2)=NC=1C(=O)NCC1=CC=C(F)C=C1 ROOWWHJTOPZXFJ-UHFFFAOYSA-N 0.000 claims description 3
- WGLILLWPZIBWTQ-UHFFFAOYSA-N n-[2-[4-[(4-fluorophenyl)methylcarbamoyl]-5-hydroxy-1-methyl-6-oxopyrimidin-2-yl]propan-2-yl]-n',n'-dimethyloxamide Chemical compound O=C1N(C)C(C(C)(C)NC(=O)C(=O)N(C)C)=NC(C(=O)NCC=2C=CC(F)=CC=2)=C1O WGLILLWPZIBWTQ-UHFFFAOYSA-N 0.000 claims description 3
- CZFFBEXEKNGXKS-UHFFFAOYSA-N raltegravir Chemical compound O1C(C)=NN=C1C(=O)NC(C)(C)C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N1C CZFFBEXEKNGXKS-UHFFFAOYSA-N 0.000 claims description 3
- HALJILNZFAWGDL-UHFFFAOYSA-N 1-[2-(dimethylamino)ethyl]-n-[(4-fluorophenyl)methyl]-5-hydroxy-2-(2-methylphenyl)-6-oxopyrimidine-4-carboxamide Chemical compound OC=1C(=O)N(CCN(C)C)C(C=2C(=CC=CC=2)C)=NC=1C(=O)NCC1=CC=C(F)C=C1 HALJILNZFAWGDL-UHFFFAOYSA-N 0.000 claims description 2
- INUPCGQJKUVPAZ-UHFFFAOYSA-N 1-[2-(dimethylamino)ethyl]-n-[(4-fluorophenyl)methyl]-5-hydroxy-6-oxopyrimidine-4-carboxamide Chemical compound O=C1N(CCN(C)C)C=NC(C(=O)NCC=2C=CC(F)=CC=2)=C1O INUPCGQJKUVPAZ-UHFFFAOYSA-N 0.000 claims description 2
- HBODMPJFESBLQE-UHFFFAOYSA-N 1-[[3-[(dimethylamino)methyl]phenyl]methyl]-n-[(4-fluorophenyl)methyl]-5-hydroxy-6-oxopyrimidine-4-carboxamide Chemical compound CN(C)CC1=CC=CC(CN2C(C(O)=C(C(=O)NCC=3C=CC(F)=CC=3)N=C2)=O)=C1 HBODMPJFESBLQE-UHFFFAOYSA-N 0.000 claims description 2
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- DVTFIKHECBTSFC-UHFFFAOYSA-N methyl 5-benzoyloxy-1-methyl-6-oxo-2-[1-(pyridine-2-carbonyl)-3,4-dihydro-2h-quinolin-2-yl]pyrimidine-4-carboxylate Chemical compound CN1C(=O)C(OC(=O)C=2C=CC=CC=2)=C(C(=O)OC)N=C1C1CCC2=CC=CC=C2N1C(=O)C1=CC=CC=N1 DVTFIKHECBTSFC-UHFFFAOYSA-N 0.000 description 1
- GBJRHCBFWYGWNQ-UHFFFAOYSA-N methyl 5-benzoyloxy-1-methyl-6-oxo-2-[2-(phenylmethoxycarbonylamino)propan-2-yl]pyrimidine-4-carboxylate Chemical compound COC(=O)C=1N=C(C(C)(C)NC(=O)OCC=2C=CC=CC=2)N(C)C(=O)C=1OC(=O)C1=CC=CC=C1 GBJRHCBFWYGWNQ-UHFFFAOYSA-N 0.000 description 1
- VIMNXOVYNCDMCB-UHFFFAOYSA-N methyl 5-benzoyloxy-1-methyl-6-oxo-2-pyrrolidin-2-ylpyrimidine-4-carboxylate Chemical compound CN1C(=O)C(OC(=O)C=2C=CC=CC=2)=C(C(=O)OC)N=C1C1CCCN1 VIMNXOVYNCDMCB-UHFFFAOYSA-N 0.000 description 1
- KEEUHMLRKZXAEX-UHFFFAOYSA-N methyl 5-benzoyloxy-2-(2,2-dimethoxyethyl)-1-methyl-6-oxopyrimidine-4-carboxylate Chemical compound O=C1N(C)C(CC(OC)OC)=NC(C(=O)OC)=C1OC(=O)C1=CC=CC=C1 KEEUHMLRKZXAEX-UHFFFAOYSA-N 0.000 description 1
- SRGYDAXUMYGKET-UHFFFAOYSA-N methyl 5-benzoyloxy-2-(2,3-dihydro-1h-indol-2-yl)-1-methyl-6-oxopyrimidine-4-carboxylate Chemical compound COC(=O)C=1N=C(C2NC3=CC=CC=C3C2)N(C)C(=O)C=1OC(=O)C1=CC=CC=C1 SRGYDAXUMYGKET-UHFFFAOYSA-N 0.000 description 1
- XSONXZYMUWRHMW-RPBOFIJWSA-N methyl 5-benzoyloxy-2-[(2s,4r)-1-benzoyl-4-phenylmethoxypyrrolidin-2-yl]-1-methyl-6-oxopyrimidine-4-carboxylate Chemical compound C([C@@H](C[C@H]1C2=NC(=C(C(=O)N2C)OC(=O)C=2C=CC=CC=2)C(=O)OC)OCC=2C=CC=CC=2)N1C(=O)C1=CC=CC=C1 XSONXZYMUWRHMW-RPBOFIJWSA-N 0.000 description 1
- FJDBKOIZVMMARN-UXHICEINSA-N methyl 5-benzoyloxy-2-[(2s,4r)-4-methoxy-1-phenylmethoxycarbonylpyrrolidin-2-yl]-1-methyl-6-oxopyrimidine-4-carboxylate Chemical compound N1([C@@H](C[C@H](C1)OC)C=1N(C(=O)C(OC(=O)C=2C=CC=CC=2)=C(C(=O)OC)N=1)C)C(=O)OCC1=CC=CC=C1 FJDBKOIZVMMARN-UXHICEINSA-N 0.000 description 1
- QZNAOLMQVYKMFD-UHFFFAOYSA-N methyl 5-benzoyloxy-2-[1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidin-2-yl]-4-oxo-1h-pyrimidine-6-carboxylate Chemical compound COC(=O)C1=NC(C2N(CCC2)C(=O)OC(C)(C)C)=NC(O)=C1OC(=O)C1=CC=CC=C1 QZNAOLMQVYKMFD-UHFFFAOYSA-N 0.000 description 1
- GXVPHPOAYVJOLB-UHFFFAOYSA-N methyl 5-hydroxy-4-oxo-1h-pyrimidine-6-carboxylate Chemical compound COC(=O)C1=NC=NC(O)=C1O GXVPHPOAYVJOLB-UHFFFAOYSA-N 0.000 description 1
- 125000004492 methyl ester group Chemical group 0.000 description 1
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- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- DWNWXQVKMRJASU-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-2-[2-[(2-morpholin-4-yl-2-oxoacetyl)amino]propan-2-yl]-6-oxopyrimidine-4-carboxamide Chemical compound OC=1C(=O)N(C)C(C(C)(C)NC(=O)C(=O)N2CCOCC2)=NC=1C(=O)NCC1=CC=C(F)C=C1 DWNWXQVKMRJASU-UHFFFAOYSA-N 0.000 description 1
- LGPINXWKVBCQRV-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-2-[4-(morpholin-4-ylmethyl)phenyl]-6-oxopyrimidine-4-carboxamide Chemical compound OC=1C(=O)N(C)C(C=2C=CC(CN3CCOCC3)=CC=2)=NC=1C(=O)NCC1=CC=C(F)C=C1 LGPINXWKVBCQRV-UHFFFAOYSA-N 0.000 description 1
- FAQIGTGQCLFKIU-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-2-morpholin-3-yl-6-oxopyrimidine-4-carboxamide Chemical compound OC=1C(=O)N(C)C(C2NCCOC2)=NC=1C(=O)NCC1=CC=C(F)C=C1 FAQIGTGQCLFKIU-UHFFFAOYSA-N 0.000 description 1
- NTPGQOSRPGSHTJ-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxo-2-(2-oxoethyl)pyrimidine-4-carboxamide Chemical compound O=C1N(C)C(CC=O)=NC(C(=O)NCC=2C=CC(F)=CC=2)=C1O NTPGQOSRPGSHTJ-UHFFFAOYSA-N 0.000 description 1
- IFYDWYVPVAMGRO-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]tetradecanamide Chemical compound CCCCCCCCCCCCCC(=O)NCCCN(C)C IFYDWYVPVAMGRO-UHFFFAOYSA-N 0.000 description 1
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- 239000007922 nasal spray Substances 0.000 description 1
- QAGYKUNXZHXKMR-HKWSIXNMSA-N nelfinavir Chemical compound CC1=C(O)C=CC=C1C(=O)N[C@H]([C@H](O)CN1[C@@H](C[C@@H]2CCCC[C@@H]2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-HKWSIXNMSA-N 0.000 description 1
- 229960000884 nelfinavir Drugs 0.000 description 1
- 150000002829 nitrogen Chemical class 0.000 description 1
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- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
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- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- VUNXBQRNMNVUMV-UHFFFAOYSA-N phenyl(piperazin-1-yl)methanone Chemical compound C=1C=CC=CC=1C(=O)N1CCNCC1 VUNXBQRNMNVUMV-UHFFFAOYSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- JSSXHAMIXJGYCS-UHFFFAOYSA-N piperazin-4-ium-2-carboxylate Chemical compound OC(=O)C1CNCCN1 JSSXHAMIXJGYCS-UHFFFAOYSA-N 0.000 description 1
- 108700004029 pol Genes Proteins 0.000 description 1
- 101150088264 pol gene Proteins 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
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- 239000003223 protective agent Substances 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
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- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 1
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
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- NUMIITGLIZNJIC-UHFFFAOYSA-N tert-butyl 2-[(z)-n'-hydroxycarbamimidoyl]pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC1C(N)=NO NUMIITGLIZNJIC-UHFFFAOYSA-N 0.000 description 1
- MDMSZBHMBCNYNO-UHFFFAOYSA-N tert-butyl 2-cyanopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC1C#N MDMSZBHMBCNYNO-UHFFFAOYSA-N 0.000 description 1
- MCSBQUCETYKRME-UHFFFAOYSA-N tert-butyl 3-(5-benzoyloxy-4-methoxy-6-methoxycarbonylpyrimidin-2-yl)morpholine-4-carboxylate Chemical compound COC(=O)C1=NC(C2N(CCOC2)C(=O)OC(C)(C)C)=NC(OC)=C1OC(=O)C1=CC=CC=C1 MCSBQUCETYKRME-UHFFFAOYSA-N 0.000 description 1
- LZHCFNBKMAWVPR-UHFFFAOYSA-N tert-butyl 3-(5-benzoyloxy-4-methoxycarbonyl-1-methyl-6-oxopyrimidin-2-yl)morpholine-4-carboxylate Chemical compound CN1C(=O)C(OC(=O)C=2C=CC=CC=2)=C(C(=O)OC)N=C1C1COCCN1C(=O)OC(C)(C)C LZHCFNBKMAWVPR-UHFFFAOYSA-N 0.000 description 1
- IPPMOUVOYGDPJP-UHFFFAOYSA-N tert-butyl 3-(5-benzoyloxy-6-methoxycarbonyl-4-oxo-1h-pyrimidin-2-yl)morpholine-4-carboxylate Chemical compound COC(=O)C1=NC(C2N(CCOC2)C(=O)OC(C)(C)C)=NC(O)=C1OC(=O)C1=CC=CC=C1 IPPMOUVOYGDPJP-UHFFFAOYSA-N 0.000 description 1
- MTAIAOFUTBJABI-UHFFFAOYSA-N tert-butyl 3-(5-hydroxy-6-methoxycarbonyl-4-oxo-1h-pyrimidin-2-yl)morpholine-4-carboxylate Chemical compound OC1=C(O)C(C(=O)OC)=NC(C2N(CCOC2)C(=O)OC(C)(C)C)=N1 MTAIAOFUTBJABI-UHFFFAOYSA-N 0.000 description 1
- JHNBDFZBWYOJPY-UHFFFAOYSA-N tert-butyl 3-(n'-hydroxycarbamimidoyl)morpholine-4-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCOCC1\C(N)=N\O JHNBDFZBWYOJPY-UHFFFAOYSA-N 0.000 description 1
- AMDFBQXRVZTTKM-UHFFFAOYSA-N tert-butyl 3-carbamoylmorpholine-4-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCOCC1C(N)=O AMDFBQXRVZTTKM-UHFFFAOYSA-N 0.000 description 1
- QSBSEJKNKHZYKD-UHFFFAOYSA-N tert-butyl 3-cyanomorpholine-4-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCOCC1C#N QSBSEJKNKHZYKD-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
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- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 1
- 125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
- C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
- C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/557—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms, e.g. orotic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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- A61P37/00—Drugs for immunological or allergic disorders
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- 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
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- 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
-
- 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
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- 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
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- 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
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
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- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
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- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
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PCT/GB2002/004753 WO2003035077A1 (en) | 2001-10-26 | 2002-10-21 | N-substituted hydroxypyrimidinone carboxamide inhibitors of hiv integrase |
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NO20042165A NO325206B1 (no) | 2001-10-26 | 2004-05-25 | N-substituerte hydroksypyrimidinonkarboksamidinhibitorer for HIV-integrase, farmasoytiske preparater som omfatter slike forbindelser, og anvendelse av forbindelsene ved fremstilling av medikamenter mot HIV og AIDS. |
NO2008007C NO2008007I1 (no) | 2001-10-26 | 2008-06-06 | Raltegravir eller et farmasoytisk akseptabelt saltderav, spesielt kaliumsaltet |
NO2020026C NO2020026I1 (no) | 2001-10-26 | 2020-08-10 | Raltegravir eller et farmasøytisk akseptabelt salt derav, spesielt kaliumsaltet |
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NO2008007C NO2008007I1 (no) | 2001-10-26 | 2008-06-06 | Raltegravir eller et farmasoytisk akseptabelt saltderav, spesielt kaliumsaltet |
NO2020026C NO2020026I1 (no) | 2001-10-26 | 2020-08-10 | Raltegravir eller et farmasøytisk akseptabelt salt derav, spesielt kaliumsaltet |
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Families Citing this family (126)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU1152702A (en) | 2000-10-12 | 2002-04-22 | Merck & Co Inc | Aza- and polyaza-naphthalenyl carboxamides useful as hiv integrase inhibitors |
ES2274913T3 (es) | 2000-10-12 | 2007-06-01 | MERCK & CO., INC. | Aza y poliaza-naftalenil carboxamidas utiles como inhibidores de vih integrada. |
US6919351B2 (en) | 2000-10-12 | 2005-07-19 | Merck & Co., Inc. | Aza-and polyaza-naphthalenyl-carboxamides useful as HIV integrase inhibitors |
EP3042894A1 (en) | 2001-08-10 | 2016-07-13 | Shionogi & Co., Ltd. | Antiviral agent |
AR036256A1 (es) | 2001-08-17 | 2004-08-25 | Merck & Co Inc | Sal sodica de un inhibidor de integrasa del vih, procesos para su preparacion, composiciones farmaceuticas que lo contienen y su uso para la manufactura de un medicamento |
SI1441735T1 (sl) * | 2001-10-26 | 2006-06-30 | Angeletti P Ist Richerche Bio | N-substituirani hidroksipirimidinon-karboksamidniinhibitorji HIV-integraze |
AU2002334205B2 (en) * | 2001-10-26 | 2007-07-05 | Istituto Di Ricerche Di Biologia Molecolara P. Angeletti Spa | Dihydroxypyrimidine carboxamide inhibitors of HIV integrase |
US7323460B2 (en) | 2002-03-15 | 2008-01-29 | Merck & Co., Inc. | N-(substituted benzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamides useful as HIV integrase inhibitors |
JP2006508030A (ja) * | 2002-05-09 | 2006-03-09 | サイトキネティクス・インコーポレーテッド | ピリミジノン化合物、組成物および方法 |
CA2483627A1 (en) * | 2002-05-23 | 2003-12-04 | Merck & Co., Inc. | Mitotic kinesin inhibitors |
US7109186B2 (en) | 2002-07-09 | 2006-09-19 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
CA2498111A1 (en) | 2002-09-11 | 2004-03-25 | Merck & Co., Inc. | Dihydroxypyridopyrazine-1,6-dione compounds useful as hiv integrase inhibitors |
US7399763B2 (en) | 2002-09-11 | 2008-07-15 | Merck & Co., Inc. | 8-hydroxy-1-oxo-tetrahydropyrrolopyrazine compounds useful as HIV integrase inhibitors |
EP1578748B1 (en) | 2002-12-27 | 2010-09-15 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | Tetrahydro-4h-pyrido[1,2-a]pyrimidines and related compounds useful as hiv integrase inhibitors |
WO2004062613A2 (en) * | 2003-01-13 | 2004-07-29 | Bristol-Myers Squibb Company | Hiv integrase inhibitors |
US7037908B2 (en) | 2003-04-24 | 2006-05-02 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
TW200510425A (en) | 2003-08-13 | 2005-03-16 | Japan Tobacco Inc | Nitrogen-containing fused ring compound and use thereof as HIV integrase inhibitor |
CN1870896A (zh) | 2003-10-20 | 2006-11-29 | 默克公司 | 用作hiv整合酶抑制剂的羟基吡啶并吡咯并吡嗪二酮化合物 |
US20050090668A1 (en) * | 2003-10-28 | 2005-04-28 | Dreher Spencer D. | Preparation of 5-hydroxy-6-oxo-1,6-dihydropyrimidine compounds |
AR046938A1 (es) * | 2003-12-12 | 2006-01-04 | Merck & Co Inc | Procedimiento para preparar hexahidropirimido[1,2-a]azepin-2-carboxilatos y compuetos similares |
JP2007518711A (ja) | 2003-12-19 | 2007-07-12 | メルク エンド カムパニー インコーポレーテッド | 有糸分裂キネシン阻害剤 |
TW200526635A (en) * | 2003-12-22 | 2005-08-16 | Shionogi & Co | Hydroxypyrimidinone derivative having HIV integrase inhibitory activity |
CN1934093A (zh) * | 2004-01-12 | 2007-03-21 | 吉里德科学公司 | 嘧啶基膦酸酯抗病毒化合物和使用方法 |
CA2557926A1 (en) | 2004-03-09 | 2005-09-22 | Monica Donghi | Hiv integrase inhibitors |
WO2005086700A2 (en) | 2004-03-09 | 2005-09-22 | Merck & Co., Inc. | Hiv integrase inhibitors |
WO2005092099A1 (en) | 2004-03-09 | 2005-10-06 | Merck & Co., Inc. | Hiv integrase inhibitors |
AU2005222391B2 (en) | 2004-03-09 | 2010-11-11 | Merck Sharp & Dohme Corp. | HIV integrase inhibitors |
WO2005110415A1 (en) * | 2004-05-07 | 2005-11-24 | Merck & Co., Inc. | Hiv integrase inhibitors |
US7273859B2 (en) * | 2004-05-12 | 2007-09-25 | Bristol-Myers Squibb Company | HIV integrase inhibitors: cyclic pyrimidinone compounds |
US7115601B2 (en) * | 2004-05-18 | 2006-10-03 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
US7173022B2 (en) | 2004-05-28 | 2007-02-06 | Bristol-Myers Squibb Company | Bicyclic heterocycles as HIV integrase inhibitors |
US7157447B2 (en) | 2004-05-28 | 2007-01-02 | Bristol-Myers Squibb Company | Bicyclic heterocycles as HIV integrase inhibitors |
US7192948B2 (en) | 2004-05-28 | 2007-03-20 | Bristol-Myers Squibb Company | Bicyclic heterocycles as HIV integrase inhibitors |
US7176196B2 (en) * | 2004-05-28 | 2007-02-13 | Bristol-Myers Squibb Company | Bicyclic heterocycles as HIV integrase inhibitors |
AU2005251820A1 (en) | 2004-06-09 | 2005-12-22 | Merck & Co., Inc. | HIV integrase inhibitors |
UA87884C2 (uk) | 2004-12-03 | 2009-08-25 | Мерк Энд Ко., Инк. | Безводна кристалічна калієва сіль інгібітора віл-інтегрази |
KR20070085702A (ko) * | 2004-12-03 | 2007-08-27 | 머크 앤드 캄파니 인코포레이티드 | Ugt1a1에 의해 대사된 약물의 약력학을 개선시키기위한 아타자나비르의 용도 |
RU2382648C2 (ru) * | 2004-12-03 | 2010-02-27 | Мерк Энд Ко., Инк. | Фармацевтический состав карбоксамидных ингибиторов интегразы вич, содержащий композицию с контролируемой скоростью высвобождения |
AU2005311714B2 (en) * | 2004-12-03 | 2010-09-30 | Merck Sharp & Dohme Corp. | Pharmaceutical composition containing an anti-nucleating agent |
CA2600832C (en) * | 2005-03-31 | 2011-12-13 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | Hiv integrase inhibitors |
DK2465580T3 (en) | 2005-04-28 | 2014-03-10 | Viiv Healthcare Co | POLYCYCLIC CARBAMOYL PYRIDONE DERIVATIVES WITH HIV INTEGRASE INHIBITIVE ACTIVITY |
EP1881825B1 (en) * | 2005-05-10 | 2013-07-24 | Merck Sharp & Dohme Corp. | Hiv integrase inhibitors |
CA2616314A1 (en) * | 2005-07-27 | 2007-02-01 | Gilead Sciences, Inc. | Antiviral phosphonate conjugates for inhibition of hiv |
ATE517899T1 (de) * | 2005-10-04 | 2011-08-15 | Angeletti P Ist Richerche Bio | Hiv-integrasehemmer |
JP2009513640A (ja) * | 2005-10-27 | 2009-04-02 | メルク エンド カムパニー インコーポレーテッド | Hivインテグラーゼインヒビター |
US20070129379A1 (en) * | 2005-12-01 | 2007-06-07 | Bristol-Myers Squibb Company | Hiv integrase inhibitors |
US20090136570A1 (en) * | 2006-01-20 | 2009-05-28 | Bhagwant Rege | Taste-Masked Tablets and Granules |
US20100056516A1 (en) * | 2006-07-17 | 2010-03-04 | Williams Peter D | 1-hydroxy naphthyridine compounds as anti-hiv agents |
CA2657034A1 (en) | 2006-07-19 | 2008-01-24 | University Of Georgia Research Foundation, Inc. | Pyridinone diketo acids: inhibitors of hiv replication in combination therapy |
JP2010506913A (ja) * | 2006-10-18 | 2010-03-04 | メルク エンド カムパニー インコーポレーテッド | Hivインテグラーゼ阻害剤 |
CN101206209B (zh) * | 2006-12-19 | 2011-08-10 | 北京德众万全药物技术开发有限公司 | 一种用hplc法分析西多福韦原料及其制剂的方法 |
US7763630B2 (en) * | 2007-06-06 | 2010-07-27 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
AU2008268627A1 (en) * | 2007-06-22 | 2008-12-31 | Bristol-Myers Squibb Company | Tableted compositions containing atazanavir |
US7687509B2 (en) * | 2007-07-09 | 2010-03-30 | Concert Pharmaceuticals Inc. | Pyrimidinecarboxamide derivatives |
EP2543368A1 (en) | 2007-12-11 | 2013-01-09 | Viamet Pharmaceuticals, Inc. | Metalloenzyme inhibitors using metal binding moieties in combination with targeting moieties |
CN101903382B (zh) | 2007-12-21 | 2012-11-28 | 弗·哈夫曼-拉罗切有限公司 | 杂环抗病毒化合物 |
EP2231621B1 (en) * | 2008-01-08 | 2016-11-02 | Merck Sharp & Dohme Corp. | Process for preparing n-substituted hydroxypyrimidinone carboxamides |
ES2408654T3 (es) * | 2008-07-02 | 2013-06-21 | Avexa Limited | Tiazopirimidinonas y uso de las mismas |
WO2010042392A2 (en) * | 2008-10-06 | 2010-04-15 | Merck & Co., Inc. | Hiv integrase inhibitors |
US8143244B2 (en) * | 2009-02-26 | 2012-03-27 | Bristol-Myers Squibb Company | Cyclopropyl fused indolobenzazepine HCV NS5B inhibitors |
US8742105B2 (en) | 2009-06-02 | 2014-06-03 | Hetero Research Foundation | Polymorphs of raltegravir potassium |
MA33416B1 (fr) * | 2009-07-06 | 2012-07-03 | Syngenta Participations Ag | Composés insecticides |
WO2011024192A2 (en) | 2009-07-27 | 2011-03-03 | Matrix Laboratories Ltd | Novel polymorphs of raltegravir |
US8383639B2 (en) | 2009-10-15 | 2013-02-26 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
EP2493312B1 (en) | 2009-10-26 | 2021-10-20 | Merck Sharp & Dohme Corp. | Solid pharmaceutical compositions containing an integrase inhibitor |
DE102009056636A1 (de) | 2009-12-02 | 2011-06-09 | Ratiopharm Gmbh | Raltegravir-Polymorphe |
US8283366B2 (en) | 2010-01-22 | 2012-10-09 | Ambrilia Biopharma, Inc. | Derivatives of pyridoxine for inhibiting HIV integrase |
KR101720824B1 (ko) | 2010-03-04 | 2017-03-28 | 머크 샤프 앤드 돔 코포레이션 | 카테콜 o-메틸 트랜스퍼라제의 억제제 및 정신병적 장애의 치료에서의 그의 용도 |
WO2011109267A1 (en) * | 2010-03-04 | 2011-09-09 | Merck Sharp & Dohme Corp. | Inhibitors of catechol o-methyl transferase and their use in the treatment of psychotic disorders |
US9260413B2 (en) | 2010-03-04 | 2016-02-16 | Merck Sharp & Dohme Corp. | Inhibitors of catechol O-methyl transferase and their use in the treatment of psychotic disorders |
EP2542077A4 (en) * | 2010-03-04 | 2013-08-21 | Merck Sharp & Dohme | CATECHOL O-METHYL TRANSFERASE INHIBITORS AND USE THEREOF IN THE TREATMENT OF PSYCHOTIC DISORDERS |
US8987272B2 (en) * | 2010-04-01 | 2015-03-24 | Critical Outcome Technologies Inc. | Compounds and method for treatment of HIV |
US20130079360A1 (en) | 2010-04-01 | 2013-03-28 | Ana KWOKAL | Raltegravir salts and crystalline forms thereof |
CN102917695A (zh) | 2010-04-09 | 2013-02-06 | 百时美施贵宝公司 | 具有改进的pH效应的阿扎那韦硫酸盐制剂 |
WO2011148381A1 (en) | 2010-05-25 | 2011-12-01 | Hetero Research Foundation | Salts of raltegravir |
WO2012009446A1 (en) | 2010-07-16 | 2012-01-19 | Concert Pharmaceuticals Inc. | Novel pyrimidinecarboxamide derivatives |
CN101914067B (zh) * | 2010-08-26 | 2012-07-11 | 陈岱岭 | N-甲基嘧啶酮的合成方法 |
WO2012103105A1 (en) * | 2011-01-24 | 2012-08-02 | Assia Chemical Industries Ltd. | Processes for preparing raltegravir and intermediates in the processes |
EP2694497A1 (en) | 2011-04-06 | 2014-02-12 | Lupin Limited | Novel salts of raltegravir |
US9968607B2 (en) | 2011-04-25 | 2018-05-15 | Hetero Research Foundation | Pharmaceutical compositions of raltegravir, methods of preparation and methods of use therof |
EP2522665A1 (en) * | 2011-05-03 | 2012-11-14 | Sandoz Ag | Crystalline sodium salt of an HIV integrase inhibitor |
EP2529741B1 (en) | 2011-06-01 | 2014-02-12 | Ratiopharm GmbH | Composition and Tablet Comprising Raltegravir |
CN103130788B (zh) * | 2011-11-24 | 2015-09-02 | 南开大学 | 嘧啶酰胺类化合物及其制备方法、抗hiv活性和抗tmv活性 |
CN103130787B (zh) * | 2011-11-24 | 2015-06-10 | 南开大学 | 嘧啶酮酰胺类化合物及其制备方法、抗hiv活性和抗tmv活性 |
AU2012345732B2 (en) | 2011-11-30 | 2016-07-14 | Emory University | Antiviral JAK inhibitors useful in treating or preventing retroviral and other viral infections |
WO2013098854A2 (en) * | 2011-12-26 | 2013-07-04 | Emcure Pharmaceuticals Limited | Synthesis of raltegravir |
US20150328215A1 (en) | 2012-01-25 | 2015-11-19 | Lupin Limited | Stable amorphous raltegravir potassium premix and process for the preparation thereof |
US20150166520A1 (en) * | 2012-07-20 | 2015-06-18 | Merck Sharp & Dohme Corp. | Amido-substituted pyrimidinone derivatives useful for the treatment of hiv infection |
BR112015002516A2 (pt) * | 2012-08-06 | 2017-07-04 | European Molecular Biology Laboratory | derivados de ácido carbônico di-hidroxipirimidina e seu uso no tratamento, melhora ou prevenção de doença viral. |
CN102911124B (zh) * | 2012-10-25 | 2015-11-25 | 山东大学 | 羟基嘧啶酮类化合物及其制备方法与应用 |
WO2014068265A1 (en) | 2012-10-29 | 2014-05-08 | Cipla Limited | Antiviral phosphonate analogues and process for preparation thereof |
US9714243B2 (en) | 2012-12-17 | 2017-07-25 | Merck Sharp & Dohme Corp. | 4-pyridinonetriazine derivatives as HIV integrase inhibitors |
MX357940B (es) | 2012-12-21 | 2018-07-31 | Gilead Sciences Inc | Compuestos de carbamoilpiridona policiclicos y su uso farmaceutico. |
EP2986291B1 (en) | 2013-04-16 | 2020-05-27 | Merck Sharp & Dohme Corp. | 4-pyridone derivative compounds and uses thereof as hiv integrase inhibitors |
HUE036384T2 (hu) | 2013-05-17 | 2018-07-30 | Merck Sharp & Dohme | Fúzionált triciklusos heterociklikus vegyületek mint HIV integráz inhibitorok |
EP3008044B1 (en) | 2013-06-13 | 2018-11-21 | Merck Sharp & Dohme Corp. | Fused tricyclic heterocyclic compounds as hiv integrase inhibitors |
NO2865735T3 (sr) | 2013-07-12 | 2018-07-21 | ||
SI3252058T1 (sl) | 2013-07-12 | 2021-03-31 | Gilead Sciences, Inc. | Policiklične karbamoilpiridonske spojine in njihova uporaba za zdravljenje okužb s HIV |
MD4794B1 (ro) | 2013-09-27 | 2022-02-28 | Merck Sharp & Dohme Corp | Derivaţi de chinolizină substituiţi utili ca inhibitori de integrază HIV |
EP3087060B1 (en) | 2013-12-23 | 2020-05-13 | Merck Sharp & Dohme Corp. | Pyrimidone carboxamide compounds as pde2 inhibitors |
US20170253585A1 (en) * | 2014-02-03 | 2017-09-07 | Mylan Laboratories Ltd. | Processes for the preparation of intermediates of raltegravir |
CA2942239C (en) | 2014-03-21 | 2020-09-22 | Mylan Laboratories Ltd. | A premix of crystalline raltegravir potassium salt and a process for the preparation thereof |
TW201613936A (en) | 2014-06-20 | 2016-04-16 | Gilead Sciences Inc | Crystalline forms of(2R,5S,13aR)-8-hydroxy-7,9-dioxo-n-(2,4,6-trifluorobenzyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazepine-10-carboxamide |
NO2717902T3 (sr) | 2014-06-20 | 2018-06-23 | ||
TWI744723B (zh) | 2014-06-20 | 2021-11-01 | 美商基利科學股份有限公司 | 多環型胺甲醯基吡啶酮化合物之合成 |
US9353093B2 (en) | 2014-10-07 | 2016-05-31 | Allergan, Inc. | Indole-1-carboxamides as kinase inhibitors |
US10259778B2 (en) | 2014-11-10 | 2019-04-16 | Aurobindo Pharma Ltd | Process for the preparation of raltegravir |
TWI738321B (zh) | 2014-12-23 | 2021-09-01 | 美商基利科學股份有限公司 | 多環胺甲醯基吡啶酮化合物及其醫藥用途 |
WO2016145614A1 (en) | 2015-03-17 | 2016-09-22 | Merck Sharp & Dohme Corp. | Triazolyl pyrimidinone compounds as pde2 inhibitors |
EP3285581B1 (en) | 2015-03-26 | 2021-08-11 | Merck Sharp & Dohme Corp. | Pyrazolyl pyrimidinone compounds as pde2 inhibitors |
EP3736274A1 (en) | 2015-04-02 | 2020-11-11 | Gilead Sciences, Inc. | Polycyclic-carbamoylpyridone compounds and their pharmaceutical use |
WO2016187788A1 (en) | 2015-05-25 | 2016-12-01 | Merck Sharp & Dohme Corp. | Fused tricyclic heterocyclic compounds useful for treating hiv infection |
EP3313852B1 (en) | 2015-06-25 | 2021-01-20 | Merck Sharp & Dohme Corp. | Substituted pyrazolo/imidazolo bicyclic compounds as pde2 inhibitors |
WO2017000277A1 (en) | 2015-07-01 | 2017-01-05 | Merck Sharp & Dohme Corp. | Substituted triazolo bicycliccompounds as pde2 inhibitors |
EP3377066B1 (en) | 2015-11-17 | 2021-04-07 | Merck Sharp & Dohme Corp. | Amido-substituted pyridotriazine derivatives useful as hiv integrase inhibitors |
WO2017106071A1 (en) | 2015-12-15 | 2017-06-22 | Merck Sharp & Dohme Corp. | Spirocyclic quinolizine derivatives useful as hiv integrase inhibitors |
WO2017113288A1 (en) | 2015-12-31 | 2017-07-06 | Merck Sharp & Dohme Corp. | Fused tricyclic heterocyclic compounds as hiv integrase inhibitors |
EP3472134B1 (en) | 2016-06-21 | 2021-10-20 | Pharmathen S.A. | Process for preparing compounds useful as intermediates for the preparation of raltegravir |
WO2018051239A1 (en) | 2016-09-15 | 2018-03-22 | Lupin Limited | Process for the preparation of pure and stable crystalline raltegravir potassium form 3 |
BR112019011074B1 (pt) | 2016-12-02 | 2021-01-19 | Merck Sharp & Dohme Corp. | Compostos heterocíclicos tricíclicos inibidores de hiv integrase, composição que oscompreende e uso dos mesmos |
JOP20190130A1 (ar) | 2016-12-02 | 2019-06-02 | Merck Sharp & Dohme | مركبات حلقية غير متجانسة رباعية الحلقات مفيدة كمثبطات إنزيم مدمج لفيروس نقص المناعة البشرية (hiv) |
EP3573984A4 (en) | 2017-01-26 | 2020-07-29 | Merck Sharp & Dohme Corp. | USEFUL SUBSTITUTE QUINOLIZINE DERIVATIVES AS HIV INTEGRASE INHIBITORS |
EP3710445B1 (en) | 2017-11-14 | 2022-03-16 | Cambrex Profarmaco Milano S.r.l. | Process for the preparation of raltegravir |
WO2021016317A1 (en) * | 2019-07-23 | 2021-01-28 | Constellation Pharmaceuticals, Inc. | Modulators of trex1 |
US20230073216A1 (en) | 2020-01-23 | 2023-03-09 | Lupin Limited | Pharmaceutical Compositions of Raltegravir |
WO2021165927A1 (en) * | 2020-02-21 | 2021-08-26 | Wockhardt Bio Ag | 2-cyanopyrroldines, -piperidines or -dazepines as hyperglycemic agents |
Family Cites Families (33)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE44464T1 (de) | 1985-03-16 | 1989-07-15 | Wellcome Found | Antivirale nukleoside. |
US5047407A (en) | 1989-02-08 | 1991-09-10 | Iaf Biochem International, Inc. | 2-substituted-5-substituted-1,3-oxathiolanes with antiviral properties |
US6642245B1 (en) | 1990-02-01 | 2003-11-04 | Emory University | Antiviral activity and resolution of 2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane |
US5637618A (en) | 1990-06-01 | 1997-06-10 | Bioresearch, Inc. | Specific eatable taste modifiers |
DE4029654A1 (de) | 1990-09-19 | 1992-04-02 | Hoechst Ag | 2-phenyl-pyrimidine, verfahren zu ihrer herstellung, sie enthaltende mittel und ihre verwendung als fungizide |
US5665720A (en) | 1992-08-07 | 1997-09-09 | Merck & Co., Inc. | Benzoxazinones as inhibitors of HIV reverse transcriptase |
TW287160B (sr) | 1992-12-10 | 1996-10-01 | Hoffmann La Roche | |
US5919776A (en) * | 1996-12-20 | 1999-07-06 | Merck & Co., Inc. | Substituted aminoquinolines as modulators of chemokine receptor activity |
US5935946A (en) | 1997-07-25 | 1999-08-10 | Gilead Sciences, Inc. | Nucleotide analog composition and synthesis method |
US6632823B1 (en) | 1997-12-22 | 2003-10-14 | Merck & Co., Inc. | Substituted pyridine compounds useful as modulators of acetylcholine receptors |
PL343249A1 (en) | 1998-03-26 | 2001-07-30 | Shionogi & Co | Indole derivatives with antiviral activity |
US6306891B1 (en) | 1998-06-03 | 2001-10-23 | Merck & Co., Inc. | HIV integrase inhibitors |
EP1086091A4 (en) | 1998-06-03 | 2001-10-10 | Merck & Co Inc | HIV INTEGRASE INHIBITORS |
EP1082121A4 (en) | 1998-06-03 | 2003-02-05 | Merck & Co Inc | INTEGRASE HIV INHIBITORS |
EP1112743B1 (en) | 1998-08-20 | 2007-10-24 | Toyama Chemical Co., Ltd. | Nitrogenous heterocyclic carboxamide derivatives or salt thereof as antiviral agents |
DE69939749D1 (de) | 1998-12-25 | 2008-11-27 | Shionogi & Co | Aromatische heterocyclen mit hiv integrase inhibierenden eigenschaften |
AU2946300A (en) | 1999-03-04 | 2000-09-21 | Korea Research Institute Of Chemical Technology | Antiviral 2,4-pyrimidinedione derivatives and process for the preparation thereof |
EP1196384A4 (en) | 1999-06-25 | 2002-10-23 | Merck & Co Inc | 1- (AROMATIC OR HETEROAROMATICALLY SUBSTITUTED) -3- (HETEROAROMATICALLY SUBSTITUTED) -1,3-PROPANDIONS AND THEIR APPLICATIONS |
CA2406562C (en) * | 2000-05-08 | 2009-09-15 | Janssen Pharmaceutica N.V. | Hiv replication inhibiting pyrimidines and triazines |
GB0017676D0 (en) * | 2000-07-19 | 2000-09-06 | Angeletti P Ist Richerche Bio | Inhibitors of viral polymerase |
AU1152702A (en) | 2000-10-12 | 2002-04-22 | Merck & Co Inc | Aza- and polyaza-naphthalenyl carboxamides useful as hiv integrase inhibitors |
US6919351B2 (en) | 2000-10-12 | 2005-07-19 | Merck & Co., Inc. | Aza-and polyaza-naphthalenyl-carboxamides useful as HIV integrase inhibitors |
ES2274913T3 (es) | 2000-10-12 | 2007-06-01 | MERCK & CO., INC. | Aza y poliaza-naftalenil carboxamidas utiles como inhibidores de vih integrada. |
US20050010048A1 (en) | 2000-10-12 | 2005-01-13 | Linghang Zhuang | Aza-and polyaza-naphthalenly ketones useful as hiv integrase inhibitors |
ATE411292T1 (de) | 2001-03-01 | 2008-10-15 | Shionogi & Co | Stickstoffhaltige heteroarylverbindungen mit hiv- integrase inhibierender wirkung |
EP3042894A1 (en) | 2001-08-10 | 2016-07-13 | Shionogi & Co., Ltd. | Antiviral agent |
SI1441735T1 (sl) | 2001-10-26 | 2006-06-30 | Angeletti P Ist Richerche Bio | N-substituirani hidroksipirimidinon-karboksamidniinhibitorji HIV-integraze |
AU2002334205B2 (en) * | 2001-10-26 | 2007-07-05 | Istituto Di Ricerche Di Biologia Molecolara P. Angeletti Spa | Dihydroxypyrimidine carboxamide inhibitors of HIV integrase |
AU2002349675A1 (en) | 2001-12-05 | 2003-06-17 | Shionogi And Co., Ltd. | Derivative having hiv integrase inhibitory activity |
US7109186B2 (en) | 2002-07-09 | 2006-09-19 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
EP3406596A1 (en) | 2002-11-20 | 2018-11-28 | Japan Tobacco Inc. | 4-oxoquinoline compound and use thereof as hiv integrase inhibitor |
WO2004062613A2 (en) | 2003-01-13 | 2004-07-29 | Bristol-Myers Squibb Company | Hiv integrase inhibitors |
US7037908B2 (en) | 2003-04-24 | 2006-05-02 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
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