JP2007528379A - Ｈｉｖインテグラーゼ阻害薬 - Google Patents
Ｈｉｖインテグラーゼ阻害薬 Download PDFInfo
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- JP2007528379A JP2007528379A JP2007502381A JP2007502381A JP2007528379A JP 2007528379 A JP2007528379 A JP 2007528379A JP 2007502381 A JP2007502381 A JP 2007502381A JP 2007502381 A JP2007502381 A JP 2007502381A JP 2007528379 A JP2007528379 A JP 2007528379A
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- alkyl
- ring
- compound
- hydroxy
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- 229940099797 HIV integrase inhibitor Drugs 0.000 title description 9
- 239000003084 hiv integrase inhibitor Substances 0.000 title description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 267
- 150000003839 salts Chemical class 0.000 claims abstract description 116
- 208000030507 AIDS Diseases 0.000 claims abstract description 47
- 208000031886 HIV Infections Diseases 0.000 claims abstract description 18
- 208000037357 HIV infectious disease Diseases 0.000 claims abstract description 18
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims abstract description 18
- 108010002459 HIV Integrase Proteins 0.000 claims abstract description 16
- 239000003443 antiviral agent Substances 0.000 claims abstract description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 16
- 208000015181 infectious disease Diseases 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 321
- -1 —O—C 1-6 haloalkyl Chemical group 0.000 claims description 79
- 229910052799 carbon Inorganic materials 0.000 claims description 78
- 238000000034 method Methods 0.000 claims description 61
- 229910052739 hydrogen Inorganic materials 0.000 claims description 58
- 125000001072 heteroaryl group Chemical group 0.000 claims description 55
- 125000005842 heteroatom Chemical group 0.000 claims description 54
- 125000001424 substituent group Chemical group 0.000 claims description 51
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 50
- 125000000623 heterocyclic group Chemical group 0.000 claims description 47
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 43
- 125000004434 sulfur atom Chemical group 0.000 claims description 36
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
- 125000003118 aryl group Chemical group 0.000 claims description 29
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 claims description 29
- 125000005843 halogen group Chemical group 0.000 claims description 26
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 24
- 239000003814 drug Substances 0.000 claims description 20
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 20
- 229910052717 sulfur Inorganic materials 0.000 claims description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims description 19
- 229910052760 oxygen Inorganic materials 0.000 claims description 19
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 17
- 125000002947 alkylene group Chemical group 0.000 claims description 17
- 239000000460 chlorine Substances 0.000 claims description 17
- 125000004122 cyclic group Chemical group 0.000 claims description 17
- 229920006395 saturated elastomer Polymers 0.000 claims description 17
- 229910052794 bromium Inorganic materials 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 15
- 229910052801 chlorine Inorganic materials 0.000 claims description 15
- 230000002265 prevention Effects 0.000 claims description 14
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 13
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 13
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 13
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 12
- 239000002777 nucleoside Substances 0.000 claims description 12
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 12
- 108010078851 HIV Reverse Transcriptase Proteins 0.000 claims description 11
- 229910052731 fluorine Inorganic materials 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 230000002401 inhibitory effect Effects 0.000 claims description 10
- 125000001624 naphthyl group Chemical group 0.000 claims description 10
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims description 10
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 239000011737 fluorine Chemical group 0.000 claims description 9
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 8
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 8
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 8
- 125000003386 piperidinyl group Chemical group 0.000 claims description 8
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 8
- SNOANKDFURQGET-UHFFFAOYSA-N 2-[(3-chloro-4-fluorophenyl)methyl]-9-hydroxy-n,n-dimethyl-1,8-dioxo-3,4-dihydropyrido[1,2-a]pyrazine-6-carboxamide Chemical compound C1CN2C(C(=O)N(C)C)=CC(=O)C(O)=C2C(=O)N1CC1=CC=C(F)C(Cl)=C1 SNOANKDFURQGET-UHFFFAOYSA-N 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 6
- 239000004030 hiv protease inhibitor Substances 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 125000004193 piperazinyl group Chemical group 0.000 claims description 6
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
- 238000006467 substitution reaction Methods 0.000 claims description 6
- YHUXEHRWCXWGRK-UHFFFAOYSA-N 7-bromo-2-[(4-fluorophenyl)methyl]-9-hydroxy-6-methyl-3,4-dihydropyrido[1,2-a]pyrazine-1,8-dione Chemical compound C1CN2C(C)=C(Br)C(=O)C(O)=C2C(=O)N1CC1=CC=C(F)C=C1 YHUXEHRWCXWGRK-UHFFFAOYSA-N 0.000 claims description 5
- 229940122440 HIV protease inhibitor Drugs 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000002757 morpholinyl group Chemical group 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- QOEHICMIIZKYOR-UHFFFAOYSA-N 2-[(4-fluorophenyl)methyl]-9-hydroxy-3,4-dihydropyrido[1,2-a]pyrazine-1,8-dione Chemical compound C1CN2C=CC(=O)C(O)=C2C(=O)N1CC1=CC=C(F)C=C1 QOEHICMIIZKYOR-UHFFFAOYSA-N 0.000 claims description 4
- RRFSPJHINRBGFW-UHFFFAOYSA-N 2-[(4-fluorophenyl)methyl]-9-hydroxy-6-methyl-3,4,6,7-tetrahydropyrazino[1,2-c]pyrimidine-1,8-dione Chemical compound CC1NC(=O)C(O)=C(C2=O)N1CCN2CC1=CC=C(F)C=C1 RRFSPJHINRBGFW-UHFFFAOYSA-N 0.000 claims description 4
- YEJBXDQCOLWWSC-UHFFFAOYSA-N 2-[(4-fluorophenyl)methyl]-9-hydroxy-6-methyl-3,4-dihydropyrazino[1,2-c]pyrimidine-1,8-dione Chemical compound C1CN2C(C)=NC(=O)C(O)=C2C(=O)N1CC1=CC=C(F)C=C1 YEJBXDQCOLWWSC-UHFFFAOYSA-N 0.000 claims description 4
- YRDPBYAZHIDAAD-UHFFFAOYSA-N 2-[(4-fluorophenyl)methyl]-9-hydroxy-7-pyridin-3-yl-3,4-dihydropyrido[1,2-a]pyrazine-1,8-dione Chemical compound C1CN2C=C(C=3C=NC=CC=3)C(=O)C(O)=C2C(=O)N1CC1=CC=C(F)C=C1 YRDPBYAZHIDAAD-UHFFFAOYSA-N 0.000 claims description 4
- AHMAXJKXLOWMBF-UHFFFAOYSA-N 7-acetyl-2-[(4-fluorophenyl)methyl]-9-hydroxy-3,4-dihydropyrido[1,2-a]pyrazine-1,8-dione Chemical compound O=C1C2=C(O)C(=O)C(C(=O)C)=CN2CCN1CC1=CC=C(F)C=C1 AHMAXJKXLOWMBF-UHFFFAOYSA-N 0.000 claims description 4
- QBXIWXWOSXEDKY-UHFFFAOYSA-N n-[1-[2-[(4-fluorophenyl)methyl]-9-hydroxy-1,8-dioxo-3,4-dihydropyrido[1,2-a]pyrazin-7-yl]ethyl]-n-methylacetamide Chemical compound O=C1C2=C(O)C(=O)C(C(N(C)C(C)=O)C)=CN2CCN1CC1=CC=C(F)C=C1 QBXIWXWOSXEDKY-UHFFFAOYSA-N 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- AUUWKCMVGVUDLA-ZIAGYGMSSA-N (+/-) trans n-[7-(4-fluorobenzyl)-5-hydroxy-4,6-dioxo-2,4,6,7,8,8a-hexahydro-1h- 3,7,8b-triazaacenaphthylen-2-yl]-n,n',n'-trimethylethanediamide Chemical compound C([C@H]1C[C@H](C2=NC(=O)C(O)=C(N12)C1=O)N(C)C(=O)C(=O)N(C)C)N1CC1=CC=C(F)C=C1 AUUWKCMVGVUDLA-ZIAGYGMSSA-N 0.000 claims description 3
- MZXSQSBNWWCJQO-UHFFFAOYSA-N 2-[(4-fluorophenyl)methyl]-9-hydroxy-6-(morpholin-4-ylmethyl)-3,4-dihydropyrazino[1,2-c]pyrimidine-1,8-dione Chemical compound C1CN2C(CN3CCOCC3)=NC(=O)C(O)=C2C(=O)N1CC1=CC=C(F)C=C1 MZXSQSBNWWCJQO-UHFFFAOYSA-N 0.000 claims description 3
- XBYHECVPDRJKLI-UHFFFAOYSA-N 2-[(4-fluorophenyl)methyl]-9-hydroxy-7-(1-hydroxyethyl)-3,4-dihydropyrido[1,2-a]pyrazine-1,8-dione Chemical compound O=C1C2=C(O)C(=O)C(C(O)C)=CN2CCN1CC1=CC=C(F)C=C1 XBYHECVPDRJKLI-UHFFFAOYSA-N 0.000 claims description 3
- AUUWKCMVGVUDLA-UHFFFAOYSA-N N'-[10-[(4-fluorophenyl)methyl]-7-hydroxy-6,9-dioxo-5,10,12-triazatricyclo[6.3.1.04,12]dodeca-4,7-dien-3-yl]-N,N,N'-trimethyloxamide Chemical compound O=C1C(N23)=C(O)C(=O)N=C3C(N(C)C(=O)C(=O)N(C)C)CC2CN1CC1=CC=C(F)C=C1 AUUWKCMVGVUDLA-UHFFFAOYSA-N 0.000 claims description 3
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
- 125000002971 oxazolyl group Chemical group 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 3
- YBOLXMSAYRVQME-UHFFFAOYSA-N 2-[(4-fluorophenyl)methyl]-9-hydroxy-7-[1-(methylamino)ethyl]-3,4-dihydropyrido[1,2-a]pyrazine-1,8-dione Chemical compound O=C1C2=C(O)C(=O)C(C(C)NC)=CN2CCN1CC1=CC=C(F)C=C1 YBOLXMSAYRVQME-UHFFFAOYSA-N 0.000 claims description 2
- 125000005275 alkylenearyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- JMMFSDRANFCVOL-UHFFFAOYSA-N 2-[(3-chloro-4-fluorophenyl)methyl]-9-hydroxy-3,4-dihydropyrido[1,2-a]pyrazine-1,8-dione Chemical compound C1CN2C=CC(=O)C(O)=C2C(=O)N1CC1=CC=C(F)C(Cl)=C1 JMMFSDRANFCVOL-UHFFFAOYSA-N 0.000 claims 2
- DSGKYMPOIUYAFD-UHFFFAOYSA-N 2-[(4-fluoro-3-methylphenyl)methyl]-9-hydroxy-3,4-dihydropyrido[1,2-a]pyrazine-1,8-dione Chemical compound C1=C(F)C(C)=CC(CN2C(C3=C(O)C(=O)C=CN3CC2)=O)=C1 DSGKYMPOIUYAFD-UHFFFAOYSA-N 0.000 claims 1
- PSJNVFWCRZVFBB-UHFFFAOYSA-N 2-[(4-fluorophenyl)methyl]-9-hydroxy-4-(2-morpholin-4-ylethyl)-3,4-dihydropyrido[1,2-a]pyrazine-1,8-dione Chemical compound C1C(CCN2CCOCC2)N2C=CC(=O)C(O)=C2C(=O)N1CC1=CC=C(F)C=C1 PSJNVFWCRZVFBB-UHFFFAOYSA-N 0.000 claims 1
- VQUGAIORJSMQTQ-UHFFFAOYSA-N 2-[(4-fluorophenyl)methyl]-9-hydroxy-4-(2-pyrrolidin-1-ylethyl)-3,4-dihydropyrido[1,2-a]pyrazine-1,8-dione Chemical compound C1C(CCN2CCCC2)N2C=CC(=O)C(O)=C2C(=O)N1CC1=CC=C(F)C=C1 VQUGAIORJSMQTQ-UHFFFAOYSA-N 0.000 claims 1
- WUFSYQZRXYMRMC-UHFFFAOYSA-N 2-[(4-fluorophenyl)methyl]-9-hydroxy-6-(methylaminomethyl)-3,4-dihydropyrazino[1,2-c]pyrimidine-1,8-dione Chemical compound C1CN2C(CNC)=NC(=O)C(O)=C2C(=O)N1CC1=CC=C(F)C=C1 WUFSYQZRXYMRMC-UHFFFAOYSA-N 0.000 claims 1
- GCTVOIZRRAFUDB-UHFFFAOYSA-N 2-[(4-fluorophenyl)methyl]-9-hydroxy-6-(piperidin-1-ylmethyl)-3,4-dihydropyrazino[1,2-c]pyrimidine-1,8-dione Chemical compound C1CN2C(CN3CCCCC3)=NC(=O)C(O)=C2C(=O)N1CC1=CC=C(F)C=C1 GCTVOIZRRAFUDB-UHFFFAOYSA-N 0.000 claims 1
- CSNAEXVGHKNJPS-UHFFFAOYSA-N 2-[(4-fluorophenyl)methyl]-9-hydroxy-6-[1-(methylamino)ethyl]-3,4-dihydropyrazino[1,2-c]pyrimidine-1,8-dione Chemical compound C1CN2C(C(C)NC)=NC(=O)C(O)=C2C(=O)N1CC1=CC=C(F)C=C1 CSNAEXVGHKNJPS-UHFFFAOYSA-N 0.000 claims 1
- QVORSQJQWUIEMQ-UHFFFAOYSA-N 2-[(4-fluorophenyl)methyl]-9-hydroxy-6-methyl-7-(1-morpholin-4-ylethyl)-3,4-dihydropyrido[1,2-a]pyrazine-1,8-dione Chemical compound CC=1N2CCN(CC=3C=CC(F)=CC=3)C(=O)C2=C(O)C(=O)C=1C(C)N1CCOCC1 QVORSQJQWUIEMQ-UHFFFAOYSA-N 0.000 claims 1
- NXQOJTKCUXFPEH-UHFFFAOYSA-N 2-[(4-fluorophenyl)methyl]-9-hydroxy-6-methyl-7-(1-pyrrolidin-1-ylethyl)-3,4-dihydropyrido[1,2-a]pyrazine-1,8-dione Chemical compound CC=1N2CCN(CC=3C=CC(F)=CC=3)C(=O)C2=C(O)C(=O)C=1C(C)N1CCCC1 NXQOJTKCUXFPEH-UHFFFAOYSA-N 0.000 claims 1
- JOUNZGRORGNQKF-UHFFFAOYSA-N 2-[(4-fluorophenyl)methyl]-9-hydroxy-7-(1-morpholin-4-ylethyl)-3,4-dihydropyrido[1,2-a]pyrazine-1,8-dione Chemical compound C=1N2CCN(CC=3C=CC(F)=CC=3)C(=O)C2=C(O)C(=O)C=1C(C)N1CCOCC1 JOUNZGRORGNQKF-UHFFFAOYSA-N 0.000 claims 1
- KIFFSSMWDVRNDT-UHFFFAOYSA-N 2-[(4-fluorophenyl)methyl]-9-hydroxy-7-(1-pyrrolidin-1-ylethyl)-3,4-dihydropyrido[1,2-a]pyrazine-1,8-dione Chemical compound C=1N2CCN(CC=3C=CC(F)=CC=3)C(=O)C2=C(O)C(=O)C=1C(C)N1CCCC1 KIFFSSMWDVRNDT-UHFFFAOYSA-N 0.000 claims 1
- IJCSHYIQPYZZQQ-UHFFFAOYSA-N 2-[(4-fluorophenyl)methyl]-9-hydroxy-7-[1-(2-methoxyethylamino)ethyl]-3,4-dihydropyrido[1,2-a]pyrazine-1,8-dione Chemical compound O=C1C2=C(O)C(=O)C(C(C)NCCOC)=CN2CCN1CC1=CC=C(F)C=C1 IJCSHYIQPYZZQQ-UHFFFAOYSA-N 0.000 claims 1
- MGGVDWGJPFBQCH-UHFFFAOYSA-N 2-[(4-fluorophenyl)methyl]-9-hydroxy-7-[1-(propan-2-ylamino)ethyl]-3,4-dihydropyrido[1,2-a]pyrazine-1,8-dione Chemical compound O=C1C2=C(O)C(=O)C(C(C)NC(C)C)=CN2CCN1CC1=CC=C(F)C=C1 MGGVDWGJPFBQCH-UHFFFAOYSA-N 0.000 claims 1
- SDKONHSBQNJNRP-UHFFFAOYSA-N 2-[(4-fluorophenyl)methyl]-9-hydroxy-7-[1-(pyridin-2-ylmethylamino)ethyl]-3,4-dihydropyrido[1,2-a]pyrazine-1,8-dione Chemical compound C=1N2CCN(CC=3C=CC(F)=CC=3)C(=O)C2=C(O)C(=O)C=1C(C)NCC1=CC=CC=N1 SDKONHSBQNJNRP-UHFFFAOYSA-N 0.000 claims 1
- XPBLHIQMAAWWKR-UHFFFAOYSA-N 2-[(4-fluorophenyl)methyl]-9-hydroxy-7-[1-(pyridin-3-ylmethylamino)ethyl]-3,4-dihydropyrido[1,2-a]pyrazine-1,8-dione Chemical compound C=1N2CCN(CC=3C=CC(F)=CC=3)C(=O)C2=C(O)C(=O)C=1C(C)NCC1=CC=CN=C1 XPBLHIQMAAWWKR-UHFFFAOYSA-N 0.000 claims 1
- ZJZCUZACTIRYSX-UHFFFAOYSA-N 2-[2-[(4-fluorophenyl)methyl]-9-hydroxy-1,8-dioxo-3,4-dihydropyrido[1,2-a]pyrazin-4-yl]-n,n-dimethylacetamide Chemical compound O=C1C2=C(O)C(=O)C=CN2C(CC(=O)N(C)C)CN1CC1=CC=C(F)C=C1 ZJZCUZACTIRYSX-UHFFFAOYSA-N 0.000 claims 1
- UMQKRFLPKMLKMY-UHFFFAOYSA-N 2-[2-[(4-fluorophenyl)methyl]-9-hydroxy-1,8-dioxo-3,4-dihydropyrido[1,2-a]pyrazin-4-yl]-n-methylacetamide Chemical compound O=C1C2=C(O)C(=O)C=CN2C(CC(=O)NC)CN1CC1=CC=C(F)C=C1 UMQKRFLPKMLKMY-UHFFFAOYSA-N 0.000 claims 1
- ZLNAZDFBTUPRLE-UHFFFAOYSA-N 2-[2-[(4-fluorophenyl)methyl]-9-hydroxy-1,8-dioxo-3,4-dihydropyrido[1,2-a]pyrazin-4-yl]acetic acid Chemical compound O=C1C2=C(O)C(=O)C=CN2C(CC(=O)O)CN1CC1=CC=C(F)C=C1 ZLNAZDFBTUPRLE-UHFFFAOYSA-N 0.000 claims 1
- PEHPFDCKYDXVTF-UHFFFAOYSA-N 3,10-bis[(4-fluorophenyl)methyl]-7-hydroxy-3-(methylamino)-5,10,12-triazatricyclo[6.3.1.04,12]dodeca-4,7-diene-6,9-dione Chemical compound C1C(N23)CN(CC=4C=CC(F)=CC=4)C(=O)C3=C(O)C(=O)N=C2C1(NC)CC1=CC=C(F)C=C1 PEHPFDCKYDXVTF-UHFFFAOYSA-N 0.000 claims 1
- OVLCJVQMKOVZEH-UHFFFAOYSA-N 3-(dimethylamino)-10-[(4-fluorophenyl)methyl]-7-hydroxy-5,10,12-triazatricyclo[6.3.1.04,12]dodeca-4,7-diene-6,9-dione Chemical compound O=C1C(N23)=C(O)C(=O)N=C3C(N(C)C)CC2CN1CC1=CC=C(F)C=C1 OVLCJVQMKOVZEH-UHFFFAOYSA-N 0.000 claims 1
- XJEVRCLTCALKKG-UHFFFAOYSA-N 6-[(dimethylamino)methyl]-2-[(4-fluorophenyl)methyl]-9-hydroxy-3,4-dihydropyrazino[1,2-c]pyrimidine-1,8-dione Chemical compound C1CN2C(CN(C)C)=NC(=O)C(O)=C2C(=O)N1CC1=CC=C(F)C=C1 XJEVRCLTCALKKG-UHFFFAOYSA-N 0.000 claims 1
- OAZVZTUGGSFLJK-UHFFFAOYSA-N 6-[1-(dimethylamino)ethyl]-2-[(4-fluorophenyl)methyl]-9-hydroxy-3,4-dihydropyrazino[1,2-c]pyrimidine-1,8-dione Chemical compound C1CN2C(C(N(C)C)C)=NC(=O)C(O)=C2C(=O)N1CC1=CC=C(F)C=C1 OAZVZTUGGSFLJK-UHFFFAOYSA-N 0.000 claims 1
- FEVBWDNKHWLTEK-UHFFFAOYSA-N 6-acetyl-2-[(4-fluorophenyl)methyl]-9-hydroxy-3,4-dihydropyrido[1,2-a]pyrazine-1,8-dione Chemical compound C1CN2C(C(=O)C)=CC(=O)C(O)=C2C(=O)N1CC1=CC=C(F)C=C1 FEVBWDNKHWLTEK-UHFFFAOYSA-N 0.000 claims 1
- NYABASQUXSOYOS-UHFFFAOYSA-N 7-[1-(dimethylamino)ethyl]-2-[(4-fluorophenyl)methyl]-9-hydroxy-3,4-dihydropyrido[1,2-a]pyrazine-1,8-dione Chemical compound O=C1C2=C(O)C(=O)C(C(N(C)C)C)=CN2CCN1CC1=CC=C(F)C=C1 NYABASQUXSOYOS-UHFFFAOYSA-N 0.000 claims 1
- ABMXEBCXEFIGGA-UHFFFAOYSA-N N'-[10-[(3-chloro-4-fluorophenyl)methyl]-7-hydroxy-6,9-dioxo-5,10,12-triazatricyclo[6.3.1.04,12]dodeca-4,7-dien-3-yl]-N,N,N'-trimethyloxamide Chemical compound O=C1C(N23)=C(O)C(=O)N=C3C(N(C)C(=O)C(=O)N(C)C)CC2CN1CC1=CC=C(F)C(Cl)=C1 ABMXEBCXEFIGGA-UHFFFAOYSA-N 0.000 claims 1
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- PRMYJKSKSUDODS-UHFFFAOYSA-N n'-[1-[2-[(4-fluorophenyl)methyl]-9-hydroxy-1,8-dioxo-3,4-dihydropyrido[1,2-a]pyrazin-7-yl]ethyl]-n,n,n'-trimethyloxamide Chemical compound O=C1C2=C(O)C(=O)C(C(N(C)C(=O)C(=O)N(C)C)C)=CN2CCN1CC1=CC=C(F)C=C1 PRMYJKSKSUDODS-UHFFFAOYSA-N 0.000 claims 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/16—Peri-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Virology (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US55160104P | 2004-03-09 | 2004-03-09 | |
| PCT/GB2005/000746 WO2005087766A1 (en) | 2004-03-09 | 2005-03-01 | Hiv integrase inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007528379A true JP2007528379A (ja) | 2007-10-11 |
| JP2007528379A5 JP2007528379A5 (https=) | 2008-09-18 |
Family
ID=34961192
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007502381A Withdrawn JP2007528379A (ja) | 2004-03-09 | 2005-03-01 | Ｈｉｖインテグラーゼ阻害薬 |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US20070161639A1 (https=) |
| EP (1) | EP1725554A1 (https=) |
| JP (1) | JP2007528379A (https=) |
| CN (1) | CN1930161A (https=) |
| AU (1) | AU2005221864A1 (https=) |
| CA (1) | CA2557926A1 (https=) |
| WO (1) | WO2005087766A1 (https=) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010147068A1 (ja) * | 2009-06-15 | 2010-12-23 | 塩野義製薬株式会社 | 置換された多環性カルバモイルピリドン誘導体 |
| JP2011195585A (ja) * | 2010-02-26 | 2011-10-06 | Japan Tobacco Inc | １，３，４，８−テトラヒドロ−２Ｈ−ピリド［１，２−ａ］ピラジン誘導体及びそのＨＩＶインテグラーゼ阻害剤としての利用 |
| JP2016518305A (ja) * | 2013-01-08 | 2016-06-23 | ザヴィラ ファーマシューティカルズ ゲーエムベーハー | ピリミドン誘導体及びウイルス性疾患の治療、改善又は予防におけるそれらの使用 |
| JP2016530314A (ja) * | 2013-09-12 | 2016-09-29 | アリオス バイオファーマ インク． | アザ−ピリドン化合物およびその用途 |
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| JP2019536791A (ja) * | 2016-12-02 | 2019-12-19 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | Ｈｉｖインテグラーゼ阻害剤として有用な四環式複素環化合物 |
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-
2005
- 2005-03-01 US US10/587,601 patent/US20070161639A1/en not_active Abandoned
- 2005-03-01 EP EP05717825A patent/EP1725554A1/en not_active Withdrawn
- 2005-03-01 AU AU2005221864A patent/AU2005221864A1/en not_active Abandoned
- 2005-03-01 JP JP2007502381A patent/JP2007528379A/ja not_active Withdrawn
- 2005-03-01 CN CNA2005800074413A patent/CN1930161A/zh active Pending
- 2005-03-01 WO PCT/GB2005/000746 patent/WO2005087766A1/en not_active Ceased
- 2005-03-01 CA CA002557926A patent/CA2557926A1/en not_active Abandoned
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2008
- 2008-12-09 US US12/316,027 patent/US20090099168A1/en not_active Abandoned
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| WO2010147068A1 (ja) * | 2009-06-15 | 2010-12-23 | 塩野義製薬株式会社 | 置換された多環性カルバモイルピリドン誘導体 |
| JPWO2010147068A1 (ja) * | 2009-06-15 | 2012-12-06 | 塩野義製薬株式会社 | 置換された多環性カルバモイルピリドン誘導体 |
| JP2015145409A (ja) * | 2009-06-15 | 2015-08-13 | 塩野義製薬株式会社 | 置換された多環性カルバモイルピリドン誘導体 |
| JP2011195585A (ja) * | 2010-02-26 | 2011-10-06 | Japan Tobacco Inc | １，３，４，８−テトラヒドロ−２Ｈ−ピリド［１，２−ａ］ピラジン誘導体及びそのＨＩＶインテグラーゼ阻害剤としての利用 |
| JP2016518305A (ja) * | 2013-01-08 | 2016-06-23 | ザヴィラ ファーマシューティカルズ ゲーエムベーハー | ピリミドン誘導体及びウイルス性疾患の治療、改善又は予防におけるそれらの使用 |
| JP2016530314A (ja) * | 2013-09-12 | 2016-09-29 | アリオス バイオファーマ インク． | アザ−ピリドン化合物およびその用途 |
| US10251882B2 (en) | 2013-09-12 | 2019-04-09 | Alios Biopharma, Inc. | Aza-pyridone compounds and uses thereof |
| US10702523B2 (en) | 2013-09-12 | 2020-07-07 | Janssen Biopharma, Inc. | AZA-pyridone compounds and uses thereof |
| US10980805B2 (en) | 2013-09-12 | 2021-04-20 | Janssen Biopharma, Inc. | Aza-pyridone compounds and uses thereof |
| JP2016531863A (ja) * | 2013-09-27 | 2016-10-13 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | Ｈｉｖインテグラーゼ阻害薬として有用な置換されたキノリジン誘導体 |
| JP2017105793A (ja) * | 2013-09-27 | 2017-06-15 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | Ｈｉｖインテグラーゼ阻害薬として有用な置換されたキノリジン誘導体 |
| JP2019536791A (ja) * | 2016-12-02 | 2019-12-19 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | Ｈｉｖインテグラーゼ阻害剤として有用な四環式複素環化合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| US20070161639A1 (en) | 2007-07-12 |
| CA2557926A1 (en) | 2005-09-22 |
| US20090099168A1 (en) | 2009-04-16 |
| AU2005221864A1 (en) | 2005-09-22 |
| WO2005087766A1 (en) | 2005-09-22 |
| EP1725554A1 (en) | 2006-11-29 |
| CN1930161A (zh) | 2007-03-14 |
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