KR20050087865A - ＨＩＶ 인테그라제 억제제로서 유용한테트라하이드로-4Ｈ-피리도[1,2-ａ]피리미딘 및 관련화합물 - Google Patents
ＨＩＶ 인테그라제 억제제로서 유용한테트라하이드로-4Ｈ-피리도[1,2-ａ]피리미딘 및 관련화합물 Download PDFInfo
- Publication number
- KR20050087865A KR20050087865A KR1020057012028A KR20057012028A KR20050087865A KR 20050087865 A KR20050087865 A KR 20050087865A KR 1020057012028 A KR1020057012028 A KR 1020057012028A KR 20057012028 A KR20057012028 A KR 20057012028A KR 20050087865 A KR20050087865 A KR 20050087865A
- Authority
- KR
- South Korea
- Prior art keywords
- oxo
- hydroxy
- amino
- fluorobenzyl
- pyrido
- 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.)
- Ceased
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 114
- UBOXAHWUKQXQEH-UHFFFAOYSA-N 2,3,4,6-tetrahydro-1h-pyrido[1,2-a]pyrimidine Chemical class C1=CCN2CCCNC2=C1 UBOXAHWUKQXQEH-UHFFFAOYSA-N 0.000 title abstract description 3
- 229940099797 HIV integrase inhibitor Drugs 0.000 title description 3
- 239000003084 hiv integrase inhibitor Substances 0.000 title description 3
- 208000030507 AIDS Diseases 0.000 claims abstract description 40
- 150000003839 salts Chemical class 0.000 claims abstract description 30
- 208000031886 HIV Infections Diseases 0.000 claims abstract description 27
- 208000037357 HIV infectious disease Diseases 0.000 claims abstract description 23
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims abstract description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 15
- 108010002459 HIV Integrase Proteins 0.000 claims abstract description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 44
- -1 4-fluoro-3-methylbenzyl Chemical group 0.000 claims description 35
- 238000000034 method Methods 0.000 claims description 31
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 28
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 26
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 19
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 11
- 230000002401 inhibitory effect Effects 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- MCDBKPBDTVBVTL-UHFFFAOYSA-N 9-[dimethylsulfamoyl(methyl)amino]-n-[(4-fluorophenyl)methyl]-3-hydroxy-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-2-carboxamide Chemical compound CN(C)S(=O)(=O)N(C)C1CCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1 MCDBKPBDTVBVTL-UHFFFAOYSA-N 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- ZQDWKAJNPJBABY-UHFFFAOYSA-N n'-[2-[(4-fluorophenyl)methylcarbamoyl]-3-hydroxy-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-9-yl]-n,n,n'-trimethyloxamide Chemical compound CN(C)C(=O)C(=O)N(C)C1CCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1 ZQDWKAJNPJBABY-UHFFFAOYSA-N 0.000 claims description 4
- FUXJMHXHGDAHPD-UHFFFAOYSA-N pyrimidine-2-carboxamide Chemical compound NC(=O)C1=NC=CC=N1 FUXJMHXHGDAHPD-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- BXGKUPHBJWLRPJ-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-3-hydroxy-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-2-carboxamide Chemical compound N1=C2CCCCN2C(=O)C(O)=C1C(=O)NCC1=CC=C(F)C=C1 BXGKUPHBJWLRPJ-UHFFFAOYSA-N 0.000 claims description 3
- AGXRVRVEFKZWCP-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-3-hydroxy-9-morpholin-4-yl-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-2-carboxamide Chemical compound C1CCN2C(=O)C(O)=C(C(=O)NCC=3C=CC(F)=CC=3)N=C2C1N1CCOCC1 AGXRVRVEFKZWCP-UHFFFAOYSA-N 0.000 claims description 3
- 125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- YLIYNHWYALYMOQ-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-3-hydroxy-9-[methyl-(4-methylpiperazin-1-yl)sulfonylamino]-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-2-carboxamide Chemical compound C1CN(C)CCN1S(=O)(=O)N(C)C1CCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1 YLIYNHWYALYMOQ-UHFFFAOYSA-N 0.000 claims 6
- SJVFREKFBRXASI-UHFFFAOYSA-N n'-[2-[(4-fluoro-3-methylphenyl)methylcarbamoyl]-3-hydroxy-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-9-yl]-n,n,n'-trimethyloxamide Chemical compound CN(C)C(=O)C(=O)N(C)C1CCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C(C)=C1 SJVFREKFBRXASI-UHFFFAOYSA-N 0.000 claims 2
- COUJNVGGWLUEHF-UHFFFAOYSA-N n'-[2-[(4-fluorophenyl)methylcarbamoyl]-3-hydroxy-8,8-dimethyl-4-oxo-7,9-dihydro-6h-pyrido[1,2-a]pyrimidin-9-yl]-n,n,n'-trimethyloxamide Chemical compound OC=1C(=O)N2CCC(C)(C)C(N(C)C(=O)C(=O)N(C)C)C2=NC=1C(=O)NCC1=CC=C(F)C=C1 COUJNVGGWLUEHF-UHFFFAOYSA-N 0.000 claims 2
- IUWUIPCTVGUKAL-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-3-hydroxy-9-[methyl(morpholin-4-ylsulfonyl)amino]-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-2-carboxamide Chemical compound C1COCCN1S(=O)(=O)N(C)C1CCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1 IUWUIPCTVGUKAL-UHFFFAOYSA-N 0.000 claims 2
- AZQUAIDLKSFERN-UHFFFAOYSA-N 4h-pyrido[1,2-a]pyrimidine-2-carboxamide Chemical compound C1=CC=CC2=NC(C(=O)N)=CCN21 AZQUAIDLKSFERN-UHFFFAOYSA-N 0.000 claims 1
- SJWPTLITARZLER-UHFFFAOYSA-N 9-[[2-(dimethylsulfamoyl)acetyl]-methylamino]-n-[(4-fluoro-3-methylphenyl)methyl]-3-hydroxy-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-2-carboxamide Chemical compound CN(C)S(=O)(=O)CC(=O)N(C)C1CCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C(C)=C1 SJWPTLITARZLER-UHFFFAOYSA-N 0.000 claims 1
- GOIXPYWYXSSRFX-UHFFFAOYSA-N 9-[azetidin-1-ylsulfonyl(methyl)amino]-n-[(4-fluorophenyl)methyl]-3-hydroxy-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-2-carboxamide Chemical compound C1CCN1S(=O)(=O)N(C)C1CCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1 GOIXPYWYXSSRFX-UHFFFAOYSA-N 0.000 claims 1
- FHMHJNJYVZSGOD-UHFFFAOYSA-N n'-[2-[(3-chloro-4-methylphenyl)methylcarbamoyl]-3-hydroxy-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-9-yl]-n,n,n'-trimethyloxamide Chemical compound CN(C)C(=O)C(=O)N(C)C1CCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(C)C(Cl)=C1 FHMHJNJYVZSGOD-UHFFFAOYSA-N 0.000 claims 1
- QMHNSONWMFDIOU-UHFFFAOYSA-N n'-[2-[(3-chlorophenyl)methylcarbamoyl]-3-hydroxy-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-9-yl]-n,n,n'-trimethyloxamide Chemical compound CN(C)C(=O)C(=O)N(C)C1CCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=CC(Cl)=C1 QMHNSONWMFDIOU-UHFFFAOYSA-N 0.000 claims 1
- PFFFBBACUGSVPN-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-3-hydroxy-9-[methyl-(2-methylsulfonylacetyl)amino]-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-2-carboxamide Chemical compound CS(=O)(=O)CC(=O)N(C)C1CCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1 PFFFBBACUGSVPN-UHFFFAOYSA-N 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 239000003443 antiviral agent Substances 0.000 abstract description 11
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- PUYCICVJCRLABY-UHFFFAOYSA-N heptane;oxolane Chemical compound C1CCOC1.CCCCCCC PUYCICVJCRLABY-UHFFFAOYSA-N 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- CBVCZFGXHXORBI-PXQQMZJSSA-N indinavir Chemical compound C([C@H](N(CC1)C[C@@H](O)C[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H]2C3=CC=CC=C3C[C@H]2O)C(=O)NC(C)(C)C)N1CC1=CC=CN=C1 CBVCZFGXHXORBI-PXQQMZJSSA-N 0.000 description 1
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- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- QNEIZSSWCVSZOS-UHFFFAOYSA-N methyl 2-phenylmethoxyacetate Chemical compound COC(=O)COCC1=CC=CC=C1 QNEIZSSWCVSZOS-UHFFFAOYSA-N 0.000 description 1
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- BERNBOUHVFAAAE-PUODRLBUSA-N methyl 3-hydroxy-4-oxo-10-[[(1r)-1-phenylethyl]amino]-7,8,9,10-tetrahydro-6h-pyrimido[1,2-a]azepine-2-carboxylate Chemical compound C1([C@@H](C)NC2C3=NC(=C(C(=O)N3CCCC2)O)C(=O)OC)=CC=CC=C1 BERNBOUHVFAAAE-PUODRLBUSA-N 0.000 description 1
- DTEOUDKGIWFDEO-UHFFFAOYSA-N methyl 3-hydroxy-9-(methylamino)-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-2-carboxylate Chemical compound CNC1CCCN2C1=NC(C(=O)OC)=C(O)C2=O DTEOUDKGIWFDEO-UHFFFAOYSA-N 0.000 description 1
- IWOUDGARURIUCJ-UHFFFAOYSA-N methyl 4-oxo-3-phenylmethoxy-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-2-carboxylate Chemical compound COC(=O)C=1N=C2CCCCN2C(=O)C=1OCC1=CC=CC=C1 IWOUDGARURIUCJ-UHFFFAOYSA-N 0.000 description 1
- RSNVSNOSNVCVTR-UHFFFAOYSA-N methyl 9-[benzyl(methyl)amino]-3-hydroxy-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-2-carboxylate;hydrochloride Chemical compound Cl.C1CCN2C(=O)C(O)=C(C(=O)OC)N=C2C1N(C)CC1=CC=CC=C1 RSNVSNOSNVCVTR-UHFFFAOYSA-N 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- JFCHSQDLLFJHOA-UHFFFAOYSA-N n,n-dimethylsulfamoyl chloride Chemical compound CN(C)S(Cl)(=O)=O JFCHSQDLLFJHOA-UHFFFAOYSA-N 0.000 description 1
- PPOHPUOKXMNCCI-UHFFFAOYSA-N n-(3,4,5,6-tetrahydro-2h-azepin-7-yl)hydroxylamine Chemical compound ONC1=NCCCCC1 PPOHPUOKXMNCCI-UHFFFAOYSA-N 0.000 description 1
- WZUWQZYLHJCNOO-OQHSHRKDSA-N n-[(4-fluorophenyl)methyl]-3-hydroxy-10-[methyl-[(1r)-1-phenylethyl]amino]-4-oxo-7,8,9,10-tetrahydro-6h-pyrimido[1,2-a]azepine-2-carboxamide Chemical compound CN([C@H](C)C=1C=CC=CC=1)C1CCCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1 WZUWQZYLHJCNOO-OQHSHRKDSA-N 0.000 description 1
- WKDJVAMTCVRQSI-QRIPLOBPSA-N n-[(4-fluorophenyl)methyl]-3-hydroxy-4-oxo-10-[[(1r)-1-phenylethyl]amino]-7,8,9,10-tetrahydro-6h-pyrimido[1,2-a]azepine-2-carboxamide Chemical compound N([C@H](C)C=1C=CC=CC=1)C1CCCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1 WKDJVAMTCVRQSI-QRIPLOBPSA-N 0.000 description 1
- QUHQMUZDZWHIPO-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-3-hydroxy-9-(methylamino)-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-2-carboxamide Chemical compound CNC1CCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1 QUHQMUZDZWHIPO-UHFFFAOYSA-N 0.000 description 1
- XMIPAKWCYIZLFV-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-3-hydroxy-9-morpholin-4-yl-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-2-carboxamide;hydrochloride Chemical compound Cl.C1CCN2C(=O)C(O)=C(C(=O)NCC=3C=CC(F)=CC=3)N=C2C1N1CCOCC1 XMIPAKWCYIZLFV-UHFFFAOYSA-N 0.000 description 1
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
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- 230000003472 neutralizing effect Effects 0.000 description 1
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- KHPXUQMNIQBQEV-UHFFFAOYSA-L oxaloacetate(2-) Chemical compound [O-]C(=O)CC(=O)C([O-])=O KHPXUQMNIQBQEV-UHFFFAOYSA-L 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
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- 244000052769 pathogen Species 0.000 description 1
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- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 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
- SIOXPEMLGUPBBT-UHFFFAOYSA-M picolinate Chemical compound [O-]C(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-M 0.000 description 1
- 108700004029 pol Genes Proteins 0.000 description 1
- 101150088264 pol gene Proteins 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- JUJWROOIHBZHMG-RALIUCGRSA-N pyridine-d5 Chemical compound [2H]C1=NC([2H])=C([2H])C([2H])=C1[2H] JUJWROOIHBZHMG-RALIUCGRSA-N 0.000 description 1
- 150000008518 pyridopyrimidines Chemical class 0.000 description 1
- ZFCHNZDUMIOWFV-UHFFFAOYSA-M pyrimidine-2-carboxylate Chemical compound [O-]C(=O)C1=NC=CC=N1 ZFCHNZDUMIOWFV-UHFFFAOYSA-M 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 125000001174 sulfone group Chemical group 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- XJBFPQUKNPHLBX-UHFFFAOYSA-N tert-butyl n-(5-cyanopentyl)-n-phenylmethoxycarbamate Chemical compound N#CCCCCCN(C(=O)OC(C)(C)C)OCC1=CC=CC=C1 XJBFPQUKNPHLBX-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- AIDS & HIV (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US43683002P | 2002-12-27 | 2002-12-27 | |
| US60/436,830 | 2002-12-27 | ||
| US52877603P | 2003-12-12 | 2003-12-12 | |
| US60/528,776 | 2003-12-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20050087865A true KR20050087865A (ko) | 2005-08-31 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020057012028A Ceased KR20050087865A (ko) | 2002-12-27 | 2003-12-18 | ＨＩＶ 인테그라제 억제제로서 유용한테트라하이드로-4Ｈ-피리도[1,2-ａ]피리미딘 및 관련화합물 |
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|---|---|
| US (2) | US7414045B2 (https=) |
| EP (1) | EP1578748B1 (https=) |
| JP (1) | JP4733986B2 (https=) |
| KR (1) | KR20050087865A (https=) |
| CN (1) | CN100343253C (https=) |
| AT (1) | ATE481401T1 (https=) |
| AU (2) | AU2003292437A1 (https=) |
| BR (1) | BR0317749A (https=) |
| CA (1) | CA2509554C (https=) |
| DE (1) | DE60334248D1 (https=) |
| EC (1) | ECSP055890A (https=) |
| HR (1) | HRP20050593A2 (https=) |
| IS (1) | IS7892A (https=) |
| MA (1) | MA27583A1 (https=) |
| MX (1) | MXPA05007010A (https=) |
| NO (1) | NO20053624L (https=) |
| NZ (1) | NZ540729A (https=) |
| PL (1) | PL377354A1 (https=) |
| RU (1) | RU2329265C2 (https=) |
| WO (2) | WO2004058757A1 (https=) |
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| WO2004062613A2 (en) * | 2003-01-13 | 2004-07-29 | Bristol-Myers Squibb Company | Hiv integrase inhibitors |
| CA2542047A1 (en) | 2003-10-20 | 2005-05-12 | Merck & Co., Inc. | Hydroxy pyridopyrrolopyrazine dione compounds useful as hiv integrase inhibitors |
| AR046938A1 (es) * | 2003-12-12 | 2006-01-04 | Merck & Co Inc | Procedimiento para preparar hexahidropirimido[1,2-a]azepin-2-carboxilatos y compuetos similares |
| TW200526635A (en) * | 2003-12-22 | 2005-08-16 | Shionogi & Co | Hydroxypyrimidinone derivative having HIV integrase inhibitory activity |
| 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 |
| US7157447B2 (en) | 2004-05-28 | 2007-01-02 | 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 |
| US7173022B2 (en) | 2004-05-28 | 2007-02-06 | 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 |
| WO2006060225A2 (en) * | 2004-11-23 | 2006-06-08 | Merck & Co., Inc. | Process for asymmetric synthesis of hexahydropyrimido[1,2-a] azepine-2-carboxamides and related compounds |
| MX2007006635A (es) * | 2004-12-03 | 2007-06-19 | Merck & Co Inc | Formulacion farmaceutica de inhibidores dela carboxamida vih integrasa que contienen una composicion que controla la velocidad de liberacion. |
| EP1819323B2 (en) * | 2004-12-03 | 2023-03-22 | Merck Sharp & Dohme Corp. | Pharmaceutical composition containing an anti-nucleating agent |
| UA87884C2 (uk) * | 2004-12-03 | 2009-08-25 | Мерк Энд Ко., Инк. | Безводна кристалічна калієва сіль інгібітора віл-інтегрази |
| RU2403066C2 (ru) * | 2004-12-03 | 2010-11-10 | Мерк Шарп Энд Домэ Корп | Применение атазанавира для улучшения фармакокинетики лекарственных средств, метаболизируемых ugt1a1 |
| ATE516026T1 (de) * | 2005-02-21 | 2011-07-15 | Shionogi & Co | Bicyclisches carbamoylpyridonderivat mit hiv- integrase-hemmender wirkung |
| CN101146811B (zh) * | 2005-03-31 | 2012-01-11 | P.安杰莱蒂分子生物学研究所 | Hiv整合酶抑制剂 |
| US8129385B2 (en) * | 2005-04-28 | 2012-03-06 | Shionogi & Co., Ltd. | Substituted 5-hydroxy-3,4,6,9,9a, 10-hexanhydro-2h-1-oxa04a,8a-diaza-anthracene-6,10-dioness |
| WO2007005404A1 (en) | 2005-06-30 | 2007-01-11 | Wyeth | AMINO-5-(6-MEMBERED)HETEROARYLIMIDAZOLONE COMPOUNDS AND THE USE THEREOF FOR ß-SECRETASE MODULATION |
| US7494984B2 (en) * | 2005-08-31 | 2009-02-24 | Bristol-Myers Squibb Company | Substituted imidazo[1,2-a]pyrimidines as HIV viral DNA integrase inhibitors |
| CA2622639C (en) * | 2005-10-04 | 2012-01-03 | Istituto Di Recerche Di Biologia Molecolare P. Angeletti S.P.A. | Hiv integrase inhibitors |
| 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 |
| EA200801144A1 (ru) | 2005-10-27 | 2008-10-30 | Сионоги Энд Ко., Лтд. | Полициклическое карбамоилпиридоновое производное, обладающее ингибиторной активностью в отношении интегразы вич |
| US7897592B2 (en) * | 2005-11-15 | 2011-03-01 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
| WO2007058646A1 (en) * | 2005-11-15 | 2007-05-24 | Bristol-Myers Squibb Company | Hiv integrase inhibitors: cyclic pyrimidinone compounds |
| US7902182B2 (en) * | 2005-11-16 | 2011-03-08 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
| US8039458B2 (en) * | 2005-11-17 | 2011-10-18 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
| WO2007064316A1 (en) * | 2005-11-30 | 2007-06-07 | Bristol-Myers Squibb Company | Bicyclic heterocycles as hiv integrase inhibitors |
| US20070129379A1 (en) * | 2005-12-01 | 2007-06-07 | Bristol-Myers Squibb Company | Hiv integrase inhibitors |
| WO2007087188A2 (en) * | 2006-01-20 | 2007-08-02 | Merck & Co., Inc. | Taste-masked tablets and granules |
| US7897593B2 (en) | 2006-05-30 | 2011-03-01 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
| US7893055B2 (en) * | 2006-06-28 | 2011-02-22 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
| US7763630B2 (en) * | 2007-06-06 | 2010-07-27 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
| US8129398B2 (en) * | 2008-03-19 | 2012-03-06 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
| WO2010042392A2 (en) * | 2008-10-06 | 2010-04-15 | Merck & Co., Inc. | Hiv integrase inhibitors |
| CA2744019C (en) * | 2008-12-11 | 2017-03-14 | Shionogi & Co., Ltd. | Synthesis of carbamoylpyridone hiv integrase inhibitors and intermediates |
| US8143244B2 (en) * | 2009-02-26 | 2012-03-27 | Bristol-Myers Squibb Company | Cyclopropyl fused indolobenzazepine HCV NS5B inhibitors |
| BRPI1015943A8 (pt) * | 2009-07-02 | 2018-01-09 | Sanofi Sa | derivados de 1,2,3,4-tetra - hidro - pirimido {1,2-a} pirimidin-6-ona, o respectivo preparo e a respectiva utilização farmacêutica. |
| WO2011045330A1 (en) | 2009-10-13 | 2011-04-21 | Tibotec Pharmaceuticals | Macrocyclic integrase inhibitors |
| US8383639B2 (en) | 2009-10-15 | 2013-02-26 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
| IN2012DN03377A (https=) | 2009-10-26 | 2015-10-23 | Merck Sharp & Dohme | |
| RU2567385C2 (ru) | 2010-04-02 | 2015-11-10 | ЯНССЕН Ар ЭНД Ди АЙРЛЭНД | Макроциклические ингибиторы интегразы |
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| MD4794B1 (ro) | 2013-09-27 | 2022-02-28 | Merck Sharp & Dohme Corp | Derivaţi de chinolizină substituiţi utili ca inhibitori de integrază HIV |
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| JP2003503386A (ja) | 1999-06-25 | 2003-01-28 | メルク エンド カムパニー インコーポレーテッド | １−（芳香族またはヘテロ芳香族置換）−３−（ヘテロ芳香族置換）−１，３−プロパンジオン類およびそれの使用 |
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| JP2004517860A (ja) | 2000-10-12 | 2004-06-17 | 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薬として有用なアザ−およびポリアザ−ナフタレニルカルボキサミド類 |
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| EP1441734B1 (en) * | 2001-10-26 | 2007-02-28 | Istituto di Richerche di Biologia Molecolare P. Angeletti S.p.A. | Dihydroxypyrimidine carboxamide inhibitors of hiv integrase |
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| US7037908B2 (en) | 2003-04-24 | 2006-05-02 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
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- 2003-12-18 AU AU2003292437A patent/AU2003292437A1/en not_active Abandoned
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- 2003-12-18 US US10/540,449 patent/US7414045B2/en not_active Expired - Lifetime
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- 2003-12-18 RU RU2005123807/04A patent/RU2329265C2/ru not_active IP Right Cessation
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- 2005-06-23 EC EC2005005890A patent/ECSP055890A/es unknown
- 2005-07-21 MA MA28407A patent/MA27583A1/fr unknown
- 2005-07-26 NO NO20053624A patent/NO20053624L/no not_active Application Discontinuation
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| CA2509554C (en) | 2011-02-01 |
| EP1578748B1 (en) | 2010-09-15 |
| US20080176869A1 (en) | 2008-07-24 |
| PL377354A1 (pl) | 2006-01-23 |
| NO20053624D0 (no) | 2005-07-26 |
| MXPA05007010A (es) | 2005-08-18 |
| CA2509554A1 (en) | 2004-07-15 |
| AU2003292436A1 (en) | 2004-07-22 |
| AU2003292437A1 (en) | 2004-07-22 |
| NO20053624L (no) | 2005-09-26 |
| ATE481401T1 (de) | 2010-10-15 |
| US7414045B2 (en) | 2008-08-19 |
| IS7892A (is) | 2005-06-13 |
| EP1578748A1 (en) | 2005-09-28 |
| JP4733986B2 (ja) | 2011-07-27 |
| HRP20050593A2 (en) | 2006-03-31 |
| US20060046985A1 (en) | 2006-03-02 |
| ECSP055890A (es) | 2005-09-20 |
| AU2003292436B2 (en) | 2009-07-30 |
| DE60334248D1 (de) | 2010-10-28 |
| US7968553B2 (en) | 2011-06-28 |
| CN100343253C (zh) | 2007-10-17 |
| CN1753892A (zh) | 2006-03-29 |
| RU2329265C2 (ru) | 2008-07-20 |
| BR0317749A (pt) | 2005-11-22 |
| JP2006513200A (ja) | 2006-04-20 |
| MA27583A1 (fr) | 2005-10-03 |
| RU2005123807A (ru) | 2006-01-20 |
| WO2004058757A1 (en) | 2004-07-15 |
| NZ540729A (en) | 2008-03-28 |
| WO2004058756A1 (en) | 2004-07-15 |
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