KR20100088142A - 비-뉴클레오사이드 역전사효소 억제제 - Google Patents

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Publication number

KR20100088142A

KR20100088142A KR1020107011127A KR20107011127A KR20100088142A KR 20100088142 A KR20100088142 A KR 20100088142A KR 1020107011127 A KR1020107011127 A KR 1020107011127A KR 20107011127 A KR20107011127 A KR 20107011127A KR 20100088142 A KR20100088142 A KR 20100088142A

Authority

KR

South Korea

Prior art keywords

alkyl

independently

compound

chloro

substituents

Prior art date

2007-11-20

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Withdrawn

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• 229940042402 non-nucleoside reverse transcriptase inhibitor Drugs 0.000 title description 4
• 239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 title description 4
• 150000001875 compounds Chemical class 0.000 claims abstract description 458
• 150000003839 salts Chemical class 0.000 claims abstract description 164
• 239000000651 prodrug Substances 0.000 claims abstract description 57
• 229940002612 prodrug Drugs 0.000 claims abstract description 57
• 108010078851 HIV Reverse Transcriptase Proteins 0.000 claims abstract description 29
• 208000030507 AIDS Diseases 0.000 claims abstract description 27
• 230000002265 prevention Effects 0.000 claims abstract description 27
• 208000015181 infectious disease Diseases 0.000 claims abstract description 18
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
• 239000003443 antiviral agent Substances 0.000 claims abstract description 17
• 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims abstract description 15
• 238000011161 development Methods 0.000 claims abstract description 13
• 125000000217 alkyl group Chemical group 0.000 claims description 300
• 125000001424 substituent group Chemical group 0.000 claims description 132
• 229910052799 carbon Inorganic materials 0.000 claims description 93
• -1 3-methyl-4-phenoxy-2-pyridinyl Chemical group 0.000 claims description 91
• 229910052739 hydrogen Inorganic materials 0.000 claims description 91
• 229910052757 nitrogen Inorganic materials 0.000 claims description 73
• 229910052801 chlorine Inorganic materials 0.000 claims description 62
• 229910052794 bromium Inorganic materials 0.000 claims description 61
• 125000001188 haloalkyl group Chemical group 0.000 claims description 59
• 238000000034 method Methods 0.000 claims description 53
• 229910052731 fluorine Inorganic materials 0.000 claims description 52
• 150000002367 halogens Chemical class 0.000 claims description 50
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 49
• 229910052736 halogen Inorganic materials 0.000 claims description 45
• 125000005842 heteroatom Chemical group 0.000 claims description 42
• 125000001072 heteroaryl group Chemical group 0.000 claims description 34
• 229910052717 sulfur Inorganic materials 0.000 claims description 34
• 125000003709 fluoroalkyl group Chemical group 0.000 claims description 30
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
• 229910052760 oxygen Inorganic materials 0.000 claims description 28
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 23
• 125000003342 alkenyl group Chemical group 0.000 claims description 22
• 125000003118 aryl group Chemical group 0.000 claims description 22
• 229920006395 saturated elastomer Polymers 0.000 claims description 21
• 125000000623 heterocyclic group Chemical group 0.000 claims description 18
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 17
• 125000004122 cyclic group Chemical group 0.000 claims description 17
• 125000001624 naphthyl group Chemical group 0.000 claims description 17
• 239000003112 inhibitor Substances 0.000 claims description 15
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 14
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
• 239000003814 drug Substances 0.000 claims description 13
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 12
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 12
• 125000002883 imidazolyl group Chemical group 0.000 claims description 12
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
• 125000002950 monocyclic group Chemical group 0.000 claims description 9
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 9
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 8
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
• 125000004432 carbon atom Chemical group C* 0.000 claims description 8
• 239000002777 nucleoside Substances 0.000 claims description 8
• 125000000081 (C5-C8) cycloalkenyl group Chemical group 0.000 claims description 7
• XUIZIBCKVKBTGV-UHFFFAOYSA-N 3-chloro-5-[4-methyl-2-oxo-1-[2-(2h-pyrazolo[3,4-b]pyridin-3-yl)ethyl]pyridin-3-yl]oxybenzonitrile Chemical compound CC=1C=CN(CCC=2C3=CC=CN=C3NN=2)C(=O)C=1OC1=CC(Cl)=CC(C#N)=C1 XUIZIBCKVKBTGV-UHFFFAOYSA-N 0.000 claims description 7
• GIOABAWLXRZDTF-UHFFFAOYSA-N 3-chloro-5-[[2-oxo-6-[2-(2h-pyrazolo[3,4-b]pyridin-3-yl)ethyl]-1h-pyridin-4-yl]oxy]benzonitrile Chemical compound N#CC1=CC(Cl)=CC(OC2=CC(=O)NC(CCC=3C4=CC=CN=C4NN=3)=C2)=C1 GIOABAWLXRZDTF-UHFFFAOYSA-N 0.000 claims description 7
• CCEYNDRKIOXUGP-UHFFFAOYSA-N 3-chloro-5-[[3-chloro-2-oxo-6-(2h-pyrazolo[3,4-b]pyridin-3-ylmethyl)-1h-pyridin-4-yl]oxy]benzonitrile Chemical compound N#CC1=CC(Cl)=CC(OC2=C(C(=O)NC(CC=3C4=CC=CN=C4NN=3)=C2)Cl)=C1 CCEYNDRKIOXUGP-UHFFFAOYSA-N 0.000 claims description 7
• GZVLIXZYBWGUTC-UHFFFAOYSA-N 3-chloro-5-[[3-chloro-2-oxo-6-[(2-oxo-3h-benzimidazol-1-yl)methyl]-1h-pyridin-4-yl]oxy]benzonitrile Chemical compound N#CC1=CC(Cl)=CC(OC2=C(C(=O)NC(CN3C(NC4=CC=CC=C43)=O)=C2)Cl)=C1 GZVLIXZYBWGUTC-UHFFFAOYSA-N 0.000 claims description 7
• NCPJKBVDFNPLLG-UHFFFAOYSA-N 3-chloro-5-[[3-chloro-2-oxo-6-[2-(2h-pyrazolo[3,4-b]pyridin-3-yl)ethyl]-1h-pyridin-4-yl]oxy]benzonitrile Chemical compound N#CC1=CC(Cl)=CC(OC2=C(C(=O)NC(CCC=3C4=CC=CN=C4NN=3)=C2)Cl)=C1 NCPJKBVDFNPLLG-UHFFFAOYSA-N 0.000 claims description 7
• YXVABPSUOVOEJJ-UHFFFAOYSA-N 2-methyl-6-[(6-phenoxypyridin-2-yl)methyl]pyridine Chemical compound CC1=CC=CC(CC=2N=C(OC=3C=CC=CC=3)C=CC=2)=N1 YXVABPSUOVOEJJ-UHFFFAOYSA-N 0.000 claims description 6
• DZUHNBJTDWFYCJ-UHFFFAOYSA-N 3-[6-[(6-amino-2h-pyrazolo[3,4-b]pyridin-3-yl)methylamino]-5-chloro-3-fluoropyridin-2-yl]oxy-5-chlorobenzonitrile Chemical compound N=1NC2=NC(N)=CC=C2C=1CNC(C(=CC=1F)Cl)=NC=1OC1=CC(Cl)=CC(C#N)=C1 DZUHNBJTDWFYCJ-UHFFFAOYSA-N 0.000 claims description 6
• TXIDGJNYVPGVEG-UHFFFAOYSA-N 3-[[6-[2-(6-amino-2h-pyrazolo[3,4-b]pyridin-3-yl)ethyl]-3-chloro-2-oxo-1h-pyridin-4-yl]oxy]-5-chlorobenzonitrile Chemical compound N=1NC2=NC(N)=CC=C2C=1CCC(NC(=O)C=1Cl)=CC=1OC1=CC(Cl)=CC(C#N)=C1 TXIDGJNYVPGVEG-UHFFFAOYSA-N 0.000 claims description 6
• CVAURPNMBSXXSS-UHFFFAOYSA-N 3-chloro-5-[2-oxo-1-(2h-pyrazolo[3,4-b]pyridin-3-ylmethyl)-4-(trifluoromethyl)pyridin-3-yl]oxybenzonitrile Chemical compound FC(F)(F)C=1C=CN(CC=2C3=CC=CN=C3NN=2)C(=O)C=1OC1=CC(Cl)=CC(C#N)=C1 CVAURPNMBSXXSS-UHFFFAOYSA-N 0.000 claims description 6
• ABOZXYNAPFTBHX-UHFFFAOYSA-N 3-chloro-5-[4,5-dichloro-2-oxo-1-(2h-pyrazolo[3,4-b]pyridin-3-ylmethyl)pyridin-3-yl]oxybenzonitrile Chemical compound N#CC1=CC(Cl)=CC(OC=2C(N(CC=3C4=CC=CN=C4NN=3)C=C(Cl)C=2Cl)=O)=C1 ABOZXYNAPFTBHX-UHFFFAOYSA-N 0.000 claims description 6
• ZSDYTNJSFLYICM-UHFFFAOYSA-N 3-chloro-5-[4-chloro-2-oxo-1-(2h-pyrazolo[3,4-b]pyridin-3-ylmethyl)pyridin-3-yl]oxybenzonitrile Chemical compound N#CC1=CC(Cl)=CC(OC=2C(N(CC=3C4=CC=CN=C4NN=3)C=CC=2Cl)=O)=C1 ZSDYTNJSFLYICM-UHFFFAOYSA-N 0.000 claims description 6
• YMRUCOCNLHJFRC-UHFFFAOYSA-N 3-chloro-5-[4-methyl-2-oxo-1-(2h-pyrazolo[3,4-b]pyridin-3-ylmethyl)pyridin-3-yl]oxybenzonitrile Chemical compound CC=1C=CN(CC=2C3=CC=CN=C3NN=2)C(=O)C=1OC1=CC(Cl)=CC(C#N)=C1 YMRUCOCNLHJFRC-UHFFFAOYSA-N 0.000 claims description 6
• RRYPCILBOZGVEJ-UHFFFAOYSA-N 3-chloro-5-[5-chloro-2-[2-(2h-pyrazolo[3,4-b]pyridin-3-yl)ethyl]pyridin-4-yl]oxybenzonitrile Chemical compound N#CC1=CC(Cl)=CC(OC=2C(=CN=C(CCC=3C4=CC=CN=C4NN=3)C=2)Cl)=C1 RRYPCILBOZGVEJ-UHFFFAOYSA-N 0.000 claims description 6
• UXWKLSXBOSOYHN-UHFFFAOYSA-N 3-chloro-5-[5-chloro-3-fluoro-6-(2h-pyrazolo[3,4-b]pyridin-3-ylmethylamino)pyridin-2-yl]oxybenzonitrile Chemical compound FC1=CC(Cl)=C(NCC=2C3=CC=CN=C3NN=2)N=C1OC1=CC(Cl)=CC(C#N)=C1 UXWKLSXBOSOYHN-UHFFFAOYSA-N 0.000 claims description 6
• MEFSIZQEXHEOCA-UHFFFAOYSA-N 3-chloro-5-[[3,5-dichloro-2-oxo-6-[2-(2h-pyrazolo[3,4-b]pyridin-3-yl)ethyl]-1h-pyridin-4-yl]oxy]benzonitrile Chemical compound N#CC1=CC(Cl)=CC(OC2=C(C(=O)NC(CCC=3C4=CC=CN=C4NN=3)=C2Cl)Cl)=C1 MEFSIZQEXHEOCA-UHFFFAOYSA-N 0.000 claims description 6
• KDKUQACKJMWZJZ-UHFFFAOYSA-N 3-chloro-5-[[3-chloro-2-oxo-6-(2h-pyrazolo[3,4-b]pyridin-3-ylmethylamino)-1h-pyridin-4-yl]oxy]benzonitrile Chemical compound N#CC1=CC(Cl)=CC(OC2=C(C(=O)NC(NCC=3C4=CC=CN=C4NN=3)=C2)Cl)=C1 KDKUQACKJMWZJZ-UHFFFAOYSA-N 0.000 claims description 6
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 6
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical group C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 6
• 125000000304 alkynyl group Chemical group 0.000 claims description 6
• 125000002619 bicyclic group Chemical group 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• TUWMDEWCUXBQJV-UHFFFAOYSA-N ethyl 3-chloro-5-[[3,5-dichloro-2-oxo-6-[2-(2h-pyrazolo[3,4-b]pyridin-3-yl)ethyl]-1h-pyridin-4-yl]oxy]benzoate Chemical compound CCOC(=O)C1=CC(Cl)=CC(OC2=C(C(=O)NC(CCC=3C4=CC=CN=C4NN=3)=C2Cl)Cl)=C1 TUWMDEWCUXBQJV-UHFFFAOYSA-N 0.000 claims description 6
• 230000009545 invasion Effects 0.000 claims description 6
• 125000001786 isothiazolyl group Chemical group 0.000 claims description 6
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 6
• 125000006574 non-aromatic ring group Chemical group 0.000 claims description 6
• 150000003833 nucleoside derivatives Chemical class 0.000 claims description 6
• 125000002971 oxazolyl group Chemical group 0.000 claims description 6
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
• 125000000335 thiazolyl group Chemical group 0.000 claims description 6
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
• ATGKQOUKJPVTKE-UHFFFAOYSA-N 2-[3-(3-chloro-5-cyanophenoxy)-2-oxo-4-(trifluoromethyl)pyridin-1-yl]-n-[(2-chlorophenyl)methyl]-n-methylacetamide Chemical compound C1=CC(C(F)(F)F)=C(OC=2C=C(C=C(Cl)C=2)C#N)C(=O)N1CC(=O)N(C)CC1=CC=CC=C1Cl ATGKQOUKJPVTKE-UHFFFAOYSA-N 0.000 claims description 5
• KHIUGRYFNXHUBT-UHFFFAOYSA-N 3-[1-[(6-amino-2h-pyrazolo[3,4-b]pyridin-3-yl)methyl]-4-chloro-2-oxopyridin-3-yl]oxy-5-chlorobenzonitrile;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N=1NC2=NC(N)=CC=C2C=1CN(C1=O)C=CC(Cl)=C1OC1=CC(Cl)=CC(C#N)=C1 KHIUGRYFNXHUBT-UHFFFAOYSA-N 0.000 claims description 5
• 229940099797 HIV integrase inhibitor Drugs 0.000 claims description 5
• 101100273648 Mus musculus Ccna2 gene Proteins 0.000 claims description 5
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 5
• 125000004452 carbocyclyl group Chemical group 0.000 claims description 5
• 229940079593 drug Drugs 0.000 claims description 5
• 239000002835 hiv fusion inhibitor Substances 0.000 claims description 5
• 239000003084 hiv integrase inhibitor Substances 0.000 claims description 5
• 239000004030 hiv protease inhibitor Substances 0.000 claims description 5
• 125000001425 triazolyl group Chemical group 0.000 claims description 5
• 229910052727 yttrium Inorganic materials 0.000 claims description 5
• 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 4
• KBLCUCFITXXEQF-UHFFFAOYSA-N 3-chloro-5-[3,5-dichloro-2-methyl-6-(2h-pyrazolo[3,4-b]pyridin-3-ylmethoxy)pyridin-4-yl]oxybenzonitrile Chemical compound ClC=1C(C)=NC(OCC=2C3=CC=CN=C3NN=2)=C(Cl)C=1OC1=CC(Cl)=CC(C#N)=C1 KBLCUCFITXXEQF-UHFFFAOYSA-N 0.000 claims description 4
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 4
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
• LIVDFVFPMFJQMJ-UHFFFAOYSA-N 3-[1-[(6-amino-1h-pyrrolo[2,3-b]pyridin-3-yl)methyl]-2-oxo-4-(trifluoromethyl)pyridin-3-yl]oxy-5-chlorobenzonitrile Chemical compound C=1NC2=NC(N)=CC=C2C=1CN(C1=O)C=CC(C(F)(F)F)=C1OC1=CC(Cl)=CC(C#N)=C1 LIVDFVFPMFJQMJ-UHFFFAOYSA-N 0.000 claims description 3
• JJIJSDYPXLKHIO-UHFFFAOYSA-N 3-chloro-5-[[3-chloro-6-[hydroxy(2h-pyrazolo[3,4-b]pyridin-3-yl)methyl]-2-oxo-1h-pyridin-4-yl]oxy]benzonitrile Chemical compound N=1NC2=NC=CC=C2C=1C(O)C(NC(=O)C=1Cl)=CC=1OC1=CC(Cl)=CC(C#N)=C1 JJIJSDYPXLKHIO-UHFFFAOYSA-N 0.000 claims description 3
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Chemical group C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 3
• BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims description 3
• 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 3
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 3
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
• 229910052709 silver Inorganic materials 0.000 claims description 3
• 239000004332 silver Substances 0.000 claims description 3
• FTFUKUWGDBEIJI-UHFFFAOYSA-N 3-chloro-5-[3-chloro-2,5-difluoro-6-(2h-pyrazolo[3,4-b]pyridin-3-ylmethylamino)pyridin-4-yl]oxybenzonitrile Chemical compound ClC=1C(F)=NC(NCC=2C3=CC=CN=C3NN=2)=C(F)C=1OC1=CC(Cl)=CC(C#N)=C1 FTFUKUWGDBEIJI-UHFFFAOYSA-N 0.000 claims description 2
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
• 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 2
• 230000004927 fusion Effects 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• 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 description 2
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 22
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims 1
• 229910052698 phosphorus Inorganic materials 0.000 claims 1
• 239000011574 phosphorus Substances 0.000 claims 1
• 230000005764 inhibitory process Effects 0.000 abstract description 15
• 239000002955 immunomodulating agent Substances 0.000 abstract description 4
• 229940121354 immunomodulator Drugs 0.000 abstract description 3
• 229960005486 vaccine Drugs 0.000 abstract description 2
• 239000003242 anti bacterial agent Substances 0.000 abstract 1
• 229940088710 antibiotic agent Drugs 0.000 abstract 1
• 150000002390 heteroarenes Chemical class 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 206
• 239000011541 reaction mixture Substances 0.000 description 122
• 239000000460 chlorine Substances 0.000 description 113
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 97
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 96
• 239000000203 mixture Substances 0.000 description 93
• 239000000243 solution Substances 0.000 description 93
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 85
• 235000019439 ethyl acetate Nutrition 0.000 description 84
• 239000007787 solid Substances 0.000 description 81
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 79
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 61
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 56
• 241000725303 Human immunodeficiency virus Species 0.000 description 49
• 239000002904 solvent Substances 0.000 description 49
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
• 239000003921 oil Substances 0.000 description 40
• 239000000047 product Substances 0.000 description 40
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 37
• 239000012267 brine Substances 0.000 description 36
• 239000000284 extract Substances 0.000 description 30
• 238000006243 chemical reaction Methods 0.000 description 29
• 229910000027 potassium carbonate Inorganic materials 0.000 description 28
• 239000000741 silica gel Substances 0.000 description 25
• 229910002027 silica gel Inorganic materials 0.000 description 25
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
• 239000003480 eluent Substances 0.000 description 23
• 230000002829 reductive effect Effects 0.000 description 23
• 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 22
• 238000004440 column chromatography Methods 0.000 description 22
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 22
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 20
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
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• 239000000706 filtrate Substances 0.000 description 20
• 239000010410 layer Substances 0.000 description 20
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• 0 *c1nc(cccc2)c2[n]1N Chemical compound *c1nc(cccc2)c2[n]1N 0.000 description 19
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