CA2673183C - Bicyclic pyrimidinones and uses thereof - Google Patents

Info

Publication number

CA2673183C

CA2673183C CA2673183A CA2673183A CA2673183C CA 2673183 C CA2673183 C CA 2673183C CA 2673183 A CA2673183 A CA 2673183A CA 2673183 A CA2673183 A CA 2673183A CA 2673183 C CA2673183 C CA 2673183C

Authority

CA

Canada

Prior art keywords

pharmaceutically acceptable

prodrug

salt

acceptable derivative

group

Prior art date

2006-12-22

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.)

Expired - Fee Related

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• -1 Bicyclic pyrimidinones Chemical class 0.000 title claims description 38
• 150000001875 compounds Chemical class 0.000 claims abstract description 225
• 150000003839 salts Chemical class 0.000 claims abstract description 77
• 239000000651 prodrug Substances 0.000 claims abstract description 72
• 229940002612 prodrug Drugs 0.000 claims abstract description 72
• 208000036142 Viral infection Diseases 0.000 claims abstract description 31
• 230000009385 viral infection Effects 0.000 claims abstract description 31
• 238000011282 treatment Methods 0.000 claims abstract description 30
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 21
• 238000011321 prophylaxis Methods 0.000 claims abstract description 20
• 239000003814 drug Substances 0.000 claims abstract description 11
• 238000002360 preparation method Methods 0.000 claims description 234
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 48
• 229910052799 carbon Inorganic materials 0.000 claims description 44
• 125000001424 substituent group Chemical group 0.000 claims description 33
• 229910052717 sulfur Inorganic materials 0.000 claims description 32
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 31
• 125000001072 heteroaryl group Chemical group 0.000 claims description 29
• 125000003118 aryl group Chemical group 0.000 claims description 27
• 125000000623 heterocyclic group Chemical group 0.000 claims description 26
• 125000005843 halogen group Chemical group 0.000 claims description 24
• 125000005842 heteroatom Chemical group 0.000 claims description 19
• 229910052757 nitrogen Inorganic materials 0.000 claims description 17
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 17
• 229910052739 hydrogen Inorganic materials 0.000 claims description 16
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 15
• 208000015181 infectious disease Diseases 0.000 claims description 15
• 230000003647 oxidation Effects 0.000 claims description 14
• 238000007254 oxidation reaction Methods 0.000 claims description 14
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
• 239000003085 diluting agent Substances 0.000 claims description 12
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
• 239000003937 drug carrier Substances 0.000 claims description 8
• 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 7
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
• 239000001257 hydrogen Substances 0.000 claims description 6
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 6
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 4
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 4
• 125000002950 monocyclic group Chemical group 0.000 claims description 4
• 150000003536 tetrazoles Chemical class 0.000 claims description 4
• 150000003852 triazoles Chemical class 0.000 claims description 4
• 125000006512 3,4-dichlorobenzyl group Chemical group [H]C1=C(Cl)C(Cl)=C([H])C(=C1[H])C([H])([H])* 0.000 claims description 3
• 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 3
• 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 3
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 3
• 125000006286 dichlorobenzyl group Chemical group 0.000 claims description 3
• 125000004175 fluorobenzyl group Chemical group 0.000 claims description 3
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 3
• VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 3
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 16
• 229910052760 oxygen Inorganic materials 0.000 claims 16
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 11
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 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 2
• 125000006287 difluorobenzyl group Chemical group 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 169
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 151
• 239000000047 product Substances 0.000 description 131
• 238000005160 1H NMR spectroscopy Methods 0.000 description 129
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 120
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 105
• 239000000203 mixture Substances 0.000 description 73
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 70
• 239000000243 solution Substances 0.000 description 62
• IXHNFOOSLAWRBQ-UHFFFAOYSA-N (3,4-dichlorophenyl)methanamine Chemical compound NCC1=CC=C(Cl)C(Cl)=C1 IXHNFOOSLAWRBQ-UHFFFAOYSA-N 0.000 description 54
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 51
• 101150041968 CDC13 gene Proteins 0.000 description 51
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 51
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
• 238000005481 NMR spectroscopy Methods 0.000 description 48
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 48
• IIFVWLUQBAIPMJ-UHFFFAOYSA-N (4-fluorophenyl)methanamine Chemical compound NCC1=CC=C(F)C=C1 IIFVWLUQBAIPMJ-UHFFFAOYSA-N 0.000 description 44
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
• 238000006243 chemical reaction Methods 0.000 description 39
• 239000007787 solid Substances 0.000 description 36
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 34
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 32
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 22
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
• 238000001914 filtration Methods 0.000 description 21
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 20
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
• 238000004440 column chromatography Methods 0.000 description 18
• 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 18
• 238000010992 reflux Methods 0.000 description 18
• 239000012267 brine Substances 0.000 description 17
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
• 239000002904 solvent Substances 0.000 description 16
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
• 238000003556 assay Methods 0.000 description 15
• 239000000872 buffer Substances 0.000 description 15
• 150000002148 esters Chemical class 0.000 description 15
• 229910052938 sodium sulfate Inorganic materials 0.000 description 15
• 235000011152 sodium sulphate Nutrition 0.000 description 15
• 239000007832 Na2SO4 Substances 0.000 description 14
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
• 239000002244 precipitate Substances 0.000 description 14
• 230000035892 strand transfer Effects 0.000 description 14
• 102100034343 Integrase Human genes 0.000 description 13
• 239000011541 reaction mixture Substances 0.000 description 13
• 210000004027 cell Anatomy 0.000 description 12
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
• 108010061833 Integrases Proteins 0.000 description 11
• 230000000694 effects Effects 0.000 description 11
• 239000012044 organic layer Substances 0.000 description 11
• 239000012074 organic phase Substances 0.000 description 11
• 108020004414 DNA Proteins 0.000 description 10
• 241000725303 Human immunodeficiency virus Species 0.000 description 10
• 239000000758 substrate Substances 0.000 description 10
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 10
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• 238000003818 flash chromatography Methods 0.000 description 9
• ZFCHNZDUMIOWFV-UHFFFAOYSA-N pyrimidine-2-carboxylic acid Chemical compound OC(=O)C1=NC=CC=N1 ZFCHNZDUMIOWFV-UHFFFAOYSA-N 0.000 description 9
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
• DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 8
• 239000012043 crude product Substances 0.000 description 8
• 238000000746 purification Methods 0.000 description 8
• 239000011734 sodium Substances 0.000 description 8
• 239000007858 starting material Substances 0.000 description 8
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
• 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 8
• 230000003612 virological effect Effects 0.000 description 8
• RMRFFCXPLWYOOY-UHFFFAOYSA-N allyl radical Chemical compound [CH2]C=C RMRFFCXPLWYOOY-UHFFFAOYSA-N 0.000 description 7
• 239000000460 chlorine Substances 0.000 description 7
• 239000000463 material Substances 0.000 description 7
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
• 229910000027 potassium carbonate Inorganic materials 0.000 description 7
• 235000017557 sodium bicarbonate Nutrition 0.000 description 7
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
• 238000001228 spectrum Methods 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
• 108010002459 HIV Integrase Proteins 0.000 description 6
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
• 239000004615 ingredient Substances 0.000 description 6
• 239000012046 mixed solvent Substances 0.000 description 6
• 235000011181 potassium carbonates Nutrition 0.000 description 6
• 238000012545 processing Methods 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• 102000004190 Enzymes Human genes 0.000 description 5
• 108090000790 Enzymes Proteins 0.000 description 5
• 208000031886 HIV Infections Diseases 0.000 description 5
• 241000700605 Viruses Species 0.000 description 5
• 229960000583 acetic acid Drugs 0.000 description 5
• 239000002253 acid Substances 0.000 description 5
• 125000000217 alkyl group Chemical group 0.000 description 5
• 230000015572 biosynthetic process Effects 0.000 description 5
• NKGXGEHGPYWBDK-BQYQJAHWSA-N dimethyl (e)-2,3-diacetyloxybut-2-enedioate Chemical compound COC(=O)C(\OC(C)=O)=C(/OC(C)=O)C(=O)OC NKGXGEHGPYWBDK-BQYQJAHWSA-N 0.000 description 5
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
• 239000003112 inhibitor Substances 0.000 description 5
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 5
• 230000035772 mutation Effects 0.000 description 5
• 230000001566 pro-viral effect Effects 0.000 description 5
• 238000001953 recrystallisation Methods 0.000 description 5
• 230000002829 reductive effect Effects 0.000 description 5
• 229920006395 saturated elastomer Polymers 0.000 description 5
• 238000003756 stirring Methods 0.000 description 5
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
• DEPDDPLQZYCHOH-UHFFFAOYSA-N 1h-imidazol-2-amine Chemical compound NC1=NC=CN1 DEPDDPLQZYCHOH-UHFFFAOYSA-N 0.000 description 4
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
• 241000283690 Bos taurus Species 0.000 description 4
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
• 108091006629 SLC13A2 Proteins 0.000 description 4
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
• 230000009471 action Effects 0.000 description 4
• 239000004480 active ingredient Substances 0.000 description 4
• 230000006978 adaptation Effects 0.000 description 4
• QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• 125000004432 carbon atom Chemical group C* 0.000 description 4
• 125000006360 carbonyl amino methylene group Chemical group [H]N(C([*:1])=O)C([H])([H])[*:2] 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• 239000003795 chemical substances by application Substances 0.000 description 4
• 125000000753 cycloalkyl group Chemical group 0.000 description 4
• 201000010099 disease Diseases 0.000 description 4
• 229960003586 elvitegravir Drugs 0.000 description 4
• 239000000706 filtrate Substances 0.000 description 4
• 239000012362 glacial acetic acid Substances 0.000 description 4
• 238000004128 high performance liquid chromatography Methods 0.000 description 4
• GHGDMYPURSIGNB-UHFFFAOYSA-N imidazo[1,2-a]pyrimidine-2-carboxylic acid Chemical compound C1=CC=NC2=NC(C(=O)O)=CN21 GHGDMYPURSIGNB-UHFFFAOYSA-N 0.000 description 4
• 229940124524 integrase inhibitor Drugs 0.000 description 4
• 239000002850 integrase inhibitor Substances 0.000 description 4
• 239000000543 intermediate Substances 0.000 description 4
• URCPKQIWJAHFIE-UHFFFAOYSA-N methyl 3-acetyloxy-4-oxo-10-(2-piperazin-1-ylethyl)pyrimido[1,2-a]benzimidazole-2-carboxylate Chemical compound C12=CC=CC=C2N2C(=O)C(OC(C)=O)=C(C(=O)OC)N=C2N1CCN1CCNCC1 URCPKQIWJAHFIE-UHFFFAOYSA-N 0.000 description 4
• FXPAATUDJDSKSM-UHFFFAOYSA-N methyl imidazo[1,2-a]pyrimidine-2-carboxylate Chemical compound C1=CC=NC2=NC(C(=O)OC)=CN21 FXPAATUDJDSKSM-UHFFFAOYSA-N 0.000 description 4
• QECNBMJRDWINKS-UHFFFAOYSA-N n-fluoro-1-phenylmethanamine Chemical compound FNCC1=CC=CC=C1 QECNBMJRDWINKS-UHFFFAOYSA-N 0.000 description 4
• 239000012299 nitrogen atmosphere Substances 0.000 description 4
• 239000002245 particle Substances 0.000 description 4
• 125000006239 protecting group Chemical group 0.000 description 4
• 235000018102 proteins Nutrition 0.000 description 4
• 102000004169 proteins and genes Human genes 0.000 description 4
• 108090000623 proteins and genes Proteins 0.000 description 4
• 229960004742 raltegravir Drugs 0.000 description 4
• 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 description 4
• CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 4
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
• XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 3
• 208000030507 AIDS Diseases 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• 125000006519 CCH3 Chemical group 0.000 description 3
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• 208000037357 HIV infectious disease Diseases 0.000 description 3
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
• 241000124008 Mammalia Species 0.000 description 3
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 3
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
• 108091034117 Oligonucleotide Proteins 0.000 description 3
• DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 3
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