BG106754A - Антипикорнавирусни съединения и състави, фармацевтичното им използване и материали за техния синтез - Google Patents

Info

Publication number

BG106754A

BG106754A BG106754A BG10675402A BG106754A BG 106754 A BG106754 A BG 106754A BG 106754 A BG106754 A BG 106754A BG 10675402 A BG10675402 A BG 10675402A BG 106754 A BG106754 A BG 106754A

Authority

BG

Bulgaria

Prior art keywords

group

pharmaceutically acceptable

compound

substituted

heterocycloalkyl

Prior art date

1999-12-03

Links

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 312
• 239000000203 mixture Substances 0.000 title claims description 95
• 230000015572 biosynthetic process Effects 0.000 title claims description 10
• 238000003786 synthesis reaction Methods 0.000 title description 10
• 239000000463 material Substances 0.000 title description 5
• 108091005804 Peptidases Proteins 0.000 claims abstract description 28
• 239000004365 Protease Substances 0.000 claims abstract description 28
• 241001144416 Picornavirales Species 0.000 claims abstract description 26
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims abstract description 24
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
• -1 each R k is H Chemical group 0.000 claims description 180
• 125000000217 alkyl group Chemical group 0.000 claims description 176
• 238000000034 method Methods 0.000 claims description 157
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 145
• 229910052757 nitrogen Inorganic materials 0.000 claims description 117
• 229910052739 hydrogen Inorganic materials 0.000 claims description 107
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 105
• 125000003118 aryl group Chemical group 0.000 claims description 101
• 150000003839 salts Chemical class 0.000 claims description 101
• 125000001424 substituent group Chemical group 0.000 claims description 88
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 86
• 125000001072 heteroaryl group Chemical group 0.000 claims description 77
• 239000012453 solvate Substances 0.000 claims description 76
• 239000000651 prodrug Substances 0.000 claims description 74
• 229940002612 prodrug Drugs 0.000 claims description 74
• 239000002207 metabolite Substances 0.000 claims description 72
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 60
• 125000004429 atom Chemical group 0.000 claims description 43
• 125000006239 protecting group Chemical group 0.000 claims description 41
• 150000002367 halogens Chemical class 0.000 claims description 38
• 229910052736 halogen Inorganic materials 0.000 claims description 37
• 125000003545 alkoxy group Chemical group 0.000 claims description 31
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 30
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 30
• 229910052717 sulfur Inorganic materials 0.000 claims description 30
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 28
• 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 27
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 26
• 125000002252 acyl group Chemical group 0.000 claims description 25
• 230000000694 effects Effects 0.000 claims description 24
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 24
• 125000005129 aryl carbonyl group Chemical group 0.000 claims description 23
• 125000004104 aryloxy group Chemical group 0.000 claims description 21
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 20
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 20
• 125000004414 alkyl thio group Chemical group 0.000 claims description 19
• 229910052731 fluorine Inorganic materials 0.000 claims description 19
• 125000001183 hydrocarbyl group Chemical group 0.000 claims description 19
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
• 229930194542 Keto Natural products 0.000 claims description 18
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 18
• 125000000468 ketone group Chemical group 0.000 claims description 18
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
• 125000003441 thioacyl group Chemical group 0.000 claims description 17
• 125000003282 alkyl amino group Chemical group 0.000 claims description 16
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 16
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 15
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 14
• 125000005110 aryl thio group Chemical group 0.000 claims description 14
• 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 14
• 230000002401 inhibitory effect Effects 0.000 claims description 14
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
• 125000001188 haloalkyl group Chemical group 0.000 claims description 13
• 125000000623 heterocyclic group Chemical group 0.000 claims description 13
• 229930195734 saturated hydrocarbon Natural products 0.000 claims description 12
• 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 11
• 238000003556 assay Methods 0.000 claims description 11
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 10
• 125000005842 heteroatom Chemical group 0.000 claims description 10
• 125000003396 thiol group Chemical class [H]S* 0.000 claims description 10
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 9
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 9
• 241000124008 Mammalia Species 0.000 claims description 8
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 8
• 125000005368 heteroarylthio group Chemical group 0.000 claims description 8
• 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 8
• 229930195735 unsaturated hydrocarbon Natural products 0.000 claims description 8
• 125000004647 alkyl sulfenyl group Chemical group 0.000 claims description 7
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
• 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 7
• 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 7
• 125000001769 aryl amino group Chemical group 0.000 claims description 7
• 125000004658 aryl carbonyl amino group Chemical group 0.000 claims description 7
• 125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 7
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 7
• 125000005241 heteroarylamino group Chemical group 0.000 claims description 7
• 125000005222 heteroarylaminocarbonyl group Chemical group 0.000 claims description 7
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 7
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 7
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 6
• 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 6
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
• 125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 6
• 125000005169 cycloalkylcarbonylamino group Chemical group 0.000 claims description 6
• 125000005226 heteroaryloxycarbonyl group Chemical group 0.000 claims description 6
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
• 241000709661 Enterovirus Species 0.000 claims description 5
• 125000004670 alkyl amino thio carbonyl group Chemical group 0.000 claims description 5
• 125000005530 alkylenedioxy group Chemical group 0.000 claims description 5
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
• 238000004113 cell culture Methods 0.000 claims description 5
• 239000003795 chemical substances by application Substances 0.000 claims description 5
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 5
• 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 5
• 125000005167 cycloalkylaminocarbonyl group Chemical group 0.000 claims description 5
• 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 5
• 239000003085 diluting agent Substances 0.000 claims description 5
• 201000010099 disease Diseases 0.000 claims description 5
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
• 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 5
• 125000005323 thioketone group Chemical group 0.000 claims description 5
• 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 4
• 229910052698 phosphorus Inorganic materials 0.000 claims description 4
• GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 claims description 3
• 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 claims description 3
• 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 claims description 3
• 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 claims description 3
• 125000005199 aryl carbonyloxy group Chemical group 0.000 claims description 3
• 229940125758 compound 15 Drugs 0.000 claims description 3
• 125000005170 cycloalkyloxycarbonyl group Chemical group 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 125000001153 fluoro group Chemical group F* 0.000 claims description 3
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 3
• 230000001404 mediated effect Effects 0.000 claims description 3
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 2
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 2
• 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 claims description 2
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
• 102000004127 Cytokines Human genes 0.000 claims 4
• 108090000695 Cytokines Proteins 0.000 claims 4
• HBAIZOJDXAXWHS-UHFFFAOYSA-M Sodium thiosalicylate Chemical group [Na+].[O-]C(=O)C1=CC=CC=C1S HBAIZOJDXAXWHS-UHFFFAOYSA-M 0.000 claims 1
• 125000004171 alkoxy aryl group Chemical group 0.000 claims 1
• 125000005224 heteroarylcarbonylamino group Chemical group 0.000 claims 1
• 239000000543 intermediate Substances 0.000 abstract description 306
• 108010091324 3C proteases Proteins 0.000 abstract description 11
• 241000709664 Picornaviridae Species 0.000 abstract description 3
• 230000004071 biological effect Effects 0.000 abstract 2
• 238000010189 synthetic method Methods 0.000 abstract 1
• 238000002360 preparation method Methods 0.000 description 198
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 135
• YIYBQIKDCADOSF-UHFFFAOYSA-N pent-2-enoic acid Chemical compound CCC=CC(O)=O YIYBQIKDCADOSF-UHFFFAOYSA-N 0.000 description 134
• 238000005481 NMR spectroscopy Methods 0.000 description 103
• 239000000047 product Substances 0.000 description 83
• 229910052799 carbon Inorganic materials 0.000 description 79
• 238000006243 chemical reaction Methods 0.000 description 79
• 241000710122 Rhinovirus B14 Species 0.000 description 72
• 239000000243 solution Substances 0.000 description 70
• 239000000460 chlorine Substances 0.000 description 64
• 235000019439 ethyl acetate Nutrition 0.000 description 63
• 230000008569 process Effects 0.000 description 59
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
• 239000012267 brine Substances 0.000 description 57
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 57
• 239000011541 reaction mixture Substances 0.000 description 56
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 54
• 150000001408 amides Chemical class 0.000 description 47
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 44
• 235000002639 sodium chloride Nutrition 0.000 description 41
• 150000001412 amines Chemical class 0.000 description 40
• 239000011734 sodium Substances 0.000 description 37
• 238000003818 flash chromatography Methods 0.000 description 36
• 238000007429 general method Methods 0.000 description 36
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
• 238000000746 purification Methods 0.000 description 35
• 239000002253 acid Substances 0.000 description 30
• 150000003254 radicals Chemical class 0.000 description 30
• 239000007787 solid Substances 0.000 description 29
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 29
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 28
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 27
• 125000004494 ethyl ester group Chemical group 0.000 description 26
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical class OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 26
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
• 241000710124 Human rhinovirus A2 Species 0.000 description 23
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 23
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 22
• 230000002829 reductive effect Effects 0.000 description 22
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
• 239000003039 volatile agent Substances 0.000 description 21
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 20
• 239000012044 organic layer Substances 0.000 description 20
• 239000012074 organic phase Substances 0.000 description 20
• 239000000126 substance Substances 0.000 description 20
• 238000003756 stirring Methods 0.000 description 19
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
• 229920006395 saturated elastomer Polymers 0.000 description 17
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 15
• XWHHYOYVRVGJJY-QMMMGPOBSA-N 4-fluoro-L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(F)C=C1 XWHHYOYVRVGJJY-QMMMGPOBSA-N 0.000 description 15
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 15
• 238000010992 reflux Methods 0.000 description 15
• HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 14
• 241000430519 Human rhinovirus sp. Species 0.000 description 14
• 239000006260 foam Substances 0.000 description 14
• 239000000725 suspension Substances 0.000 description 13
• KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 13
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
• 238000010511 deprotection reaction Methods 0.000 description 12
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• 150000001299 aldehydes Chemical class 0.000 description 11
• 239000012298 atmosphere Substances 0.000 description 11
• 238000010828 elution Methods 0.000 description 11
• MYVZEVHZIPBPCH-UHFFFAOYSA-N 6-but-3-enyl-2-oxo-1h-pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=C(CCC=C)N=C1O MYVZEVHZIPBPCH-UHFFFAOYSA-N 0.000 description 10
• 241001635223 Coxsackievirus B2 Species 0.000 description 10
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• 229910052786 argon Inorganic materials 0.000 description 10
• 208000015181 infectious disease Diseases 0.000 description 10
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 10
• 229910000104 sodium hydride Inorganic materials 0.000 description 10
• 238000011282 treatment Methods 0.000 description 10
• WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 10
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
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• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
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• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 9
• VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 9
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• 235000019198 oils Nutrition 0.000 description 9
• BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 9
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
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• 241000710130 Human rhinovirus 1A Species 0.000 description 8
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 8
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• 125000003277 amino group Chemical group 0.000 description 8
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 8
• 239000002480 mineral oil Substances 0.000 description 8
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• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 8
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• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 8
• 230000003612 virological effect Effects 0.000 description 8
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• XMVNMWDLOGSUSM-UHFFFAOYSA-N 5-methyl-1,2-oxazole-3-carbonyl chloride Chemical compound CC1=CC(C(Cl)=O)=NO1 XMVNMWDLOGSUSM-UHFFFAOYSA-N 0.000 description 7
• 239000007821 HATU Substances 0.000 description 7
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• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
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• 125000002619 bicyclic group Chemical group 0.000 description 7
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 7
• 239000006185 dispersion Substances 0.000 description 7
• 239000001257 hydrogen Substances 0.000 description 7
• GXHMMDRXHUIUMN-UHFFFAOYSA-N methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O GXHMMDRXHUIUMN-UHFFFAOYSA-N 0.000 description 7
• 230000009467 reduction Effects 0.000 description 7
• 238000006722 reduction reaction Methods 0.000 description 7
• 238000010898 silica gel chromatography Methods 0.000 description 7
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