MXPA04012245A

MXPA04012245A - Compuestos de pirazolo[1,5a]pirimidina como agentes antivirales.

Compuestos de pirazolo[1,5a]pirimidina como agentes antivirales.

Info

Publication number: MXPA04012245A
Authority: MX; Mexico
Prior art keywords: aryl; heteroaryl; alkyl; group; saturated
Prior art date: 2002-06-04

Application number

MXPA04012245A

Other languages

English (en)

Spanish (es)

Inventor

Patrick J Curran

Original Assignee

Neogenesis Pharmaceuticals Inc

Priority date

2002-06-04

Filing date

2003-06-02

Publication date

2005-09-30

2003-06-02 Application filed by Neogenesis Pharmaceuticals Inc filed Critical Neogenesis Pharmaceuticals Inc

2005-09-30 Publication of MXPA04012245A publication Critical patent/MXPA04012245A/es

Links

239000003443 antiviral agent Substances 0.000 title description 4
150000003230 pyrimidines Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 97
238000000034 method Methods 0.000 claims abstract description 41
230000010076 replication Effects 0.000 claims abstract description 16
230000002401 inhibitory effect Effects 0.000 claims abstract description 15
125000001072 heteroaryl group Chemical group 0.000 claims description 396
125000003118 aryl group Chemical group 0.000 claims description 336
229920006395 saturated elastomer Polymers 0.000 claims description 276
125000000217 alkyl group Chemical group 0.000 claims description 264
125000000753 cycloalkyl group Chemical group 0.000 claims description 241
-1 amino, formyl Chemical group 0.000 claims description 198
125000000623 heterocyclic group Chemical group 0.000 claims description 191
239000001257 hydrogen Substances 0.000 claims description 186
229910052739 hydrogen Inorganic materials 0.000 claims description 186
125000003545 alkoxy group Chemical group 0.000 claims description 175
125000003710 aryl alkyl group Chemical group 0.000 claims description 171
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 162
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 153
125000004414 alkyl thio group Chemical group 0.000 claims description 101
125000004093 cyano group Chemical group *C#N 0.000 claims description 95
125000005843 halogen group Chemical group 0.000 claims description 90
150000003839 salts Chemical class 0.000 claims description 60
125000003282 alkyl amino group Chemical group 0.000 claims description 58
125000003709 fluoroalkyl group Chemical group 0.000 claims description 58
125000004104 aryloxy group Chemical group 0.000 claims description 57
125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 53
125000005110 aryl thio group Chemical group 0.000 claims description 49
229910052757 nitrogen Inorganic materials 0.000 claims description 37
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 35
229910052799 carbon Inorganic materials 0.000 claims description 33
125000001424 substituent group Chemical group 0.000 claims description 33
125000003342 alkenyl group Chemical group 0.000 claims description 32
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 30
125000000304 alkynyl group Chemical group 0.000 claims description 30
229910052717 sulfur Inorganic materials 0.000 claims description 30
125000004659 aryl alkyl thio group Chemical group 0.000 claims description 29
125000001153 fluoro group Chemical group F* 0.000 claims description 29
229910052760 oxygen Inorganic materials 0.000 claims description 29
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 29
150000003254 radicals Chemical group 0.000 claims description 29
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 28
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 27
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 27
125000001769 aryl amino group Chemical group 0.000 claims description 25
125000005241 heteroarylamino group Chemical group 0.000 claims description 25
125000005553 heteroaryloxy group Chemical group 0.000 claims description 25
125000005368 heteroarylthio group Chemical group 0.000 claims description 25
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 22
125000004423 acyloxy group Chemical group 0.000 claims description 22
125000004103 aminoalkyl group Chemical group 0.000 claims description 22
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 22
125000004043 oxo group Chemical group O=* 0.000 claims description 22
125000005116 aryl carbamoyl group Chemical group 0.000 claims description 21
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 21
125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 20
125000003435 aroyl group Chemical group 0.000 claims description 20
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 20
125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 19
125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 18
125000005421 aryl sulfonamido group Chemical group 0.000 claims description 18
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 18
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 17
125000005117 dialkylcarbamoyl group Chemical group 0.000 claims description 17
125000004663 dialkyl amino group Chemical group 0.000 claims description 15
125000005135 aryl sulfinyl group Chemical group 0.000 claims description 13
125000004986 diarylamino group Chemical group 0.000 claims description 12
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
239000008194 pharmaceutical composition Substances 0.000 claims description 12
125000003226 pyrazolyl group Chemical group 0.000 claims description 12
125000000714 pyrimidinyl group Chemical group 0.000 claims description 12
201000010099 disease Diseases 0.000 claims description 11
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 11
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 10
239000003814 drug Substances 0.000 claims description 10
125000000041 C6-C10 aryl group Chemical group 0.000 claims description 9
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 9
239000003085 diluting agent Substances 0.000 claims description 9
239000003937 drug carrier Substances 0.000 claims description 8
239000000546 pharmaceutical excipient Substances 0.000 claims description 8
MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 7
125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 6
125000003275 alpha amino acid group Chemical group 0.000 claims description 6
150000001412 amines Chemical class 0.000 claims description 6
150000001576 beta-amino acids Chemical class 0.000 claims description 6
125000003831 tetrazolyl group Chemical group 0.000 claims description 6
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 5
125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 4
GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 claims description 4
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 3
125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 3
125000005140 aralkylsulfonyl group Chemical group 0.000 claims description 3
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 3
125000004366 heterocycloalkenyl group Chemical group 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
125000004945 acylaminoalkyl group Chemical group 0.000 claims description 2
125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 2
125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 2
IYWRCNFZPNEADN-CXODAYGWSA-N tert-butyl n-[(2s)-1-[(2s,4r)-2-[[(1r,2s)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]carbamoyl]-4-(6-methoxyisoquinolin-1-yl)oxypyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamate Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC=1C2=CC=C(C=C2C=CN=1)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C IYWRCNFZPNEADN-CXODAYGWSA-N 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 94
125000001589 carboacyl group Chemical group 0.000 claims 24
YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 claims 14
125000002877 alkyl aryl group Chemical group 0.000 claims 9
125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims 7
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 6
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 6
125000005488 carboaryl group Chemical group 0.000 claims 5
125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 claims 3
101150079116 MT-CO1 gene Chemical group 0.000 claims 1
101100311330 Schizosaccharomyces pombe (strain 972 / ATCC 24843) uap56 gene Proteins 0.000 claims 1
125000005041 acyloxyalkyl group Chemical group 0.000 claims 1
101150018444 sub2 gene Proteins 0.000 claims 1
239000000203 mixture Substances 0.000 abstract description 134
241000711549 Hepacivirus C Species 0.000 abstract description 79
108060004795 Methyltransferase Proteins 0.000 abstract description 39
208000015181 infectious disease Diseases 0.000 abstract description 12
238000011321 prophylaxis Methods 0.000 abstract description 8
238000011282 treatment Methods 0.000 abstract description 8
230000002255 enzymatic effect Effects 0.000 abstract description 4
230000005764 inhibitory process Effects 0.000 abstract description 4
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 216
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 198
239000000243 solution Substances 0.000 description 131
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 99
239000011541 reaction mixture Substances 0.000 description 86
238000005481 NMR spectroscopy Methods 0.000 description 73
235000019439 ethyl acetate Nutrition 0.000 description 72
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 70
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 66
239000007787 solid Substances 0.000 description 66
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 58
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 58
230000015572 biosynthetic process Effects 0.000 description 56
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 54
238000003786 synthesis reaction Methods 0.000 description 53
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
238000006243 chemical reaction Methods 0.000 description 49
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 48
239000002253 acid Substances 0.000 description 46
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 44
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 43
229910052938 sodium sulfate Inorganic materials 0.000 description 39
235000011152 sodium sulphate Nutrition 0.000 description 39
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 35
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 32
239000000047 product Substances 0.000 description 32
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 31
229910052786 argon Inorganic materials 0.000 description 29
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 28
239000012267 brine Substances 0.000 description 28
238000010992 reflux Methods 0.000 description 28
102000004190 Enzymes Human genes 0.000 description 27
108090000790 Enzymes Proteins 0.000 description 27
108091032973 (ribonucleotides)n+m Proteins 0.000 description 26
239000000741 silica gel Substances 0.000 description 26
229910002027 silica gel Inorganic materials 0.000 description 26
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 24
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 24
238000004809 thin layer chromatography Methods 0.000 description 24
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical class CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
239000000284 extract Substances 0.000 description 21
238000004108 freeze drying Methods 0.000 description 21
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 20
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 20
150000002431 hydrogen Chemical class 0.000 description 20
125000004356 hydroxy functional group Chemical group O* 0.000 description 20
239000003112 inhibitor Substances 0.000 description 20
238000000746 purification Methods 0.000 description 20
238000004366 reverse phase liquid chromatography Methods 0.000 description 20
239000003054 catalyst Substances 0.000 description 19
238000012360 testing method Methods 0.000 description 19
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
238000004458 analytical method Methods 0.000 description 17
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 16
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 16
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 15
239000000463 material Substances 0.000 description 15
239000002244 precipitate Substances 0.000 description 15
239000007858 starting material Substances 0.000 description 15
239000003795 chemical substances by application Substances 0.000 description 14
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 13
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
229960000583 acetic acid Drugs 0.000 description 13
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 13
239000003921 oil Substances 0.000 description 13
235000019198 oils Nutrition 0.000 description 13
239000012044 organic layer Substances 0.000 description 13
239000012453 solvate Substances 0.000 description 13
210000004027 cell Anatomy 0.000 description 12
150000004702 methyl esters Chemical class 0.000 description 12
229940002612 prodrug Drugs 0.000 description 11
239000000651 prodrug Substances 0.000 description 11
238000007127 saponification reaction Methods 0.000 description 11
239000011780 sodium chloride Substances 0.000 description 11
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 10
241001465754 Metazoa Species 0.000 description 10
150000001413 amino acids Chemical class 0.000 description 10
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 10
229910000041 hydrogen chloride Inorganic materials 0.000 description 10
229910052763 palladium Inorganic materials 0.000 description 10
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 10
102000004169 proteins and genes Human genes 0.000 description 10
108090000623 proteins and genes Proteins 0.000 description 10
239000002904 solvent Substances 0.000 description 10
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 10
125000004432 carbon atom Chemical group C* 0.000 description 9
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 9
CSOYDALHEQEMAK-UHFFFAOYSA-N 2h-pyrimidine-1-carboxylic acid Chemical compound OC(=O)N1CN=CC=C1 CSOYDALHEQEMAK-UHFFFAOYSA-N 0.000 description 8
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 8
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 8
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 8
229910000024 caesium carbonate Inorganic materials 0.000 description 8
150000001732 carboxylic acid derivatives Chemical class 0.000 description 8
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 8
238000010828 elution Methods 0.000 description 8
YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 8
229910000160 potassium phosphate Inorganic materials 0.000 description 8
235000011009 potassium phosphates Nutrition 0.000 description 8
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
150000001721 carbon Chemical group 0.000 description 7
239000013078 crystal Substances 0.000 description 7
125000004494 ethyl ester group Chemical group 0.000 description 7
238000002474 experimental method Methods 0.000 description 7
230000004048 modification Effects 0.000 description 7
238000012986 modification Methods 0.000 description 7
125000004433 nitrogen atom Chemical group N* 0.000 description 7
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 7
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
239000007821 HATU Substances 0.000 description 6
108010090804 Streptavidin Proteins 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
230000008878 coupling Effects 0.000 description 6
238000010168 coupling process Methods 0.000 description 6
238000005859 coupling reaction Methods 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
125000005842 heteroatom Chemical group 0.000 description 6
239000003999 initiator Substances 0.000 description 6
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
150000003536 tetrazoles Chemical class 0.000 description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
238000004587 chromatography analysis Methods 0.000 description 5
229910052681 coesite Inorganic materials 0.000 description 5
238000004440 column chromatography Methods 0.000 description 5
229910052906 cristobalite Inorganic materials 0.000 description 5
230000000694 effects Effects 0.000 description 5
239000008241 heterogeneous mixture Substances 0.000 description 5
230000002209 hydrophobic effect Effects 0.000 description 5
229910001629 magnesium chloride Inorganic materials 0.000 description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
229910052682 stishovite Inorganic materials 0.000 description 5
239000000758 substrate Substances 0.000 description 5
229910052905 tridymite Inorganic materials 0.000 description 5
238000005160 1H NMR spectroscopy Methods 0.000 description 4
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 4
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 4
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 description 4
PUGZXCYHRQRTBZ-UHFFFAOYSA-N 7-cyclohexyl-6-(4-phenylmethoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-amine Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1C=1C=NC2=C(N)C=NN2C=1C1CCCCC1 PUGZXCYHRQRTBZ-UHFFFAOYSA-N 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 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
GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 4
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 4
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
229910021626 Tin(II) chloride Inorganic materials 0.000 description 4
ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 description 4
125000002252 acyl group Chemical group 0.000 description 4
125000004442 acylamino group Chemical group 0.000 description 4
125000001931 aliphatic group Chemical group 0.000 description 4
229910052794 bromium Inorganic materials 0.000 description 4
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 4
230000001419 dependent effect Effects 0.000 description 4
238000010790 dilution Methods 0.000 description 4
239000012895 dilution Substances 0.000 description 4
CAGWWUITCSUUDU-UHFFFAOYSA-N ethyl 3-oxo-3-(4-phenylmethoxyphenyl)propanoate Chemical compound C1=CC(C(=O)CC(=O)OCC)=CC=C1OCC1=CC=CC=C1 CAGWWUITCSUUDU-UHFFFAOYSA-N 0.000 description 4
238000001914 filtration Methods 0.000 description 4
108700008776 hepatitis C virus NS-5 Proteins 0.000 description 4
229920001519 homopolymer Polymers 0.000 description 4
230000002519 immonomodulatory effect Effects 0.000 description 4
239000012535 impurity Substances 0.000 description 4
125000000468 ketone group Chemical group 0.000 description 4
239000010410 layer Substances 0.000 description 4
GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 4
108010052968 leupeptin Proteins 0.000 description 4
YUCXOMOBVORXCR-UHFFFAOYSA-N methyl 2-cyclohexyl-3-oxo-3-(4-phenylmethoxyphenyl)propanoate Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1C(=O)C(C(=O)OC)C1CCCCC1 YUCXOMOBVORXCR-UHFFFAOYSA-N 0.000 description 4
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
239000002773 nucleotide Substances 0.000 description 4
125000003729 nucleotide group Chemical group 0.000 description 4
VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
125000004076 pyridyl group Chemical group 0.000 description 4
239000011347 resin Substances 0.000 description 4
229920005989 resin Polymers 0.000 description 4
125000006413 ring segment Chemical group 0.000 description 4
239000004576 sand Substances 0.000 description 4
239000000377 silicon dioxide Substances 0.000 description 4
229910000104 sodium hydride Inorganic materials 0.000 description 4
235000011150 stannous chloride Nutrition 0.000 description 4
239000000725 suspension Substances 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
125000001544 thienyl group Chemical group 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 4
230000009466 transformation Effects 0.000 description 4
238000000844 transformation Methods 0.000 description 4
FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 4
238000005406 washing Methods 0.000 description 4
239000004246 zinc acetate Substances 0.000 description 4
NLLGFYPSWCMUIV-UHFFFAOYSA-N (3-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC(B(O)O)=C1 NLLGFYPSWCMUIV-UHFFFAOYSA-N 0.000 description 3
SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 3
MYYYZNVAUZVXBO-UHFFFAOYSA-N 1-(bromomethyl)-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(CBr)=C1 MYYYZNVAUZVXBO-UHFFFAOYSA-N 0.000 description 3
KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 3
LIRTURDHKVELCN-UHFFFAOYSA-N 4-[3-(trifluoromethyl)phenoxy]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1OC1=CC=CC(C(F)(F)F)=C1 LIRTURDHKVELCN-UHFFFAOYSA-N 0.000 description 3
FFNKBQRKZRMYCL-UHFFFAOYSA-N 5-amino-1h-pyrazole-4-carbonitrile Chemical compound NC1=NNC=C1C#N FFNKBQRKZRMYCL-UHFFFAOYSA-N 0.000 description 3
MOYBSECGIZZCIW-UHFFFAOYSA-N 6-cyclohexyl-5-(furan-2-yl)-7-oxo-1h-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid Chemical compound C1CCCCC1C=1C(=O)N2NC(C(=O)O)=CC2=NC=1C1=CC=CO1 MOYBSECGIZZCIW-UHFFFAOYSA-N 0.000 description 3
DBWNJRPFMZCMCV-UHFFFAOYSA-N 7-(2-methylpropyl)-6-(4-phenylmethoxyphenyl)-3-(2h-tetrazol-5-yl)pyrazolo[1,5-a]pyrimidine Chemical compound C1=NN2C(CC(C)C)=C(C=3C=CC(OCC=4C=CC=CC=4)=CC=3)C=NC2=C1C1=NN=NN1 DBWNJRPFMZCMCV-UHFFFAOYSA-N 0.000 description 3
ATBIFOIEJPMDBU-UHFFFAOYSA-N 7-cyclohexyl-6-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C=1C=NC2=C(C(=O)O)C=NN2C=1C1CCCCC1 ATBIFOIEJPMDBU-UHFFFAOYSA-N 0.000 description 3
DETAYAKVHNUNNH-UHFFFAOYSA-N 7-cyclohexyl-6-(4-hydroxyphenyl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile Chemical compound C1=CC(O)=CC=C1C1=C(C2CCCCC2)N2N=CC(C#N)=C2N=C1 DETAYAKVHNUNNH-UHFFFAOYSA-N 0.000 description 3
DQUYDOLQTNZEQK-UHFFFAOYSA-N 7-cyclohexyl-6-(4-iodophenyl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile Chemical compound C1=CC(I)=CC=C1C1=C(C2CCCCC2)N2N=CC(C#N)=C2N=C1 DQUYDOLQTNZEQK-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
108090000626 DNA-directed RNA polymerases Proteins 0.000 description 3
102000004163 DNA-directed RNA polymerases Human genes 0.000 description 3
241000588724 Escherichia coli Species 0.000 description 3
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
229930194542 Keto Natural products 0.000 description 3
241000124008 Mammalia Species 0.000 description 3
101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 3
108091005804 Peptidases Proteins 0.000 description 3
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
239000004365 Protease Substances 0.000 description 3
101800001554 RNA-directed RNA polymerase Proteins 0.000 description 3
102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 3
102000006382 Ribonucleases Human genes 0.000 description 3
108010083644 Ribonucleases Proteins 0.000 description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
241000700605 Viruses Species 0.000 description 3
KZHKVXWPEKRAEL-UHFFFAOYSA-N [7-cyclohexyl-6-(4-phenylmethoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]methanol Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1C=1C=NC2=C(CO)C=NN2C=1C1CCCCC1 KZHKVXWPEKRAEL-UHFFFAOYSA-N 0.000 description 3
150000001447 alkali salts Chemical class 0.000 description 3
125000003368 amide group Chemical group 0.000 description 3
150000001408 amides Chemical class 0.000 description 3
239000012298 atmosphere Substances 0.000 description 3
239000011324 bead Substances 0.000 description 3
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
230000004071 biological effect Effects 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
239000011575 calcium Substances 0.000 description 3
239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
238000004113 cell culture Methods 0.000 description 3
OGEBRHQLRGFBNV-RZDIXWSQSA-N chembl2036808 Chemical compound C12=NC(NCCCC)=NC=C2C(C=2C=CC(F)=CC=2)=NN1C[C@H]1CC[C@H](N)CC1 OGEBRHQLRGFBNV-RZDIXWSQSA-N 0.000 description 3
UXWAMEHBIVXAEX-UHFFFAOYSA-N chembl565413 Chemical compound C1CCCCC1CCC=1C(=O)N2N=C(C(=O)O)C=C2NC=1C(C=C1)=CC=C1OCC1=CC=CC=C1 UXWAMEHBIVXAEX-UHFFFAOYSA-N 0.000 description 3
239000000460 chlorine Substances 0.000 description 3
238000001816 cooling Methods 0.000 description 3
239000010949 copper Substances 0.000 description 3
238000010511 deprotection reaction Methods 0.000 description 3
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 3
WAWUPXNYYZMUHB-UHFFFAOYSA-N ethyl 6-bromo-7-cyclohexylpyrazolo[1,5-a]pyrimidine-3-carboxylate Chemical compound BrC=1C=NC2=C(C(=O)OCC)C=NN2C=1C1CCCCC1 WAWUPXNYYZMUHB-UHFFFAOYSA-N 0.000 description 3
PYFMAAFCQDFHJX-UHFFFAOYSA-N ethyl pyrimidine-2-carboxylate Chemical compound CCOC(=O)C1=NC=CC=N1 PYFMAAFCQDFHJX-UHFFFAOYSA-N 0.000 description 3
125000002541 furyl group Chemical group 0.000 description 3
102000037865 fusion proteins Human genes 0.000 description 3
108020001507 fusion proteins Proteins 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
150000004694 iodide salts Chemical class 0.000 description 3
229910052740 iodine Inorganic materials 0.000 description 3
239000011630 iodine Substances 0.000 description 3
238000004020 luminiscence type Methods 0.000 description 3
125000002950 monocyclic group Chemical group 0.000 description 3
HXRAMSFGUAOAJR-UHFFFAOYSA-N n,n,n',n'-tetramethyl-1-[(2-methylpropan-2-yl)oxy]methanediamine Chemical compound CN(C)C(N(C)C)OC(C)(C)C HXRAMSFGUAOAJR-UHFFFAOYSA-N 0.000 description 3
HEGSGKPQLMEBJL-RKQHYHRCSA-N octyl beta-D-glucopyranoside Chemical compound CCCCCCCCO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HEGSGKPQLMEBJL-RKQHYHRCSA-N 0.000 description 3
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 3
229920002704 polyhistidine Polymers 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
230000017854 proteolysis Effects 0.000 description 3
ZFCHNZDUMIOWFV-UHFFFAOYSA-N pyrimidine-2-carboxylic acid Chemical compound OC(=O)C1=NC=CC=N1 ZFCHNZDUMIOWFV-UHFFFAOYSA-N 0.000 description 3
208000024891 symptom Diseases 0.000 description 3
VDUKDQTYMWUSAC-UHFFFAOYSA-N (4-methylsulfonylphenyl)boronic acid Chemical compound CS(=O)(=O)C1=CC=C(B(O)O)C=C1 VDUKDQTYMWUSAC-UHFFFAOYSA-N 0.000 description 2
NCIMAYPZWJQYGN-UHFFFAOYSA-N 1-methoxy-n,n,n',n'-tetramethylmethanediamine Chemical compound COC(N(C)C)N(C)C NCIMAYPZWJQYGN-UHFFFAOYSA-N 0.000 description 2
KOPFEFZSAMLEHK-UHFFFAOYSA-N 1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1C=CNN=1 KOPFEFZSAMLEHK-UHFFFAOYSA-N 0.000 description 2
YCMLQMDWSXFTIF-UHFFFAOYSA-N 2-methylbenzenesulfonimidic acid Chemical compound CC1=CC=CC=C1S(N)(=O)=O YCMLQMDWSXFTIF-UHFFFAOYSA-N 0.000 description 2
CRDDRQWHQLBWAN-UHFFFAOYSA-N 3-(cyclopenten-1-yl)-6-pyridin-4-ylpyrazolo[1,5-a]pyrimidine Chemical compound C1CCC=C1C1=C2N=CC(C=3C=CN=CC=3)=CN2N=C1 CRDDRQWHQLBWAN-UHFFFAOYSA-N 0.000 description 2
XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical class OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 2
ICEKEZSKMGHZNT-UHFFFAOYSA-N 4-phenylmethoxybenzoyl chloride Chemical compound C1=CC(C(=O)Cl)=CC=C1OCC1=CC=CC=C1 ICEKEZSKMGHZNT-UHFFFAOYSA-N 0.000 description 2
BTRGEZSJUWMONZ-UHFFFAOYSA-N 6-cyclohexyl-7-methoxy-5-(4-phenylmethoxyphenyl)pyrazolo[1,5-a]pyrimidine-2-carboxylic acid Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1C1=NC2=CC(C(O)=O)=NN2C(OC)=C1C1CCCCC1 BTRGEZSJUWMONZ-UHFFFAOYSA-N 0.000 description 2
PRDFGFWMNKMFKA-UHFFFAOYSA-N 6-cyclohexyl-7-oxo-5-(4-phenylmethoxyphenyl)-1h-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid Chemical compound C1CCCCC1C=1C(=O)N2NC(C(=O)O)=CC2=NC=1C(C=C1)=CC=C1OCC1=CC=CC=C1 PRDFGFWMNKMFKA-UHFFFAOYSA-N 0.000 description 2
DRVMBMXXNQICFO-UHFFFAOYSA-N 6-methyl-7-propan-2-yl-3-(2h-tetrazol-5-yl)pyrazolo[1,5-a]pyrimidine Chemical compound C1=NN2C(C(C)C)=C(C)C=NC2=C1C1=NN=NN1 DRVMBMXXNQICFO-UHFFFAOYSA-N 0.000 description 2
PKCUZZDGHHNCFG-UHFFFAOYSA-N 7-chloro-6-(4-phenylmethoxyphenyl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile Chemical compound C1=NC2=C(C#N)C=NN2C(Cl)=C1C(C=C1)=CC=C1OCC1=CC=CC=C1 PKCUZZDGHHNCFG-UHFFFAOYSA-N 0.000 description 2
YCZQHXPIKQHABJ-UHFFFAOYSA-N 7-chloropyrazolo[1,5-a]pyrimidine Chemical compound ClC1=CC=NC2=CC=NN12 YCZQHXPIKQHABJ-UHFFFAOYSA-N 0.000 description 2
JUCOZXUYVXTLFS-UHFFFAOYSA-N 7-cyclohexyl-6-(4-methylsulfinylphenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid Chemical compound C1=CC(S(=O)C)=CC=C1C1=C(C2CCCCC2)N2N=CC(C(O)=O)=C2N=C1 JUCOZXUYVXTLFS-UHFFFAOYSA-N 0.000 description 2
KXFSITUDVMXIMC-UHFFFAOYSA-N 7-cyclohexyl-6-(4-methylsulfonylphenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C2CCCCC2)N2N=CC(C(O)=O)=C2N=C1 KXFSITUDVMXIMC-UHFFFAOYSA-N 0.000 description 2
MCKJHUPVBDHNEI-UHFFFAOYSA-N 7-cyclohexyl-6-(4-phenylmethoxyphenyl)pyrazolo[1,5-a]pyrimidine Chemical compound C=1C=CC=CC=1COC(C=C1)=CC=C1C=1C=NC2=CC=NN2C=1C1CCCCC1 MCKJHUPVBDHNEI-UHFFFAOYSA-N 0.000 description 2
RONJSBADDDLNNI-UHFFFAOYSA-N 7-cyclohexyl-6-[4-(3-methoxyphenoxy)phenyl]-3-(2h-tetrazol-5-yl)pyrazolo[1,5-a]pyrimidine Chemical compound COC1=CC=CC(OC=2C=CC(=CC=2)C2=C(N3N=CC(=C3N=C2)C=2NN=NN=2)C2CCCCC2)=C1 RONJSBADDDLNNI-UHFFFAOYSA-N 0.000 description 2
KUSIWWSXSXADQF-UHFFFAOYSA-N 7-cyclohexyl-6-[4-(4-methylsulfonylphenyl)phenyl]-3-(2h-tetrazol-5-yl)pyrazolo[1,5-a]pyrimidine Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=CC=C(C2=C(N3N=CC(=C3N=C2)C=2NN=NN=2)C2CCCCC2)C=C1 KUSIWWSXSXADQF-UHFFFAOYSA-N 0.000 description 2
UXNKZKBZVPSXQW-UHFFFAOYSA-N 7-cyclohexyl-6-[4-(4-methylsulfonylphenyl)phenyl]pyrazolo[1,5-a]pyrimidine-3-carbonitrile Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=CC=C(C2=C(N3N=CC(=C3N=C2)C#N)C2CCCCC2)C=C1 UXNKZKBZVPSXQW-UHFFFAOYSA-N 0.000 description 2
HDTLEULQUVBUBQ-UHFFFAOYSA-N 7-morpholin-4-yl-6-(4-phenylmethoxyphenyl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1C=1C=NC2=C(C#N)C=NN2C=1N1CCOCC1 HDTLEULQUVBUBQ-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
SISYLBHPYCJQSY-UHFFFAOYSA-N C1CCCCC1C=1C(=O)N2N=C(C(=O)NC(CO)C(O)=O)C=C2NC=1C(C=C1)=CC=C1OCC1=CC=CC=C1 Chemical compound C1CCCCC1C=1C(=O)N2N=C(C(=O)NC(CO)C(O)=O)C=C2NC=1C(C=C1)=CC=C1OCC1=CC=CC=C1 SISYLBHPYCJQSY-UHFFFAOYSA-N 0.000 description 2
AUMBATHUMKUWTH-UHFFFAOYSA-N CC1=NOC(C)=C1C1=CC=C(C2=C(C(=O)N3N=C(C=C3N2)C(O)=O)C2CCCCC2)C=C1 Chemical compound CC1=NOC(C)=C1C1=CC=C(C2=C(C(=O)N3N=C(C=C3N2)C(O)=O)C2CCCCC2)C=C1 AUMBATHUMKUWTH-UHFFFAOYSA-N 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
244000166102 Eucalyptus leucoxylon Species 0.000 description 2
235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
102000014150 Interferons Human genes 0.000 description 2
108010050904 Interferons Proteins 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
239000004743 Polypropylene Substances 0.000 description 2
241000288906 Primates Species 0.000 description 2
IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 2
108091028664 Ribonucleotide Proteins 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
208000036142 Viral infection Diseases 0.000 description 2
238000002835 absorbance Methods 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
230000000840 anti-viral effect Effects 0.000 description 2
230000008901 benefit Effects 0.000 description 2
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 2
NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 2
125000002619 bicyclic group Chemical group 0.000 description 2
150000001649 bromium compounds Chemical class 0.000 description 2
UFYVYVVHZBONGH-UHFFFAOYSA-N chembl565403 Chemical compound C1CCCCC1C=1C(=O)N2N=C(C(=O)O)C=C2NC=1C(C=C1)=CC=C1OC1=CC=CC(C(F)(F)F)=C1 UFYVYVVHZBONGH-UHFFFAOYSA-N 0.000 description 2
RCSPWOLZGRSRKM-UHFFFAOYSA-N chembl567494 Chemical compound C1CCCCC1C=1C(=O)N2N=C(C(=O)O)C=C2NC=1C1=CC=CC(F)=C1 RCSPWOLZGRSRKM-UHFFFAOYSA-N 0.000 description 2
SWZNGSZHFNZJRC-UHFFFAOYSA-N chembl583893 Chemical compound C1CCCCC1C=1C(=O)N2N=C(C(=O)O)C=C2NC=1C(C=C1)=CC=C1CC1=CC=CC=C1 SWZNGSZHFNZJRC-UHFFFAOYSA-N 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
239000012230 colorless oil Substances 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 2
GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 2
229940043279 diisopropylamine Drugs 0.000 description 2
239000006185 dispersion Substances 0.000 description 2
241001493065 dsRNA viruses Species 0.000 description 2
CPQKGGOPHDHAMN-UHFFFAOYSA-N ethyl 3-amino-1h-pyrazole-5-carboxylate Chemical compound CCOC(=O)C1=CC(N)=NN1 CPQKGGOPHDHAMN-UHFFFAOYSA-N 0.000 description 2
YPXGHKWOJXQLQU-UHFFFAOYSA-N ethyl 5-amino-1h-pyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NNC=1N YPXGHKWOJXQLQU-UHFFFAOYSA-N 0.000 description 2
KIICOKDOEODKEP-UHFFFAOYSA-N ethyl 6-bromo-7-cyclohexyl-2-methylpyrazolo[1,5-a]pyrimidine-3-carboxylate Chemical compound BrC=1C=NC2=C(C(=O)OCC)C(C)=NN2C=1C1CCCCC1 KIICOKDOEODKEP-UHFFFAOYSA-N 0.000 description 2
BNQHHYVPPPLPRW-UHFFFAOYSA-N ethyl 7-cyclohexyl-6-(4-iodophenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylate Chemical compound C=1C=C(I)C=CC=1C=1C=NC2=C(C(=O)OCC)C=NN2C=1C1CCCCC1 BNQHHYVPPPLPRW-UHFFFAOYSA-N 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
229910052731 fluorine Inorganic materials 0.000 description 2
238000009472 formulation Methods 0.000 description 2
239000000499 gel Substances 0.000 description 2
238000003306 harvesting Methods 0.000 description 2
210000003494 hepatocyte Anatomy 0.000 description 2
125000004475 heteroaralkyl group Chemical group 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
238000010348 incorporation Methods 0.000 description 2
125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
229940079322 interferon Drugs 0.000 description 2
238000002955 isolation Methods 0.000 description 2
239000011777 magnesium Substances 0.000 description 2
239000003550 marker Substances 0.000 description 2
230000001404 mediated effect Effects 0.000 description 2
PUCNWRPDWSRMNB-UHFFFAOYSA-N methyl 2-cyclohexyl-3-(furan-2-yl)-3-oxopropanoate Chemical compound C=1C=COC=1C(=O)C(C(=O)OC)C1CCCCC1 PUCNWRPDWSRMNB-UHFFFAOYSA-N 0.000 description 2
IMXBRVLCKXGWSS-UHFFFAOYSA-N methyl 2-cyclohexylacetate Chemical compound COC(=O)CC1CCCCC1 IMXBRVLCKXGWSS-UHFFFAOYSA-N 0.000 description 2
DACNWTKINAJHOM-UHFFFAOYSA-N methyl 3-(dimethylamino)-2-(4-phenylmethoxyphenyl)prop-2-enoate Chemical compound C1=CC(C(=CN(C)C)C(=O)OC)=CC=C1OCC1=CC=CC=C1 DACNWTKINAJHOM-UHFFFAOYSA-N 0.000 description 2
WUKSVVOCYHTIMV-UHFFFAOYSA-N methyl 3-amino-1h-pyrazole-5-carboxylate Chemical compound COC(=O)C=1C=C(N)NN=1 WUKSVVOCYHTIMV-UHFFFAOYSA-N 0.000 description 2
JJQCNRYKPSJKSW-UHFFFAOYSA-N methyl 4-[3-(trifluoromethyl)phenoxy]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1OC1=CC=CC(C(F)(F)F)=C1 JJQCNRYKPSJKSW-UHFFFAOYSA-N 0.000 description 2
RSKJKFPEPLRPKG-UHFFFAOYSA-N methyl 6-cyclohexyl-7-methoxy-5-(4-phenylmethoxyphenyl)pyrazolo[1,5-a]pyrimidine-2-carboxylate Chemical compound C1CCCCC1C1=C(OC)N2N=C(C(=O)OC)C=C2N=C1C(C=C1)=CC=C1OCC1=CC=CC=C1 RSKJKFPEPLRPKG-UHFFFAOYSA-N 0.000 description 2
239000002480 mineral oil Substances 0.000 description 2
235000010446 mineral oil Nutrition 0.000 description 2
UKHIXZRGUBEFJT-UHFFFAOYSA-N n-benzylsulfonyl-7-cyclohexyl-6-(4-fluorophenyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=CC(F)=CC=C1C1=C(C2CCCCC2)N2N=CC(C(=O)NS(=O)(=O)CC=3C=CC=CC=3)=C2N=C1 UKHIXZRGUBEFJT-UHFFFAOYSA-N 0.000 description 2
125000001624 naphthyl group Chemical group 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
239000006174 pH buffer Substances 0.000 description 2
229920001155 polypropylene Polymers 0.000 description 2
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
238000011533 pre-incubation Methods 0.000 description 2
230000008569 process Effects 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
DZPAOAZDQHZRGG-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine-2-carboxylic acid Chemical compound N1=CC=CN2N=C(C(=O)O)C=C21 DZPAOAZDQHZRGG-UHFFFAOYSA-N 0.000 description 2
VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 2
125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 description 2
229960000329 ribavirin Drugs 0.000 description 2
HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 2
239000002336 ribonucleotide Substances 0.000 description 2
125000002652 ribonucleotide group Chemical group 0.000 description 2
239000003730 rna directed rna polymerase inhibitor Substances 0.000 description 2
238000007789 sealing Methods 0.000 description 2
235000012239 silicon dioxide Nutrition 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
238000003756 stirring Methods 0.000 description 2
238000003860 storage Methods 0.000 description 2
238000006467 substitution reaction Methods 0.000 description 2
238000010998 test method Methods 0.000 description 2
125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 2
125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 2
DQKVZWAEWJUKAX-UHFFFAOYSA-N thiane-4-carbonitrile Chemical compound N#CC1CCSCC1 DQKVZWAEWJUKAX-UHFFFAOYSA-N 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
238000012546 transfer Methods 0.000 description 2
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
230000009385 viral infection Effects 0.000 description 2
UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 2
LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical class CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
BRQKYVQSAUQHNC-UHFFFAOYSA-N (2,4-dimethyl-1,3-thiazol-5-yl)methanol Chemical compound CC1=NC(C)=C(CO)S1 BRQKYVQSAUQHNC-UHFFFAOYSA-N 0.000 description 1
UERNRFHISLXQFU-DFWYDOINSA-N (2S)-5-oxopyrrolidine-2-carboxylic acid pyridine Chemical compound c1ccncc1.OC(=O)[C@@H]1CCC(=O)N1 UERNRFHISLXQFU-DFWYDOINSA-N 0.000 description 1
ZBPRUZRYHWEEEK-UHFFFAOYSA-N (3,5-dimethyl-2h-1,2-oxazol-3-yl)boronic acid Chemical compound CC1=CC(C)(B(O)O)NO1 ZBPRUZRYHWEEEK-UHFFFAOYSA-N 0.000 description 1
CAYQIZIAYYNFCS-UHFFFAOYSA-N (4-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C=C1 CAYQIZIAYYNFCS-UHFFFAOYSA-N 0.000 description 1
IVUHTLFKBDDICS-UHFFFAOYSA-N (4-methylsulfanylphenyl)boronic acid Chemical compound CSC1=CC=C(B(O)O)C=C1 IVUHTLFKBDDICS-UHFFFAOYSA-N 0.000 description 1
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
LSJVNJUFIFHWKG-UHFFFAOYSA-N 1-(3-phenoxyphenyl)-2-phenylethanone Chemical compound C=1C=CC(OC=2C=CC=CC=2)=CC=1C(=O)CC1=CC=CC=C1 LSJVNJUFIFHWKG-UHFFFAOYSA-N 0.000 description 1
DXVALSKCLLBZEB-UHFFFAOYSA-N 1-(4-chlorophenyl)-2-phenylethanone Chemical compound C1=CC(Cl)=CC=C1C(=O)CC1=CC=CC=C1 DXVALSKCLLBZEB-UHFFFAOYSA-N 0.000 description 1
MKYMYZJJFMPDOA-UHFFFAOYSA-N 1-(4-phenylmethoxyphenyl)ethanone Chemical compound C1=CC(C(=O)C)=CC=C1OCC1=CC=CC=C1 MKYMYZJJFMPDOA-UHFFFAOYSA-N 0.000 description 1
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical class CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
VUQPJRPDRDVQMN-UHFFFAOYSA-N 1-chlorooctadecane Chemical class CCCCCCCCCCCCCCCCCCCl VUQPJRPDRDVQMN-UHFFFAOYSA-N 0.000 description 1
RIFKADJTWUGDOV-UHFFFAOYSA-N 1-cyclohexylethanone Chemical compound CC(=O)C1CCCCC1 RIFKADJTWUGDOV-UHFFFAOYSA-N 0.000 description 1
125000006039 1-hexenyl group Chemical group 0.000 description 1
KQMIWCAOEFUBQK-UHFFFAOYSA-N 1-methoxy-3-phenylbenzene Chemical group COC1=CC=CC(C=2C=CC=CC=2)=C1 KQMIWCAOEFUBQK-UHFFFAOYSA-N 0.000 description 1
125000006023 1-pentenyl group Chemical group 0.000 description 1
RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
125000006017 1-propenyl group Chemical group 0.000 description 1
125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical compound NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 1
KEUDMLLLHGLIGH-UHFFFAOYSA-N 1h-pyrazole;pyrimidine Chemical compound C=1C=NNC=1.C1=CN=CN=C1 KEUDMLLLHGLIGH-UHFFFAOYSA-N 0.000 description 1
QZFZPVVDBGXQTB-UHFFFAOYSA-N 2,2,3,3,4,4,5,5,6,6,6-undecafluorohexan-1-ol Chemical compound OCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F QZFZPVVDBGXQTB-UHFFFAOYSA-N 0.000 description 1
WGSMVIHKBMAWRN-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1-benzofuran Chemical compound C1C=CC=C2OCCC21 WGSMVIHKBMAWRN-UHFFFAOYSA-N 0.000 description 1
KELIOZMTDOSCMM-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1-benzothiophene Chemical compound C1C=CC=C2SCCC21 KELIOZMTDOSCMM-UHFFFAOYSA-N 0.000 description 1
FRUWMYWEARDNTC-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1h-indole Chemical compound C1C=CC=C2NCCC21 FRUWMYWEARDNTC-UHFFFAOYSA-N 0.000 description 1
OBSLLHNATPQFMJ-UHFFFAOYSA-N 2,4-Dimethylthiazole Chemical compound CC1=CSC(C)=N1 OBSLLHNATPQFMJ-UHFFFAOYSA-N 0.000 description 1
FJSHTWVDFAUNCO-UHFFFAOYSA-N 2-(4-iodophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(I)C=C1 FJSHTWVDFAUNCO-UHFFFAOYSA-N 0.000 description 1
RMPXUPUAZGKDBN-UHFFFAOYSA-N 2-(4-iodophenyl)propanoic acid Chemical compound OC(=O)C(C)C1=CC=C(I)C=C1 RMPXUPUAZGKDBN-UHFFFAOYSA-N 0.000 description 1
GXUZGYVNJWERGG-UHFFFAOYSA-N 2-(4-phenylmethoxyphenyl)propanoic acid Chemical compound C1=CC(C(C(O)=O)C)=CC=C1OCC1=CC=CC=C1 GXUZGYVNJWERGG-UHFFFAOYSA-N 0.000 description 1
JRQAAYVLPPGEHT-UHFFFAOYSA-N 2-bromoethylcyclohexane Chemical compound BrCCC1CCCCC1 JRQAAYVLPPGEHT-UHFFFAOYSA-N 0.000 description 1
VOBIHUAWDXUCPH-UHFFFAOYSA-N 2-chloro-5,5-dimethylcyclohexane-1,3-dione Chemical compound CC1(C)CC(=O)C(Cl)C(=O)C1 VOBIHUAWDXUCPH-UHFFFAOYSA-N 0.000 description 1
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical class BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
BFKYQYMHJANOTR-UHFFFAOYSA-N 2h-pyrimidine-1-carbonitrile Chemical compound N#CN1CN=CC=C1 BFKYQYMHJANOTR-UHFFFAOYSA-N 0.000 description 1
ULRPISSMEBPJLN-UHFFFAOYSA-N 2h-tetrazol-5-amine Chemical compound NC1=NN=NN1 ULRPISSMEBPJLN-UHFFFAOYSA-N 0.000 description 1
JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 1
TYWWNGGXXIJCGM-UHFFFAOYSA-N 3-(4-oxocyclohexa-1,5-dien-1-yl)propanoic acid Chemical compound OC(=O)CCC1=CCC(=O)C=C1 TYWWNGGXXIJCGM-UHFFFAOYSA-N 0.000 description 1
MNVWCEBTSFBQAO-UHFFFAOYSA-N 3-(cyclohexen-1-yl)-6-pyridin-4-ylpyrazolo[1,5-a]pyrimidine Chemical compound C1CCCC(C2=C3N=CC(=CN3N=C2)C=2C=CN=CC=2)=C1 MNVWCEBTSFBQAO-UHFFFAOYSA-N 0.000 description 1
ALKYHXVLJMQRLQ-UHFFFAOYSA-N 3-Hydroxy-2-naphthoate Chemical class C1=CC=C2C=C(O)C(C(=O)O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-N 0.000 description 1
LLJJDLHGZUOMQP-UHFFFAOYSA-N 3-[1-[3-(dimethylamino)propyl]-5-methoxy-3-indolyl]-4-(1H-indol-3-yl)pyrrole-2,5-dione Chemical compound C1=CC=C2C(C3=C(C(NC3=O)=O)C3=CN(CCCN(C)C)C4=CC=C(C=C43)OC)=CNC2=C1 LLJJDLHGZUOMQP-UHFFFAOYSA-N 0.000 description 1
RMTDSXQVNSXONV-UHFFFAOYSA-N 3-amino-1h-pyrazole-5-carboxamide Chemical compound NC(=O)C=1C=C(N)NN=1 RMTDSXQVNSXONV-UHFFFAOYSA-N 0.000 description 1
ICASMSGEUGPHGI-UHFFFAOYSA-N 3-amino-1h-pyrazole-5-carboxylic acid Chemical compound NC=1C=C(C(O)=O)NN=1 ICASMSGEUGPHGI-UHFFFAOYSA-N 0.000 description 1
GTRZSCCKTZSLBG-UHFFFAOYSA-N 3-bromo-7-cyclohexyl-6-(4-phenylmethoxyphenyl)pyrazolo[1,5-a]pyrimidine-2-carboxylic acid Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1C=1C=NC2=C(Br)C(C(=O)O)=NN2C=1C1CCCCC1 GTRZSCCKTZSLBG-UHFFFAOYSA-N 0.000 description 1
125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical class OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
MXNBDFWNYRNIBH-UHFFFAOYSA-N 3-fluorobenzoic acid Chemical compound OC(=O)C1=CC=CC(F)=C1 MXNBDFWNYRNIBH-UHFFFAOYSA-N 0.000 description 1
125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
ZAIQNYMNZNXUAF-FOWTUZBSSA-N 3-geranyl-2,4,6-trihydroxybenzophenone Chemical compound CC(C)=CCC\C(C)=C\CC1=C(O)C=C(O)C(C(=O)C=2C=CC=CC=2)=C1O ZAIQNYMNZNXUAF-FOWTUZBSSA-N 0.000 description 1
KKSMCBOXKQGHAQ-UHFFFAOYSA-N 4-[6-(4-phenylmethoxyphenyl)-3-(2h-tetrazol-5-yl)pyrazolo[1,5-a]pyrimidin-7-yl]morpholine Chemical compound C=1C=CC=CC=1COC(C=C1)=CC=C1C=1C=NC2=C(C=3NN=NN=3)C=NN2C=1N1CCOCC1 KKSMCBOXKQGHAQ-UHFFFAOYSA-N 0.000 description 1
WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 1
LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 1
AQSCHALQLXXKKC-UHFFFAOYSA-N 4-phenylmethoxybenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1OCC1=CC=CC=C1 AQSCHALQLXXKKC-UHFFFAOYSA-N 0.000 description 1
HEFPHLANFNHABC-UHFFFAOYSA-N 5-(4-chlorophenyl)-7-(4-phenoxyphenyl)pyrazolo[1,5-a]pyrimidine-2-carboxylic acid Chemical compound N12N=C(C(=O)O)C=C2N=C(C=2C=CC(Cl)=CC=2)C=C1C(C=C1)=CC=C1OC1=CC=CC=C1 HEFPHLANFNHABC-UHFFFAOYSA-N 0.000 description 1
AFJVLXCRQAXWRT-UHFFFAOYSA-N 5-[[4-[7-cyclohexyl-3-(2h-tetrazol-5-yl)pyrazolo[1,5-a]pyrimidin-6-yl]phenoxy]methyl]-2,4-dimethyl-1,3-thiazole Chemical compound S1C(C)=NC(C)=C1COC1=CC=C(C2=C(N3N=CC(=C3N=C2)C=2NN=NN=2)C2CCCCC2)C=C1 AFJVLXCRQAXWRT-UHFFFAOYSA-N 0.000 description 1
NVKJOXRVEKMMHS-UHFFFAOYSA-N 5-nitro-1,2,4-triazol-3-one Chemical compound [O-][N+](=O)C1=NC(=O)N=N1 NVKJOXRVEKMMHS-UHFFFAOYSA-N 0.000 description 1
SLULCEOJZDCANW-UHFFFAOYSA-N 6-(4-phenylmethoxyphenyl)-3-(2h-tetrazol-5-yl)-7-(thian-4-yl)pyrazolo[1,5-a]pyrimidine Chemical compound C=1C=CC=CC=1COC(C=C1)=CC=C1C=1C=NC2=C(C=3NN=NN=3)C=NN2C=1C1CCSCC1 SLULCEOJZDCANW-UHFFFAOYSA-N 0.000 description 1
NWKKTLWXJZNFSB-UHFFFAOYSA-N 7-(oxan-4-yl)-6-(4-phenylmethoxyphenyl)-3-(2h-tetrazol-5-yl)pyrazolo[1,5-a]pyrimidine Chemical compound C=1C=CC=CC=1COC(C=C1)=CC=C1C=1C=NC2=C(C=3NN=NN=3)C=NN2C=1C1CCOCC1 NWKKTLWXJZNFSB-UHFFFAOYSA-N 0.000 description 1
FFPADHFMSPZEIQ-UHFFFAOYSA-N 7-cyclohexyl-3-nitro-6-(4-phenylmethoxyphenyl)pyrazolo[1,5-a]pyrimidine Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1C=1C=NC2=C([N+](=O)[O-])C=NN2C=1C1CCCCC1 FFPADHFMSPZEIQ-UHFFFAOYSA-N 0.000 description 1
FOQBXWFFKRPTEU-UHFFFAOYSA-N 7-cyclohexyl-6-(4-fluorophenyl)-2-methylpyrazolo[1,5-a]pyrimidine-3-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C=1C=NC2=C(C(O)=O)C(C)=NN2C=1C1CCCCC1 FOQBXWFFKRPTEU-UHFFFAOYSA-N 0.000 description 1
OZQMKNSLSGJQTE-UHFFFAOYSA-N 7-cyclohexyl-6-(4-methylsulfanylphenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid Chemical compound C1=CC(SC)=CC=C1C1=C(C2CCCCC2)N2N=CC(C(O)=O)=C2N=C1 OZQMKNSLSGJQTE-UHFFFAOYSA-N 0.000 description 1
SICMCCKLRZPFPE-UHFFFAOYSA-N 7-cyclohexyl-6-(4-phenylmethoxyphenyl)pyrazolo[1,5-a]pyrimidine-2-carboxylic acid Chemical compound C1CCCCC1C=1N2N=C(C(=O)O)C=C2N=CC=1C(C=C1)=CC=C1OCC1=CC=CC=C1 SICMCCKLRZPFPE-UHFFFAOYSA-N 0.000 description 1
ZQQPGDWCQNYENU-UHFFFAOYSA-N 7-cyclohexyl-6-(4-phenylmethoxyphenyl)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1C=1C=NC2=C(C=O)C=NN2C=1C1CCCCC1 ZQQPGDWCQNYENU-UHFFFAOYSA-N 0.000 description 1
UKLUAFIOQCCJAJ-UHFFFAOYSA-N 7-cyclohexyl-6-(4-phenylmethoxyphenyl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1C=1C=NC2=C(C#N)C=NN2C=1C1CCCCC1 UKLUAFIOQCCJAJ-UHFFFAOYSA-N 0.000 description 1
AHSFJXPGRJBQSH-UHFFFAOYSA-N 7-cyclohexyl-6-(furan-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid Chemical compound C1=COC=C1C=1C=NC2=C(C(=O)O)C=NN2C=1C1CCCCC1 AHSFJXPGRJBQSH-UHFFFAOYSA-N 0.000 description 1
XATSYVIZAVKUKY-UHFFFAOYSA-N 7-cyclohexyl-6-[4-(3-methoxyphenoxy)phenyl]pyrazolo[1,5-a]pyrimidine-3-carbonitrile Chemical compound COC1=CC=CC(OC=2C=CC(=CC=2)C2=C(N3N=CC(=C3N=C2)C#N)C2CCCCC2)=C1 XATSYVIZAVKUKY-UHFFFAOYSA-N 0.000 description 1
WNELCOVKQFMWFU-UHFFFAOYSA-N 7-cyclohexyl-6-[4-(3-methoxyphenyl)phenyl]pyrazolo[1,5-a]pyrimidine-3-carboxylic acid Chemical compound COC1=CC=CC(C=2C=CC(=CC=2)C2=C(N3N=CC(=C3N=C2)C(O)=O)C2CCCCC2)=C1 WNELCOVKQFMWFU-UHFFFAOYSA-N 0.000 description 1
LURTWQRURNWBGD-UHFFFAOYSA-N 7-cyclohexyl-6-[4-[[3-(trifluoromethyl)phenyl]methoxy]phenyl]pyrazolo[1,5-a]pyrimidine-3-carbonitrile Chemical compound FC(F)(F)C1=CC=CC(COC=2C=CC(=CC=2)C2=C(N3N=CC(=C3N=C2)C#N)C2CCCCC2)=C1 LURTWQRURNWBGD-UHFFFAOYSA-N 0.000 description 1
OYYMMOKBRAVBNP-UHFFFAOYSA-N 7-cyclohexyl-6-methylpyrazolo[1,5-a]pyrimidine-3-carboxylic acid Chemical compound CC=1C=NC2=C(C(O)=O)C=NN2C=1C1CCCCC1 OYYMMOKBRAVBNP-UHFFFAOYSA-N 0.000 description 1
IYKAQIZJHGUAKK-UHFFFAOYSA-N 7-ethyl-3-(2h-tetrazol-5-yl)pyrazolo[1,5-a]pyrimidine Chemical compound C1=NN2C(CC)=CC=NC2=C1C1=NN=NN1 IYKAQIZJHGUAKK-UHFFFAOYSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
IQRBNRFCRAJXJF-UHFFFAOYSA-N 9-benzyl-9-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1B2CC1=CC=CC=C1 IQRBNRFCRAJXJF-UHFFFAOYSA-N 0.000 description 1
108010087765 Antipain Proteins 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
UGMWRJMFFSRNNN-UHFFFAOYSA-N C1CCCCC1C=1C(=O)N2N=C(C(=O)N)C=C2NC=1C(C=C1)=CC=C1OCC1=CC=CC=C1 Chemical compound C1CCCCC1C=1C(=O)N2N=C(C(=O)N)C=C2NC=1C(C=C1)=CC=C1OCC1=CC=CC=C1 UGMWRJMFFSRNNN-UHFFFAOYSA-N 0.000 description 1
GIBSRKHTHSHGGC-UHFFFAOYSA-N C1CCCCC1C=1C(=O)N2N=C(C(=O)OC)C=C2NC=1C(C=C1)=CC=C1CC1=CC=CC=C1 Chemical compound C1CCCCC1C=1C(=O)N2N=C(C(=O)OC)C=C2NC=1C(C=C1)=CC=C1CC1=CC=CC=C1 GIBSRKHTHSHGGC-UHFFFAOYSA-N 0.000 description 1
LNOQHAXJIFIYJW-UHFFFAOYSA-N C1CCCCC1C=1C(=O)N2N=C(C(=O)OC)C=C2NC=1C(C=C1)=CC=C1OCC1=CC=CC=C1 Chemical compound C1CCCCC1C=1C(=O)N2N=C(C(=O)OC)C=C2NC=1C(C=C1)=CC=C1OCC1=CC=CC=C1 LNOQHAXJIFIYJW-UHFFFAOYSA-N 0.000 description 1
YUDDUEBESBQOJL-UHFFFAOYSA-N C1CCCCC1C=1C(=O)N2N=C(C(=O)OC)C=C2NC=1C1=CC=CO1 Chemical compound C1CCCCC1C=1C(=O)N2N=C(C(=O)OC)C=C2NC=1C1=CC=CO1 YUDDUEBESBQOJL-UHFFFAOYSA-N 0.000 description 1
125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
JQRUIUWQENFCBE-UHFFFAOYSA-N C=1C(=O)N2N=C(C(=O)O)C=C2NC=1C1=CC=CC=C1 Chemical compound C=1C(=O)N2N=C(C(=O)O)C=C2NC=1C1=CC=CC=C1 JQRUIUWQENFCBE-UHFFFAOYSA-N 0.000 description 1
ROKJGGQUZZNYRC-UHFFFAOYSA-N CC=1C(=C(C=CC1C(=O)O)C1=CC=C(C=C1)Cl)C Chemical compound CC=1C(=C(C=CC1C(=O)O)C1=CC=C(C=C1)Cl)C ROKJGGQUZZNYRC-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
102100031059 Cancer/testis antigen 55 Human genes 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
206010008909 Chronic Hepatitis Diseases 0.000 description 1
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 1
102100022404 E3 ubiquitin-protein ligase Midline-1 Human genes 0.000 description 1
101710102210 E3 ubiquitin-protein ligase Midline-1 Proteins 0.000 description 1
GKKZMYDNDDMXSE-UHFFFAOYSA-N Ethyl 3-oxo-3-phenylpropanoate Chemical compound CCOC(=O)CC(=O)C1=CC=CC=C1 GKKZMYDNDDMXSE-UHFFFAOYSA-N 0.000 description 1
NHXSTXWKZVAVOQ-UHFFFAOYSA-N Ethyl furoate Chemical compound CCOC(=O)C1=CC=CO1 NHXSTXWKZVAVOQ-UHFFFAOYSA-N 0.000 description 1
HYTRYEXINDDXJK-UHFFFAOYSA-N Ethyl isopropyl ketone Chemical compound CCC(=O)C(C)C HYTRYEXINDDXJK-UHFFFAOYSA-N 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
206010016654 Fibrosis Diseases 0.000 description 1
241000710781 Flaviviridae Species 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
208000005176 Hepatitis C Diseases 0.000 description 1
101000922015 Homo sapiens Cancer/testis antigen 55 Proteins 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical class CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
CVSUNVOHHWVUJC-UHFFFAOYSA-N OC(=O)C=1C=NN(C(C=2)=O)C=1NC=2C1=CC=CC=C1Cl Chemical compound OC(=O)C=1C=NN(C(C=2)=O)C=1NC=2C1=CC=CC=C1Cl CVSUNVOHHWVUJC-UHFFFAOYSA-N 0.000 description 1
240000007817 Olea europaea Species 0.000 description 1
235000019502 Orange oil Nutrition 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
108020002230 Pancreatic Ribonuclease Proteins 0.000 description 1
102000005891 Pancreatic ribonuclease Human genes 0.000 description 1
CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 1
208000037581 Persistent Infection Diseases 0.000 description 1
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
101710172711 Structural protein Proteins 0.000 description 1
238000006069 Suzuki reaction reaction Methods 0.000 description 1
108020000999 Viral RNA Proteins 0.000 description 1
CPPSKBIDQKJJKE-UHFFFAOYSA-N [3-(trifluoromethyl)phenoxy]boronic acid Chemical compound OB(O)OC1=CC=CC(C(F)(F)F)=C1 CPPSKBIDQKJJKE-UHFFFAOYSA-N 0.000 description 1
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
YBCVMFKXIKNREZ-UHFFFAOYSA-N acoh acetic acid Chemical compound CC(O)=O.CC(O)=O YBCVMFKXIKNREZ-UHFFFAOYSA-N 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
239000000853 adhesive Substances 0.000 description 1
230000001070 adhesive effect Effects 0.000 description 1
WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical class OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
125000004448 alkyl carbonyl group Chemical group 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
230000009435 amidation Effects 0.000 description 1
238000007112 amidation reaction Methods 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
239000000427 antigen Substances 0.000 description 1
102000036639 antigens Human genes 0.000 description 1
108091007433 antigens Proteins 0.000 description 1
SDNYTAYICBFYFH-TUFLPTIASA-N antipain Chemical compound NC(N)=NCCC[C@@H](C=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SDNYTAYICBFYFH-TUFLPTIASA-N 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
125000001691 aryl alkyl amino group Chemical group 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
125000003289 ascorbyl group Chemical class [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 description 1
CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical class N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
239000002585 base Substances 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
150000001558 benzoic acid derivatives Chemical class 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
230000037396 body weight Effects 0.000 description 1
150000001642 boronic acid derivatives Chemical class 0.000 description 1
239000000872 buffer Substances 0.000 description 1
150000004648 butanoic acid derivatives Chemical class 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical class C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
210000000234 capsid Anatomy 0.000 description 1
239000002775 capsule Substances 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
229910021386 carbon form Inorganic materials 0.000 description 1
125000005626 carbonium group Chemical group 0.000 description 1
150000007942 carboxylates Chemical class 0.000 description 1
239000000969 carrier Substances 0.000 description 1
230000008859 change Effects 0.000 description 1
ZOZFQXYTPYXBGQ-UHFFFAOYSA-N chembl567909 Chemical compound C1=C2NC(C=3OC=CC=3)=C(C3CCCCC3)C(=O)N2N=C1C(=O)NS(=O)(=O)CC1=CC=CC=C1 ZOZFQXYTPYXBGQ-UHFFFAOYSA-N 0.000 description 1
238000001311 chemical methods and process Methods 0.000 description 1
230000007882 cirrhosis Effects 0.000 description 1
208000019425 cirrhosis of liver Diseases 0.000 description 1
150000001860 citric acid derivatives Chemical class 0.000 description 1
229940125898 compound 5 Drugs 0.000 description 1
BRCFHPXVZRBXNF-UHFFFAOYSA-N copper dinitrate dihydrate Chemical compound O.O.[Cu+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O BRCFHPXVZRBXNF-UHFFFAOYSA-N 0.000 description 1
SFJMFSWCBVEHBA-UHFFFAOYSA-M copper(i)-thiophene-2-carboxylate Chemical compound [Cu+].[O-]C(=O)C1=CC=CS1 SFJMFSWCBVEHBA-UHFFFAOYSA-M 0.000 description 1
FDIRIOAEXPIEBL-UHFFFAOYSA-L copper;thiophene-2-carboxylate Chemical compound [Cu+2].[O-]C(=O)C1=CC=CS1.[O-]C(=O)C1=CC=CS1 FDIRIOAEXPIEBL-UHFFFAOYSA-L 0.000 description 1
210000004748 cultured cell Anatomy 0.000 description 1
238000012258 culturing Methods 0.000 description 1
125000000000 cycloalkoxy group Chemical group 0.000 description 1
125000005112 cycloalkylalkoxy group Chemical group 0.000 description 1
125000004367 cycloalkylaryl group Chemical group 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
RVOJTCZRIKWHDX-UHFFFAOYSA-N cyclohexanecarbonyl chloride Chemical compound ClC(=O)C1CCCCC1 RVOJTCZRIKWHDX-UHFFFAOYSA-N 0.000 description 1
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 1
125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
150000008050 dialkyl sulfates Chemical class 0.000 description 1
125000002576 diazepinyl group Chemical group N1N=C(C=CC=C1)* 0.000 description 1
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
125000000532 dioxanyl group Chemical group 0.000 description 1
125000005879 dioxolanyl group Chemical group 0.000 description 1
GAFRWLVTHPVQGK-UHFFFAOYSA-N dipentyl sulfate Chemical class CCCCCOS(=O)(=O)OCCCCC GAFRWLVTHPVQGK-UHFFFAOYSA-N 0.000 description 1
CZZYITDELCSZES-UHFFFAOYSA-N diphenylmethane Chemical group C=1C=CC=CC=1CC1=CC=CC=C1 CZZYITDELCSZES-UHFFFAOYSA-N 0.000 description 1
230000008034 disappearance Effects 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
UZZWBUYVTBPQIV-UHFFFAOYSA-N dme dimethoxyethane Chemical compound COCCOC.COCCOC UZZWBUYVTBPQIV-UHFFFAOYSA-N 0.000 description 1
CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical class CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
229940079593 drug Drugs 0.000 description 1
238000001647 drug administration Methods 0.000 description 1
238000009510 drug design Methods 0.000 description 1
238000001035 drying Methods 0.000 description 1
150000002085 enols Chemical class 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical class CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
FRYHCSODNHYDPU-UHFFFAOYSA-N ethanesulfonyl chloride Chemical compound CCS(Cl)(=O)=O FRYHCSODNHYDPU-UHFFFAOYSA-N 0.000 description 1
OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
DLFBNTUSDQSFOF-UHFFFAOYSA-N ethyl 3-(2-chlorophenyl)-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)C1=CC=CC=C1Cl DLFBNTUSDQSFOF-UHFFFAOYSA-N 0.000 description 1
OVPIQFGJQAQWAJ-UHFFFAOYSA-N ethyl 3-(furan-3-yl)-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)C=1C=COC=1 OVPIQFGJQAQWAJ-UHFFFAOYSA-N 0.000 description 1
VVEUCKVLCCZSOK-UHFFFAOYSA-N ethyl 4-cyclohexyl-2-(4-phenylmethoxybenzoyl)butanoate Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1C(=O)C(C(=O)OCC)CCC1CCCCC1 VVEUCKVLCCZSOK-UHFFFAOYSA-N 0.000 description 1
PHPHHQJFNJUIDA-UHFFFAOYSA-N ethyl 6-(4-benzylphenyl)-7-cyclohexylpyrazolo[1,5-a]pyrimidine-3-carboxylate Chemical compound C=1C=C(CC=2C=CC=CC=2)C=CC=1C=1C=NC2=C(C(=O)OCC)C=NN2C=1C1CCCCC1 PHPHHQJFNJUIDA-UHFFFAOYSA-N 0.000 description 1
DKSGMBUVAQAHSN-UHFFFAOYSA-N ethyl 7-cyclohexyl-6-[4-(3-methoxyphenyl)phenyl]pyrazolo[1,5-a]pyrimidine-3-carboxylate Chemical compound C=1C=C(C=2C=C(OC)C=CC=2)C=CC=1C=1C=NC2=C(C(=O)OCC)C=NN2C=1C1CCCCC1 DKSGMBUVAQAHSN-UHFFFAOYSA-N 0.000 description 1
239000002024 ethyl acetate extract Substances 0.000 description 1
TVQGDYNRXLTQAP-UHFFFAOYSA-N ethyl heptanoate Chemical compound CCCCCCC(=O)OCC TVQGDYNRXLTQAP-UHFFFAOYSA-N 0.000 description 1
OZECFIJVSAYAPH-UHFFFAOYSA-N ethyl-di(propan-2-yl)azanium;chloride Chemical compound Cl.CCN(C(C)C)C(C)C OZECFIJVSAYAPH-UHFFFAOYSA-N 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
230000003203 everyday effect Effects 0.000 description 1
239000000945 filler Substances 0.000 description 1
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
125000004428 fluoroalkoxy group Chemical group 0.000 description 1
UHCBBWUQDAVSMS-UHFFFAOYSA-N fluoroethane Chemical compound CCF UHCBBWUQDAVSMS-UHFFFAOYSA-N 0.000 description 1
VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 description 1
235000013305 food Nutrition 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
239000011521 glass Substances 0.000 description 1
150000002315 glycerophosphates Chemical class 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
208000006454 hepatitis Diseases 0.000 description 1
206010073071 hepatocellular carcinoma Diseases 0.000 description 1
231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical class CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical class CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
244000052637 human pathogen Species 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
125000005956 isoquinolyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
150000003893 lactate salts Chemical class 0.000 description 1
239000007788 liquid Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
150000002688 maleic acid derivatives Chemical class 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
239000002609 medium Substances 0.000 description 1
COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
229910052753 mercury Inorganic materials 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
XGDZEDRBLVIUMX-UHFFFAOYSA-N methyl 2-(4-hydroxyphenyl)acetate Chemical compound COC(=O)CC1=CC=C(O)C=C1 XGDZEDRBLVIUMX-UHFFFAOYSA-N 0.000 description 1
SLZYKGNMDRJRFP-UHFFFAOYSA-N methyl 2-(4-iodophenyl)propanoate Chemical compound COC(=O)C(C)C1=CC=C(I)C=C1 SLZYKGNMDRJRFP-UHFFFAOYSA-N 0.000 description 1
LKSKOETWXHOHKU-UHFFFAOYSA-N methyl 3-bromo-7-cyclohexyl-6-(4-phenylmethoxyphenyl)pyrazolo[1,5-a]pyrimidine-2-carboxylate Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1C=1C=NC2=C(Br)C(C(=O)OC)=NN2C=1C1CCCCC1 LKSKOETWXHOHKU-UHFFFAOYSA-N 0.000 description 1
PPRXASCJLRCKSO-UHFFFAOYSA-N methyl 3-cyclohexyl-2-(4-iodophenyl)-3-oxopropanoate Chemical compound C=1C=C(I)C=CC=1C(C(=O)OC)C(=O)C1CCCCC1 PPRXASCJLRCKSO-UHFFFAOYSA-N 0.000 description 1
KFEQRLJBEMQBGS-UHFFFAOYSA-N methyl 4-(4-chlorophenyl)-3-methylbenzoate Chemical compound CC1=CC(C(=O)OC)=CC=C1C1=CC=C(Cl)C=C1 KFEQRLJBEMQBGS-UHFFFAOYSA-N 0.000 description 1
GTZTYNPAPQKIIR-UHFFFAOYSA-N methyl 4-bromo-3-methylbenzoate Chemical compound COC(=O)C1=CC=C(Br)C(C)=C1 GTZTYNPAPQKIIR-UHFFFAOYSA-N 0.000 description 1
DKQFFACIPRKJHQ-UHFFFAOYSA-N methyl 7-cyclohexyl-6-(4-phenylmethoxyphenyl)pyrazolo[1,5-a]pyrimidine-2-carboxylate Chemical compound C1CCCCC1C=1N2N=C(C(=O)OC)C=C2N=CC=1C(C=C1)=CC=C1OCC1=CC=CC=C1 DKQFFACIPRKJHQ-UHFFFAOYSA-N 0.000 description 1
JOQJEWAXHQDQAG-UHFFFAOYSA-N methyl pyrimidine-2-carboxylate Chemical compound COC(=O)C1=NC=CC=N1 JOQJEWAXHQDQAG-UHFFFAOYSA-N 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
VYQNWZOUAUKGHI-UHFFFAOYSA-N monobenzone Chemical compound C1=CC(O)=CC=C1OCC1=CC=CC=C1 VYQNWZOUAUKGHI-UHFFFAOYSA-N 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
PEECTLLHENGOKU-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=NC=C1 PEECTLLHENGOKU-UHFFFAOYSA-N 0.000 description 1
SPDAVRRYWNJMGU-UHFFFAOYSA-N n-benzyl-1-ethyl-6-fluoro-7-[4-(furan-2-carbonyl)piperazin-1-yl]-4-oxoquinoline-3-carboxamide Chemical compound O=C1C2=CC(F)=C(N3CCN(CC3)C(=O)C=3OC=CC=3)C=C2N(CC)C=C1C(=O)NCC1=CC=CC=C1 SPDAVRRYWNJMGU-UHFFFAOYSA-N 0.000 description 1
DUORWTDJXKEGFC-UHFFFAOYSA-N n-benzylsulfonyl-6-cyclohexyl-5-(furan-2-yl)-7-oxo-1h-pyrazolo[1,5-a]pyrimidine-2-carboxamide Chemical compound C=1C2=NC(C=3OC=CC=3)=C(C3CCCCC3)C(=O)N2NC=1C(=O)NS(=O)(=O)CC1=CC=CC=C1 DUORWTDJXKEGFC-UHFFFAOYSA-N 0.000 description 1
KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical class C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
150000002814 niacins Chemical class 0.000 description 1
235000001968 nicotinic acid Nutrition 0.000 description 1
150000002823 nitrates Chemical class 0.000 description 1
229910000069 nitrogen hydride Inorganic materials 0.000 description 1
ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical compound O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000003891 oxalate salts Chemical class 0.000 description 1
125000000160 oxazolidinyl group Chemical group 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
150000002923 oximes Chemical class 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
235000019371 penicillin G benzathine Nutrition 0.000 description 1
125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
238000011056 performance test Methods 0.000 description 1
150000002978 peroxides Chemical class 0.000 description 1
JRKICGRDRMAZLK-UHFFFAOYSA-L persulfate group Chemical group S(=O)(=O)([O-])OOS(=O)(=O)[O-] JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 1
OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
125000005547 pivalate group Chemical group 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000002243 precursor Substances 0.000 description 1
238000002953 preparative HPLC Methods 0.000 description 1
238000012746 preparative thin layer chromatography Methods 0.000 description 1
238000004393 prognosis Methods 0.000 description 1
VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000006308 propyl amino group Chemical group 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
HNYVPKNVKSTVJO-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine-3-carboxylic acid Chemical compound C1=CC=NC2=C(C(=O)O)C=NN21 HNYVPKNVKSTVJO-UHFFFAOYSA-N 0.000 description 1
125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
125000005554 pyridyloxy group Chemical group 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000004929 pyrrolidonyl group Chemical group N1(C(CCC1)=O)* 0.000 description 1
125000001422 pyrrolinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
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 1
125000005493 quinolyl group Chemical group 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
235000020095 red wine Nutrition 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000002787 reinforcement Effects 0.000 description 1
238000012552 review Methods 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
150000003873 salicylate salts Chemical class 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
IFGCUJZIWBUILZ-UHFFFAOYSA-N sodium 2-[[2-[[hydroxy-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyphosphoryl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid Chemical compound [Na+].C=1NC2=CC=CC=C2C=1CC(C(O)=O)NC(=O)C(CC(C)C)NP(O)(=O)OC1OC(C)C(O)C(O)C1O IFGCUJZIWBUILZ-UHFFFAOYSA-N 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
238000012358 sourcing Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000012536 storage buffer Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
125000000565 sulfonamide group Chemical group 0.000 description 1
125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
150000003871 sulfonates Chemical class 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
HKYHBMLIEAMWRO-UHFFFAOYSA-N sy002454 Chemical compound OC(=O)C1=CC([N+]([O-])=O)=NN1 HKYHBMLIEAMWRO-UHFFFAOYSA-N 0.000 description 1
239000003826 tablet Substances 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
SHJFQCHBHKANBY-AWEZNQCLSA-N tert-butyl (2s)-2-amino-3-[4-[(2-methylpropan-2-yl)oxy]phenyl]propanoate Chemical compound CC(C)(C)OC(=O)[C@@H](N)CC1=CC=C(OC(C)(C)C)C=C1 SHJFQCHBHKANBY-AWEZNQCLSA-N 0.000 description 1
RDWZQVGVBTYCBD-UHFFFAOYSA-N tert-butyl 2-amino-3-[(2-methylpropan-2-yl)oxy]propanoate;hydrochloride Chemical compound Cl.CC(C)(C)OCC(N)C(=O)OC(C)(C)C RDWZQVGVBTYCBD-UHFFFAOYSA-N 0.000 description 1
WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
238000011285 therapeutic regimen Methods 0.000 description 1
OVRJVKCZJCNSOW-UHFFFAOYSA-N thian-4-one Chemical compound O=C1CCSCC1 OVRJVKCZJCNSOW-UHFFFAOYSA-N 0.000 description 1
SCKSQOIXSGPVJS-UHFFFAOYSA-N thiane-4-carboxylic acid Chemical compound OC(=O)C1CCSCC1 SCKSQOIXSGPVJS-UHFFFAOYSA-N 0.000 description 1
125000005308 thiazepinyl group Chemical group S1N=C(C=CC=C1)* 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000005302 thiazolylmethyl group Chemical group [H]C1=C([H])N=C(S1)C([H])([H])* 0.000 description 1
150000003567 thiocyanates Chemical class 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-M toluenesulfonate group Chemical group C=1(C(=CC=CC1)S(=O)(=O)[O-])C LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 description 1
125000005490 tosylate group Chemical group 0.000 description 1
JKVRTUCVPZTEQZ-UHFFFAOYSA-N tributyltin azide Chemical compound CCCC[Sn](CCCC)(CCCC)N=[N+]=[N-] JKVRTUCVPZTEQZ-UHFFFAOYSA-N 0.000 description 1
ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical class CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
150000003672 ureas Chemical class 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
239000008096 xylene Substances 0.000 description 1
150000003738 xylenes Chemical class 0.000 description 1
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1