JP2007506788A - Ｈｃｖ感染阻害剤とその使用法 - Google Patents
Ｈｃｖ感染阻害剤とその使用法 Download PDFInfo
- Publication number
- JP2007506788A JP2007506788A JP2006528300A JP2006528300A JP2007506788A JP 2007506788 A JP2007506788 A JP 2007506788A JP 2006528300 A JP2006528300 A JP 2006528300A JP 2006528300 A JP2006528300 A JP 2006528300A JP 2007506788 A JP2007506788 A JP 2007506788A
- Authority
- JP
- Japan
- Prior art keywords
- quinoline
- alkyl
- carboxamide
- chloro
- tetrazolo
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 208000015181 infectious disease Diseases 0.000 title abstract description 15
- 239000003112 inhibitor Substances 0.000 title abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 127
- 239000000203 mixture Substances 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 18
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 9
- 241000124008 Mammalia Species 0.000 claims abstract description 6
- 239000003937 drug carrier Substances 0.000 claims abstract description 5
- -1 C 1 -C 6 -alkyl-OH Chemical group 0.000 claims description 97
- 239000001257 hydrogen Substances 0.000 claims description 65
- 229910052739 hydrogen Inorganic materials 0.000 claims description 65
- 125000003118 aryl group Chemical group 0.000 claims description 53
- 125000001072 heteroaryl group Chemical group 0.000 claims description 42
- 125000005843 halogen group Chemical group 0.000 claims description 41
- 150000002431 hydrogen Chemical class 0.000 claims description 37
- 229910052736 halogen Inorganic materials 0.000 claims description 35
- 125000000623 heterocyclic group Chemical group 0.000 claims description 34
- 150000002367 halogens Chemical class 0.000 claims description 31
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 25
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 22
- 125000001475 halogen functional group Chemical group 0.000 claims description 20
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 101100516568 Caenorhabditis elegans nhr-7 gene Proteins 0.000 claims description 6
- 150000001540 azides Chemical class 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
- DDTGYDHKNWYLBW-UHFFFAOYSA-N 8-chloro-N-hydroxytetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound ONC(=O)C1=CC2=CC=C(Cl)C=C2N2C1=NN=N2 DDTGYDHKNWYLBW-UHFFFAOYSA-N 0.000 claims description 5
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 5
- 125000001246 bromo group Chemical group Br* 0.000 claims description 5
- 150000001721 carbon Chemical group 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 150000001768 cations Chemical class 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000002346 iodo group Chemical group I* 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
- 229920002554 vinyl polymer Polymers 0.000 claims description 4
- OKZVBLCFOITNEW-UHFFFAOYSA-N ethyl 7,9-dichloro-[1,2,4]triazolo[4,3-a]quinoline-4-carboxylate Chemical compound CCOC(=O)C1=CC2=CC(Cl)=CC(Cl)=C2N2C1=NN=C2 OKZVBLCFOITNEW-UHFFFAOYSA-N 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 2
- LEWDKQKVAFOMPI-UHFFFAOYSA-N quinoline-4-carboxamide Chemical compound C1=CC=C2C(C(=O)N)=CC=NC2=C1 LEWDKQKVAFOMPI-UHFFFAOYSA-N 0.000 claims 3
- KDDGJCDUHXXMLH-UHFFFAOYSA-N 8-chloro-4-(3,4-difluorophenyl)tetrazolo[1,5-a]quinoline Chemical compound C1=C(F)C(F)=CC=C1C1=CC2=CC=C(Cl)C=C2N2C1=NN=N2 KDDGJCDUHXXMLH-UHFFFAOYSA-N 0.000 claims 2
- CXOYSXOWNLSGAO-UHFFFAOYSA-N 8-chloro-4-[2-(trifluoromethyl)phenyl]tetrazolo[1,5-a]quinoline Chemical compound FC(F)(F)C1=CC=CC=C1C1=CC2=CC=C(Cl)C=C2N2C1=NN=N2 CXOYSXOWNLSGAO-UHFFFAOYSA-N 0.000 claims 2
- DEUIAEXOWPWFDU-UHFFFAOYSA-N 8-chlorotetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound NC(=O)C1=CC2=CC=C(Cl)C=C2N2C1=NN=N2 DEUIAEXOWPWFDU-UHFFFAOYSA-N 0.000 claims 2
- PWHGVECHCHHHPL-UHFFFAOYSA-N 9-(trifluoromethyl)tetrazolo[1,5-a]quinoline-4-carboxylic acid Chemical compound OC(=O)C1=CC2=CC=CC(C(F)(F)F)=C2N2C1=NN=N2 PWHGVECHCHHHPL-UHFFFAOYSA-N 0.000 claims 2
- RCXYSMWMBZENQN-UHFFFAOYSA-N 9-chloro-n-(2-methylpropoxy)tetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound CC(C)CONC(=O)C1=CC2=CC=CC(Cl)=C2N2C1=NN=N2 RCXYSMWMBZENQN-UHFFFAOYSA-N 0.000 claims 2
- NNXIHPDKJSKCFQ-UHFFFAOYSA-N 9-chloro-n-ethoxytetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound CCONC(=O)C1=CC2=CC=CC(Cl)=C2N2C1=NN=N2 NNXIHPDKJSKCFQ-UHFFFAOYSA-N 0.000 claims 2
- SHDKLYXCHWGDMP-UHFFFAOYSA-N 9-chloro-n-propan-2-yloxytetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound CC(C)ONC(=O)C1=CC2=CC=CC(Cl)=C2N2C1=NN=N2 SHDKLYXCHWGDMP-UHFFFAOYSA-N 0.000 claims 2
- HULKNLWPLXPCQD-UHFFFAOYSA-N 9-chloro-n-propoxytetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound CCCONC(=O)C1=CC2=CC=CC(Cl)=C2N2C1=NN=N2 HULKNLWPLXPCQD-UHFFFAOYSA-N 0.000 claims 2
- GEPYMTRVVIHGHF-UHFFFAOYSA-N tetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound NC(=O)C1=CC2=CC=CC=C2N2C1=NN=N2 GEPYMTRVVIHGHF-UHFFFAOYSA-N 0.000 claims 2
- HGPBQTVIAUITCB-UHFFFAOYSA-N 1-(8-chlorotetrazolo[1,5-a]quinolin-4-yl)-3-methylurea Chemical compound CNC(=O)NC1=CC2=CC=C(Cl)C=C2N2C1=NN=N2 HGPBQTVIAUITCB-UHFFFAOYSA-N 0.000 claims 1
- CWVQAOTUAFYFIQ-UHFFFAOYSA-N 1-(8-ethyltetrazolo[1,5-a]quinolin-4-yl)-n-methoxymethanimine Chemical compound C1=C(C=NOC)C2=NN=NN2C2=CC(CC)=CC=C21 CWVQAOTUAFYFIQ-UHFFFAOYSA-N 0.000 claims 1
- VZMHVLAVYYNZRZ-UHFFFAOYSA-N 1-(benzenesulfonyl)-3-(8-chlorotetrazolo[1,5-a]quinolin-4-yl)urea Chemical compound C12=NN=NN2C2=CC(Cl)=CC=C2C=C1NC(=O)NS(=O)(=O)C1=CC=CC=C1 VZMHVLAVYYNZRZ-UHFFFAOYSA-N 0.000 claims 1
- VFLGJOLLSLRBFU-UHFFFAOYSA-N 1-chloro-8-fluoro-n-hydroxy-[1,2,4]triazolo[4,3-a]quinoline-4-carboxamide Chemical compound ONC(=O)C1=CC2=CC=C(F)C=C2N2C1=NN=C2Cl VFLGJOLLSLRBFU-UHFFFAOYSA-N 0.000 claims 1
- USWKATACKGFEJT-UHFFFAOYSA-N 2-(8-chlorotetrazolo[1,5-a]quinolin-4-yl)benzonitrile Chemical compound C12=NN=NN2C2=CC(Cl)=CC=C2C=C1C1=CC=CC=C1C#N USWKATACKGFEJT-UHFFFAOYSA-N 0.000 claims 1
- DHNMJRIZBXIEOU-UHFFFAOYSA-N 2-(dichloromethyl)-5-(tetrazolo[1,5-a]quinolin-5-yl)-1,3,4-oxadiazole Chemical compound O1C(C(Cl)Cl)=NN=C1C1=CC2=NN=NN2C2=CC=CC=C12 DHNMJRIZBXIEOU-UHFFFAOYSA-N 0.000 claims 1
- JVFUGOQEGOULRF-UHFFFAOYSA-N 3,4,5,6,14-pentazapentacyclo[11.7.0.02,6.07,12.015,20]icosa-1(13),2,4,7,9,11,15,17,19-nonaene Chemical compound C12=NN=NN2C2=CC=CC=C2C2=C1C1=CC=CC=C1N2 JVFUGOQEGOULRF-UHFFFAOYSA-N 0.000 claims 1
- LIRHINFDFZWXPL-UHFFFAOYSA-N 4-(2h-tetrazol-5-yl)tetrazolo[1,5-a]quinoline Chemical compound C=1C=CC=C(N2N=NN=C22)C=1C=C2C=1N=NNN=1 LIRHINFDFZWXPL-UHFFFAOYSA-N 0.000 claims 1
- IYNNWROSEXQPTA-UHFFFAOYSA-N 4-[3,5-bis(trifluoromethyl)phenyl]-8-chlorotetrazolo[1,5-a]quinoline Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C=2C3=NN=NN3C3=CC(Cl)=CC=C3C=2)=C1 IYNNWROSEXQPTA-UHFFFAOYSA-N 0.000 claims 1
- XPINKUJGISQSEO-UHFFFAOYSA-N 5-methyltetrazolo[1,5-a]quinoline-4-carboxylic acid Chemical compound C1=CC=C2C(C)=C(C(O)=O)C3=NN=NN3C2=C1 XPINKUJGISQSEO-UHFFFAOYSA-N 0.000 claims 1
- UDCVFAWOMCICDM-UHFFFAOYSA-N 5-phenyltetrazolo[1,5-a]quinoline-4-carboxylic acid Chemical compound C12=CC=CC=C2N2N=NN=C2C(C(=O)O)=C1C1=CC=CC=C1 UDCVFAWOMCICDM-UHFFFAOYSA-N 0.000 claims 1
- COSTWHPVXQXHAE-UHFFFAOYSA-N 6-chloro-N-hydroxytetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound ONC(=O)C1=CC2=C(Cl)C=CC=C2N2C1=NN=N2 COSTWHPVXQXHAE-UHFFFAOYSA-N 0.000 claims 1
- SAMJJAMISAFPFF-UHFFFAOYSA-N 6-methyltetrazolo[1,5-a]quinoline-4-carboxylic acid Chemical compound C1=C(C(O)=O)C2=NN=NN2C2=C1C(C)=CC=C2 SAMJJAMISAFPFF-UHFFFAOYSA-N 0.000 claims 1
- UMXNWJUCQCKDLA-UHFFFAOYSA-N 7,8-dimethoxytetrazolo[1,5-a]quinoline-4-carbaldehyde Chemical compound C1=C(C=O)C2=NN=NN2C2=C1C=C(OC)C(OC)=C2 UMXNWJUCQCKDLA-UHFFFAOYSA-N 0.000 claims 1
- RNXRPXAHGZQSEZ-UHFFFAOYSA-N 7,8-dimethoxytetrazolo[1,5-a]quinoline-4-carboxylic acid Chemical compound C1=C(C(O)=O)C2=NN=NN2C2=C1C=C(OC)C(OC)=C2 RNXRPXAHGZQSEZ-UHFFFAOYSA-N 0.000 claims 1
- DUHCPEDSCGDXDJ-UHFFFAOYSA-N 7,8-dimethyltetrazolo[1,5-a]quinoline-4-carboxylic acid Chemical compound C1=C(C(O)=O)C2=NN=NN2C2=C1C=C(C)C(C)=C2 DUHCPEDSCGDXDJ-UHFFFAOYSA-N 0.000 claims 1
- VSLVIMVKOHONQB-UHFFFAOYSA-N 7,9-dichloro-N-hydroxytetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound ONC(=O)C1=CC2=CC(Cl)=CC(Cl)=C2N2C1=NN=N2 VSLVIMVKOHONQB-UHFFFAOYSA-N 0.000 claims 1
- LWFMXTCGXIXNGB-UHFFFAOYSA-N 7,9-dichloro-[1,2,4]triazolo[4,3-a]quinoline-4-carboxylic acid Chemical compound OC(=O)C1=CC2=CC(Cl)=CC(Cl)=C2N2C1=NN=C2 LWFMXTCGXIXNGB-UHFFFAOYSA-N 0.000 claims 1
- SPUNPOMBXPLCOC-UHFFFAOYSA-N 7,9-dichloro-n-(oxan-2-yloxy)-[1,2,4]triazolo[4,3-a]quinoline-4-carboxamide Chemical compound C=1C(Cl)=CC(Cl)=C(N2C=NN=C22)C=1C=C2C(=O)NOC1CCCCO1 SPUNPOMBXPLCOC-UHFFFAOYSA-N 0.000 claims 1
- WKLAMSXASRKVMT-UHFFFAOYSA-N 7,9-dichloro-n-hydroxy-[1,2,4]triazolo[4,3-a]quinoline-4-carboxamide Chemical compound ONC(=O)C1=CC2=CC(Cl)=CC(Cl)=C2N2C1=NN=C2 WKLAMSXASRKVMT-UHFFFAOYSA-N 0.000 claims 1
- INYZBCOIFKSUBO-UHFFFAOYSA-N 7-bromotetrazolo[1,5-a]quinoline-4-carboxylic acid Chemical compound OC(=O)C1=CC2=CC(Br)=CC=C2N2C1=NN=N2 INYZBCOIFKSUBO-UHFFFAOYSA-N 0.000 claims 1
- JAZKRDMIFAWNBQ-UHFFFAOYSA-N 7-chloro-N-hydroxytetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound ONC(=O)C1=CC2=CC(Cl)=CC=C2N2C1=NN=N2 JAZKRDMIFAWNBQ-UHFFFAOYSA-N 0.000 claims 1
- SZPVXTFMYQECNS-UHFFFAOYSA-N 7-chloro-n-(oxan-2-yloxy)-[1,2,4]triazolo[4,3-a]quinoline-4-carboxamide Chemical compound C=1C(Cl)=CC=C(N2C=NN=C22)C=1C=C2C(=O)NOC1CCCCO1 SZPVXTFMYQECNS-UHFFFAOYSA-N 0.000 claims 1
- FCCDDQUZXWXHQK-UHFFFAOYSA-N 7-chloro-n-hydroxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoline-4-carboxamide Chemical compound ClC1=CC=C2N3C(C)=NN=C3C(C(=O)NO)=CC2=C1 FCCDDQUZXWXHQK-UHFFFAOYSA-N 0.000 claims 1
- UTCROWSGSPDXBH-UHFFFAOYSA-N 7-chloro-n-hydroxy-[1,2,4]triazolo[4,3-a]quinoline-4-carboxamide Chemical compound ONC(=O)C1=CC2=CC(Cl)=CC=C2N2C1=NN=C2 UTCROWSGSPDXBH-UHFFFAOYSA-N 0.000 claims 1
- PQXHXUSZQIYQIO-UHFFFAOYSA-N 7-chlorotetrazolo[1,5-a]quinoline-4-carboxylic acid Chemical compound OC(=O)C1=CC2=CC(Cl)=CC=C2N2C1=NN=N2 PQXHXUSZQIYQIO-UHFFFAOYSA-N 0.000 claims 1
- YJRANNFIFFMKEY-UHFFFAOYSA-N 7-fluoro-N-hydroxytetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound ONC(=O)C1=CC2=CC(F)=CC=C2N2C1=NN=N2 YJRANNFIFFMKEY-UHFFFAOYSA-N 0.000 claims 1
- ICVNUJBAFJWFQH-UHFFFAOYSA-N 8-(trifluoromethoxy)tetrazolo[1,5-a]quinoline-4-carboxylic acid Chemical compound OC(=O)C1=CC2=CC=C(OC(F)(F)F)C=C2N2C1=NN=N2 ICVNUJBAFJWFQH-UHFFFAOYSA-N 0.000 claims 1
- LTZVUBITQQJLAI-UHFFFAOYSA-N 8-chloro-4-(3-fluorophenyl)tetrazolo[1,5-a]quinoline Chemical compound FC1=CC=CC(C=2C3=NN=NN3C3=CC(Cl)=CC=C3C=2)=C1 LTZVUBITQQJLAI-UHFFFAOYSA-N 0.000 claims 1
- WOQOOPOVMWZXNS-UHFFFAOYSA-N 8-chloro-4-[3-(trifluoromethoxy)phenyl]tetrazolo[1,5-a]quinoline Chemical compound FC(F)(F)OC1=CC=CC(C=2C3=NN=NN3C3=CC(Cl)=CC=C3C=2)=C1 WOQOOPOVMWZXNS-UHFFFAOYSA-N 0.000 claims 1
- DLVPUTGSCDEBRW-UHFFFAOYSA-N 8-chloro-4-[4-(trifluoromethoxy)phenyl]tetrazolo[1,5-a]quinoline Chemical compound C1=CC(OC(F)(F)F)=CC=C1C1=CC2=CC=C(Cl)C=C2N2C1=NN=N2 DLVPUTGSCDEBRW-UHFFFAOYSA-N 0.000 claims 1
- PHTMAUOFIUJJMR-UHFFFAOYSA-N 8-chloro-4-imidazol-1-yltetrazolo[1,5-a]quinoline Chemical compound C12=NN=NN2C2=CC(Cl)=CC=C2C=C1N1C=CN=C1 PHTMAUOFIUJJMR-UHFFFAOYSA-N 0.000 claims 1
- OTWRRFGQUTZVBJ-UHFFFAOYSA-N 8-chloro-4-pyridin-2-ylsulfonyltetrazolo[1,5-a]quinoline Chemical compound C12=NN=NN2C2=CC(Cl)=CC=C2C=C1S(=O)(=O)C1=CC=CC=N1 OTWRRFGQUTZVBJ-UHFFFAOYSA-N 0.000 claims 1
- MAQHFKAGUKUSSR-UHFFFAOYSA-N 8-chloro-7-methoxytetrazolo[1,5-a]quinoline-4-carbaldehyde Chemical compound C1=C(C=O)C2=NN=NN2C2=C1C=C(OC)C(Cl)=C2 MAQHFKAGUKUSSR-UHFFFAOYSA-N 0.000 claims 1
- YJXHIVRBMRDLCW-UHFFFAOYSA-N 8-chloro-7-methoxytetrazolo[1,5-a]quinoline-4-carboxylic acid Chemical compound C1=C(C(O)=O)C2=NN=NN2C2=C1C=C(OC)C(Cl)=C2 YJXHIVRBMRDLCW-UHFFFAOYSA-N 0.000 claims 1
- SOCJUVBQFYOIEW-UHFFFAOYSA-N 8-chloro-N-hydroxy-7-methoxytetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound C1=C(C(=O)NO)C2=NN=NN2C2=C1C=C(OC)C(Cl)=C2 SOCJUVBQFYOIEW-UHFFFAOYSA-N 0.000 claims 1
- RYOLJLMJDXZSGA-UHFFFAOYSA-N 8-chloro-n-(oxan-2-yloxy)tetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound C12=NN=NN2C2=CC(Cl)=CC=C2C=C1C(=O)NOC1CCCCO1 RYOLJLMJDXZSGA-UHFFFAOYSA-N 0.000 claims 1
- XFNUMICOXOOYPH-UHFFFAOYSA-N 8-chloro-n-hydroxy-n-methyltetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound CN(O)C(=O)C1=CC2=CC=C(Cl)C=C2N2C1=NN=N2 XFNUMICOXOOYPH-UHFFFAOYSA-N 0.000 claims 1
- MBPXGTGMOLMQMS-UHFFFAOYSA-N 8-cyclopentyloxytetrazolo[1,5-a]quinoline-4-carbaldehyde Chemical compound C1=C2N3N=NN=C3C(C=O)=CC2=CC=C1OC1CCCC1 MBPXGTGMOLMQMS-UHFFFAOYSA-N 0.000 claims 1
- RRIJFEZOBOHYFS-UHFFFAOYSA-N 8-ethyltetrazolo[1,5-a]quinoline-4-carboxylic acid Chemical compound C1=C(C(O)=O)C2=NN=NN2C2=CC(CC)=CC=C21 RRIJFEZOBOHYFS-UHFFFAOYSA-N 0.000 claims 1
- CVFKXMFUMWRFGN-UHFFFAOYSA-N 8-fluoro-[1,2,4]triazolo[4,3-a]quinoline-4-carboxylic acid Chemical compound OC(=O)C1=CC2=CC=C(F)C=C2N2C1=NN=C2 CVFKXMFUMWRFGN-UHFFFAOYSA-N 0.000 claims 1
- ZPCPXFIMJQIQMO-UHFFFAOYSA-N 8-fluoro-n-(2h-tetrazol-5-yl)tetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound C12=NN=NN2C2=CC(F)=CC=C2C=C1C(=O)NC1=NN=NN1 ZPCPXFIMJQIQMO-UHFFFAOYSA-N 0.000 claims 1
- BGBWNDUMVSMUIY-UHFFFAOYSA-N 8-methoxytetrazolo[1,5-a]quinoline-4-carbaldehyde Chemical compound C1=C(C=O)C2=NN=NN2C2=CC(OC)=CC=C21 BGBWNDUMVSMUIY-UHFFFAOYSA-N 0.000 claims 1
- HQVANFACLZYYAW-UHFFFAOYSA-N 8-methylsulfanyltetrazolo[1,5-a]quinoline-4-carbaldehyde Chemical compound C1=C(C=O)C2=NN=NN2C2=CC(SC)=CC=C21 HQVANFACLZYYAW-UHFFFAOYSA-N 0.000 claims 1
- DZPAWGYBIQHQCG-UHFFFAOYSA-N 8-methylsulfonyltetrazolo[1,5-a]quinoline-4-carboxylic acid Chemical compound C1=C(C(O)=O)C2=NN=NN2C2=CC(S(=O)(=O)C)=CC=C21 DZPAWGYBIQHQCG-UHFFFAOYSA-N 0.000 claims 1
- NWEKWRGATCIRGC-UHFFFAOYSA-N 8-propan-2-yltetrazolo[1,5-a]quinoline-4-carboxylic acid Chemical compound C1=C(C(O)=O)C2=NN=NN2C2=CC(C(C)C)=CC=C21 NWEKWRGATCIRGC-UHFFFAOYSA-N 0.000 claims 1
- KEBZWPDXLSEAKA-UHFFFAOYSA-N 9-chloro-N-hydroxytetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound ONC(=O)C1=CC2=CC=CC(Cl)=C2N2C1=NN=N2 KEBZWPDXLSEAKA-UHFFFAOYSA-N 0.000 claims 1
- LEBIHZRZVKWPJT-UHFFFAOYSA-N 9-methoxytetrazolo[1,5-a]quinoline-4-carboxylic acid Chemical compound C1=C(C(O)=O)C2=NN=NN2C2=C1C=CC=C2OC LEBIHZRZVKWPJT-UHFFFAOYSA-N 0.000 claims 1
- AKDKWURLXQDXAL-UHFFFAOYSA-N 9-methyltetrazolo[1,5-a]quinoline-4-carboxylic acid Chemical compound C1=C(C(O)=O)C2=NN=NN2C2=C1C=CC=C2C AKDKWURLXQDXAL-UHFFFAOYSA-N 0.000 claims 1
- ATGAIDRWSPTYGY-UHFFFAOYSA-N C=1C=2SC=CC=2N2N=NN=C2C=1C(=O)NOC1CCCCO1 Chemical compound C=1C=2SC=CC=2N2N=NN=C2C=1C(=O)NOC1CCCCO1 ATGAIDRWSPTYGY-UHFFFAOYSA-N 0.000 claims 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 claims 1
- OBQHUCTUYOGARU-UHFFFAOYSA-N N-hydroxy-5-thia-1,10,11,12-tetrazatricyclo[7.3.0.02,6]dodeca-2(6),3,7,9,11-pentaene-8-carboxamide Chemical compound N12N=NN=C2C(C(=O)NO)=CC2=C1C=CS2 OBQHUCTUYOGARU-UHFFFAOYSA-N 0.000 claims 1
- VXQDMFJWMFGJRE-UHFFFAOYSA-N N-hydroxy-7,8-dimethoxytetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound C1=C(C(=O)NO)C2=NN=NN2C2=C1C=C(OC)C(OC)=C2 VXQDMFJWMFGJRE-UHFFFAOYSA-N 0.000 claims 1
- GPMCHNLCAOXGNK-UHFFFAOYSA-N N-hydroxy-7,9-dimethyltetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound C1=C(C(=O)NO)C2=NN=NN2C2=C(C)C=C(C)C=C21 GPMCHNLCAOXGNK-UHFFFAOYSA-N 0.000 claims 1
- MCIUAUYORSGRQP-UHFFFAOYSA-N N-hydroxy-8-(trifluoromethoxy)tetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound ONC(=O)C1=CC2=CC=C(OC(F)(F)F)C=C2N2C1=NN=N2 MCIUAUYORSGRQP-UHFFFAOYSA-N 0.000 claims 1
- LTWXNXLYHZQBBP-UHFFFAOYSA-N N-hydroxy-8-(trifluoromethyl)tetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound ONC(=O)C1=CC2=CC=C(C(F)(F)F)C=C2N2C1=NN=N2 LTWXNXLYHZQBBP-UHFFFAOYSA-N 0.000 claims 1
- XUBCQNORMXQLAL-UHFFFAOYSA-N N-hydroxy-8-methoxytetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound C1=C(C(=O)NO)C2=NN=NN2C2=CC(OC)=CC=C21 XUBCQNORMXQLAL-UHFFFAOYSA-N 0.000 claims 1
- LBUPZFXAQHHEKA-UHFFFAOYSA-N N-hydroxy-9-methyltetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound C1=C(C(=O)NO)C2=NN=NN2C2=C1C=CC=C2C LBUPZFXAQHHEKA-UHFFFAOYSA-N 0.000 claims 1
- DHPGAGVZEGPNIY-UHFFFAOYSA-N N-hydroxytetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound ONC(=O)C1=CC2=CC=CC=C2N2C1=NN=N2 DHPGAGVZEGPNIY-UHFFFAOYSA-N 0.000 claims 1
- NVTSAIMVJCJXGY-UHFFFAOYSA-N N-hydroxytetrazolo[1,5-a]quinoline-5-carboxamide Chemical compound C1=CC=C2C(C(=O)NO)=CC3=NN=NN3C2=C1 NVTSAIMVJCJXGY-UHFFFAOYSA-N 0.000 claims 1
- 125000005336 allyloxy group Chemical group 0.000 claims 1
- ZUUOZKXWNOWREL-UHFFFAOYSA-N butyl 9-chlorotetrazolo[1,5-a]quinoline-4-carboxylate Chemical compound CCCCOC(=O)C1=CC2=CC=CC(Cl)=C2N2C1=NN=N2 ZUUOZKXWNOWREL-UHFFFAOYSA-N 0.000 claims 1
- DHUHJNCZUFMEGC-UHFFFAOYSA-N ethyl 5-(3-hydroxyanilino)-8-(trifluoromethyl)tetrazolo[1,5-a]quinoline-4-carboxylate Chemical compound C12=CC=C(C(F)(F)F)C=C2N2N=NN=C2C(C(=O)OCC)=C1NC1=CC=CC(O)=C1 DHUHJNCZUFMEGC-UHFFFAOYSA-N 0.000 claims 1
- XDNHKLHSBNCBBV-UHFFFAOYSA-N ethyl 6-azidotetrazolo[1,5-a]quinoline-4-carboxylate Chemical compound CCOC(=O)C1=CC2=C(N=[N+]=[N-])C=CC=C2N2C1=NN=N2 XDNHKLHSBNCBBV-UHFFFAOYSA-N 0.000 claims 1
- KLVUJQORENLEAH-UHFFFAOYSA-N ethyl 7-chloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoline-4-carboxylate Chemical compound CCOC(=O)C1=CC2=CC(Cl)=CC=C2N2C1=NN=C2C KLVUJQORENLEAH-UHFFFAOYSA-N 0.000 claims 1
- RJTLIVLTJRAWNR-UHFFFAOYSA-N ethyl 7-chloro-[1,2,4]triazolo[4,3-a]quinoline-4-carboxylate Chemical compound CCOC(=O)C1=CC2=CC(Cl)=CC=C2N2C1=NN=C2 RJTLIVLTJRAWNR-UHFFFAOYSA-N 0.000 claims 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims 1
- SOPNTFJFKMKSBN-UHFFFAOYSA-N methyl 8-aminotetrazolo[1,5-a]quinoline-4-carboxylate Chemical compound COC(=O)C1=CC2=CC=C(N)C=C2N2C1=NN=N2 SOPNTFJFKMKSBN-UHFFFAOYSA-N 0.000 claims 1
- DPOUSSTXFUBAKF-UHFFFAOYSA-N methyl 8-fluoro-[1,2,4]triazolo[4,3-a]quinoline-4-carboxylate Chemical compound COC(=O)C1=CC2=CC=C(F)C=C2N2C1=NN=C2 DPOUSSTXFUBAKF-UHFFFAOYSA-N 0.000 claims 1
- MQCOHSXAIGOLOW-UHFFFAOYSA-N n-(oxan-2-yloxy)tetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound C=1C2=CC=CC=C2N2N=NN=C2C=1C(=O)NOC1CCCCO1 MQCOHSXAIGOLOW-UHFFFAOYSA-N 0.000 claims 1
- WTVFJFAGBFMQTM-UHFFFAOYSA-N n-(oxan-2-yloxy)tetrazolo[1,5-a]quinoline-5-carboxamide Chemical compound C=1C2=NN=NN2C2=CC=CC=C2C=1C(=O)NOC1CCCCO1 WTVFJFAGBFMQTM-UHFFFAOYSA-N 0.000 claims 1
- IPOWHJMXFNRDSP-UHFFFAOYSA-N n-[(7-methoxytetrazolo[1,5-a]quinolin-4-yl)methylidene]hydroxylamine Chemical compound C1=C(C=NO)C2=NN=NN2C2=CC=C(OC)C=C21 IPOWHJMXFNRDSP-UHFFFAOYSA-N 0.000 claims 1
- FCRZHQIPWMZKNY-UHFFFAOYSA-N n-benzyl-8-chlorotetrazolo[1,5-a]quinoline-4-carboxamide Chemical compound C12=NN=NN2C2=CC(Cl)=CC=C2C=C1C(=O)NCC1=CC=CC=C1 FCRZHQIPWMZKNY-UHFFFAOYSA-N 0.000 claims 1
- UZHZIVLVBDOIMH-UHFFFAOYSA-N n-benzyltetrazolo[1,5-a]quinolin-5-amine Chemical compound C=1C2=NN=NN2C2=CC=CC=C2C=1NCC1=CC=CC=C1 UZHZIVLVBDOIMH-UHFFFAOYSA-N 0.000 claims 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- MUQTUZBFQDRNNT-UHFFFAOYSA-N tert-butyl n-(8-chlorotetrazolo[1,5-a]quinolin-4-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC2=CC=C(Cl)C=C2N2C1=NN=N2 MUQTUZBFQDRNNT-UHFFFAOYSA-N 0.000 claims 1
- LSNNEKGGOWITEK-UHFFFAOYSA-N tetrazolo[1,5-a]quinoline-4-carboxylic acid Chemical compound OC(=O)C1=CC2=CC=CC=C2N2C1=NN=N2 LSNNEKGGOWITEK-UHFFFAOYSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 4
- 230000005764 inhibitory process Effects 0.000 abstract description 3
- 241000711549 Hepacivirus C Species 0.000 description 32
- 210000004027 cell Anatomy 0.000 description 32
- 238000011282 treatment Methods 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
- 238000002360 preparation method Methods 0.000 description 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 13
- 239000007787 solid Substances 0.000 description 11
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- 208000005176 Hepatitis C Diseases 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 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 9
- 239000000460 chlorine Substances 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 229960000329 ribavirin Drugs 0.000 description 9
- 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 9
- 239000011780 sodium chloride Substances 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 108010050904 Interferons Proteins 0.000 description 8
- 102000014150 Interferons Human genes 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 238000002648 combination therapy Methods 0.000 description 8
- 229940079322 interferon Drugs 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 8
- 238000001308 synthesis method Methods 0.000 description 8
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 7
- 125000000753 cycloalkyl group Chemical group 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 235000019439 ethyl acetate Nutrition 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- JQJASWYVVSAOBN-UHFFFAOYSA-N 2,7-dichloroquinoline-3-carbaldehyde Chemical compound C1=C(C=O)C(Cl)=NC2=CC(Cl)=CC=C21 JQJASWYVVSAOBN-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 241000700605 Viruses Species 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 125000003710 aryl alkyl group Chemical group 0.000 description 6
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 5
- 235000010323 ascorbic acid Nutrition 0.000 description 5
- 239000011668 ascorbic acid Substances 0.000 description 5
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- SOWBFZRMHSNYGE-UHFFFAOYSA-N oxamic acid Chemical compound NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 208000006154 Chronic hepatitis C Diseases 0.000 description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 4
- 108060001084 Luciferase Proteins 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 208000010710 hepatitis C virus infection Diseases 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 208000019423 liver disease Diseases 0.000 description 4
- 125000004043 oxo group Chemical group O=* 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 238000009097 single-agent therapy Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- RDCFTBNMRICBFD-UHFFFAOYSA-N 2,7-dichloroquinoline-3-carboxylic acid Chemical compound C1=C(Cl)C=C2N=C(Cl)C(C(=O)O)=CC2=C1 RDCFTBNMRICBFD-UHFFFAOYSA-N 0.000 description 3
- YAQRBHUDQORYIN-UHFFFAOYSA-N 2-amino-4-(trifluoromethyl)benzaldehyde Chemical compound NC1=CC(C(F)(F)F)=CC=C1C=O YAQRBHUDQORYIN-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 206010016654 Fibrosis Diseases 0.000 description 3
- 101000600434 Homo sapiens Putative uncharacterized protein encoded by MIR7-3HG Proteins 0.000 description 3
- 239000005089 Luciferase Substances 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 102100037401 Putative uncharacterized protein encoded by MIR7-3HG Human genes 0.000 description 3
- 239000013614 RNA sample Substances 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 239000000783 alginic acid Substances 0.000 description 3
- 235000010443 alginic acid Nutrition 0.000 description 3
- 229920000615 alginic acid Polymers 0.000 description 3
- 229960001126 alginic acid Drugs 0.000 description 3
- 150000004781 alginic acids Chemical class 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 3
- 229960005070 ascorbic acid Drugs 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 235000019445 benzyl alcohol Nutrition 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000007882 cirrhosis Effects 0.000 description 3
- 208000019425 cirrhosis of liver Diseases 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 229920001971 elastomer Polymers 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- HXJZXMVUPGVLPB-UHFFFAOYSA-N ethyl 2-chloro-7-(trifluoromethyl)quinoline-3-carboxylate Chemical compound C1=C(C(F)(F)F)C=C2N=C(Cl)C(C(=O)OCC)=CC2=C1 HXJZXMVUPGVLPB-UHFFFAOYSA-N 0.000 description 3
- ZHOABSFECCBWOI-UHFFFAOYSA-N ethyl 6,8-dichloro-2-hydrazinylquinoline-4-carboxylate Chemical compound C1=C(Cl)C=C2C(C(=O)OCC)=CC(NN)=NC2=C1Cl ZHOABSFECCBWOI-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 125000000160 oxazolidinyl group Chemical group 0.000 description 3
- 108010092853 peginterferon alfa-2a Proteins 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- 125000003386 piperidinyl group Chemical group 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 3
- 150000003254 radicals Chemical group 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 2
- PYHXGXCGESYPCW-UHFFFAOYSA-M 2,2-diphenylacetate Chemical compound C=1C=CC=CC=1C(C(=O)[O-])C1=CC=CC=C1 PYHXGXCGESYPCW-UHFFFAOYSA-M 0.000 description 2
- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- ICNCOMYUODLTAI-UHFFFAOYSA-N 2-chloroquinoline-4-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CC(Cl)=NC2=C1 ICNCOMYUODLTAI-UHFFFAOYSA-N 0.000 description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 2
- MFSHNFBQNVGXJX-UHFFFAOYSA-N 2-oxo-1,2-dihydroquinoline-4-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CC(=O)NC2=C1 MFSHNFBQNVGXJX-UHFFFAOYSA-N 0.000 description 2
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- VQDFBYAFHWGFQW-UHFFFAOYSA-N 8-(trifluoromethyl)tetrazolo[1,5-a]quinoline-4-carboxylic acid Chemical compound OC(=O)C1=CC2=CC=C(C(F)(F)F)C=C2N2C1=NN=N2 VQDFBYAFHWGFQW-UHFFFAOYSA-N 0.000 description 2
- FDMSOZNKKLSMAN-UHFFFAOYSA-N 8-chlorotetrazolo[1,5-a]quinoline-4-carboxylic acid Chemical compound OC(=O)C1=CC2=CC=C(Cl)C=C2N2C1=NN=N2 FDMSOZNKKLSMAN-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 206010008909 Chronic Hepatitis Diseases 0.000 description 2
- 206010057573 Chronic hepatic failure Diseases 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 208000010334 End Stage Liver Disease Diseases 0.000 description 2
- 239000001263 FEMA 3042 Substances 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 2
- 102100040018 Interferon alpha-2 Human genes 0.000 description 2
- 108010047761 Interferon-alpha Proteins 0.000 description 2
- 102000006992 Interferon-alpha Human genes 0.000 description 2
- 108010079944 Interferon-alpha2b Proteins 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 229920002230 Pectic acid Polymers 0.000 description 2
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 108010020346 Polyglutamic Acid Proteins 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- BBAWTPDTGRXPDG-UHFFFAOYSA-N [1,3]thiazolo[4,5-b]pyridine Chemical compound C1=CC=C2SC=NC2=N1 BBAWTPDTGRXPDG-UHFFFAOYSA-N 0.000 description 2
- 125000004442 acylamino group Chemical group 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 125000003368 amide group Chemical group 0.000 description 2
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000005140 aralkylsulfonyl group Chemical group 0.000 description 2
- 125000003435 aroyl group Chemical group 0.000 description 2
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 2
- 125000004104 aryloxy group Chemical group 0.000 description 2
- 229940072107 ascorbate Drugs 0.000 description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
- 229940050390 benzoate Drugs 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 229960004365 benzoic acid Drugs 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 2
- 125000005518 carboxamido group Chemical group 0.000 description 2
- 150000007942 carboxylates Chemical class 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 208000011444 chronic liver failure Diseases 0.000 description 2
- 229940114081 cinnamate Drugs 0.000 description 2
- 229940001468 citrate Drugs 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- FJWYVZDPWAPMGN-UHFFFAOYSA-N ethyl quinoline-4-carboxylate Chemical compound C1=CC=C2C(C(=O)OCC)=CC=NC2=C1 FJWYVZDPWAPMGN-UHFFFAOYSA-N 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- LRBQNJMCXXYXIU-QWKBTXIPSA-N gallotannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@H]2[C@@H]([C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-QWKBTXIPSA-N 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 208000006454 hepatitis Diseases 0.000 description 2
- 125000004404 heteroalkyl group Chemical group 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229940049920 malate Drugs 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000001630 malic acid Substances 0.000 description 2
- 235000011090 malic acid Nutrition 0.000 description 2
- 229940099690 malic acid Drugs 0.000 description 2
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical compound C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 2
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 229940126701 oral medication Drugs 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- 229940116315 oxalic acid Drugs 0.000 description 2
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 108010092851 peginterferon alfa-2b Proteins 0.000 description 2
- 239000008024 pharmaceutical diluent Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 229920000728 polyester Polymers 0.000 description 2
- 239000010318 polygalacturonic acid Substances 0.000 description 2
- 229920002643 polyglutamic acid Polymers 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 238000004393 prognosis Methods 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- 229960004889 salicylic acid Drugs 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- PVGBHEUCHKGFQP-UHFFFAOYSA-N sodium;n-[5-amino-2-(4-aminophenyl)sulfonylphenyl]sulfonylacetamide Chemical compound [Na+].CC(=O)NS(=O)(=O)C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=C1 PVGBHEUCHKGFQP-UHFFFAOYSA-N 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 235000015523 tannic acid Nutrition 0.000 description 2
- 229920002258 tannic acid Polymers 0.000 description 2
- 229940033123 tannic acid Drugs 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 229960001367 tartaric acid Drugs 0.000 description 2
- 229940095064 tartrate Drugs 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- VGNCBRNRHXEODV-XXVHXNRLSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-6-dodecoxy-4,7-dihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@H](O)[C@H](C(O2)(C(O)=O)C(O)(C(O1)C(O)=O)C(O)=O)OCCCCCCCCCCCC)C1=CC=CC=C1 VGNCBRNRHXEODV-XXVHXNRLSA-N 0.000 description 1
- 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 1
- 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 1
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
- 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 1
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
- 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 description 1
- 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 description 1
- 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
- BBYWOYAFBUOUFP-JOCHJYFZSA-N 1-stearoyl-sn-glycero-3-phosphoethanolamine zwitterion Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)COP(O)(=O)OCCN BBYWOYAFBUOUFP-JOCHJYFZSA-N 0.000 description 1
- 125000005955 1H-indazolyl group Chemical group 0.000 description 1
- LTMRRSWNXVJMBA-UHFFFAOYSA-N 2,2-diethylpropanedioic acid Chemical compound CCC(CC)(C(O)=O)C(O)=O LTMRRSWNXVJMBA-UHFFFAOYSA-N 0.000 description 1
- RKTYQZQYACRKAC-UHFFFAOYSA-N 2-oxo-7-(trifluoromethyl)-1h-quinoline-3-carboxylic acid Chemical compound C1=C(C(F)(F)F)C=C2NC(=O)C(C(=O)O)=CC2=C1 RKTYQZQYACRKAC-UHFFFAOYSA-N 0.000 description 1
- 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 1
- IKNZBNHVVQIRTO-UHFFFAOYSA-N 2h-tetrazole-5-carboxylic acid Chemical compound OC(=O)C=1N=NNN=1 IKNZBNHVVQIRTO-UHFFFAOYSA-N 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 125000005986 4-piperidonyl group Chemical group 0.000 description 1
- HCJMNOSIAGSZBM-UHFFFAOYSA-N 6-methylsalicylic acid Chemical compound CC1=CC=CC(O)=C1C(O)=O HCJMNOSIAGSZBM-UHFFFAOYSA-N 0.000 description 1
- 206010065051 Acute hepatitis C Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 125000004411 C5-C6 heterocyclyl group Chemical group 0.000 description 1
- 125000000041 C6-C10 aryl group Chemical group 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 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 1
- 239000004593 Epoxy Substances 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 208000037581 Persistent Infection Diseases 0.000 description 1
- QPFYXYFORQJZEC-FOCLMDBBSA-N Phenazopyridine Chemical compound NC1=NC(N)=CC=C1\N=N\C1=CC=CC=C1 QPFYXYFORQJZEC-FOCLMDBBSA-N 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000037621 acute hepatitis C virus infection Diseases 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 125000005115 alkyl carbamoyl group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 125000004659 aryl alkyl thio group Chemical group 0.000 description 1
- 125000001769 aryl amino group Chemical group 0.000 description 1
- 125000005129 aryl carbonyl group Chemical group 0.000 description 1
- 125000005135 aryl sulfinyl group Chemical group 0.000 description 1
- 125000005110 aryl thio group Chemical group 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- UKXSKSHDVLQNKG-UHFFFAOYSA-N benzilic acid Chemical class C=1C=CC=CC=1C(O)(C(=O)O)C1=CC=CC=C1 UKXSKSHDVLQNKG-UHFFFAOYSA-N 0.000 description 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000005512 benztetrazolyl group Chemical group 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 125000004623 carbolinyl group Chemical group 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
- 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 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
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical group [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 1
- SOCTUWSJJQCPFX-UHFFFAOYSA-N dichromate(2-) Chemical compound [O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O SOCTUWSJJQCPFX-UHFFFAOYSA-N 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- VXNZUUAINFGPBY-UHFFFAOYSA-N ethyl ethylene Natural products CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 1
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 235000013861 fat-free Nutrition 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 239000010408 film 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
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000003838 furazanyl group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 125000004475 heteroaralkyl group Chemical group 0.000 description 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
- 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 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 125000004926 indolenyl group Chemical group 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 229910001867 inorganic solvent Inorganic materials 0.000 description 1
- 239000003049 inorganic solvent Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000005438 isoindazolyl group Chemical group 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
- 238000002514 liquid chromatography mass spectrum Methods 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- 238000012317 liver biopsy Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 150000004712 monophosphates Chemical class 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- MUUQHCOAOLLHIL-UHFFFAOYSA-N n-(3-chlorophenyl)acetamide Chemical compound CC(=O)NC1=CC=CC(Cl)=C1 MUUQHCOAOLLHIL-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 125000004930 octahydroisoquinolinyl group Chemical group C1(NCCC2CCCC=C12)* 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 238000011369 optimal treatment Methods 0.000 description 1
- 239000008203 oral pharmaceutical composition Substances 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- QNNHQVPFZIFNFK-UHFFFAOYSA-N oxazolo[4,5-b]pyridine Chemical compound C1=CC=C2OC=NC2=N1 QNNHQVPFZIFNFK-UHFFFAOYSA-N 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229940002988 pegasys Drugs 0.000 description 1
- 229960003930 peginterferon alfa-2a Drugs 0.000 description 1
- 229960003931 peginterferon alfa-2b Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
- 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000005954 phenoxathiinyl group Chemical group 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000004928 piperidonyl group Chemical group 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 125000004591 piperonyl group Chemical group C(C1=CC=2OCOC2C=C1)* 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 229940070891 pyridium Drugs 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 125000000565 sulfonamide group Chemical group 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 125000004963 sulfonylalkyl group Chemical group 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical class OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Gastroenterology & Hepatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US50655603P | 2003-09-26 | 2003-09-26 | |
| US57653604P | 2004-06-03 | 2004-06-03 | |
| PCT/US2004/031705 WO2005030774A1 (en) | 2003-09-26 | 2004-09-27 | Hcv inhibitors and methods of using them |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007506788A true JP2007506788A (ja) | 2007-03-22 |
| JP2007506788A5 JP2007506788A5 (https=) | 2007-10-25 |
Family
ID=34396322
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006528300A Pending JP2007506788A (ja) | 2003-09-26 | 2004-09-27 | Ｈｃｖ感染阻害剤とその使用法 |
Country Status (5)
| Country | Link |
|---|---|
| US (2) | US7358259B2 (https=) |
| EP (1) | EP1668009A1 (https=) |
| JP (1) | JP2007506788A (https=) |
| CA (1) | CA2540021A1 (https=) |
| WO (1) | WO2005030774A1 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014192936A1 (ja) * | 2013-05-31 | 2014-12-04 | 日産化学工業株式会社 | 複素環アミド化合物 |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005121138A2 (en) * | 2004-06-03 | 2005-12-22 | Rigel Pharmaceuticals, Inc. | Heterotricyclic compounds for use as hcv inhibitors |
| JP2009523820A (ja) | 2006-01-23 | 2009-06-25 | アミラ ファーマシューティカルス，インコーポレーテッド | ５−リポキシゲナーゼの三環系抑制剤 |
| CN111285839A (zh) * | 2020-02-26 | 2020-06-16 | 唐美荣 | 一种医药中间体6-氨基胡椒醛的制备方法 |
| PE20251588A1 (es) * | 2022-11-15 | 2025-06-16 | Lilly Co Eli | Agonistas de ahr |
| CN115850240B (zh) * | 2022-12-28 | 2023-09-19 | 北京康立生医药技术开发有限公司 | 一种治疗急性髓系白血病药物奥卢他西尼的合成方法 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4828642A (https=) * | 1971-08-16 | 1973-04-16 | ||
| US4000151A (en) * | 1974-09-11 | 1976-12-28 | The Upjohn Company | Triazolyl benzophenone compounds |
| JPS59176287A (ja) * | 1983-03-25 | 1984-10-05 | メレル・ダウ・フア−マス−テイカルズ・インコ−ポレイテツド | （１Ｈ−テトラゾ−ル−５−イル）テトラゾロ〔１，５−ａ〕−キノリン類と関連化合物 |
| JPH09510968A (ja) * | 1994-03-25 | 1997-11-04 | メリル．フアーマシユウテイカルズ・インコーポレイテツド | （１Ｈ−テトラゾル−５−イル）テトラゾロ〔１，５−ａ〕キノリン類およびナフチリジン類の製造方法 |
| JP2000512995A (ja) * | 1996-06-21 | 2000-10-03 | ミネソタ マイニング アンド マニュファクチャリング カンパニー | イミダゾキノリンアミン調製方法 |
| WO2002028837A1 (en) * | 2000-10-02 | 2002-04-11 | Janssen Pharmaceutica N.V. | Metabotropic glutamate receptor antagonists |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3891653A (en) * | 1970-07-08 | 1975-06-24 | Lilly Co Eli | Substituted 4-5 dehydro-tetrazolo(1,5-a)quinolenes |
| GB1347493A (en) * | 1971-02-11 | 1974-02-27 | Aspro Nicholas Ltd | Benzazine derivatives |
| US3775417A (en) * | 1971-08-05 | 1973-11-27 | Mallinckrodt Chemical Works | Selective hydrogenation of tri-and tetrazoloisoquinolines |
| US4581455A (en) * | 1984-10-10 | 1986-04-08 | Merrell Dow Pharmaceuticals Inc. | Tetrazolothienopyridines |
| DK1140935T3 (da) | 1998-12-23 | 2003-09-01 | Janssen Pharmaceutica Nv | 1,2-anellerede quinolinderivater |
| EP1162196A4 (en) * | 1999-12-27 | 2003-04-16 | Japan Tobacco Inc | COMPOUNDS WITH JOINED CYCLES AND THEIR USE AS MEDICAMENTS |
| JP4974437B2 (ja) * | 2000-09-25 | 2012-07-11 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ファルネシルトランスフェラーゼを阻害する６−［（置換フェニル）メチル］−キノリンおよびキナゾリン誘導体 |
| CA2448737C (en) * | 2001-07-20 | 2010-06-01 | Boehringer Ingelheim (Canada) Ltd. | Viral polymerase inhibitors |
| MY151199A (en) | 2001-11-02 | 2014-04-30 | Rigel Pharmaceuticals Inc | Substituted diphenyl heterocycles useful for treating hcv infection |
| CA2370396A1 (en) | 2002-02-01 | 2003-08-01 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis c inhibitor tri-peptides |
-
2004
- 2004-09-27 JP JP2006528300A patent/JP2007506788A/ja active Pending
- 2004-09-27 EP EP04789112A patent/EP1668009A1/en not_active Withdrawn
- 2004-09-27 WO PCT/US2004/031705 patent/WO2005030774A1/en not_active Ceased
- 2004-09-27 US US10/951,181 patent/US7358259B2/en not_active Expired - Lifetime
- 2004-09-27 CA CA002540021A patent/CA2540021A1/en not_active Abandoned
-
2006
- 2006-12-07 US US11/567,786 patent/US20070149520A1/en not_active Abandoned
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4828642A (https=) * | 1971-08-16 | 1973-04-16 | ||
| US4000151A (en) * | 1974-09-11 | 1976-12-28 | The Upjohn Company | Triazolyl benzophenone compounds |
| JPS59176287A (ja) * | 1983-03-25 | 1984-10-05 | メレル・ダウ・フア−マス−テイカルズ・インコ−ポレイテツド | （１Ｈ−テトラゾ−ル−５−イル）テトラゾロ〔１，５−ａ〕−キノリン類と関連化合物 |
| JPH09510968A (ja) * | 1994-03-25 | 1997-11-04 | メリル．フアーマシユウテイカルズ・インコーポレイテツド | （１Ｈ−テトラゾル−５−イル）テトラゾロ〔１，５−ａ〕キノリン類およびナフチリジン類の製造方法 |
| JP2000512995A (ja) * | 1996-06-21 | 2000-10-03 | ミネソタ マイニング アンド マニュファクチャリング カンパニー | イミダゾキノリンアミン調製方法 |
| WO2002028837A1 (en) * | 2000-10-02 | 2002-04-11 | Janssen Pharmaceutica N.V. | Metabotropic glutamate receptor antagonists |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014192936A1 (ja) * | 2013-05-31 | 2014-12-04 | 日産化学工業株式会社 | 複素環アミド化合物 |
| JPWO2014192936A1 (ja) * | 2013-05-31 | 2017-02-23 | 日産化学工業株式会社 | 複素環アミド化合物 |
| US9708314B2 (en) | 2013-05-31 | 2017-07-18 | Nissan Chemical Industries, Ltd. | Heterocyclic amide compound |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2005030774A1 (en) | 2005-04-07 |
| US7358259B2 (en) | 2008-04-15 |
| EP1668009A1 (en) | 2006-06-14 |
| US20070149520A1 (en) | 2007-06-28 |
| CA2540021A1 (en) | 2005-04-07 |
| US20050090521A1 (en) | 2005-04-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8969373B2 (en) | HCV protease inhibitors | |
| WO2020221006A1 (zh) | 一种bet蛋白抑制剂、其制备方法及用途 | |
| JP2006505571A (ja) | 置換されたインドール及びｈｃｖ阻害剤としてのその使用 | |
| CN102099353A (zh) | 丙型肝炎病毒抑制剂 | |
| JP2003512375A (ja) | Ｈｉｖ逆転写酵素阻害剤としての縮合ナフチリジン | |
| US7569580B2 (en) | Heterotricyclic compounds for use as HCV inhibitors | |
| CN114555607B (zh) | 一类靶向蛋白质水解通路的功能分子及其制备和应用 | |
| CN107056755A (zh) | 五元杂环酰胺类wnt通路抑制剂 | |
| JP2022549923A (ja) | Ｎヘテロ五員環含有カプシドタンパク質集合阻害剤の結晶形及びその使用 | |
| KR20040077735A (ko) | Ｈｉｖ 역전사효소 저해제로서 유용한 트리시클릭2-피리미돈 화합물 | |
| US10266489B2 (en) | Pyrrolic amide compound and preparation method and application thereof | |
| JP2007506788A (ja) | Ｈｃｖ感染阻害剤とその使用法 | |
| JP2007506788A5 (https=) | ||
| CN116444499A (zh) | 一种含4-喹唑啉酮的苯丙氨酸类衍生物及其制备方法与应用 | |
| WO2024040768A1 (zh) | 5-吡啶-1h-吲唑类化合物、药物组合物和应用 | |
| CN115368306B (zh) | 含四氢异喹啉类结构的hdac抑制剂、组合物及其用途 | |
| CN109081818A (zh) | 新型吲哚胺2,3-双加氧化酶抑制剂 | |
| CN117343064B (zh) | 一种具有抗病毒作用的嘧啶衍生物的制备与应用 | |
| CN115322120A (zh) | 一类小分子化合物及在制备治疗dhodh介导疾病药物中的用途 | |
| CN107619392A (zh) | 1h‑吲唑‑4‑醚类化合物及其作为ido抑制剂的用途 | |
| CN107805255B (zh) | 呋喃[3，2-b]吡啶-2(1H)-酮类化合物、制备方法和医药用途 | |
| CN108201539B (zh) | 联苯核苷氨基磷酸酯化合物的应用 | |
| WO2016107541A1 (zh) | 吡咯酰胺类化合物及其制备方法与用途 | |
| CN115197164B (zh) | 新型噻唑类化合物及其制备方法和用途 | |
| CN103694254B (zh) | 含磺酰内酯的丁烯内酯类化合物及其合成方法和用途 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20070906 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20070906 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110127 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20110628 |