CA2916623C - Bicyclic compounds useful for treating diseases caused by retroviruses - Google Patents
Bicyclic compounds useful for treating diseases caused by retroviruses Download PDFInfo
- Publication number
- CA2916623C CA2916623C CA2916623A CA2916623A CA2916623C CA 2916623 C CA2916623 C CA 2916623C CA 2916623 A CA2916623 A CA 2916623A CA 2916623 A CA2916623 A CA 2916623A CA 2916623 C CA2916623 C CA 2916623C
- Authority
- CA
- Canada
- Prior art keywords
- virus
- group
- hydrogen atom
- amine
- mhz
- 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.)
- Active
Links
- 241001430294 unidentified retrovirus Species 0.000 title claims abstract description 178
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 114
- 201000010099 disease Diseases 0.000 title claims abstract description 112
- 125000002619 bicyclic group Chemical group 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 192
- 241000282414 Homo sapiens Species 0.000 claims abstract description 105
- 208000032839 leukemia Diseases 0.000 claims abstract description 101
- 150000003839 salts Chemical class 0.000 claims abstract description 71
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 57
- 206010038997 Retroviral infections Diseases 0.000 claims abstract description 43
- 241000714260 Human T-lymphotropic virus 1 Species 0.000 claims abstract description 32
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 165
- 125000000217 alkyl group Chemical group 0.000 claims description 64
- 125000003545 alkoxy group Chemical group 0.000 claims description 31
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 22
- -1 N-methylpiperazinyl group Chemical group 0.000 claims description 10
- RZAUIOKDXQWSQE-UHFFFAOYSA-N quinolin-7-amine Chemical compound C1=CC=NC2=CC(N)=CC=C21 RZAUIOKDXQWSQE-UHFFFAOYSA-N 0.000 claims description 10
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 7
- TWLGPWZTMALXOR-UHFFFAOYSA-N quinoline-4,7-diamine Chemical compound NC1=CC=NC2=CC(N)=CC=C21 TWLGPWZTMALXOR-UHFFFAOYSA-N 0.000 claims description 5
- PFFGMKJSHDWGGT-UHFFFAOYSA-N 4-methoxy-n-[4-(trifluoromethoxy)phenyl]quinolin-7-amine Chemical compound C=1C=C2C(OC)=CC=NC2=CC=1NC1=CC=C(OC(F)(F)F)C=C1 PFFGMKJSHDWGGT-UHFFFAOYSA-N 0.000 claims description 3
- 241000700605 Viruses Species 0.000 description 129
- 101150041968 CDC13 gene Proteins 0.000 description 122
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 122
- 229910052799 carbon Inorganic materials 0.000 description 78
- 238000005160 1H NMR spectroscopy Methods 0.000 description 77
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 75
- 210000004027 cell Anatomy 0.000 description 61
- 208000015181 infectious disease Diseases 0.000 description 54
- 238000005481 NMR spectroscopy Methods 0.000 description 50
- 125000005843 halogen group Chemical group 0.000 description 49
- 241000714165 Feline leukemia virus Species 0.000 description 48
- 241000714266 Bovine leukemia virus Species 0.000 description 47
- 241000714230 Avian leukemia virus Species 0.000 description 46
- 241000713730 Equine infectious anemia virus Species 0.000 description 46
- 241000713800 Feline immunodeficiency virus Species 0.000 description 46
- 208000006961 tropical spastic paraparesis Diseases 0.000 description 46
- 241000713673 Human foamy virus Species 0.000 description 45
- 241000714177 Murine leukemia virus Species 0.000 description 45
- 241000713756 Caprine arthritis encephalitis virus Species 0.000 description 44
- 241000713821 Mason-Pfizer monkey virus Species 0.000 description 43
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 36
- 241000725303 Human immunodeficiency virus Species 0.000 description 34
- 241000713311 Simian immunodeficiency virus Species 0.000 description 34
- 229910052757 nitrogen Inorganic materials 0.000 description 30
- 239000003795 chemical substances by application Substances 0.000 description 28
- 208000030507 AIDS Diseases 0.000 description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 27
- 241000714474 Rous sarcoma virus Species 0.000 description 26
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 26
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 26
- 206010006187 Breast cancer Diseases 0.000 description 24
- 241000519954 Feline foamy virus Species 0.000 description 24
- 241000288906 Primates Species 0.000 description 24
- 125000003709 fluoroalkyl group Chemical group 0.000 description 24
- 241000713826 Avian leukosis virus Species 0.000 description 23
- 241001529936 Murinae Species 0.000 description 23
- 241000282577 Pan troglodytes Species 0.000 description 23
- 241000713656 Simian foamy virus Species 0.000 description 23
- 206010044696 Tropical spastic paresis Diseases 0.000 description 23
- 208000010094 Visna Diseases 0.000 description 23
- 241000713325 Visna/maedi virus Species 0.000 description 23
- 241001533396 Walleye dermal sarcoma virus Species 0.000 description 23
- 230000001684 chronic effect Effects 0.000 description 23
- 208000023275 Autoimmune disease Diseases 0.000 description 22
- 241001227615 Bovine foamy virus Species 0.000 description 22
- 208000014644 Brain disease Diseases 0.000 description 22
- 201000004624 Dermatitis Diseases 0.000 description 22
- 241000714259 Human T-lymphotropic virus 2 Species 0.000 description 22
- 206010061598 Immunodeficiency Diseases 0.000 description 22
- 208000029462 Immunodeficiency disease Diseases 0.000 description 22
- 208000019693 Lung disease Diseases 0.000 description 22
- 206010025323 Lymphomas Diseases 0.000 description 22
- 241000700564 Rabbit fibroma virus Species 0.000 description 22
- 241001529934 Simian T-lymphotropic virus 3 Species 0.000 description 22
- 206010042971 T-cell lymphoma Diseases 0.000 description 22
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 22
- 206010046851 Uveitis Diseases 0.000 description 22
- 230000001154 acute effect Effects 0.000 description 22
- 230000002489 hematologic effect Effects 0.000 description 22
- 230000007813 immunodeficiency Effects 0.000 description 22
- 230000002757 inflammatory effect Effects 0.000 description 22
- 238000000034 method Methods 0.000 description 22
- 208000005987 polymyositis Diseases 0.000 description 22
- 206010039073 rheumatoid arthritis Diseases 0.000 description 22
- 241000984553 Banana streak virus Species 0.000 description 21
- 208000012902 Nervous system disease Diseases 0.000 description 21
- 206010035664 Pneumonia Diseases 0.000 description 21
- 206010035742 Pneumonitis Diseases 0.000 description 21
- 241000724205 Rice stripe tenuivirus Species 0.000 description 21
- GCMNJUJAKQGROZ-UHFFFAOYSA-N 1,2-Dihydroquinolin-2-imine Chemical compound C1=CC=CC2=NC(N)=CC=C21 GCMNJUJAKQGROZ-UHFFFAOYSA-N 0.000 description 20
- 208000027866 inflammatory disease Diseases 0.000 description 20
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 19
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 19
- 229910052727 yttrium Inorganic materials 0.000 description 17
- 239000000203 mixture Substances 0.000 description 15
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 description 13
- 229910000024 caesium carbonate Inorganic materials 0.000 description 13
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 13
- 238000012512 characterization method Methods 0.000 description 12
- 108090000623 proteins and genes Proteins 0.000 description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 10
- 229910052801 chlorine Inorganic materials 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 8
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 229940095064 tartrate Drugs 0.000 description 8
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 8
- 150000001721 carbon Chemical group 0.000 description 7
- 125000001309 chloro group Chemical group Cl* 0.000 description 7
- 108020004999 messenger RNA Proteins 0.000 description 7
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 108091060211 Expressed sequence tag Proteins 0.000 description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 5
- VAXOCTXTVIVOQE-UHFFFAOYSA-N 2,8-dichloroquinoline Chemical compound C1=CC=C(Cl)C2=NC(Cl)=CC=C21 VAXOCTXTVIVOQE-UHFFFAOYSA-N 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 5
- 241000598436 Human T-cell lymphotropic virus Species 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 125000004093 cyano group Chemical group *C#N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000003623 enhancer Substances 0.000 description 5
- 229910052731 fluorine Inorganic materials 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- SVNCRRZKBNSMIV-UHFFFAOYSA-N 3-Aminoquinoline Chemical compound C1=CC=CC2=CC(N)=CN=C21 SVNCRRZKBNSMIV-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- 241000713666 Lentivirus Species 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 4
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 4
- 229940072107 ascorbate Drugs 0.000 description 4
- 235000010323 ascorbic acid Nutrition 0.000 description 4
- 239000011668 ascorbic acid Substances 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 150000002475 indoles Chemical class 0.000 description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- PVNIIMVLHYAWGP-UHFFFAOYSA-M nicotinate Chemical compound [O-]C(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-M 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 239000003586 protic polar solvent Substances 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- 241000282326 Felis catus Species 0.000 description 3
- 241000713333 Mouse mammary tumor virus Species 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 241000713675 Spumavirus Species 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000009830 intercalation Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- YOWAEZWWQFSEJD-UHFFFAOYSA-N quinoxalin-2-amine Chemical compound C1=CC=CC2=NC(N)=CN=C21 YOWAEZWWQFSEJD-UHFFFAOYSA-N 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 3
- UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 3
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
- GRFNBEZIAWKNCO-UHFFFAOYSA-N 3-pyridinol Chemical compound OC1=CC=CN=C1 GRFNBEZIAWKNCO-UHFFFAOYSA-N 0.000 description 2
- ORLGLBZRQYOWNA-UHFFFAOYSA-N 4-methylpyridin-2-amine Chemical compound CC1=CC=NC(N)=C1 ORLGLBZRQYOWNA-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 241001664176 Alpharetrovirus Species 0.000 description 2
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241001231757 Betaretrovirus Species 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 241001663879 Deltaretrovirus Species 0.000 description 2
- 241001663878 Epsilonretrovirus Species 0.000 description 2
- 108700024394 Exon Proteins 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 241001663880 Gammaretrovirus Species 0.000 description 2
- 206010020460 Human T-cell lymphotropic virus type I infection Diseases 0.000 description 2
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 2
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 208000026350 Inborn Genetic disease Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-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
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 229950011175 aminopicoline Drugs 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000000074 antisense oligonucleotide Substances 0.000 description 2
- 238000012230 antisense oligonucleotides Methods 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000007541 cellular toxicity Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- CTSPAMFJBXKSOY-UHFFFAOYSA-N ellipticine Chemical class N1=CC=C2C(C)=C(NC=3C4=CC=CC=3)C4=C(C)C2=C1 CTSPAMFJBXKSOY-UHFFFAOYSA-N 0.000 description 2
- 206010014599 encephalitis Diseases 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 208000016361 genetic disease Diseases 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 239000000138 intercalating agent Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- 230000001177 retroviral effect Effects 0.000 description 2
- 230000003584 silencer Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 125000004950 trifluoroalkyl group Chemical group 0.000 description 2
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 1
- CBCKQZAAMUWICA-UHFFFAOYSA-N 1,4-phenylenediamine Chemical compound NC1=CC=C(N)C=C1 CBCKQZAAMUWICA-UHFFFAOYSA-N 0.000 description 1
- FXWXPPMZBPDNTC-UHFFFAOYSA-N 2-(quinolin-2-ylamino)pyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC(NC=2N=C3C=CC=CC3=CC=2)=C1 FXWXPPMZBPDNTC-UHFFFAOYSA-N 0.000 description 1
- PLFPWCLLFOJLBI-UHFFFAOYSA-N 2-(quinolin-3-ylamino)pyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC(NC=2C=C3C=CC=CC3=NC=2)=C1 PLFPWCLLFOJLBI-UHFFFAOYSA-N 0.000 description 1
- SXYZJVGUCCEKGQ-UHFFFAOYSA-N 2-[(8-chloroquinolin-2-yl)amino]pyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC(NC=2N=C3C(Cl)=CC=CC3=CC=2)=C1 SXYZJVGUCCEKGQ-UHFFFAOYSA-N 0.000 description 1
- UMYPPRQNLXTIEQ-UHFFFAOYSA-N 2-chloro-3-methylquinoline Chemical compound C1=CC=C2N=C(Cl)C(C)=CC2=C1 UMYPPRQNLXTIEQ-UHFFFAOYSA-N 0.000 description 1
- UUOLETYDNTVQDY-UHFFFAOYSA-N 2-chloro-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CN=C1Cl UUOLETYDNTVQDY-UHFFFAOYSA-N 0.000 description 1
- BYHVGQHIAFURIL-UHFFFAOYSA-N 2-chloroquinoxaline Chemical compound C1=CC=CC2=NC(Cl)=CN=C21 BYHVGQHIAFURIL-UHFFFAOYSA-N 0.000 description 1
- LQYGHYLIGWZTLP-UHFFFAOYSA-N 2-n-(4-methylpyridin-2-yl)quinoline-2,8-diamine Chemical compound CC1=CC=NC(NC=2N=C3C(N)=CC=CC3=CC=2)=C1 LQYGHYLIGWZTLP-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- YRKSELLNQXQCRF-UHFFFAOYSA-N 3-methyl-n-(4-methylpyridin-2-yl)quinolin-2-amine Chemical compound CC1=CC=NC(NC=2C(=CC3=CC=CC=C3N=2)C)=C1 YRKSELLNQXQCRF-UHFFFAOYSA-N 0.000 description 1
- WTXUYUSDSQGBAN-UHFFFAOYSA-N 3-methyl-n-(6-methylpyridin-2-yl)quinolin-2-amine Chemical compound CC1=CC=CC(NC=2C(=CC3=CC=CC=C3N=2)C)=N1 WTXUYUSDSQGBAN-UHFFFAOYSA-N 0.000 description 1
- BFRIMUUKUWOPBW-UHFFFAOYSA-N 3-methyl-n-pyrazin-2-ylquinolin-2-amine Chemical compound CC1=CC2=CC=CC=C2N=C1NC1=CN=CC=N1 BFRIMUUKUWOPBW-UHFFFAOYSA-N 0.000 description 1
- PJKUHBGZFLHCNB-UHFFFAOYSA-N 3-methyl-n-pyridin-2-ylquinolin-2-amine Chemical compound CC1=CC2=CC=CC=C2N=C1NC1=CC=CC=N1 PJKUHBGZFLHCNB-UHFFFAOYSA-N 0.000 description 1
- MPOYBFYHRQBZPM-UHFFFAOYSA-N 3h-pyridin-4-one Chemical group O=C1CC=NC=C1 MPOYBFYHRQBZPM-UHFFFAOYSA-N 0.000 description 1
- XUJFOSLZQITUOI-UHFFFAOYSA-N 4-(trifluoromethoxy)aniline Chemical compound NC1=CC=C(OC(F)(F)F)C=C1 XUJFOSLZQITUOI-UHFFFAOYSA-N 0.000 description 1
- JKWLLRXHEBZOLZ-UHFFFAOYSA-N 4-methoxy-n-(4-methylpyridin-2-yl)quinolin-7-amine Chemical compound C=1C=C2C(OC)=CC=NC2=CC=1NC1=CC(C)=CC=N1 JKWLLRXHEBZOLZ-UHFFFAOYSA-N 0.000 description 1
- GAWOGCFTXVIYQT-UHFFFAOYSA-N 4-methoxy-n-pyridin-2-ylquinolin-7-amine Chemical compound C=1C=C2C(OC)=CC=NC2=CC=1NC1=CC=CC=N1 GAWOGCFTXVIYQT-UHFFFAOYSA-N 0.000 description 1
- KQHZIQRXEWLDJA-UHFFFAOYSA-N 4-methyl-n-(4-methylpyridin-2-yl)quinolin-2-amine Chemical compound CC1=CC=NC(NC=2N=C3C=CC=CC3=C(C)C=2)=C1 KQHZIQRXEWLDJA-UHFFFAOYSA-N 0.000 description 1
- GHJMOXJEERLACS-UHFFFAOYSA-N 4-methyl-n-(5-nitropyridin-2-yl)quinolin-2-amine Chemical compound N=1C2=CC=CC=C2C(C)=CC=1NC1=CC=C([N+]([O-])=O)C=N1 GHJMOXJEERLACS-UHFFFAOYSA-N 0.000 description 1
- BICKHJDFQUBMDX-UHFFFAOYSA-N 4-methyl-n-(6-methylpyridin-2-yl)quinolin-2-amine Chemical compound CC1=CC=CC(NC=2N=C3C=CC=CC3=C(C)C=2)=N1 BICKHJDFQUBMDX-UHFFFAOYSA-N 0.000 description 1
- WZMXBKQUZOMDOY-UHFFFAOYSA-N 4-methyl-n-pyrazin-2-ylquinolin-2-amine Chemical compound N=1C2=CC=CC=C2C(C)=CC=1NC1=CN=CC=N1 WZMXBKQUZOMDOY-UHFFFAOYSA-N 0.000 description 1
- ADHHGODRRRVYSR-UHFFFAOYSA-N 4-methyl-n-pyridin-2-ylquinolin-2-amine Chemical compound N=1C2=CC=CC=C2C(C)=CC=1NC1=CC=CC=N1 ADHHGODRRRVYSR-UHFFFAOYSA-N 0.000 description 1
- PRWOBUDMRAPIGE-UHFFFAOYSA-N 5,8-dimethyl-n-(5-methylpyridin-2-yl)isoquinolin-6-amine Chemical compound N1=CC(C)=CC=C1NC1=CC(C)=C(C=NC=C2)C2=C1C PRWOBUDMRAPIGE-UHFFFAOYSA-N 0.000 description 1
- YJTXQLYMECWULH-UHFFFAOYSA-N 5-fluoropyridin-2-amine Chemical compound NC1=CC=C(F)C=N1 YJTXQLYMECWULH-UHFFFAOYSA-N 0.000 description 1
- LHEPULDUSUAMAY-UHFFFAOYSA-N 6-(quinolin-2-ylamino)pyridine-3-carbonitrile Chemical compound N1=CC(C#N)=CC=C1NC1=CC=C(C=CC=C2)C2=N1 LHEPULDUSUAMAY-UHFFFAOYSA-N 0.000 description 1
- YTYBSSXNNMYTMP-UHFFFAOYSA-N 6-(quinolin-2-ylamino)pyridine-3-carbonitrile;hydrochloride Chemical compound [Cl-].[NH+]1=CC(C#N)=CC=C1NC1=CC=C(C=CC=C2)C2=N1 YTYBSSXNNMYTMP-UHFFFAOYSA-N 0.000 description 1
- YKAUOMYYVJQVGG-UHFFFAOYSA-N 6-(quinoxalin-2-ylamino)pyridine-3-carbonitrile Chemical compound N1=CC(C#N)=CC=C1NC1=CN=C(C=CC=C2)C2=N1 YKAUOMYYVJQVGG-UHFFFAOYSA-N 0.000 description 1
- IBUBFGTWZXLKGA-UHFFFAOYSA-N 6-[(3-methoxypyridin-2-yl)amino]-5,8-dimethyl-2h-isoquinolin-1-one Chemical compound COC1=CC=CN=C1NC1=CC(C)=C2C(=O)NC=CC2=C1C IBUBFGTWZXLKGA-UHFFFAOYSA-N 0.000 description 1
- VZZOWEGAADNEDX-UHFFFAOYSA-N 6-[(3-methylquinolin-2-yl)amino]pyridine-3-carbonitrile Chemical compound CC1=CC2=CC=CC=C2N=C1NC1=CC=C(C#N)C=N1 VZZOWEGAADNEDX-UHFFFAOYSA-N 0.000 description 1
- YZUSLURXWJRRKQ-UHFFFAOYSA-N 6-[(4-methylquinolin-2-yl)amino]pyridine-3-carbonitrile Chemical compound N=1C2=CC=CC=C2C(C)=CC=1NC1=CC=C(C#N)C=N1 YZUSLURXWJRRKQ-UHFFFAOYSA-N 0.000 description 1
- HYQKEYKCHFZSNV-UHFFFAOYSA-N 6-[(8-chloroquinolin-2-yl)amino]-2-methylpyridine-3-carbonitrile Chemical compound C1=C(C#N)C(C)=NC(NC=2N=C3C(Cl)=CC=CC3=CC=2)=C1 HYQKEYKCHFZSNV-UHFFFAOYSA-N 0.000 description 1
- NQUSIBMZMQGZJP-UHFFFAOYSA-N 6-[(8-chloroquinolin-2-yl)amino]pyridine-3-carbonitrile Chemical compound N1=C2C(Cl)=CC=CC2=CC=C1NC1=CC=C(C#N)C=N1 NQUSIBMZMQGZJP-UHFFFAOYSA-N 0.000 description 1
- YGTLRZXTQCCYGE-UHFFFAOYSA-N 6-chloro-n-(4-methylpyridin-2-yl)quinolin-2-amine Chemical compound CC1=CC=NC(NC=2N=C3C=CC(Cl)=CC3=CC=2)=C1 YGTLRZXTQCCYGE-UHFFFAOYSA-N 0.000 description 1
- HPJXFVDJZJVWKH-UHFFFAOYSA-N 6-chloro-n-(4-methylpyridin-2-yl)quinoxalin-2-amine Chemical compound CC1=CC=NC(NC=2N=C3C=CC(Cl)=CC3=NC=2)=C1 HPJXFVDJZJVWKH-UHFFFAOYSA-N 0.000 description 1
- FDBFJLXCAOZZFL-UHFFFAOYSA-N 6-chloro-n-(5-fluoropyridin-2-yl)quinolin-2-amine Chemical compound N1=CC(F)=CC=C1NC1=CC=C(C=C(Cl)C=C2)C2=N1 FDBFJLXCAOZZFL-UHFFFAOYSA-N 0.000 description 1
- CUQCIXHRKSXWOV-UHFFFAOYSA-N 6-chloro-n-(5-methylpyridin-2-yl)quinolin-2-amine Chemical compound N1=CC(C)=CC=C1NC1=CC=C(C=C(Cl)C=C2)C2=N1 CUQCIXHRKSXWOV-UHFFFAOYSA-N 0.000 description 1
- GSBHDTFVSXZRQJ-UHFFFAOYSA-N 6-chloro-n-(6-ethylpyridin-2-yl)quinolin-2-amine Chemical compound CCC1=CC=CC(NC=2N=C3C=CC(Cl)=CC3=CC=2)=N1 GSBHDTFVSXZRQJ-UHFFFAOYSA-N 0.000 description 1
- XTHMFTROJRWDRJ-UHFFFAOYSA-N 6-chloro-n-(6-methylpyridin-2-yl)quinolin-2-amine Chemical compound CC1=CC=CC(NC=2N=C3C=CC(Cl)=CC3=CC=2)=N1 XTHMFTROJRWDRJ-UHFFFAOYSA-N 0.000 description 1
- ABFXUMAJZGUCJM-UHFFFAOYSA-N 6-chloro-n-[4-(trifluoromethoxy)phenyl]quinolin-2-amine Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC1=CC=C(C=C(Cl)C=C2)C2=N1 ABFXUMAJZGUCJM-UHFFFAOYSA-N 0.000 description 1
- FOKFEEOICXUAED-UHFFFAOYSA-N 6-chloro-n-[5-(trifluoromethyl)pyridin-2-yl]quinolin-2-amine Chemical compound N1=CC(C(F)(F)F)=CC=C1NC1=CC=C(C=C(Cl)C=C2)C2=N1 FOKFEEOICXUAED-UHFFFAOYSA-N 0.000 description 1
- ZUSBYXKHPAAGKP-UHFFFAOYSA-N 6-chloro-n-pyrazin-2-ylquinolin-2-amine Chemical compound C1=CC2=CC(Cl)=CC=C2N=C1NC1=CN=CC=N1 ZUSBYXKHPAAGKP-UHFFFAOYSA-N 0.000 description 1
- KLDBYFPTUGYQSF-UHFFFAOYSA-N 8-bromo-n-(4-methylpyridin-2-yl)quinolin-2-amine Chemical compound CC1=CC=NC(NC=2N=C3C(Br)=CC=CC3=CC=2)=C1 KLDBYFPTUGYQSF-UHFFFAOYSA-N 0.000 description 1
- MLMZDTAOJFGGJT-UHFFFAOYSA-N 8-bromo-n-[4-(trifluoromethoxy)phenyl]quinolin-2-amine Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC1=CC=C(C=CC=C2Br)C2=N1 MLMZDTAOJFGGJT-UHFFFAOYSA-N 0.000 description 1
- IYLUIBBHBDWNTE-UHFFFAOYSA-N 8-bromo-n-pyrazin-2-ylquinolin-2-amine Chemical compound N1=C2C(Br)=CC=CC2=CC=C1NC1=CN=CC=N1 IYLUIBBHBDWNTE-UHFFFAOYSA-N 0.000 description 1
- RUURRABBFPPQTD-UHFFFAOYSA-N 8-chloro-n-(3-chloro-4-methoxyphenyl)quinolin-2-amine Chemical compound C1=C(Cl)C(OC)=CC=C1NC1=CC=C(C=CC=C2Cl)C2=N1 RUURRABBFPPQTD-UHFFFAOYSA-N 0.000 description 1
- VXBYNYBZMRMLGW-UHFFFAOYSA-N 8-chloro-n-(3-ethyl-6-methylpyridin-2-yl)quinolin-2-amine Chemical compound CCC1=CC=C(C)N=C1NC1=CC=C(C=CC=C2Cl)C2=N1 VXBYNYBZMRMLGW-UHFFFAOYSA-N 0.000 description 1
- UKMWIGDFVUOYBF-UHFFFAOYSA-N 8-chloro-n-(3-fluorophenyl)quinolin-2-amine Chemical compound FC1=CC=CC(NC=2N=C3C(Cl)=CC=CC3=CC=2)=C1 UKMWIGDFVUOYBF-UHFFFAOYSA-N 0.000 description 1
- FPOCSJDULFADOD-UHFFFAOYSA-N 8-chloro-n-(4,6-dimethylpyridin-2-yl)quinolin-2-amine Chemical compound CC1=CC(C)=NC(NC=2N=C3C(Cl)=CC=CC3=CC=2)=C1 FPOCSJDULFADOD-UHFFFAOYSA-N 0.000 description 1
- SVMQCHZHOIOPBT-UHFFFAOYSA-N 8-chloro-n-(4-chloropyridin-2-yl)quinolin-2-amine Chemical compound ClC1=CC=NC(NC=2N=C3C(Cl)=CC=CC3=CC=2)=C1 SVMQCHZHOIOPBT-UHFFFAOYSA-N 0.000 description 1
- QIIKTTKZMMJAOF-UHFFFAOYSA-N 8-chloro-n-(4-ethylpyridin-2-yl)quinolin-2-amine Chemical compound CCC1=CC=NC(NC=2N=C3C(Cl)=CC=CC3=CC=2)=C1 QIIKTTKZMMJAOF-UHFFFAOYSA-N 0.000 description 1
- ONRLMLQEVUKZKC-UHFFFAOYSA-N 8-chloro-n-(4-methoxyphenyl)quinolin-2-amine Chemical compound C1=CC(OC)=CC=C1NC1=CC=C(C=CC=C2Cl)C2=N1 ONRLMLQEVUKZKC-UHFFFAOYSA-N 0.000 description 1
- VGRDQPQJPXXCSR-UHFFFAOYSA-N 8-chloro-n-(4-methylpyridin-2-yl)quinolin-2-amine;hydrochloride Chemical compound [Cl-].CC1=CC=[NH+]C(NC=2N=C3C(Cl)=CC=CC3=CC=2)=C1 VGRDQPQJPXXCSR-UHFFFAOYSA-N 0.000 description 1
- VVUYNQGZFMNEFR-UHFFFAOYSA-N 8-chloro-n-(5-methylpyridin-2-yl)quinolin-2-amine Chemical compound N1=CC(C)=CC=C1NC1=CC=C(C=CC=C2Cl)C2=N1 VVUYNQGZFMNEFR-UHFFFAOYSA-N 0.000 description 1
- YVQAPMHRGKJEHA-UHFFFAOYSA-N 8-chloro-n-(6-ethylpyridin-2-yl)quinolin-2-amine Chemical compound CCC1=CC=CC(NC=2N=C3C(Cl)=CC=CC3=CC=2)=N1 YVQAPMHRGKJEHA-UHFFFAOYSA-N 0.000 description 1
- CGOGWGRRNFBRTN-UHFFFAOYSA-N 8-chloro-n-(6-methylpyridin-2-yl)quinolin-2-amine Chemical compound CC1=CC=CC(NC=2N=C3C(Cl)=CC=CC3=CC=2)=N1 CGOGWGRRNFBRTN-UHFFFAOYSA-N 0.000 description 1
- QQHGKWJGEQGJGO-UHFFFAOYSA-N 8-chloro-n-[3-(trifluoromethoxy)phenyl]quinolin-2-amine Chemical compound FC(F)(F)OC1=CC=CC(NC=2N=C3C(Cl)=CC=CC3=CC=2)=C1 QQHGKWJGEQGJGO-UHFFFAOYSA-N 0.000 description 1
- OZOGDCZJYVSUBR-UHFFFAOYSA-N 8-chloro-n-[4-(trifluoromethoxy)phenyl]quinolin-2-amine Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC1=CC=C(C=CC=C2Cl)C2=N1 OZOGDCZJYVSUBR-UHFFFAOYSA-N 0.000 description 1
- ZYUBUXKVZUJXAK-UHFFFAOYSA-N 8-chloro-n-[4-(trifluoromethyl)pyridin-2-yl]quinolin-2-amine Chemical compound FC(F)(F)C1=CC=NC(NC=2N=C3C(Cl)=CC=CC3=CC=2)=C1 ZYUBUXKVZUJXAK-UHFFFAOYSA-N 0.000 description 1
- CTJGXKWQWHICPP-UHFFFAOYSA-N 8-chloro-n-[5-(trifluoromethyl)pyridin-2-yl]quinolin-2-amine Chemical compound N1=CC(C(F)(F)F)=CC=C1NC1=CC=C(C=CC=C2Cl)C2=N1 CTJGXKWQWHICPP-UHFFFAOYSA-N 0.000 description 1
- ZCIMXMMWBLMIKS-UHFFFAOYSA-N 8-chloro-n-[6-(trifluoromethyl)pyridin-2-yl]quinolin-2-amine Chemical compound FC(F)(F)C1=CC=CC(NC=2N=C3C(Cl)=CC=CC3=CC=2)=N1 ZCIMXMMWBLMIKS-UHFFFAOYSA-N 0.000 description 1
- WIZXEYUXFXEMET-UHFFFAOYSA-N 8-chloro-n-pyrazin-2-ylquinolin-2-amine Chemical compound N1=C2C(Cl)=CC=CC2=CC=C1NC1=CN=CC=N1 WIZXEYUXFXEMET-UHFFFAOYSA-N 0.000 description 1
- AZUPXAKEVZEVGM-UHFFFAOYSA-N 8-fluoro-n-(4-methylpyridin-2-yl)quinolin-2-amine Chemical compound CC1=CC=NC(NC=2N=C3C(F)=CC=CC3=CC=2)=C1 AZUPXAKEVZEVGM-UHFFFAOYSA-N 0.000 description 1
- JKCVPDYTKRGXRQ-UHFFFAOYSA-N 8-fluoro-n-[4-(trifluoromethoxy)phenyl]quinolin-2-amine Chemical compound N1=C2C(F)=CC=CC2=CC=C1NC1=CC=C(OC(F)(F)F)C=C1 JKCVPDYTKRGXRQ-UHFFFAOYSA-N 0.000 description 1
- TZUPDIOVNPBGBH-UHFFFAOYSA-N 8-methoxy-n-(4-methylpyridin-2-yl)quinolin-2-amine Chemical compound N1=C2C(OC)=CC=CC2=CC=C1NC1=CC(C)=CC=N1 TZUPDIOVNPBGBH-UHFFFAOYSA-N 0.000 description 1
- JIJMLBPEQULHTQ-UHFFFAOYSA-N 8-methyl-n-(4-methylpyridin-2-yl)quinolin-2-amine Chemical compound CC1=CC=NC(NC=2N=C3C(C)=CC=CC3=CC=2)=C1 JIJMLBPEQULHTQ-UHFFFAOYSA-N 0.000 description 1
- PAZITGANORKJQX-UHFFFAOYSA-N 8-methyl-n-[4-(trifluoromethoxy)phenyl]quinolin-2-amine Chemical compound N1=C2C(C)=CC=CC2=CC=C1NC1=CC=C(OC(F)(F)F)C=C1 PAZITGANORKJQX-UHFFFAOYSA-N 0.000 description 1
- DUVUANQFUWEQTA-UHFFFAOYSA-N 8-methyl-n-pyrazin-2-ylquinolin-2-amine Chemical compound N1=C2C(C)=CC=CC2=CC=C1NC1=CN=CC=N1 DUVUANQFUWEQTA-UHFFFAOYSA-N 0.000 description 1
- 208000016683 Adult T-cell leukemia/lymphoma Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 238000009010 Bradford assay Methods 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 241000709691 Enterovirus E Species 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 108091027974 Mature messenger RNA Proteins 0.000 description 1
- 206010028570 Myelopathy Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 101710149951 Protein Tat Proteins 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102000004243 Tubulin Human genes 0.000 description 1
- 108090000704 Tubulin Proteins 0.000 description 1
- FJWIHTNNFSITSP-UHFFFAOYSA-N [2-(quinoxalin-2-ylamino)pyridin-4-yl]methanol Chemical compound OCC1=CC=NC(NC=2N=C3C=CC=CC3=NC=2)=C1 FJWIHTNNFSITSP-UHFFFAOYSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 239000000370 acceptor Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 201000006966 adult T-cell leukemia Diseases 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000005859 coupling reaction Methods 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
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 230000002122 leukaemogenic effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 208000037819 metastatic cancer Diseases 0.000 description 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
- RNMAOVZACIEZRY-UHFFFAOYSA-N methyl 6-(quinolin-2-ylamino)pyridine-3-carboxylate Chemical compound N1=CC(C(=O)OC)=CC=C1NC1=CC=C(C=CC=C2)C2=N1 RNMAOVZACIEZRY-UHFFFAOYSA-N 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- CUOAGPLCYXTZFB-UHFFFAOYSA-N n-(3,5-dichloro-4-methylpyridin-2-yl)quinoxalin-2-amine Chemical compound CC1=C(Cl)C=NC(NC=2N=C3C=CC=CC3=NC=2)=C1Cl CUOAGPLCYXTZFB-UHFFFAOYSA-N 0.000 description 1
- JSKBVMQTOGGRCE-UHFFFAOYSA-N n-(3-fluorophenyl)quinolin-2-amine Chemical compound FC1=CC=CC(NC=2N=C3C=CC=CC3=CC=2)=C1 JSKBVMQTOGGRCE-UHFFFAOYSA-N 0.000 description 1
- MXQIQAXLTPMUGA-UHFFFAOYSA-N n-(3-methoxypyridin-2-yl)quinolin-6-amine Chemical compound COC1=CC=CN=C1NC1=CC=C(N=CC=C2)C2=C1 MXQIQAXLTPMUGA-UHFFFAOYSA-N 0.000 description 1
- KBXOKJZDVJGBFH-UHFFFAOYSA-N n-(3-nitropyridin-2-yl)quinolin-2-amine Chemical compound [O-][N+](=O)C1=CC=CN=C1NC1=CC=C(C=CC=C2)C2=N1 KBXOKJZDVJGBFH-UHFFFAOYSA-N 0.000 description 1
- XXDPXWRBTKQMSI-UHFFFAOYSA-N n-(3-nitropyridin-2-yl)quinolin-3-amine Chemical compound [O-][N+](=O)C1=CC=CN=C1NC1=CN=C(C=CC=C2)C2=C1 XXDPXWRBTKQMSI-UHFFFAOYSA-N 0.000 description 1
- JZVGQBIINWZGJR-UHFFFAOYSA-N n-(4,6-dimethylpyridin-2-yl)quinoxalin-2-amine Chemical compound CC1=CC(C)=NC(NC=2N=C3C=CC=CC3=NC=2)=C1 JZVGQBIINWZGJR-UHFFFAOYSA-N 0.000 description 1
- JNSCAEPZOZUIHU-UHFFFAOYSA-N n-(4-ethylpyridin-2-yl)quinoxalin-2-amine Chemical compound CCC1=CC=NC(NC=2N=C3C=CC=CC3=NC=2)=C1 JNSCAEPZOZUIHU-UHFFFAOYSA-N 0.000 description 1
- GQACZYQLUYMKPJ-UHFFFAOYSA-N n-(4-methoxyphenyl)quinolin-2-amine Chemical compound C1=CC(OC)=CC=C1NC1=CC=C(C=CC=C2)C2=N1 GQACZYQLUYMKPJ-UHFFFAOYSA-N 0.000 description 1
- GSRHJQVZZBVVNF-UHFFFAOYSA-N n-(4-methoxyphenyl)quinolin-3-amine Chemical compound C1=CC(OC)=CC=C1NC1=CN=C(C=CC=C2)C2=C1 GSRHJQVZZBVVNF-UHFFFAOYSA-N 0.000 description 1
- FZVLZGBHFVRNLB-UHFFFAOYSA-N n-(4-methyl-5-nitropyridin-2-yl)quinoxalin-2-amine Chemical compound C1=C([N+]([O-])=O)C(C)=CC(NC=2N=C3C=CC=CC3=NC=2)=N1 FZVLZGBHFVRNLB-UHFFFAOYSA-N 0.000 description 1
- BSHNAVOQNSIGLC-UHFFFAOYSA-N n-(4-methylpyridin-2-yl)quinoxalin-2-amine Chemical compound CC1=CC=NC(NC=2N=C3C=CC=CC3=NC=2)=C1 BSHNAVOQNSIGLC-UHFFFAOYSA-N 0.000 description 1
- HMSBPHQTMVDQHH-UHFFFAOYSA-N n-(4-nitrophenyl)quinolin-2-amine Chemical compound C1=CC([N+](=O)[O-])=CC=C1NC1=CC=C(C=CC=C2)C2=N1 HMSBPHQTMVDQHH-UHFFFAOYSA-N 0.000 description 1
- DFNDJRRFQJXVJE-UHFFFAOYSA-N n-(4-phenoxyphenyl)quinolin-2-amine Chemical compound C=1C=C2C=CC=CC2=NC=1NC(C=C1)=CC=C1OC1=CC=CC=C1 DFNDJRRFQJXVJE-UHFFFAOYSA-N 0.000 description 1
- BLOLQFVGPGAZBB-UHFFFAOYSA-N n-(5-bromo-4-methylpyridin-2-yl)quinoxalin-2-amine Chemical compound C1=C(Br)C(C)=CC(NC=2N=C3C=CC=CC3=NC=2)=N1 BLOLQFVGPGAZBB-UHFFFAOYSA-N 0.000 description 1
- VAQHPHVXGHQBEP-UHFFFAOYSA-N n-(5-fluoropyridin-2-yl)quinolin-2-amine Chemical compound N1=CC(F)=CC=C1NC1=CC=C(C=CC=C2)C2=N1 VAQHPHVXGHQBEP-UHFFFAOYSA-N 0.000 description 1
- TZRNPIATCDHHCP-UHFFFAOYSA-N n-(5-methylpyridin-2-yl)quinolin-2-amine Chemical compound N1=CC(C)=CC=C1NC1=CC=C(C=CC=C2)C2=N1 TZRNPIATCDHHCP-UHFFFAOYSA-N 0.000 description 1
- UIARFWFFSUIOQX-UHFFFAOYSA-N n-(5-methylpyridin-2-yl)quinolin-6-amine Chemical compound N1=CC(C)=CC=C1NC1=CC=C(N=CC=C2)C2=C1 UIARFWFFSUIOQX-UHFFFAOYSA-N 0.000 description 1
- URFTWAYRGCNQTE-UHFFFAOYSA-N n-(5-nitropyridin-2-yl)quinolin-2-amine Chemical compound N1=CC([N+](=O)[O-])=CC=C1NC1=CC=C(C=CC=C2)C2=N1 URFTWAYRGCNQTE-UHFFFAOYSA-N 0.000 description 1
- ZTKSVFASFFNDNT-UHFFFAOYSA-N n-(6-methylpyridin-2-yl)quinolin-2-amine Chemical compound CC1=CC=CC(NC=2N=C3C=CC=CC3=CC=2)=N1 ZTKSVFASFFNDNT-UHFFFAOYSA-N 0.000 description 1
- PKWLZRUXTBCYEG-UHFFFAOYSA-N n-(6-methylpyridin-2-yl)quinolin-3-amine Chemical compound CC1=CC=CC(NC=2C=C3C=CC=CC3=NC=2)=N1 PKWLZRUXTBCYEG-UHFFFAOYSA-N 0.000 description 1
- RCLQZXYDLVWBFO-UHFFFAOYSA-N n-(6-methylpyridin-2-yl)quinoxalin-2-amine Chemical compound CC1=CC=CC(NC=2N=C3C=CC=CC3=NC=2)=N1 RCLQZXYDLVWBFO-UHFFFAOYSA-N 0.000 description 1
- NOFXAEONSDUIOM-UHFFFAOYSA-N n-[2-(trifluoromethoxy)phenyl]quinolin-2-amine Chemical compound FC(F)(F)OC1=CC=CC=C1NC1=CC=C(C=CC=C2)C2=N1 NOFXAEONSDUIOM-UHFFFAOYSA-N 0.000 description 1
- DIHJTBLMXALNBS-UHFFFAOYSA-N n-[2-(trifluoromethoxy)phenyl]quinoxalin-2-amine Chemical compound FC(F)(F)OC1=CC=CC=C1NC1=CN=C(C=CC=C2)C2=N1 DIHJTBLMXALNBS-UHFFFAOYSA-N 0.000 description 1
- NVOIOZMCFMHTMV-UHFFFAOYSA-N n-[3-(trifluoromethoxy)phenyl]quinolin-2-amine Chemical compound FC(F)(F)OC1=CC=CC(NC=2N=C3C=CC=CC3=CC=2)=C1 NVOIOZMCFMHTMV-UHFFFAOYSA-N 0.000 description 1
- BXOAUNVKKPBHQR-UHFFFAOYSA-N n-[3-(trifluoromethoxy)phenyl]quinoxalin-2-amine Chemical compound FC(F)(F)OC1=CC=CC(NC=2N=C3C=CC=CC3=NC=2)=C1 BXOAUNVKKPBHQR-UHFFFAOYSA-N 0.000 description 1
- IFKURQMAQPEGBY-UHFFFAOYSA-N n-[4-(trifluoromethoxy)phenyl]quinolin-3-amine Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC1=CN=C(C=CC=C2)C2=C1 IFKURQMAQPEGBY-UHFFFAOYSA-N 0.000 description 1
- KYQIWVOWNUXADS-UHFFFAOYSA-N n-[4-(trifluoromethoxy)phenyl]quinoxalin-2-amine Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC1=CN=C(C=CC=C2)C2=N1 KYQIWVOWNUXADS-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- UQECIBDLOFNABS-UHFFFAOYSA-N n-pyrazin-2-ylquinolin-2-amine Chemical compound C=1C=C2C=CC=CC2=NC=1NC1=CN=CC=N1 UQECIBDLOFNABS-UHFFFAOYSA-N 0.000 description 1
- YQZNQAOPVNOFQW-UHFFFAOYSA-N n-pyridin-2-ylquinolin-3-amine Chemical compound C=1N=C2C=CC=CC2=CC=1NC1=CC=CC=N1 YQZNQAOPVNOFQW-UHFFFAOYSA-N 0.000 description 1
- YYFITUYWFOTKBO-UHFFFAOYSA-N n-pyridin-4-ylquinolin-3-amine Chemical compound C=1N=C2C=CC=CC2=CC=1NC1=CC=NC=C1 YYFITUYWFOTKBO-UHFFFAOYSA-N 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 229940125268 obefazimod Drugs 0.000 description 1
- 229940099990 ogen Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
- 125000005009 perfluoropropyl group Chemical group FC(C(C(F)(F)F)(F)F)(F)* 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- XFTQRUTUGRCSGO-UHFFFAOYSA-N pyrazin-2-amine Chemical compound NC1=CN=CC=N1 XFTQRUTUGRCSGO-UHFFFAOYSA-N 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- RJSRSRITMWVIQT-UHFFFAOYSA-N quinolin-6-amine Chemical compound N1=CC=CC2=CC(N)=CC=C21 RJSRSRITMWVIQT-UHFFFAOYSA-N 0.000 description 1
- 230000014493 regulation of gene expression Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007886 soft shell capsule Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- 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
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Virology (AREA)
- Immunology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Neurology (AREA)
- Hematology (AREA)
- Molecular Biology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Pulmonology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361843155P | 2013-07-05 | 2013-07-05 | |
| US61/843,155 | 2013-07-05 | ||
| PCT/IB2014/062849 WO2015001518A1 (en) | 2013-07-05 | 2014-07-04 | Bicyclic compounds useful for treating diseases caused by retroviruses |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2916623A1 CA2916623A1 (en) | 2015-01-08 |
| CA2916623C true CA2916623C (en) | 2021-09-14 |
Family
ID=51453778
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2916623A Active CA2916623C (en) | 2013-07-05 | 2014-07-04 | Bicyclic compounds useful for treating diseases caused by retroviruses |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US9827237B2 (OSRAM) |
| EP (1) | EP3016656B1 (OSRAM) |
| JP (2) | JP6895251B2 (OSRAM) |
| KR (1) | KR102326068B1 (OSRAM) |
| CN (1) | CN105530938B (OSRAM) |
| AU (1) | AU2014285733B2 (OSRAM) |
| BR (1) | BR112016000127B1 (OSRAM) |
| CA (1) | CA2916623C (OSRAM) |
| ES (1) | ES2898385T3 (OSRAM) |
| HR (1) | HRP20211839T1 (OSRAM) |
| MX (1) | MX382692B (OSRAM) |
| PL (1) | PL3016656T3 (OSRAM) |
| PT (1) | PT3016656T (OSRAM) |
| RU (1) | RU2681943C9 (OSRAM) |
| WO (1) | WO2015001518A1 (OSRAM) |
| ZA (1) | ZA201600317B (OSRAM) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2974729A1 (en) | 2014-07-17 | 2016-01-20 | Abivax | Quinoline derivatives for use in the treatment of inflammatory diseases |
| EP3059591A1 (en) * | 2015-02-23 | 2016-08-24 | Abivax | Methods for screening compounds for treating or preventing a viral infection or a virus-related condition |
| EP3059236A1 (en) * | 2015-02-23 | 2016-08-24 | Abivax | A new quinoline derivative for use in the treatment and prevention of viral infections |
| EP3058940A1 (en) * | 2015-02-23 | 2016-08-24 | Abivax | Quinoline derivatives for use in the treatment or prevention of viral infection |
| KR20170109160A (ko) | 2016-03-18 | 2017-09-28 | 현대자동차주식회사 | 엔진마운트의 체결구조 |
| EP3484528B1 (en) | 2016-07-18 | 2020-11-25 | Janssen Pharmaceutica NV | Tau pet imaging ligands |
| EP3594206A1 (en) * | 2018-07-09 | 2020-01-15 | Abivax | Phenyl-n-quinoline derivatives for treating a rna virus infection |
| EP3594205A1 (en) * | 2018-07-09 | 2020-01-15 | Abivax | Phenyl-n-aryl derivatives for treating a rna virus infection |
| EP3669873A1 (en) | 2018-12-20 | 2020-06-24 | Abivax | Quinoline derivatives for use ine the traeatment of inflammation diseases |
| EP3848356A1 (en) * | 2020-01-07 | 2021-07-14 | Abivax | Aryl-n-aryl derivatives for treating a rna virus infection |
| US11691971B2 (en) | 2020-06-19 | 2023-07-04 | Incyte Corporation | Naphthyridinone compounds as JAK2 V617F inhibitors |
| US11753413B2 (en) | 2020-06-19 | 2023-09-12 | Incyte Corporation | Substituted pyrrolo[2,1-f][1,2,4]triazine compounds as JAK2 V617F inhibitors |
| RS66978B1 (sr) | 2020-07-02 | 2025-07-31 | Incyte Corp | Triciklična jedinjenja uree kao inhibitori jak2 v617f |
| WO2022006456A1 (en) | 2020-07-02 | 2022-01-06 | Incyte Corporation | Tricyclic pyridone compounds as jak2 v617f inhibitors |
| US11661422B2 (en) | 2020-08-27 | 2023-05-30 | Incyte Corporation | Tricyclic urea compounds as JAK2 V617F inhibitors |
| TW202237119A (zh) | 2020-12-10 | 2022-10-01 | 美商住友製藥腫瘤公司 | Ａｌｋ﹘５抑制劑和彼之用途 |
| US11919908B2 (en) | 2020-12-21 | 2024-03-05 | Incyte Corporation | Substituted pyrrolo[2,3-d]pyrimidine compounds as JAK2 V617F inhibitors |
| WO2022182839A1 (en) | 2021-02-25 | 2022-09-01 | Incyte Corporation | Spirocyclic lactams as jak2 v617f inhibitors |
| JP2024519993A (ja) | 2021-05-27 | 2024-05-21 | 江▲蘇▼恒瑞医▲薬▼股▲フン▼有限公司 | キノリンアミン系化合物、その調製方法及びその医薬的応用 |
| KR20240163688A (ko) | 2022-03-17 | 2024-11-19 | 인사이트 코포레이션 | Jak2 v617f 억제제로서의 삼환계 우레아 화합물 |
| CN116120282B (zh) * | 2022-08-04 | 2024-02-20 | 苏州系统医学研究所 | 具有ev71和/或cva16病毒抑制活性的化合物及其应用 |
| KR20250112264A (ko) | 2022-11-25 | 2025-07-23 | 지앙수 헨그루이 파마슈티컬스 컴퍼니 리미티드 | 퀴놀린아민계 화합물의 결정형 및 이의 제조 방법 |
| CN118373771A (zh) | 2023-01-20 | 2024-07-23 | 江苏柯菲平医药股份有限公司 | 一种喹啉衍生化合物或其可药用的盐及其制备方法和应用 |
| WO2025045123A1 (zh) * | 2023-08-30 | 2025-03-06 | 江苏正大丰海制药有限公司 | 用于调节微小rna-124活性的化合物 |
Family Cites Families (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB585362A (en) | 1944-08-31 | 1947-02-05 | Francis Henry Swinden Curd | New heterocyclic compounds |
| BE486034A (OSRAM) | 1947-11-28 | |||
| DE958647C (de) | 1952-12-28 | 1957-02-21 | Hoechst Ag | Verfahren zur Herstellung von 7-Amino-2-oxy-4-methyl-chinolinen |
| FR2387229A1 (fr) | 1977-04-13 | 1978-11-10 | Anvar | Dipyrido (4,3-b) (3,4-f) indoles, procede d'obtention, application therapeutique et compositions pharmaceutiques les contenant |
| FR2436786A1 (fr) | 1978-09-21 | 1980-04-18 | Anvar | Nouveaux derives des pyrido (4,3-b) carbazoles (ellipticines), substitues en position 1 par une chaine polyaminee, leur obtention et leur application a titre de medicaments |
| FR2627493B1 (fr) | 1988-02-23 | 1991-10-31 | Sanofi Sa | Procede de preparation de derives d'isoquinoleine |
| FR2645861A1 (fr) | 1989-04-17 | 1990-10-19 | Inst Nat Sante Rech Med | Utilisation de dipyrido (4,3-b) (3,4-f) indoles pour la preparation de medicaments utiles pour le traitement du sida |
| US6177401B1 (en) | 1992-11-13 | 2001-01-23 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften | Use of organic compounds for the inhibition of Flk-1 mediated vasculogenesis and angiogenesis |
| DE60008509T2 (de) | 1999-04-05 | 2004-12-16 | City Of Hope, Duarte | Neue Hemmer von fortgeschrittenen Glykosilierungsendprodukten (AGEs) |
| UA75055C2 (uk) | 1999-11-30 | 2006-03-15 | Пфайзер Продактс Інк. | Похідні бензоімідазолу, що використовуються як антипроліферативний засіб, фармацевтична композиція на їх основі |
| DE10013318A1 (de) | 2000-03-17 | 2001-09-20 | Merck Patent Gmbh | Formulierung enthaltend Chinoxalinderivate |
| JP4223287B2 (ja) | 2001-01-22 | 2009-02-12 | メモリー・ファーマスーティカルズ・コーポレーション | 新規な化合物及び製薬上許容し得るそれらの塩並びにそれらを用いた薬剤組成物 |
| PL375552A1 (en) | 2002-05-22 | 2005-11-28 | Amgen Inc. | Vanilloid receptor ligands and their medical applications |
| AU2002950217A0 (en) | 2002-07-16 | 2002-09-12 | Prana Biotechnology Limited | 8- Hydroxy Quinoline Derivatives |
| US7405230B2 (en) | 2002-07-19 | 2008-07-29 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors, including N-substituted aniline and diphenylamine analogs |
| FR2849474B3 (fr) | 2002-12-27 | 2004-12-03 | Olivier Jean Noel Juin | Installation de transformation de l'energie cinetique d'un fluide en energie electrique |
| WO2004078731A1 (en) | 2003-03-06 | 2004-09-16 | 'chemical Diversity Research Institute', Ltd. | Quinoline-carboxylic acids and the derivatives thereof, a focused library |
| FR2859475A1 (fr) | 2003-09-04 | 2005-03-11 | Centre Nat Rech Scient | Utilisation de composes derives d'ellipticine et d'aza-ellipticine pour la preparation d'un medicament utile pour le traitement de maladies genetiques resultant de l'alteration des processus d'epissage |
| FR2859474B1 (fr) | 2003-09-04 | 2006-01-13 | Centre Nat Rech Scient | Utilisation de composes derives d'indole pour la preparation d'un medicament utile pour le traitement de maladies genetiques resultant de l'alteration des processus d'epissage |
| BRPI0416692A (pt) | 2003-11-19 | 2007-01-30 | Array Biopharma Inc | inibidores heterocìclicos de mek e métodos de emprego destes |
| EP1853265B1 (en) | 2005-01-28 | 2016-01-27 | The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services | Farnesyltransferase inhibitors for use in the treatment of laminopathies, cellular aging and atherosclerosis |
| FR2903312B1 (fr) | 2006-07-05 | 2008-09-26 | Univ Aix Marseille Ii | Utilisation d'inhibiteurs d'hmg-coa reductase et de farnesyl-pyrophosphate synthase dans la preparation d'un medicament |
| WO2008008234A1 (en) | 2006-07-07 | 2008-01-17 | Targegen, Inc. | 2-amino-5-substituted pyrimidine inhibitors |
| EA200900959A1 (ru) | 2007-01-19 | 2010-02-26 | Арди Байосайенсиз, Инк. | Ингибиторы мек |
| FR2912745A1 (fr) | 2007-02-19 | 2008-08-22 | Centre Nat Rech Scient | Nouveaux composes derives d'indole et compositions pharmaceutiques les contenant |
| CA2681481A1 (en) | 2007-03-16 | 2008-09-25 | Mount Sinai School Of Medicine | Induction and/or maintenance of tumor dormancy by disruption of urokinase plasminogen activator receptor-integrin interaction |
| DE112008001206B4 (de) | 2007-05-17 | 2019-01-31 | Lg Chem. Ltd. | Neue Anthrazen-Derivate und organische elektronische Vorrichtung, die diese verwendet |
| EP2184990A4 (en) | 2007-08-15 | 2011-10-19 | Memory Pharm Corp | 3'-SUBSTITUTED COMPOUNDS WITH 5-HT6 RECEPTOR AFFINITY |
| WO2009029617A1 (en) | 2007-08-27 | 2009-03-05 | Kalypsys, Inc. | Diarylamine-substituted quinolones useful as inducible nitric oxide synthase inhibitors |
| FR2926297B1 (fr) | 2008-01-10 | 2013-03-08 | Centre Nat Rech Scient | Molecules chimiques inhibitrices du mecanisme d'epissage pour traiter des maladies resultant d'anomalies d'epissage. |
| EP2266972A1 (en) * | 2009-06-12 | 2010-12-29 | Splicos | New chemical molecules that inhibit the splicing mechanism for treating diseases resulting from splicing anomalies |
| KR20120051643A (ko) * | 2009-06-12 | 2012-05-22 | 쏘시에떼 스플리코 | 조기 노화, 구체적으로 조로증을 치료하는데 유용한 화합물 |
| US8962583B2 (en) | 2009-06-25 | 2015-02-24 | The Brigham And Women's Hospital, Inc. | Treatment of inflammatory diseases using miR-124 |
| EP2465502A1 (en) * | 2010-12-15 | 2012-06-20 | Société Splicos | Compounds useful for treating AIDS |
| JP2016504268A (ja) * | 2012-10-04 | 2016-02-12 | オヤジェン インコーポレイテッドＯｙａＧｅｎ， Ｉｎｃ． | Ｖｉｆの自己会合を撹乱する抗ｈｉｖ剤としての小分子及びその使用方法 |
| EP2757161A1 (en) * | 2013-01-17 | 2014-07-23 | Splicos | miRNA-124 as a biomarker of viral infection |
-
2014
- 2014-07-04 JP JP2016522952A patent/JP6895251B2/ja active Active
- 2014-07-04 BR BR112016000127-3A patent/BR112016000127B1/pt active IP Right Grant
- 2014-07-04 PT PT147581680T patent/PT3016656T/pt unknown
- 2014-07-04 RU RU2016103217A patent/RU2681943C9/ru active
- 2014-07-04 KR KR1020167003323A patent/KR102326068B1/ko active Active
- 2014-07-04 WO PCT/IB2014/062849 patent/WO2015001518A1/en not_active Ceased
- 2014-07-04 ES ES14758168T patent/ES2898385T3/es active Active
- 2014-07-04 CN CN201480038497.4A patent/CN105530938B/zh active Active
- 2014-07-04 AU AU2014285733A patent/AU2014285733B2/en active Active
- 2014-07-04 MX MX2015017599A patent/MX382692B/es unknown
- 2014-07-04 US US14/902,935 patent/US9827237B2/en active Active
- 2014-07-04 HR HRP20211839TT patent/HRP20211839T1/hr unknown
- 2014-07-04 CA CA2916623A patent/CA2916623C/en active Active
- 2014-07-04 PL PL14758168T patent/PL3016656T3/pl unknown
- 2014-07-04 EP EP14758168.0A patent/EP3016656B1/en active Active
-
2016
- 2016-01-14 ZA ZA2016/00317A patent/ZA201600317B/en unknown
-
2019
- 2019-04-26 JP JP2019086240A patent/JP2019142946A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| HK1217447A1 (zh) | 2017-01-13 |
| PL3016656T3 (pl) | 2022-02-21 |
| CA2916623A1 (en) | 2015-01-08 |
| WO2015001518A1 (en) | 2015-01-08 |
| RU2681943C9 (ru) | 2019-05-16 |
| AU2014285733A1 (en) | 2016-01-21 |
| JP2016523893A (ja) | 2016-08-12 |
| JP2019142946A (ja) | 2019-08-29 |
| HRP20211839T1 (hr) | 2022-03-04 |
| KR20160032724A (ko) | 2016-03-24 |
| US20160151348A1 (en) | 2016-06-02 |
| CN105530938B (zh) | 2019-10-22 |
| RU2016103217A (ru) | 2017-08-10 |
| AU2014285733B2 (en) | 2019-05-16 |
| EP3016656A1 (en) | 2016-05-11 |
| ZA201600317B (en) | 2018-07-25 |
| MX382692B (es) | 2025-03-13 |
| EP3016656B1 (en) | 2021-09-08 |
| CN105530938A (zh) | 2016-04-27 |
| BR112016000127A8 (pt) | 2018-01-23 |
| ES2898385T3 (es) | 2022-03-07 |
| MX2015017599A (es) | 2016-04-07 |
| PT3016656T (pt) | 2021-11-26 |
| RU2681943C2 (ru) | 2019-03-14 |
| KR102326068B1 (ko) | 2021-11-11 |
| US9827237B2 (en) | 2017-11-28 |
| BR112016000127B1 (pt) | 2022-02-15 |
| JP6895251B2 (ja) | 2021-06-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2916623C (en) | Bicyclic compounds useful for treating diseases caused by retroviruses | |
| JP7042245B2 (ja) | Ａｉｄｓを治療する為に有用な化合物 | |
| JP6049630B2 (ja) | Ａｉｄｓを処置する為に有用な化合物 | |
| JP6606577B2 (ja) | Ａｉｄｓを治療する為に有用な化合物 | |
| HK40086860A (en) | Preparation of compounds useful for treating aids | |
| HK1217447B (zh) | 用於治疗由逆转录病毒引起的疾病的化合物 | |
| RU2575845C2 (ru) | Соединения, пригодные для лечения спида |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20190510 |