AU2012325971B2 - Compounds and methods for enhancing innate immune responses - Google Patents
Compounds and methods for enhancing innate immune responses Download PDFInfo
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- AU2012325971B2 AU2012325971B2 AU2012325971A AU2012325971A AU2012325971B2 AU 2012325971 B2 AU2012325971 B2 AU 2012325971B2 AU 2012325971 A AU2012325971 A AU 2012325971A AU 2012325971 A AU2012325971 A AU 2012325971A AU 2012325971 B2 AU2012325971 B2 AU 2012325971B2
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- Australia
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- trifluoromethyl
- hydrogen
- imidazo
- methyl
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 235
- 238000000034 method Methods 0.000 title claims abstract description 74
- 230000002708 enhancing effect Effects 0.000 title description 11
- 230000015788 innate immune response Effects 0.000 title description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 93
- 208000036142 Viral infection Diseases 0.000 claims abstract description 81
- 230000009385 viral infection Effects 0.000 claims abstract description 81
- 229910052739 hydrogen Inorganic materials 0.000 claims description 382
- 239000001257 hydrogen Substances 0.000 claims description 382
- -1 -R 12 Chemical group 0.000 claims description 249
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 231
- 150000002431 hydrogen Chemical class 0.000 claims description 204
- 150000002825 nitriles Chemical class 0.000 claims description 203
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 193
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 192
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 185
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 164
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 164
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 149
- 125000001153 fluoro group Chemical group F* 0.000 claims description 147
- 125000001246 bromo group Chemical group Br* 0.000 claims description 146
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 124
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 124
- 229910052757 nitrogen Inorganic materials 0.000 claims description 120
- 125000001072 heteroaryl group Chemical group 0.000 claims description 111
- 125000000623 heterocyclic group Chemical group 0.000 claims description 111
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 105
- 125000005475 oxolanyl group Chemical group 0.000 claims description 105
- 125000002757 morpholinyl group Chemical group 0.000 claims description 100
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 98
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 94
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 85
- 125000005843 halogen group Chemical group 0.000 claims description 82
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 82
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 78
- 125000003386 piperidinyl group Chemical group 0.000 claims description 78
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 77
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 76
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 74
- 125000002541 furyl group Chemical group 0.000 claims description 71
- 125000002883 imidazolyl group Chemical group 0.000 claims description 69
- 125000004076 pyridyl group Chemical group 0.000 claims description 68
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 67
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 66
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 63
- 125000001544 thienyl group Chemical group 0.000 claims description 57
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 56
- 125000003118 aryl group Chemical group 0.000 claims description 54
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 47
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 42
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 42
- 125000005842 heteroatom Chemical group 0.000 claims description 40
- 229910052717 sulfur Inorganic materials 0.000 claims description 39
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 38
- 229940124530 sulfonamide Drugs 0.000 claims description 36
- 150000003456 sulfonamides Chemical class 0.000 claims description 36
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 claims description 32
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 32
- 125000000160 oxazolidinyl group Chemical group 0.000 claims description 32
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 claims description 32
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 31
- 150000003457 sulfones Chemical class 0.000 claims description 27
- 150000003462 sulfoxides Chemical class 0.000 claims description 27
- 125000002971 oxazolyl group Chemical group 0.000 claims description 26
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 25
- 229910052799 carbon Inorganic materials 0.000 claims description 24
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 24
- 125000004043 oxo group Chemical group O=* 0.000 claims description 23
- UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 claims description 22
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 16
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 16
- 210000004400 mucous membrane Anatomy 0.000 claims description 14
- 239000012190 activator Substances 0.000 claims description 13
- 150000003857 carboxamides Chemical class 0.000 claims description 13
- 125000004509 1,3,4-oxadiazol-2-yl group Chemical group O1C(=NN=C1)* 0.000 claims description 12
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 11
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 11
- XSRCLMHZKWWMMN-UHFFFAOYSA-N 2-[2-chloro-4-(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridin-8-yl]-1,3,4-oxadiazole Chemical compound FC(F)(F)C1=CC(Cl)=NC(N2C=3)=C1C=CC2=NC=3C1=NN=CO1 XSRCLMHZKWWMMN-UHFFFAOYSA-N 0.000 claims description 10
- YDVJBLJCSLVMSY-UHFFFAOYSA-N carbamoyl cyanide Chemical compound NC(=O)C#N YDVJBLJCSLVMSY-UHFFFAOYSA-N 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 8
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 8
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
- ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 claims description 6
- IYKWLKMNKIDWIV-UHFFFAOYSA-N N1C=2C3=NC(C(F)(F)F)=CC(C(F)(F)F)=C3C=CC=2C=C1C1=NN=CO1 Chemical compound N1C=2C3=NC(C(F)(F)F)=CC(C(F)(F)F)=C3C=CC=2C=C1C1=NN=CO1 IYKWLKMNKIDWIV-UHFFFAOYSA-N 0.000 claims description 6
- NXWFZLSDGBWCMN-UHFFFAOYSA-N 1,3-oxazol-4-amine Chemical compound NC1=COC=N1 NXWFZLSDGBWCMN-UHFFFAOYSA-N 0.000 claims description 5
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 claims description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 5
- AARLOGDETIISCE-UHFFFAOYSA-N 1-cyano-N-ethoxy-N-propan-2-yloxyformamide Chemical compound CCON(OC(C)C)C(=O)C#N AARLOGDETIISCE-UHFFFAOYSA-N 0.000 claims description 4
- GKAUJNGBWGBWPN-UHFFFAOYSA-N 2-[1-benzyl-6,8-bis(trifluoromethyl)pyrrolo[3,2-h]quinolin-2-yl]-1,3,4-oxadiazole Chemical compound C=1C=CC=CC=1CN1C=2C3=NC(C(F)(F)F)=CC(C(F)(F)F)=C3C=CC=2C=C1C1=NN=CO1 GKAUJNGBWGBWPN-UHFFFAOYSA-N 0.000 claims description 4
- GRHYZVJEXKTJOS-UHFFFAOYSA-N 2-[2,4-bis(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridin-8-yl]-1,3,4-oxadiazole Chemical compound C=1N2C3=NC(C(F)(F)F)=CC(C(F)(F)F)=C3C=CC2=NC=1C1=NN=CO1 GRHYZVJEXKTJOS-UHFFFAOYSA-N 0.000 claims description 4
- RXFCBIOFXJLRDT-UHFFFAOYSA-N 2-[2-cyclopentyl-4-(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridin-8-yl]-1,3,4-oxadiazole Chemical compound FC(F)(F)C1=CC(C2CCCC2)=NC(N2C=3)=C1C=CC2=NC=3C1=NN=CO1 RXFCBIOFXJLRDT-UHFFFAOYSA-N 0.000 claims description 4
- DJEMXTIXIBTHNG-UHFFFAOYSA-N 2-[9-methyl-2,4-bis(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridin-8-yl]-1,3,4-oxadiazole Chemical compound N1=C2C=CC3=C(C(F)(F)F)C=C(C(F)(F)F)N=C3N2C(C)=C1C1=NN=CO1 DJEMXTIXIBTHNG-UHFFFAOYSA-N 0.000 claims description 4
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- CQRMHSRHWONGKT-UHFFFAOYSA-N 5-[2,4-bis(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridin-8-yl]-1,3-oxazole Chemical compound C=1N2C3=NC(C(F)(F)F)=CC(C(F)(F)F)=C3C=CC2=NC=1C1=CN=CO1 CQRMHSRHWONGKT-UHFFFAOYSA-N 0.000 claims description 4
- XLHJXZQVTKBZGE-UHFFFAOYSA-N C=1C=2C3=NC(C(F)(F)F)=CC(C(F)(F)F)=C3C=CC=2NC=1C1=NN=CO1 Chemical compound C=1C=2C3=NC(C(F)(F)F)=CC(C(F)(F)F)=C3C=CC=2NC=1C1=NN=CO1 XLHJXZQVTKBZGE-UHFFFAOYSA-N 0.000 claims description 4
- 230000004163 JAK-STAT signaling pathway Effects 0.000 claims description 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 4
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 4
- SKQVDXYIOKNAMW-UHFFFAOYSA-N difluoromethyl hypochlorite Chemical compound FC(F)OCl SKQVDXYIOKNAMW-UHFFFAOYSA-N 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 4
- QBUBXOFXOWEBHR-UHFFFAOYSA-N 2-[2-(furan-3-yl)-4-(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridin-8-yl]-1,3,4-oxadiazole Chemical compound FC(F)(F)C1=CC(C2=COC=C2)=NC(N2C=3)=C1C=CC2=NC=3C1=NN=CO1 QBUBXOFXOWEBHR-UHFFFAOYSA-N 0.000 claims description 3
- FAYSDPVMSHSKCO-UHFFFAOYSA-N 2-[2-cyclopropyl-4-(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridin-8-yl]-1,3,4-oxadiazole Chemical compound FC(F)(F)C1=CC(C2CC2)=NC(N2C=3)=C1C=CC2=NC=3C1=NN=CO1 FAYSDPVMSHSKCO-UHFFFAOYSA-N 0.000 claims description 3
- YVDRGFKZVNBSHE-UHFFFAOYSA-N 2-[2-ethoxy-4-(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridin-8-yl]-1,3,4-oxadiazole Chemical compound C=1N2C3=NC(OCC)=CC(C(F)(F)F)=C3C=CC2=NC=1C1=NN=CO1 YVDRGFKZVNBSHE-UHFFFAOYSA-N 0.000 claims description 3
- RXORGTVUKXHNKO-UHFFFAOYSA-N 2-[2-thiophen-3-yl-4-(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridin-8-yl]-1,3,4-oxadiazole Chemical compound FC(F)(F)C1=CC(C2=CSC=C2)=NC(N2C=3)=C1C=CC2=NC=3C1=NN=CO1 RXORGTVUKXHNKO-UHFFFAOYSA-N 0.000 claims description 3
- ZCHCHJQEWYIJDQ-UHFFFAOYSA-N 2-methyl-1,3-oxazole Chemical compound CC1=NC=CO1 ZCHCHJQEWYIJDQ-UHFFFAOYSA-N 0.000 claims description 3
- YVBPNYXAQNAMLH-UHFFFAOYSA-N 1-hydroxy-2-methylpyrrolidine Chemical compound CC1CCCN1O YVBPNYXAQNAMLH-UHFFFAOYSA-N 0.000 claims description 2
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 2
- 125000006637 cyclobutyl carbonyl group Chemical group 0.000 claims description 2
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 23
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 10
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 6
- 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims 6
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 5
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 2
- NVZFORKBKKRTPC-UHFFFAOYSA-N 1-[2-(1,3,4-oxadiazol-2-yl)-6,8-bis(trifluoromethyl)pyrrolo[3,2-h]quinolin-1-yl]ethanone Chemical compound C=1C2=CC=C3C(C(F)(F)F)=CC(C(F)(F)F)=NC3=C2N(C(=O)C)C=1C1=NN=CO1 NVZFORKBKKRTPC-UHFFFAOYSA-N 0.000 claims 2
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 claims 2
- PWIDBQONFRLSHB-UHFFFAOYSA-N 2-(2,4-dimethylimidazo[1,2-a][1,8]naphthyridin-8-yl)-1,3,4-oxadiazole Chemical compound C=1N2C3=NC(C)=CC(C)=C3C=CC2=NC=1C1=NN=CO1 PWIDBQONFRLSHB-UHFFFAOYSA-N 0.000 claims 2
- OVDQMFOFJGKNQJ-UHFFFAOYSA-N 2-(4-chloro-2-propan-2-ylimidazo[1,2-a][1,8]naphthyridin-8-yl)-1,3,4-oxadiazole Chemical compound C=1N2C3=NC(C(C)C)=CC(Cl)=C3C=CC2=NC=1C1=NN=CO1 OVDQMFOFJGKNQJ-UHFFFAOYSA-N 0.000 claims 2
- SXJCXTRJWBFKTG-UHFFFAOYSA-N 2-(4-phenyl-2-propan-2-ylimidazo[1,2-a][1,8]naphthyridin-8-yl)-1,3,4-oxadiazole Chemical compound C=12C=CC3=NC(C=4OC=NN=4)=CN3C2=NC(C(C)C)=CC=1C1=CC=CC=C1 SXJCXTRJWBFKTG-UHFFFAOYSA-N 0.000 claims 2
- FYDPIVQTBUDNFZ-UHFFFAOYSA-N 2-[1-methyl-6,8-bis(trifluoromethyl)pyrrolo[3,2-h]quinolin-2-yl]-1,3,4-oxadiazole Chemical compound C=1C2=CC=C3C(C(F)(F)F)=CC(C(F)(F)F)=NC3=C2N(C)C=1C1=NN=CO1 FYDPIVQTBUDNFZ-UHFFFAOYSA-N 0.000 claims 2
- QWVRUQREZXNEJA-UHFFFAOYSA-N 2-[2,4-bis(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridin-8-yl]-1,3-oxazole Chemical compound C=1N2C3=NC(C(F)(F)F)=CC(C(F)(F)F)=C3C=CC2=NC=1C1=NC=CO1 QWVRUQREZXNEJA-UHFFFAOYSA-N 0.000 claims 2
- FMTRHOIWPWHRKP-UHFFFAOYSA-N 2-[2,4-di(propan-2-yl)imidazo[1,2-a][1,8]naphthyridin-8-yl]-1,3,4-oxadiazole Chemical compound C=1N2C3=NC(C(C)C)=CC(C(C)C)=C3C=CC2=NC=1C1=NN=CO1 FMTRHOIWPWHRKP-UHFFFAOYSA-N 0.000 claims 2
- OZSBUQCOVZFGGH-UHFFFAOYSA-N 2-[2-(difluoromethoxy)-4-(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridin-8-yl]-1,3,4-oxadiazole Chemical compound C=1N2C3=NC(OC(F)F)=CC(C(F)(F)F)=C3C=CC2=NC=1C1=NN=CO1 OZSBUQCOVZFGGH-UHFFFAOYSA-N 0.000 claims 2
- KNEJRARJYGTLGH-UHFFFAOYSA-N 2-[2-ethyl-4-(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridin-8-yl]-1,3,4-oxadiazole Chemical compound C=1N2C3=NC(CC)=CC(C(F)(F)F)=C3C=CC2=NC=1C1=NN=CO1 KNEJRARJYGTLGH-UHFFFAOYSA-N 0.000 claims 2
- MLTVDJZRACHHIX-UHFFFAOYSA-N 2-[2-methyl-4-(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridin-8-yl]-1,3,4-oxadiazole Chemical compound C=1N2C3=NC(C)=CC(C(F)(F)F)=C3C=CC2=NC=1C1=NN=CO1 MLTVDJZRACHHIX-UHFFFAOYSA-N 0.000 claims 2
- PKUZIWSJMAJAFL-UHFFFAOYSA-N 2-[2-propan-2-yl-4-(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridin-8-yl]-1,3,4-oxadiazole Chemical compound C=1N2C3=NC(C(C)C)=CC(C(F)(F)F)=C3C=CC2=NC=1C1=NN=CO1 PKUZIWSJMAJAFL-UHFFFAOYSA-N 0.000 claims 2
- PZOGDYJGGWPWII-UHFFFAOYSA-N 2-[2-pyridin-3-yl-4-(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridin-8-yl]-1,3,4-oxadiazole Chemical compound FC(F)(F)C1=CC(C=2C=NC=CC=2)=NC(N2C=3)=C1C=CC2=NC=3C1=NN=CO1 PZOGDYJGGWPWII-UHFFFAOYSA-N 0.000 claims 2
- LKUWFBQVSIRPML-UHFFFAOYSA-N 2-[6,8-bis(trifluoromethyl)imidazo[1,2-a]quinolin-2-yl]-1,3,4-oxadiazole Chemical compound C=1N2C3=CC(C(F)(F)F)=CC(C(F)(F)F)=C3C=CC2=NC=1C1=NN=CO1 LKUWFBQVSIRPML-UHFFFAOYSA-N 0.000 claims 2
- ODUJRHUJULQYER-UHFFFAOYSA-N 2-[9-chloro-2,4-bis(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridin-8-yl]-1,3,4-oxadiazole Chemical compound ClC=1N2C3=NC(C(F)(F)F)=CC(C(F)(F)F)=C3C=CC2=NC=1C1=NN=CO1 ODUJRHUJULQYER-UHFFFAOYSA-N 0.000 claims 2
- MYAVWTCDDATPRC-UHFFFAOYSA-N 5-[6,8-bis(trifluoromethyl)-3h-imidazo[4,5-h]quinolin-2-yl]-1,3-oxazole Chemical compound N=1C=2C3=NC(C(F)(F)F)=CC(C(F)(F)F)=C3C=CC=2NC=1C1=CN=CO1 MYAVWTCDDATPRC-UHFFFAOYSA-N 0.000 claims 2
- MPTASBRELSDHLR-UHFFFAOYSA-N 8-(furan-2-yl)-2,4-bis(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridine Chemical compound C=1N2C3=NC(C(F)(F)F)=CC(C(F)(F)F)=C3C=CC2=NC=1C1=CC=CO1 MPTASBRELSDHLR-UHFFFAOYSA-N 0.000 claims 2
- OIKZFUOILGIONH-UHFFFAOYSA-N cyclobutyl-[2-(1,3,4-oxadiazol-2-yl)-6,8-bis(trifluoromethyl)pyrrolo[3,2-h]quinolin-1-yl]methanone Chemical compound C1CCC1C(=O)N1C=2C3=NC(C(F)(F)F)=CC(C(F)(F)F)=C3C=CC=2C=C1C1=NN=CO1 OIKZFUOILGIONH-UHFFFAOYSA-N 0.000 claims 2
- WELMECWTULNKJJ-ZDUSSCGKSA-N (5r)-5-[2,4-bis(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridin-8-yl]-4,4-dimethyl-5h-1,3-oxazole Chemical compound CC1(C)N=CO[C@H]1C1=CN2C3=NC(C(F)(F)F)=CC(C(F)(F)F)=C3C=CC2=N1 WELMECWTULNKJJ-ZDUSSCGKSA-N 0.000 claims 1
- VVDNEMLZPLYFGY-UHFFFAOYSA-N 1-[2,4-bis(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridin-8-yl]-n,n-dimethylmethanamine Chemical compound C1=C(C(F)(F)F)N=C2N3C=C(CN(C)C)N=C3C=CC2=C1C(F)(F)F VVDNEMLZPLYFGY-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- 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
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- 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
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- 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
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- 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
- A61P31/20—Antivirals for DNA viruses
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- 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
- A61P37/04—Immunostimulants
-
- 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
-
- 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
- C07D491/02—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 two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Animal Behavior & Ethology (AREA)
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- Immunology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
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| US9758518B2 (en) | 2015-03-04 | 2017-09-12 | Pimera, Inc. | Compositions, uses and methods for making them |
| EP3200778A4 (en) * | 2014-09-29 | 2018-05-23 | The Trustees Of The University Of Pennsylvania | Antivirals against molluscum contagiosum virus |
| CN104529893B (zh) * | 2014-12-30 | 2016-08-24 | 中国科学技术大学 | 一类可以作为高尔基体细胞器探针的喹啉染料 |
| CN105175277B (zh) * | 2015-05-18 | 2018-04-03 | 中山大学肿瘤防治中心 | 一种3‑磷酸甘油醛脱氢酶的抑制剂及其制备方法和应用 |
| WO2018043747A1 (ja) * | 2016-09-05 | 2018-03-08 | 国立大学法人京都大学 | 抗ｂ型肝炎ウイルス剤 |
| CN110709400A (zh) | 2017-03-28 | 2020-01-17 | 皮梅拉股份有限公司 | Pol1抑制剂的新型晶体形式 |
| EP3870581B1 (en) | 2018-10-23 | 2023-06-14 | Basf Se | Tricyclic pesticidal compounds |
| CN114681472B (zh) * | 2019-03-13 | 2023-06-30 | 中国人民解放军军事科学院军事医学研究院 | 氨基葡萄糖及其衍生物作为抗病毒药物的应用 |
| KR20230002396A (ko) | 2020-04-14 | 2023-01-05 | 바스프 에스이 | 트리시클릭 살충 화합물 |
| WO2022049521A1 (en) * | 2020-09-03 | 2022-03-10 | Glaxosmithkline Intellectual Property Development Limited | Imidazonaphthyridines and imidazopyridopyrimidines as ifnar2 agonists for treating sars-cov-2 infections |
| WO2022175425A1 (en) | 2021-02-22 | 2022-08-25 | Glaxosmithkline Intellectual Property Development Limited | Inhaled mtor kinase inhibitors for use in the treatment or the prevention of a respiratory rna virus infection |
| US12030883B2 (en) | 2021-09-21 | 2024-07-09 | Incyte Corporation | Hetero-tricyclic compounds as inhibitors of KRAS |
| CA3234375A1 (en) | 2021-10-01 | 2023-04-06 | Incyte Corporation | Pyrazoloquinoline kras inhibitors |
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| WO2023244672A1 (en) | 2022-06-14 | 2023-12-21 | Assembly Biosciences, Inc. | 2-(imidazo[1, 2-a]1,8-naphthyridin-8-yl)-1,3,4-oxadiazole derivatives as enhancers of innate immune response for the treatment of viral infections |
| CN120916763A (zh) * | 2023-04-14 | 2025-11-07 | 人福医药美国公司 | 用于治疗疼痛和相关医学病症的单酰甘油脂肪酶（magl）抑制剂 |
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| US8545732B2 (en) * | 2009-03-31 | 2013-10-01 | Daikin Industries, Ltd. | Electrode film for polymer actuator element, and polymer actuator element comprising the same |
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| GB201002409D0 (en) * | 2010-02-12 | 2010-03-31 | Univ Nottingham | Methods |
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| D1 : GUEIFFIER el al."Synthesis, Structure and Reactivity ot Imidazo[1,2-a](1.B]naphthyridines" J.Heterocyclic Chem., 34, 765 (1997). * |
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| AR088793A1 (es) | 2014-07-10 |
| CA2851801A1 (en) | 2013-04-25 |
| DOP2014000081A (es) | 2014-07-15 |
| PE20141359A1 (es) | 2014-10-13 |
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| SG10201505664WA (en) | 2015-09-29 |
| JP2014532626A (ja) | 2014-12-08 |
| EP2768506A2 (en) | 2014-08-27 |
| ZA201402392B (en) | 2017-09-27 |
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| CN103957910A (zh) | 2014-07-30 |
| IL231894A0 (en) | 2014-05-28 |
| PH12014500865A1 (en) | 2014-05-26 |
| MX2014004814A (es) | 2014-05-27 |
| AU2012325971A1 (en) | 2014-04-17 |
| CL2014001016A1 (es) | 2015-01-16 |
| US20140249143A1 (en) | 2014-09-04 |
| EA201490610A1 (ru) | 2014-09-30 |
| TW201542567A (zh) | 2015-11-16 |
| CR20140175A (es) | 2014-06-03 |
| WO2013059559A3 (en) | 2013-11-14 |
| SG11201400988SA (en) | 2014-07-30 |
| WO2013059559A2 (en) | 2013-04-25 |
| UY34406A (es) | 2013-05-31 |
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