CA3056551A1 - Fused bicyclic compounds, compositions and applications thereof - Google Patents
Fused bicyclic compounds, compositions and applications thereof Download PDFInfo
- Publication number
- CA3056551A1 CA3056551A1 CA3056551A CA3056551A CA3056551A1 CA 3056551 A1 CA3056551 A1 CA 3056551A1 CA 3056551 A CA3056551 A CA 3056551A CA 3056551 A CA3056551 A CA 3056551A CA 3056551 A1 CA3056551 A1 CA 3056551A1
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- Prior art keywords
- alkyl
- cycloalkyl
- heterocyclyl
- heteroaryl
- aryl
- 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.)
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- 125000002619 bicyclic group Chemical group 0.000 title claims abstract description 142
- 239000000203 mixture Substances 0.000 title claims description 23
- 150000001875 compounds Chemical class 0.000 claims abstract description 153
- -1 polymorphs Substances 0.000 claims abstract description 102
- 150000003839 salts Chemical class 0.000 claims abstract description 78
- 239000012453 solvate Substances 0.000 claims abstract description 60
- 239000000651 prodrug Substances 0.000 claims abstract description 56
- 229940002612 prodrug Drugs 0.000 claims abstract description 56
- 101000879116 Homo sapiens Succinate receptor 1 Proteins 0.000 claims abstract description 51
- 102100037464 Succinate receptor 1 Human genes 0.000 claims abstract description 46
- 238000000034 method Methods 0.000 claims abstract description 43
- 238000011282 treatment Methods 0.000 claims abstract description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 23
- 238000002360 preparation method Methods 0.000 claims abstract description 14
- 230000008569 process Effects 0.000 claims abstract description 12
- 230000002265 prevention Effects 0.000 claims abstract description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 410
- 125000000217 alkyl group Chemical group 0.000 claims description 386
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 320
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 280
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 224
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 197
- 239000001257 hydrogen Substances 0.000 claims description 180
- 229910052739 hydrogen Inorganic materials 0.000 claims description 180
- 229910052736 halogen Inorganic materials 0.000 claims description 174
- 150000002367 halogens Chemical class 0.000 claims description 174
- 125000003118 aryl group Chemical group 0.000 claims description 156
- 125000005842 heteroatom Chemical group 0.000 claims description 140
- 229910052757 nitrogen Inorganic materials 0.000 claims description 138
- 125000002950 monocyclic group Chemical group 0.000 claims description 137
- 125000003545 alkoxy group Chemical group 0.000 claims description 124
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 121
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 121
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 109
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 92
- 125000001424 substituent group Chemical group 0.000 claims description 81
- 229920006395 saturated elastomer Polymers 0.000 claims description 79
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 76
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 73
- 150000002431 hydrogen Chemical group 0.000 claims description 71
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 64
- 229910052717 sulfur Inorganic materials 0.000 claims description 54
- 229910052705 radium Inorganic materials 0.000 claims description 47
- 229910052701 rubidium Inorganic materials 0.000 claims description 47
- 239000000243 solution Substances 0.000 claims description 47
- 229910052760 oxygen Inorganic materials 0.000 claims description 39
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 38
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 38
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 37
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 36
- 125000000033 alkoxyamino group Chemical group 0.000 claims description 35
- 125000001072 heteroaryl group Chemical group 0.000 claims description 35
- 125000003367 polycyclic group Chemical group 0.000 claims description 34
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 28
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 24
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 24
- 125000005189 alkyl hydroxy group Chemical group 0.000 claims description 22
- 125000005843 halogen group Chemical group 0.000 claims description 19
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 16
- 206010028980 Neoplasm Diseases 0.000 claims description 15
- 201000011510 cancer Diseases 0.000 claims description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 15
- 229940127089 cytotoxic agent Drugs 0.000 claims description 12
- 239000002254 cytotoxic agent Substances 0.000 claims description 12
- 201000010099 disease Diseases 0.000 claims description 11
- 208000002780 macular degeneration Diseases 0.000 claims description 11
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 9
- 239000013078 crystal Substances 0.000 claims description 8
- 206010020772 Hypertension Diseases 0.000 claims description 7
- 229910006069 SO3H Inorganic materials 0.000 claims description 7
- 230000001404 mediated effect Effects 0.000 claims description 7
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 208000010706 fatty liver disease Diseases 0.000 claims description 6
- 231100000065 noncytotoxic Toxicity 0.000 claims description 6
- 230000002020 noncytotoxic effect Effects 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 5
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 5
- UWIXEEXXLDCDBJ-UHFFFAOYSA-N 3-[3-[4-(2,3-dihydro-1H-inden-1-yloxy)-2-(trifluoromethyl)phenoxy]phenyl]propanoic acid Chemical compound C1(CCC2=CC=CC=C12)OC1=CC(=C(OC=2C=C(C=CC=2)CCC(=O)O)C=C1)C(F)(F)F UWIXEEXXLDCDBJ-UHFFFAOYSA-N 0.000 claims description 5
- 230000002062 proliferating effect Effects 0.000 claims description 5
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 4
- 208000035475 disorder Diseases 0.000 claims description 4
- 208000019423 liver disease Diseases 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 230000004263 retinal angiogenesis Effects 0.000 claims description 4
- 125000000172 C5-C10 aryl group Chemical group 0.000 claims description 3
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 3
- 206010061218 Inflammation Diseases 0.000 claims description 3
- 206010029113 Neovascularisation Diseases 0.000 claims description 3
- 230000001476 alcoholic effect Effects 0.000 claims description 3
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 230000004054 inflammatory process Effects 0.000 claims description 3
- 208000030159 metabolic disease Diseases 0.000 claims description 3
- 239000000725 suspension Substances 0.000 claims description 3
- RAPBYIQPOZBOOI-UHFFFAOYSA-N 2-[3-[4-(1-chloroisoquinolin-8-yl)oxy-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound ClC1=NC=CC2=CC=CC(=C12)OC1=CC(=C(OC=2C=C(C=CC=2)CC(=O)O)C=C1)C(F)(F)F RAPBYIQPOZBOOI-UHFFFAOYSA-N 0.000 claims description 2
- ACYSAQDHTDXING-UHFFFAOYSA-N 2-[3-[4-(1-methylindazol-4-yl)oxy-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound CN1N=CC2=C(C=CC=C12)OC1=CC(=C(OC=2C=C(C=CC=2)CC(=O)O)C=C1)C(F)(F)F ACYSAQDHTDXING-UHFFFAOYSA-N 0.000 claims description 2
- GQMUSEMFORQZMQ-UHFFFAOYSA-N 2-[3-[4-(1H-indazol-4-yloxy)-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound N1N=CC2=C(C=CC=C12)OC1=CC(=C(OC=2C=C(C=CC=2)CC(=O)O)C=C1)C(F)(F)F GQMUSEMFORQZMQ-UHFFFAOYSA-N 0.000 claims description 2
- VVLUZNZPHJYBAB-UHFFFAOYSA-N 2-[3-[4-(2-methylindazol-4-yl)oxy-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound CN1N=C2C=CC=C(C2=C1)OC1=CC(=C(OC=2C=C(C=CC=2)CC(=O)O)C=C1)C(F)(F)F VVLUZNZPHJYBAB-UHFFFAOYSA-N 0.000 claims description 2
- FTNSWYXUIMTNTM-UHFFFAOYSA-N 2-[3-[4-(3,4-dihydro-2H-1,4-benzoxazin-6-yloxy)-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC(OC2=C(C=C(OC3=CC4=C(OCCN4)C=C3)C=C2)C(F)(F)F)=CC=C1 FTNSWYXUIMTNTM-UHFFFAOYSA-N 0.000 claims description 2
- QBDALWBIVUJZER-UHFFFAOYSA-N 2-[3-[4-(3-methylimidazo[1,5-a]pyridin-5-yl)oxy-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound CC1=NC=C2C=CC=C(OC3=CC(=C(OC4=CC=CC(CC(O)=O)=C4)C=C3)C(F)(F)F)N12 QBDALWBIVUJZER-UHFFFAOYSA-N 0.000 claims description 2
- ZSSMPBPKUFVTHF-UHFFFAOYSA-N 2-[3-[4-(3-methylimidazo[1,5-a]pyridin-8-yl)oxy-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound CC1=NC=C2N1C=CC=C2OC1=CC(=C(OC2=CC=CC(CC(O)=O)=C2)C=C1)C(F)(F)F ZSSMPBPKUFVTHF-UHFFFAOYSA-N 0.000 claims description 2
- XTRHBOCAGSVFIW-UHFFFAOYSA-N 2-[3-[4-(8-chlorophthalazin-5-yl)oxy-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound ClC=1C=CC(=C2C=NN=CC=12)OC1=CC(=C(OC=2C=C(C=CC=2)CC(=O)O)C=C1)C(F)(F)F XTRHBOCAGSVFIW-UHFFFAOYSA-N 0.000 claims description 2
- GLIPRLRHTCRJEF-UHFFFAOYSA-N 2-[3-[4-([1,2,4]triazolo[4,3-a]pyridin-5-yloxy)-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC(OC2=C(C=C(OC3=CC=CC4=NN=CN34)C=C2)C(F)(F)F)=CC=C1 GLIPRLRHTCRJEF-UHFFFAOYSA-N 0.000 claims description 2
- ZOQXCJSKIOEXMX-UHFFFAOYSA-N 2-[3-[4-([1,2,4]triazolo[4,3-a]pyridin-7-yloxy)-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC(OC2=C(C=C(OC3=CC4=NN=CN4C=C3)C=C2)C(F)(F)F)=CC=C1 ZOQXCJSKIOEXMX-UHFFFAOYSA-N 0.000 claims description 2
- DSUBAFUIMPPVTG-UHFFFAOYSA-N 2-[3-[4-[(3-cyano-1H-indazol-5-yl)oxy]-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound C(#N)C1=NNC2=CC=C(C=C12)OC1=CC(=C(OC=2C=C(C=CC=2)CC(=O)O)C=C1)C(F)(F)F DSUBAFUIMPPVTG-UHFFFAOYSA-N 0.000 claims description 2
- FLXKSTZJBPZINJ-UHFFFAOYSA-N 2-[3-[4-[1-(oxetan-3-yl)imidazo[4,5-b]pyridin-6-yl]oxy-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC(OC2=C(C=C(OC3=CN=C4N=CN(C5COC5)C4=C3)C=C2)C(F)(F)F)=CC=C1 FLXKSTZJBPZINJ-UHFFFAOYSA-N 0.000 claims description 2
- RAFXHYZOTNZEAZ-UHFFFAOYSA-N 2-[3-[4-[1-(oxetan-3-yl)indazol-5-yl]oxy-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC(OC2=C(C=C(OC3=CC=C4N(N=CC4=C3)C3COC3)C=C2)C(F)(F)F)=CC=C1 RAFXHYZOTNZEAZ-UHFFFAOYSA-N 0.000 claims description 2
- VDWXIUFGJFXGNT-UHFFFAOYSA-N 2-[3-[4-[1-(oxetan-3-yl)indazol-6-yl]oxy-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC(OC2=C(C=C(OC3=CC=C4C=NN(C5COC5)C4=C3)C=C2)C(F)(F)F)=CC=C1 VDWXIUFGJFXGNT-UHFFFAOYSA-N 0.000 claims description 2
- FIXVDBMUYKXOPB-UHFFFAOYSA-N 2-[3-[4-[1-(oxetan-3-yl)pyrrolo[2,3-b]pyridin-6-yl]oxy-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC(OC2=C(C=C(OC3=CC=C4C=CN(C5COC5)C4=N3)C=C2)C(F)(F)F)=CC=C1 FIXVDBMUYKXOPB-UHFFFAOYSA-N 0.000 claims description 2
- QGZKZWMMDBUOKI-UHFFFAOYSA-N 2-[3-[4-[2-(oxetan-3-yl)indazol-5-yl]oxy-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound O1CC(C1)N1N=C2C=CC(=CC2=C1)OC1=CC(=C(OC=2C=C(C=CC=2)CC(=O)O)C=C1)C(F)(F)F QGZKZWMMDBUOKI-UHFFFAOYSA-N 0.000 claims description 2
- AYTBUZIDBBBQGJ-UHFFFAOYSA-N 2-[3-[4-[2-(oxetan-3-yl)indazol-6-yl]oxy-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound O1CC(C1)N1N=C2C=C(C=CC2=C1)OC1=CC(=C(OC=2C=C(C=CC=2)CC(=O)O)C=C1)C(F)(F)F AYTBUZIDBBBQGJ-UHFFFAOYSA-N 0.000 claims description 2
- JYVHRDPVMBGOPL-UHFFFAOYSA-N 2-[3-[4-[3-(oxetan-3-yl)benzimidazol-5-yl]oxy-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound O1CC(C1)N1C=NC2=C1C=C(C=C2)OC1=CC(=C(OC=2C=C(C=CC=2)CC(=O)O)C=C1)C(F)(F)F JYVHRDPVMBGOPL-UHFFFAOYSA-N 0.000 claims description 2
- PVNNZJBAZBDQDC-UHFFFAOYSA-N 2-[3-[4-[3-(oxetan-3-yl)benzotriazol-5-yl]oxy-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound O1CC(C1)N1N=NC2=C1C=C(C=C2)OC1=CC(=C(OC=2C=C(C=CC=2)CC(=O)O)C=C1)C(F)(F)F PVNNZJBAZBDQDC-UHFFFAOYSA-N 0.000 claims description 2
- FXNYRKBXAHDVMR-UHFFFAOYSA-N 2-[3-[4-[3-(oxetan-3-yl)imidazo[1,5-a]pyridin-6-yl]oxy-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC(OC2=C(C=C(OC3=CN4C(=CN=C4C4COC4)C=C3)C=C2)C(F)(F)F)=CC=C1 FXNYRKBXAHDVMR-UHFFFAOYSA-N 0.000 claims description 2
- PDWKHIRXZXHUTD-UHFFFAOYSA-N 2-[3-[4-imidazo[1,5-a]pyridin-5-yloxy-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC(OC2=C(C=C(OC3=CC=CC4=CN=CN34)C=C2)C(F)(F)F)=CC=C1 PDWKHIRXZXHUTD-UHFFFAOYSA-N 0.000 claims description 2
- XCRNXGMEZIZDMZ-UHFFFAOYSA-N 2-[3-[4-imidazo[1,5-a]pyridin-8-yloxy-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC(OC2=C(C=C(OC3=CC=CN4C=NC=C34)C=C2)C(F)(F)F)=CC=C1 XCRNXGMEZIZDMZ-UHFFFAOYSA-N 0.000 claims description 2
- JCSVKXAJXNDRSW-UHFFFAOYSA-N 2-[3-[4-isoquinolin-8-yloxy-2-(trifluoromethyl)phenoxy]phenyl]acetamide Chemical compound C1=NC=CC2=CC=CC(=C12)OC1=CC(=C(OC=2C=C(C=CC=2)CC(=O)N)C=C1)C(F)(F)F JCSVKXAJXNDRSW-UHFFFAOYSA-N 0.000 claims description 2
- KGXDTXLGXHPLEB-UHFFFAOYSA-N 2-[3-[4-isoquinolin-8-yloxy-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound C1=NC=CC2=CC=CC(=C12)OC1=CC(=C(OC=2C=C(C=CC=2)CC(=O)O)C=C1)C(F)(F)F KGXDTXLGXHPLEB-UHFFFAOYSA-N 0.000 claims description 2
- QOKNHPNWSGLMIJ-UHFFFAOYSA-N 2-[3-[4-isoquinolin-8-yloxy-3-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound C1=NC=CC2=CC=CC(=C12)OC1=C(C=C(OC=2C=C(C=CC=2)CC(=O)O)C=C1)C(F)(F)F QOKNHPNWSGLMIJ-UHFFFAOYSA-N 0.000 claims description 2
- VVESOPXXJCDYIF-UHFFFAOYSA-N 2-[3-[4-phthalazin-5-yloxy-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound C1=NN=CC2=C(C=CC=C12)OC1=CC(=C(OC=2C=C(C=CC=2)CC(=O)O)C=C1)C(F)(F)F VVESOPXXJCDYIF-UHFFFAOYSA-N 0.000 claims description 2
- PWIAIIJGDAWRHA-UHFFFAOYSA-N 2-[3-[4-quinazolin-5-yloxy-2-(trifluoromethyl)phenoxy]phenyl]acetic acid Chemical compound N1=CN=CC2=C(C=CC=C12)OC1=CC(=C(OC=2C=C(C=CC=2)CC(=O)O)C=C1)C(F)(F)F PWIAIIJGDAWRHA-UHFFFAOYSA-N 0.000 claims description 2
- XEZTXBXTVJBXOL-UHFFFAOYSA-N 2-[3-[5-isoquinolin-8-yloxy-3-(trifluoromethyl)pyridin-2-yl]oxyphenyl]acetic acid Chemical compound C1=NC=CC2=CC=CC(=C12)OC=1C=C(C(=NC=1)OC=1C=C(C=CC=1)CC(=O)O)C(F)(F)F XEZTXBXTVJBXOL-UHFFFAOYSA-N 0.000 claims description 2
- HXBLYGHNTRPYEK-UHFFFAOYSA-N 3-[3-[4-(1,2,3,4-tetrahydroisoquinolin-8-yloxy)-2-(trifluoromethyl)phenoxy]phenyl]propanoic acid Chemical compound C1NCCC2=CC=CC(=C12)OC1=CC(=C(OC=2C=C(C=CC=2)CCC(=O)O)C=C1)C(F)(F)F HXBLYGHNTRPYEK-UHFFFAOYSA-N 0.000 claims description 2
- AOZOZASXNMSWLJ-UHFFFAOYSA-N 3-[3-[4-(1H-indazol-5-yloxy)-2-(trifluoromethyl)phenoxy]phenyl]propanoic acid Chemical compound N1N=CC2=CC(=CC=C12)OC1=CC(=C(OC=2C=C(C=CC=2)CCC(=O)O)C=C1)C(F)(F)F AOZOZASXNMSWLJ-UHFFFAOYSA-N 0.000 claims description 2
- ZZGPZSJLFWIRTF-UHFFFAOYSA-N 3-[3-[4-(2,3-dihydro-1,4-benzodioxin-5-yloxy)-2-(trifluoromethyl)phenoxy]phenyl]propanoic acid Chemical compound OC(=O)CCC1=CC(OC2=C(C=C(OC3=C4OCCOC4=CC=C3)C=C2)C(F)(F)F)=CC=C1 ZZGPZSJLFWIRTF-UHFFFAOYSA-N 0.000 claims description 2
- FWSYYMMZLRDYIG-UHFFFAOYSA-N 3-[3-[4-(2-methylindazol-5-yl)oxy-2-(trifluoromethyl)phenoxy]phenyl]propanoic acid Chemical compound CN1N=C2C=CC(=CC2=C1)OC1=CC(=C(OC=2C=C(C=CC=2)CCC(=O)O)C=C1)C(F)(F)F FWSYYMMZLRDYIG-UHFFFAOYSA-N 0.000 claims description 2
- ZDMDCGLEMMTWFX-UHFFFAOYSA-N 3-[3-[4-imidazo[1,2-a]pyridin-5-yloxy-2-(trifluoromethyl)phenoxy]phenyl]propanoic acid Chemical compound OC(=O)CCC1=CC(OC2=C(C=C(OC3=CC=CC4=NC=CN34)C=C2)C(F)(F)F)=CC=C1 ZDMDCGLEMMTWFX-UHFFFAOYSA-N 0.000 claims description 2
- GQLAQUSXEFCRJC-UHFFFAOYSA-N 3-[3-[4-imidazo[1,2-a]pyridin-8-yloxy-2-(trifluoromethyl)phenoxy]phenyl]propanoic acid Chemical compound OC(=O)CCC1=CC(OC2=C(C=C(OC3=CC=CN4C=CN=C34)C=C2)C(F)(F)F)=CC=C1 GQLAQUSXEFCRJC-UHFFFAOYSA-N 0.000 claims description 2
- YAXVYZJJXRQPCQ-UHFFFAOYSA-N 3-[3-[4-isoquinolin-5-yloxy-2-(trifluoromethyl)phenoxy]phenyl]propanoic acid Chemical compound C1=NC=CC2=C(C=CC=C12)OC1=CC(=C(OC=2C=C(C=CC=2)CCC(=O)O)C=C1)C(F)(F)F YAXVYZJJXRQPCQ-UHFFFAOYSA-N 0.000 claims description 2
- OPVSINUYKQJWDH-UHFFFAOYSA-N 3-[3-[4-isoquinolin-8-yloxy-2-(trifluoromethyl)phenoxy]phenyl]propanamide Chemical compound C1=NC=CC2=CC=CC(=C12)OC1=CC(=C(OC=2C=C(C=CC=2)CCC(=O)N)C=C1)C(F)(F)F OPVSINUYKQJWDH-UHFFFAOYSA-N 0.000 claims description 2
- LPHICRZKBRICMQ-UHFFFAOYSA-N 3-[3-[4-isoquinolin-8-yloxy-2-(trifluoromethyl)phenoxy]phenyl]propanoic acid Chemical compound C1=NC=CC2=CC=CC(=C12)OC1=CC(=C(OC=2C=C(C=CC=2)CCC(=O)O)C=C1)C(F)(F)F LPHICRZKBRICMQ-UHFFFAOYSA-N 0.000 claims description 2
- KPINORXHWSPYHQ-UHFFFAOYSA-N 3-[3-[4-phthalazin-5-yloxy-2-(trifluoromethyl)phenoxy]phenyl]propanoic acid Chemical compound C1=NN=CC2=C(C=CC=C12)OC1=CC(=C(OC=2C=C(C=CC=2)CCC(=O)O)C=C1)C(F)(F)F KPINORXHWSPYHQ-UHFFFAOYSA-N 0.000 claims description 2
- LPRORPSBUCCVAF-UHFFFAOYSA-N 3-[3-[4-quinolin-4-yloxy-2-(trifluoromethyl)phenoxy]phenyl]propanoic acid Chemical compound N1=CC=C(C2=CC=CC=C12)OC1=CC(=C(OC=2C=C(C=CC=2)CCC(=O)O)C=C1)C(F)(F)F LPRORPSBUCCVAF-UHFFFAOYSA-N 0.000 claims description 2
- SAUYZGAEUYVXEE-UHFFFAOYSA-N 3-[3-[4-quinolin-8-yloxy-2-(trifluoromethyl)phenoxy]phenyl]propanoic acid Chemical compound N1=CC=CC2=CC=CC(=C12)OC1=CC(=C(OC=2C=C(C=CC=2)CCC(=O)O)C=C1)C(F)(F)F SAUYZGAEUYVXEE-UHFFFAOYSA-N 0.000 claims description 2
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- 230000004491 retinal development Effects 0.000 description 1
- 210000001116 retinal neuron Anatomy 0.000 description 1
- 239000000790 retinal pigment Substances 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000004055 small Interfering RNA Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 229940074404 sodium succinate Drugs 0.000 description 1
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000005017 substituted alkenyl group Chemical group 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000004426 substituted alkynyl group Chemical group 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960000814 tetanus toxoid Drugs 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 230000004102 tricarboxylic acid cycle Effects 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000001845 vibrational spectrum Methods 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/24—Oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/233—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/30—Phthalazines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/74—Quinazolines; Hydrogenated quinazolines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to ring carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
- C07D265/36—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings condensed with one six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
- C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
- C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Indole Compounds (AREA)
- Quinoline Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN201741008624 | 2017-03-13 | ||
| IN201741008624 | 2017-03-13 | ||
| PCT/IN2018/050136 WO2018167800A1 (en) | 2017-03-13 | 2018-03-13 | Fused bicyclic compounds, compositions and applications thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3056551A1 true CA3056551A1 (en) | 2018-09-20 |
Family
ID=61768371
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3056551A Pending CA3056551A1 (en) | 2017-03-13 | 2018-03-13 | Fused bicyclic compounds, compositions and applications thereof |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US11098026B2 (enExample) |
| EP (1) | EP3596051B1 (enExample) |
| JP (1) | JP7301758B2 (enExample) |
| CA (1) | CA3056551A1 (enExample) |
| WO (1) | WO2018167800A1 (enExample) |
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| ES3028093T3 (en) * | 2018-06-07 | 2025-06-18 | Disarm Therapeutics Inc | Inhibitors of sarm1 |
| US12391695B2 (en) | 2019-06-10 | 2025-08-19 | Lupin Limited | PRMT5 inhibitors |
| WO2021111322A1 (en) | 2019-12-03 | 2021-06-10 | Lupin Limited | Substituted nucleoside analogs as prmt5 inhibitors |
| WO2021161230A1 (en) * | 2020-02-12 | 2021-08-19 | Curadev Pharma Pvt. Ltd. | Small molecule sting antagonists |
| US20240165108A1 (en) * | 2022-08-09 | 2024-05-23 | Glaxosmithkline Intellectual Property Development Limited | Novel use |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5821672A (ja) * | 1981-07-28 | 1983-02-08 | Nippon Tokushu Noyaku Seizo Kk | ベンゾイソチアゾ−ル誘導体、その製法、及び農業用殺菌剤 |
| US5977117A (en) * | 1996-01-05 | 1999-11-02 | Texas Biotechnology Corporation | Substituted phenyl compounds and derivatives thereof that modulate the activity of endothelin |
| US6525051B2 (en) | 2000-03-27 | 2003-02-25 | Schering Aktiengesellschaft | N-heterocyclic derivatives as NOS inhibitors |
| JP5987220B2 (ja) | 2011-07-19 | 2016-09-07 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ロイコトリエンa4ヒドロラーゼの阻害剤としてのアリールピラゾールエーテル |
| EP2928886B1 (en) * | 2012-12-07 | 2016-11-02 | Boehringer Ingelheim International GmbH | New indanyloxydihydrobenzofuranylacetic acids |
-
2018
- 2018-03-13 EP EP18713373.1A patent/EP3596051B1/en active Active
- 2018-03-13 JP JP2019571826A patent/JP7301758B2/ja active Active
- 2018-03-13 WO PCT/IN2018/050136 patent/WO2018167800A1/en not_active Ceased
- 2018-03-13 US US16/494,239 patent/US11098026B2/en active Active
- 2018-03-13 CA CA3056551A patent/CA3056551A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP2020515631A (ja) | 2020-05-28 |
| WO2018167800A1 (en) | 2018-09-20 |
| EP3596051B1 (en) | 2022-04-27 |
| EP3596051A1 (en) | 2020-01-22 |
| JP7301758B2 (ja) | 2023-07-03 |
| US20200087281A1 (en) | 2020-03-19 |
| US11098026B2 (en) | 2021-08-24 |
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