KR20210112316A - 치료제로서의 cgas 활성 억제제 - Google Patents
치료제로서의 cgas 활성 억제제 Download PDFInfo
- Publication number
- KR20210112316A KR20210112316A KR1020217020729A KR20217020729A KR20210112316A KR 20210112316 A KR20210112316 A KR 20210112316A KR 1020217020729 A KR1020217020729 A KR 1020217020729A KR 20217020729 A KR20217020729 A KR 20217020729A KR 20210112316 A KR20210112316 A KR 20210112316A
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- KR
- South Korea
- Prior art keywords
- pyrimidin
- methylbenzofuro
- carboxylic acid
- pyrrolidine
- compound
- 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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- 102100031256 Cyclic GMP-AMP synthase Human genes 0.000 title claims 2
- 239000003112 inhibitor Substances 0.000 title description 33
- 239000003814 drug Substances 0.000 title description 23
- 230000000694 effects Effects 0.000 title description 23
- 101150031621 CGAS gene Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 261
- 238000000034 method Methods 0.000 claims abstract description 58
- 239000000203 mixture Substances 0.000 claims abstract description 43
- 230000004913 activation Effects 0.000 claims abstract description 24
- 108010050904 Interferons Proteins 0.000 claims abstract description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 23
- 102000014150 Interferons Human genes 0.000 claims abstract description 22
- 229940079322 interferon Drugs 0.000 claims abstract description 22
- 230000004044 response Effects 0.000 claims abstract description 9
- 108010014726 Interferon Type I Proteins 0.000 claims abstract description 8
- 102000002227 Interferon Type I Human genes 0.000 claims abstract description 8
- -1 substituted Chemical class 0.000 claims description 109
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 38
- 125000001072 heteroaryl group Chemical group 0.000 claims description 31
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 27
- 125000000217 alkyl group Chemical group 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 25
- 125000003118 aryl group Chemical group 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 23
- 208000033237 Aicardi-Goutières syndrome Diseases 0.000 claims description 19
- 208000023275 Autoimmune disease Diseases 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 17
- 150000001204 N-oxides Chemical class 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 239000012453 solvate Substances 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 230000005764 inhibitory process Effects 0.000 claims description 14
- 125000003107 substituted aryl group Chemical group 0.000 claims description 13
- 238000011282 treatment Methods 0.000 claims description 13
- 239000003085 diluting agent Substances 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 125000004122 cyclic group Chemical group 0.000 claims description 10
- 150000002431 hydrogen Chemical class 0.000 claims description 10
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 9
- 208000021386 Sjogren Syndrome Diseases 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- 239000002671 adjuvant Substances 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 7
- 230000001976 improved effect Effects 0.000 claims description 7
- 230000010472 type I IFN response Effects 0.000 claims description 7
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 6
- 230000002490 cerebral effect Effects 0.000 claims description 6
- 206010025135 lupus erythematosus Diseases 0.000 claims description 6
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
- 125000002393 azetidinyl group Chemical group 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 4
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 4
- 206010039710 Scleroderma Diseases 0.000 claims description 4
- 150000007514 bases Chemical class 0.000 claims description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 208000002780 macular degeneration Diseases 0.000 claims description 3
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 3
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 3
- 206010033645 Pancreatitis Diseases 0.000 claims description 2
- 208000018737 Parkinson disease Diseases 0.000 claims description 2
- 208000028867 ischemia Diseases 0.000 claims description 2
- 230000002207 retinal effect Effects 0.000 claims description 2
- 229910052698 phosphorus Inorganic materials 0.000 claims 2
- 239000011574 phosphorus Substances 0.000 claims 2
- IDFAEZXUNKYKNB-DLOVCJGASA-N (1S,3S,5S)-2-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-2-azabicyclo[3.1.0]hexane-3-carboxylic acid Chemical compound CC=1N=C(C2=C(N=1)C1=C(O2)C=CC=C1)N1[C@H]2C[C@H]2C[C@H]1C(=O)O IDFAEZXUNKYKNB-DLOVCJGASA-N 0.000 claims 1
- PCTGHCYZDMFWIU-JTQLQIEISA-N (2S)-1-(2-ethyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)azetidine-2-carboxylic acid Chemical compound C(C)C=1N=C(C2=C(N=1)C1=C(O2)C=CC=C1)N1[C@@H](CC1)C(=O)O PCTGHCYZDMFWIU-JTQLQIEISA-N 0.000 claims 1
- MLJOVWBMKHRKJD-JTQLQIEISA-N (2S)-2-[(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)amino]pentanedioic acid Chemical compound CC=1N=C(C2=C(N=1)C1=C(O2)C=CC=C1)N[C@@H](CCC(=O)O)C(=O)O MLJOVWBMKHRKJD-JTQLQIEISA-N 0.000 claims 1
- HHIZJCWZPRTSEW-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-(1,3-oxazol-2-ylamino)pyrrolidine-2-carboxylic acid Chemical compound CC=1N=C(C2=C(N=1)C1=C(O2)C=CC=C1)N1C(CC(C1)NC=1OC=CN=1)C(=O)O HHIZJCWZPRTSEW-UHFFFAOYSA-N 0.000 claims 1
- PDHASZPBBSLSNQ-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-(1H-pyrazol-4-ylamino)pyrrolidine-2-carboxylic acid Chemical compound N1N=CC(=C1)NC1CC(N(C1)C=1C2=C(N=C(N=1)C)C1=C(O2)C=CC=C1)C(=O)O PDHASZPBBSLSNQ-UHFFFAOYSA-N 0.000 claims 1
- WGZPPBVHDRRZPU-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-(1H-pyrazol-5-ylamino)pyrrolidine-2-carboxylic acid Chemical compound N1N=C(C=C1)NC1CC(N(C1)C=1C2=C(N=C(N=1)C)C1=C(O2)C=CC=C1)C(=O)O WGZPPBVHDRRZPU-UHFFFAOYSA-N 0.000 claims 1
- NQONZGNZVCKJKT-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-(1H-pyrazole-4-carbonylamino)pyrrolidine-2-carboxylic acid Chemical compound CC=1N=C(C2=C(N=1)C1=C(O2)C=CC=C1)N1C(CC(C1)NC(=O)C=1C=NNC=1)C(=O)O NQONZGNZVCKJKT-UHFFFAOYSA-N 0.000 claims 1
- PWLGEXAYAPKIMU-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-(1H-pyrazole-5-carbonylamino)pyrrolidine-2-carboxylic acid Chemical compound CC=1N=C(C2=C(N=1)C1=C(O2)C=CC=C1)N1C(CC(C1)NC(=O)C1=NNC=C1)C(=O)O PWLGEXAYAPKIMU-UHFFFAOYSA-N 0.000 claims 1
- KRKUUMZEZGBHPK-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-(2H-tetrazol-5-ylmethyl)pyrrolidine-2-carboxylic acid Chemical compound N1N=NN=C1CC1CC(N(C1)C=1C2=C(N=C(N=1)C)C1=C(O2)C=CC=C1)C(=O)O KRKUUMZEZGBHPK-UHFFFAOYSA-N 0.000 claims 1
- AEWOEOYZQYVVHR-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-(piperidin-3-ylamino)pyrrolidine-2-carboxylic acid Chemical compound CC=1N=C(C2=C(N=1)C1=C(O2)C=CC=C1)N1C(CC(C1)NC1CNCCC1)C(=O)O AEWOEOYZQYVVHR-UHFFFAOYSA-N 0.000 claims 1
- YKSZROTXQLPXHJ-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-(pyridin-3-ylamino)pyrrolidine-2-carboxylic acid Chemical compound CC=1N=C(C2=C(N=1)C1=C(O2)C=CC=C1)N1C(CC(C1)NC=1C=NC=CC=1)C(=O)O YKSZROTXQLPXHJ-UHFFFAOYSA-N 0.000 claims 1
- LWZFBYNTONODKG-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-(pyridin-4-ylamino)pyrrolidine-2-carboxylic acid Chemical compound CC=1N=C(C2=C(N=1)C1=C(O2)C=CC=C1)N1C(CC(C1)NC1=CC=NC=C1)C(=O)O LWZFBYNTONODKG-UHFFFAOYSA-N 0.000 claims 1
- OTGIIDGDLQKMRV-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-[(1-pyridin-4-ylcyclopropanecarbonyl)amino]pyrrolidine-2-carboxylic acid Chemical compound CC=1N=C(C2=C(N=1)C1=C(O2)C=CC=C1)N1C(CC(C1)NC(=O)C1(CC1)C1=CC=NC=C1)C(=O)O OTGIIDGDLQKMRV-UHFFFAOYSA-N 0.000 claims 1
- YNBOZGGTAQDTDP-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-[(2-methyl-2-pyridin-4-ylpropanoyl)amino]pyrrolidine-2-carboxylic acid Chemical compound CC(C(=O)NC1CC(N(C1)C=1C2=C(N=C(N=1)C)C1=C(O2)C=CC=C1)C(=O)O)(C)C1=CC=NC=C1 YNBOZGGTAQDTDP-UHFFFAOYSA-N 0.000 claims 1
- RGANLSVOJHYFFI-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-[(2-pyridin-3-ylacetyl)amino]pyrrolidine-2-carboxylic acid Chemical compound CC=1N=C(C2=C(N=1)C1=C(O2)C=CC=C1)N1C(CC(C1)NC(CC=1C=NC=CC=1)=O)C(=O)O RGANLSVOJHYFFI-UHFFFAOYSA-N 0.000 claims 1
- VYODUCOJSBEXGP-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-[(4-methyl-1H-pyrazol-5-yl)amino]pyrrolidine-2-carboxylic acid Chemical compound CC=1C(=NNC=1)NC1CC(N(C1)C=1C2=C(N=C(N=1)C)C1=C(O2)C=CC=C1)C(=O)O VYODUCOJSBEXGP-UHFFFAOYSA-N 0.000 claims 1
- VEIAEHDFHWTDSU-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-[(4-phenyl-1H-pyrazol-5-yl)amino]pyrrolidine-2-carboxylic acid Chemical compound CC=1N=C(C2=C(N=1)C1=C(O2)C=CC=C1)N1C(CC(C1)NC1=NNC=C1C1=CC=CC=C1)C(=O)O VEIAEHDFHWTDSU-UHFFFAOYSA-N 0.000 claims 1
- YBCQRYUCMILLCO-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-[(4-propan-2-yl-1H-pyrazol-5-yl)amino]pyrrolidine-2-carboxylic acid Chemical compound C(C)(C)C=1C(=NNC=1)NC1CC(N(C1)C=1C2=C(N=C(N=1)C)C1=C(O2)C=CC=C1)C(=O)O YBCQRYUCMILLCO-UHFFFAOYSA-N 0.000 claims 1
- GLIBAYXYHHMOMA-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-[2-oxo-2-(1H-pyrazol-4-ylamino)ethyl]pyrrolidine-2-carboxylic acid Chemical compound N1N=CC(=C1)NC(CC1CC(N(C1)C=1C2=C(N=C(N=1)C)C1=C(O2)C=CC=C1)C(=O)O)=O GLIBAYXYHHMOMA-UHFFFAOYSA-N 0.000 claims 1
- RBBMHOLRKKCSFJ-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-[2-oxo-2-(pyridin-2-ylamino)ethyl]pyrrolidine-2-carboxylic acid Chemical compound CC=1N=C(C2=C(N=1)C1=C(O2)C=CC=C1)N1C(CC(C1)CC(NC1=NC=CC=C1)=O)C(=O)O RBBMHOLRKKCSFJ-UHFFFAOYSA-N 0.000 claims 1
- YCQPLARUWCECQR-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-[2-oxo-2-(pyridin-4-ylamino)ethyl]pyrrolidine-2-carboxylic acid Chemical compound CC=1N=C(C2=C(N=1)C1=C(O2)C=CC=C1)N1C(CC(C1)CC(NC1=CC=NC=C1)=O)C(=O)O YCQPLARUWCECQR-UHFFFAOYSA-N 0.000 claims 1
- SUOFGKZJBNCSIP-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-[[2-(1H-pyrazol-4-yl)acetyl]amino]pyrrolidine-2-carboxylic acid Chemical compound N1N=CC(=C1)CC(=O)NC1CC(N(C1)C=1C2=C(N=C(N=1)C)C1=C(O2)C=CC=C1)C(=O)O SUOFGKZJBNCSIP-UHFFFAOYSA-N 0.000 claims 1
- KGDOUOBLTSCNLK-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-[[2-(1H-pyrazol-5-yl)acetyl]amino]pyrrolidine-2-carboxylic acid Chemical compound N1N=C(C=C1)CC(=O)NC1CC(N(C1)C=1C2=C(N=C(N=1)C)C1=C(O2)C=CC=C1)C(=O)O KGDOUOBLTSCNLK-UHFFFAOYSA-N 0.000 claims 1
- BDBOGTDRNLHVGR-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-[[2-(2-methylpyridin-4-yl)acetyl]amino]pyrrolidine-2-carboxylic acid Chemical compound CC=1N=C(C2=C(N=1)C1=C(O2)C=CC=C1)N1C(CC(C1)NC(CC1=CC(=NC=C1)C)=O)C(=O)O BDBOGTDRNLHVGR-UHFFFAOYSA-N 0.000 claims 1
- VIGPLJARUPIRNW-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-[[2-(5-methylpyridin-3-yl)acetyl]amino]pyrrolidine-2-carboxylic acid Chemical compound CC=1N=C(C2=C(N=1)C1=C(O2)C=CC=C1)N1C(CC(C1)NC(CC=1C=NC=C(C=1)C)=O)C(=O)O VIGPLJARUPIRNW-UHFFFAOYSA-N 0.000 claims 1
- QEKJJDNXTQMCBA-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-[[2-(6-methylpyridin-3-yl)acetyl]amino]pyrrolidine-2-carboxylic acid Chemical compound CC=1N=C(C2=C(N=1)C1=C(O2)C=CC=C1)N1C(CC(C1)NC(CC=1C=NC(=CC=1)C)=O)C(=O)O QEKJJDNXTQMCBA-UHFFFAOYSA-N 0.000 claims 1
- AJVUPGSOQCYDPI-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-[[2-methyl-2-(1H-pyrazol-4-yl)propanoyl]amino]pyrrolidine-2-carboxylic acid Chemical compound CC(C(=O)NC1CC(N(C1)C=1C2=C(N=C(N=1)C)C1=C(O2)C=CC=C1)C(=O)O)(C)C=1C=NNC=1 AJVUPGSOQCYDPI-UHFFFAOYSA-N 0.000 claims 1
- UAGWCMXIQFOLGE-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-[[2-methyl-2-[2-(trifluoromethyl)pyridin-4-yl]propanoyl]amino]pyrrolidine-2-carboxylic acid Chemical compound CC(C(=O)NC1CC(N(C1)C=1C2=C(N=C(N=1)C)C1=C(O2)C=CC=C1)C(=O)O)(C)C1=CC(=NC=C1)C(F)(F)F UAGWCMXIQFOLGE-UHFFFAOYSA-N 0.000 claims 1
- WWESOYMESWTKJU-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-[methyl-(2-pyridin-4-ylacetyl)amino]pyrrolidine-2-carboxylic acid Chemical compound CN(C(CC1=CC=NC=C1)=O)C1CC(N(C1)C=1C2=C(N=C(N=1)C)C1=C(O2)C=CC=C1)C(=O)O WWESOYMESWTKJU-UHFFFAOYSA-N 0.000 claims 1
- FOWVLSUXTQAWGV-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-[methyl-(4-methyl-1H-pyrazol-5-yl)amino]pyrrolidine-2-carboxylic acid Chemical compound CN(C1CC(N(C1)C=1C2=C(N=C(N=1)C)C1=C(O2)C=CC=C1)C(=O)O)C1=NNC=C1C FOWVLSUXTQAWGV-UHFFFAOYSA-N 0.000 claims 1
- BHDQBZQHJOQUCW-UHFFFAOYSA-N 1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)azetidine-2-carboxylic acid Chemical compound CC=1N=C(C2=C(N=1)C1=C(O2)C=CC=C1)N1C(CC1)C(=O)O BHDQBZQHJOQUCW-UHFFFAOYSA-N 0.000 claims 1
- FEIYUMGWAQSAQD-UHFFFAOYSA-N 1-(7-fluoro-2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-[(4-phenyl-1H-pyrazol-5-yl)amino]pyrrolidine-2-carboxylic acid Chemical compound FC1=CC2=C(C=C1)C=1N=C(N=C(C=1O2)N1C(CC(C1)NC1=NNC=C1C1=CC=CC=C1)C(=O)O)C FEIYUMGWAQSAQD-UHFFFAOYSA-N 0.000 claims 1
- LBRKCVGAOHQCQM-UHFFFAOYSA-N 1-(7-fluoro-2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-4-[[2-methyl-2-(1H-pyrazol-4-yl)propanoyl]amino]pyrrolidine-2-carboxylic acid Chemical compound FC1=CC2=C(C=C1)C=1N=C(N=C(C=1O2)N1C(CC(C1)NC(C(C)(C=1C=NNC=1)C)=O)C(=O)O)C LBRKCVGAOHQCQM-UHFFFAOYSA-N 0.000 claims 1
- FRKVAHBEYUCGNP-UHFFFAOYSA-N 1-([1]benzofuro[3,2-d]pyrimidin-4-yl)piperidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CCCN1C1=NC=NC2=C1OC1=CC=CC=C12 FRKVAHBEYUCGNP-UHFFFAOYSA-N 0.000 claims 1
- JQANAYYRDYDPFB-UHFFFAOYSA-N 2-[(2-ethyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)-methylamino]acetic acid Chemical compound C(C)C=1N=C(C2=C(N=1)C1=C(O2)C=CC=C1)N(CC(=O)O)C JQANAYYRDYDPFB-UHFFFAOYSA-N 0.000 claims 1
- HYHCFJCCDXGIKT-UHFFFAOYSA-N 2-[(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)azaniumyl]acetate Chemical compound C1=CC=C2C3=NC(C)=NC(NCC(O)=O)=C3OC2=C1 HYHCFJCCDXGIKT-UHFFFAOYSA-N 0.000 claims 1
- XXIMMYBCFAYQEV-UHFFFAOYSA-N 2-[(2-phenyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)azaniumyl]acetate Chemical compound N=1C=2C3=CC=CC=C3OC=2C(NCC(=O)O)=NC=1C1=CC=CC=C1 XXIMMYBCFAYQEV-UHFFFAOYSA-N 0.000 claims 1
- JGMFVCWSWDOWNG-UHFFFAOYSA-N 4-(1H-imidazol-5-ylamino)-1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)pyrrolidine-2-carboxylic acid Chemical compound N1C=NC(=C1)NC1CC(N(C1)C=1C2=C(N=C(N=1)C)C1=C(O2)C=CC=C1)C(=O)O JGMFVCWSWDOWNG-UHFFFAOYSA-N 0.000 claims 1
- PGVGQTWEHVQAFE-UHFFFAOYSA-N 4-(1H-imidazole-2-carbonylamino)-1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)pyrrolidine-2-carboxylic acid Chemical compound N1C(=NC=C1)C(=O)NC1CC(N(C1)C=1C2=C(N=C(N=1)C)C1=C(O2)C=CC=C1)C(=O)O PGVGQTWEHVQAFE-UHFFFAOYSA-N 0.000 claims 1
- ARRGRSOGXORGKJ-UHFFFAOYSA-N 4-(1H-imidazole-5-carbonylamino)-1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)pyrrolidine-2-carboxylic acid Chemical compound N1C=NC(=C1)C(=O)NC1CC(N(C1)C=1C2=C(N=C(N=1)C)C1=C(O2)C=CC=C1)C(=O)O ARRGRSOGXORGKJ-UHFFFAOYSA-N 0.000 claims 1
- XTDGFXHFPMBTMR-UHFFFAOYSA-N 4-(1H-indazol-3-ylamino)-1-(2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-yl)pyrrolidine-2-carboxylic acid Chemical compound N1N=C(C2=CC=CC=C12)NC1CC(N(C1)C=1C2=C(N=C(N=1)C)C1=C(O2)C=CC=C1)C(=O)O XTDGFXHFPMBTMR-UHFFFAOYSA-N 0.000 claims 1
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- 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
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- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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| PCT/US2020/012243 WO2020142729A1 (en) | 2019-01-04 | 2020-01-03 | Inhibitors of cgas activity as therapeutic agents |
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| AU2021349249A1 (en) * | 2020-09-24 | 2023-04-13 | Ventus Therapeutics U.S., Inc. | Pyrido(4,3-b)indole derivatives and their use as pharmaceuticals |
| US20240174684A1 (en) * | 2021-02-11 | 2024-05-30 | Bellbrook Labs, Llc | INHIBITORS OF cGAS ACTIVITY AS THERAPEUTIC AGENTS |
| CN117337291A (zh) * | 2021-05-12 | 2024-01-02 | 勃林格殷格翰国际有限公司 | 作为cGAS抑制剂的具有C-连接环状取代基的吡啶衍生物 |
| CN119119063A (zh) | 2021-05-12 | 2024-12-13 | 勃林格殷格翰国际有限公司 | 作为cGAS抑制剂的具有N-连接环状取代基的吡啶衍生物 |
| WO2022238335A1 (en) | 2021-05-12 | 2022-11-17 | Boehringer Ingelheim International Gmbh | Pyridine derivatives with c-linked cyclic substituents as cgas inhibitors |
| JP2025528113A (ja) * | 2022-08-10 | 2025-08-26 | ベルブルック ラボズ,エルエルシー | 治療剤としてのcGAS活性の阻害剤 |
| KR20250103719A (ko) | 2022-11-09 | 2025-07-07 | 베링거 인겔하임 인터내셔날 게엠베하 | cGAS 억제제로서의 사이클릭 벤즈이미다졸 유도체 |
| AU2023376006A1 (en) * | 2022-11-09 | 2025-03-13 | Boehringer Ingelheim International Gmbh | Cyclic pyridine derivatives as cgas inhibitors |
| WO2025172882A1 (en) | 2024-02-14 | 2025-08-21 | Janssen Pharmaceutica Nv | Substituted pyrrolidine-2-carboxylic acid derivatives as cgas inhibitors |
| WO2025233174A1 (en) | 2024-05-08 | 2025-11-13 | Boehringer Ingelheim International Gmbh | Benzimidazole derivatives as cgas inhibitors |
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| US3755583A (en) * | 1970-06-05 | 1973-08-28 | Chas0!nhx | |
| DE10348023A1 (de) * | 2003-10-15 | 2005-05-19 | Imtm Gmbh | Neue Alanyl-Aminopeptidasen-Inhibitoren zur funktionellen Beeinflussung unterschiedlicher Zellen und zur Behandlung immunologischer, entzündlicher, neuronaler und anderer Erkrankungen |
| EP1812113A1 (en) * | 2004-11-11 | 2007-08-01 | Argenta Discovery Limited | Pyrimidine compounds as histamine modulators |
| EP1767537A1 (en) * | 2005-09-21 | 2007-03-28 | Cellzome (UK) Ltd. | Pyrimidine compounds for the treatment of inflammatory disorders |
| KR20090028819A (ko) * | 2006-07-11 | 2009-03-19 | 얀센 파마슈티카 엔.브이. | 히스타민 h4 수용체의 벤조푸로- 및 벤조티에노피리미딘 조절제 |
| WO2009086303A2 (en) * | 2007-12-21 | 2009-07-09 | University Of Rochester | Method for altering the lifespan of eukaryotic organisms |
| GB2465405A (en) * | 2008-11-10 | 2010-05-19 | Univ Basel | Triazine, pyrimidine and pyridine analogues and their use in therapy |
| WO2013115167A1 (ja) * | 2012-01-31 | 2013-08-08 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | アムバチニブ誘導体 |
| CN104513258B (zh) * | 2013-09-26 | 2018-04-03 | 广东东阳光药业有限公司 | 取代脲衍生物及其在药物中的应用 |
| KR20250065420A (ko) * | 2015-12-25 | 2025-05-12 | 가부시키가이샤 한도오따이 에네루기 켄큐쇼 | 화합물, 발광 소자, 표시 장치, 전자 기기, 및 조명 장치 |
| WO2019084271A1 (en) * | 2017-10-25 | 2019-05-02 | Children's Medical Center Corporation | PAPD5 INHIBITORS AND METHODS OF USE |
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- 2020-01-03 AU AU2020205114A patent/AU2020205114A1/en not_active Abandoned
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| US20220073532A1 (en) | 2022-03-10 |
| EP3906241A1 (en) | 2021-11-10 |
| EP3906241A4 (en) | 2022-11-02 |
| AU2020205114A1 (en) | 2021-07-22 |
| WO2020142729A1 (en) | 2020-07-09 |
| JP2022518148A (ja) | 2022-03-14 |
| CA3125625A1 (en) | 2020-07-09 |
| JP7507161B2 (ja) | 2024-06-27 |
| CN113302194A (zh) | 2021-08-24 |
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