BR112020008425A2 - compostos e composições farmacêuticas dos mesmos para uso no tratamento de doenças fibróticas - Google Patents

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Publication number

BR112020008425A2

BR112020008425A2 BR112020008425-5A BR112020008425A BR112020008425A2 BR 112020008425 A2 BR112020008425 A2 BR 112020008425A2 BR 112020008425 A BR112020008425 A BR 112020008425A BR 112020008425 A2 BR112020008425 A2 BR 112020008425A2

Authority

BR

Brazil

Prior art keywords

dihydro

ylmethoxy

alisoquinolin

pyrimido

methyl

Prior art date

2017-11-15

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 232
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 88
• 201000010099 disease Diseases 0.000 title claims abstract description 84
• 238000011282 treatment Methods 0.000 title claims abstract description 77
• 230000003176 fibrotic effect Effects 0.000 title claims abstract description 58
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 34
• 238000011321 prophylaxis Methods 0.000 claims abstract description 37
• -1 - Gié o H Chemical group 0.000 claims description 1269
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 229
• 125000005842 heteroatom Chemical group 0.000 claims description 111
• 125000000217 alkyl group Chemical group 0.000 claims description 110
• 125000005843 halogen group Chemical group 0.000 claims description 108
• 229910052760 oxygen Inorganic materials 0.000 claims description 90
• 229910052717 sulfur Inorganic materials 0.000 claims description 81
• HIZVCIIORGCREW-UHFFFAOYSA-N 1,4-dioxene Chemical compound C1COC=CO1 HIZVCIIORGCREW-UHFFFAOYSA-N 0.000 claims description 63
• 125000003545 alkoxy group Chemical group 0.000 claims description 48
• 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 42
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 41
• 125000003118 aryl group Chemical group 0.000 claims description 35
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 33
• LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 claims description 32
• 239000002253 acid Substances 0.000 claims description 32
• 239000003814 drug Substances 0.000 claims description 32
• 229910052757 nitrogen Inorganic materials 0.000 claims description 32
• 125000001072 heteroaryl group Chemical group 0.000 claims description 30
• 150000003839 salts Chemical class 0.000 claims description 30
• 125000002947 alkylene group Chemical group 0.000 claims description 28
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 27
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 24
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 21
• WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 18
• 125000004366 heterocycloalkenyl group Chemical group 0.000 claims description 17
• 239000012453 solvate Substances 0.000 claims description 17
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
• 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims description 15
• 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 15
• 125000006578 monocyclic heterocycloalkyl group Chemical group 0.000 claims description 15
• 239000003795 chemical substances by application Substances 0.000 claims description 14
• 229940124597 therapeutic agent Drugs 0.000 claims description 14
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 12
• 125000001475 halogen functional group Chemical group 0.000 claims description 12
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 10
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 10
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 10
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
• 125000002619 bicyclic group Chemical group 0.000 claims description 9
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 8
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 8
• 125000004450 alkenylene group Chemical group 0.000 claims description 7
• DGCWHOHVNONFSD-UHFFFAOYSA-N quinolizin-2-one Chemical compound C1=CC=CC2=CC(=O)C=CN21 DGCWHOHVNONFSD-UHFFFAOYSA-N 0.000 claims description 7
• 239000002904 solvent Substances 0.000 claims description 7
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 6
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 6
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
• ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
• 125000001617 2,3-dimethoxy phenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 4
• FPZWZCWUIYYYBU-UHFFFAOYSA-N 2-(2-ethoxyethoxy)ethyl acetate Chemical group CCOCCOCCOC(C)=O FPZWZCWUIYYYBU-UHFFFAOYSA-N 0.000 claims description 4
• 125000004791 2-fluoroethoxy group Chemical group FCCO* 0.000 claims description 4
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 4
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
• ABBZLRIDTWRRIR-UHFFFAOYSA-N 6h-quinolizine-1-carboxamide Chemical compound C1C=CC=C2C(C(=O)N)=CC=CN21 ABBZLRIDTWRRIR-UHFFFAOYSA-N 0.000 claims description 4
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 3
• 230000003042 antagnostic effect Effects 0.000 claims description 3
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 3
• 229940098779 methanesulfonic acid Drugs 0.000 claims description 3
• MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims description 3
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
• 231100000331 toxic Toxicity 0.000 claims description 3
• 230000002588 toxic effect Effects 0.000 claims description 3
• NIQZIMGAKHLKOF-UHFFFAOYSA-N 1-ethyl-4-(oxolan-2-ylmethylamino)-9-(2,2,2-trifluoroethoxy)-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound C(C)C=1C(C=C(N2CCC3=C(C=12)C=CC(=C3)OCC(F)(F)F)NCC1OCCC1)=O NIQZIMGAKHLKOF-UHFFFAOYSA-N 0.000 claims description 2
• CCGAZPULKVWMBM-UHFFFAOYSA-N 1-ethyl-9-hydroxy-4-(oxolan-2-ylmethylamino)-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound C(C)C=1C(C=C(N2CCC3=C(C=12)C=CC(=C3)O)NCC1OCCC1)=O CCGAZPULKVWMBM-UHFFFAOYSA-N 0.000 claims description 2
• ZQCKYPBJXLJWRD-UHFFFAOYSA-N 1-methyl-4-(oxan-2-ylmethoxy)-9-(oxan-3-ylmethoxy)-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound CC=1C(C=C(N2CCC3=C(C=12)C=CC(=C3)OCC1COCCC1)OCC1OCCCC1)=O ZQCKYPBJXLJWRD-UHFFFAOYSA-N 0.000 claims description 2
• OEOJTJOSJFIQIC-UHFFFAOYSA-N 1-methyl-4-(oxan-2-ylmethoxy)-9-(pyridin-2-ylmethoxy)-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound CC=1C(C=C(N2CCC3=C(C=12)C=CC(=C3)OCC1=NC=CC=C1)OCC1OCCCC1)=O OEOJTJOSJFIQIC-UHFFFAOYSA-N 0.000 claims description 2
• WARDCCFAOURMLN-UHFFFAOYSA-N 1-methyl-4-(oxan-2-ylmethoxy)-9-phenylmethoxy-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound C(C1=CC=CC=C1)OC1=CC2=C(C3=C(C(C=C(N3CC2)OCC2OCCCC2)=O)C)C=C1 WARDCCFAOURMLN-UHFFFAOYSA-N 0.000 claims description 2
• HQIACJMMZUTWKM-UHFFFAOYSA-N 1-methyl-4-(oxan-2-ylmethylamino)-9-(2,2,2-trifluoroethoxy)-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound CC=1C(C=C(N2CCC3=C(C=12)C=CC(=C3)OCC(F)(F)F)NCC1OCCCC1)=O HQIACJMMZUTWKM-UHFFFAOYSA-N 0.000 claims description 2
• WMHDLAQZMROIAH-UHFFFAOYSA-N 1-methyl-4-(oxetan-2-ylmethoxy)-9-phenylmethoxy-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound C(C1=CC=CC=C1)OC1=CC2=C(C3=C(C(C=C(N3CC2)OCC2OCC2)=O)C)C=C1 WMHDLAQZMROIAH-UHFFFAOYSA-N 0.000 claims description 2
• QEPYZIPTGZUYAT-UHFFFAOYSA-N 1-methyl-4-(oxolan-2-ylmethoxy)-9-(pyridin-2-ylmethoxy)-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound CC=1C(C=C(N2CCC3=C(C=12)C=CC(=C3)OCC1=NC=CC=C1)OCC1OCCC1)=O QEPYZIPTGZUYAT-UHFFFAOYSA-N 0.000 claims description 2
• PMBGXWZSMHOLOX-UHFFFAOYSA-N 1-methyl-4-(oxolan-2-ylmethylamino)-9-(2,2,2-trifluoroethoxy)-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound CC=1C(C=C(N2CCC3=C(C=12)C=CC(=C3)OCC(F)(F)F)NCC1OCCC1)=O PMBGXWZSMHOLOX-UHFFFAOYSA-N 0.000 claims description 2
• SYHNHSPLEWJSQF-UHFFFAOYSA-N 1-methyl-4-[(2-methyloxolan-2-yl)methoxy]-9-phenylmethoxy-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound C(C1=CC=CC=C1)OC1=CC2=C(C3=C(C(C=C(N3CC2)OCC2(OCCC2)C)=O)C)C=C1 SYHNHSPLEWJSQF-UHFFFAOYSA-N 0.000 claims description 2
• AJEZTVNHETXVHX-QFIPXVFZSA-N 1-methyl-4-[[(2S)-oxolan-2-yl]methoxy]-9-phenylmethoxy-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound C(C1=CC=CC=C1)OC1=CC2=C(C3=C(C(C=C(N3CC2)OC[C@H]2OCCC2)=O)C)C=C1 AJEZTVNHETXVHX-QFIPXVFZSA-N 0.000 claims description 2
• PMBGXWZSMHOLOX-INIZCTEOSA-N 1-methyl-4-[[(2S)-oxolan-2-yl]methylamino]-9-(2,2,2-trifluoroethoxy)-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound CC=1C(C=C(N2CCC3=C(C=12)C=CC(=C3)OCC(F)(F)F)NC[C@H]1OCCC1)=O PMBGXWZSMHOLOX-INIZCTEOSA-N 0.000 claims description 2
• HZUDNNDWZNSOGH-UHFFFAOYSA-N 1-methyl-9-(oxan-3-ylmethoxy)-4-(oxolan-2-ylmethoxy)-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound CC=1C(C=C(N2CCC3=C(C=12)C=CC(=C3)OCC1COCCC1)OCC1OCCC1)=O HZUDNNDWZNSOGH-UHFFFAOYSA-N 0.000 claims description 2
• 125000004909 2,2-dimethylbutylamino group Chemical group CC(CN*)(CC)C 0.000 claims description 2
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
• 125000003635 2-dimethylaminoethoxy group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 claims description 2
• ATMCNQUFEQSMTA-UHFFFAOYSA-N 4-(1,4-dioxan-2-ylmethylamino)-8,9-dimethoxy-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound O1C(COCC1)CNC=1N2CCC3=C(C2=CC(C=1)=O)C=CC(=C3OC)OC ATMCNQUFEQSMTA-UHFFFAOYSA-N 0.000 claims description 2
• MLMLXCPENKEOKB-UHFFFAOYSA-N 4-(1,4-dioxan-2-ylmethylamino)-8-hydroxy-9-methoxy-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound O1C(COCC1)CNC=1N2CCC3=C(C2=CC(C=1)=O)C=CC(=C3O)OC MLMLXCPENKEOKB-UHFFFAOYSA-N 0.000 claims description 2
• NUCBUWPRKSARJE-UHFFFAOYSA-N 4-(1,4-dioxan-2-ylmethylamino)-9-hydroxy-8-methoxy-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound O1C(COCC1)CNC=1N2CCC3=C(C2=CC(C=1)=O)C=CC(=C3OC)O NUCBUWPRKSARJE-UHFFFAOYSA-N 0.000 claims description 2
• ZGQJBKDYVVOZNN-UHFFFAOYSA-N 4-[(4,4-dimethyloxetan-2-yl)methoxy]-1-methyl-9-phenylmethoxy-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound C(C1=CC=CC=C1)OC1=CC2=C(C3=C(C(C=C(N3CC2)OCC2OC(C2)(C)C)=O)C)C=C1 ZGQJBKDYVVOZNN-UHFFFAOYSA-N 0.000 claims description 2
• MNHBLOKNSAKLGP-UHFFFAOYSA-N 4-[(5,5-dimethyloxolan-2-yl)methoxy]-1-methyl-9-phenylmethoxy-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound C(C1=CC=CC=C1)OC1=CC2=C(C3=C(C(C=C(N3CC2)OCC2OC(CC2)(C)C)=O)C)C=C1 MNHBLOKNSAKLGP-UHFFFAOYSA-N 0.000 claims description 2
• ZHIPSAQRCJTNEI-MRXNPFEDSA-N 4-[[(2R)-1,4-dioxan-2-yl]methylamino]-1-methyl-9-(2,2,2-trifluoroethoxy)-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound O1[C@@H](COCC1)CNC=1N2CCC3=C(C2=C(C(C=1)=O)C)C=CC(=C3)OCC(F)(F)F ZHIPSAQRCJTNEI-MRXNPFEDSA-N 0.000 claims description 2
• WXRINQOGUCEOFB-OAHLLOKOSA-N 4-[[(2R)-1,4-dioxan-2-yl]methylamino]-9,10-dimethoxy-1-methyl-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound O1[C@@H](COCC1)CNC=1N2CCC3=C(C2=C(C(C=1)=O)C)C=C(C(=C3)OC)OC WXRINQOGUCEOFB-OAHLLOKOSA-N 0.000 claims description 2
• SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 claims description 2
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 2
• 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 claims description 2
• DIUKGQCXFKKMFJ-UHFFFAOYSA-N 5-ethyl-1,2,4-oxadiazole Chemical compound CCC1=NC=NO1 DIUKGQCXFKKMFJ-UHFFFAOYSA-N 0.000 claims description 2
• KLSPDJJSASRRKE-UHFFFAOYSA-N 6H-quinolizine-1-carbonitrile Chemical compound C1C=CC=C2C(C#N)=CC=CN21 KLSPDJJSASRRKE-UHFFFAOYSA-N 0.000 claims description 2
• MXHLMGBSIRWXQL-UHFFFAOYSA-N 8,9-dimethoxy-1-methyl-4-(oxan-2-ylmethoxy)-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound COC1=C(C=CC2=C1CCN1C(=CC(C(=C21)C)=O)OCC1OCCCC1)OC MXHLMGBSIRWXQL-UHFFFAOYSA-N 0.000 claims description 2
• ANQNKJIHWIGYCK-UHFFFAOYSA-N 8,9-dimethoxy-1-methyl-4-(oxan-2-ylmethylamino)-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound COC1=C(C=CC2=C1CCN1C(=CC(C(=C21)C)=O)NCC1OCCCC1)OC ANQNKJIHWIGYCK-UHFFFAOYSA-N 0.000 claims description 2
• LIFDKYNPSYUKAP-UHFFFAOYSA-N 8,9-dimethoxy-1-methyl-4-(oxolan-2-ylmethoxy)-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound COC1=C(C=CC2=C1CCN1C(=CC(C(=C21)C)=O)OCC1OCCC1)OC LIFDKYNPSYUKAP-UHFFFAOYSA-N 0.000 claims description 2
• LXGOQSFYCHQTSH-UHFFFAOYSA-N 8,9-dimethoxy-1-methyl-4-(oxolan-2-ylmethylamino)-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound COC1=C(C=CC2=C1CCN1C(=CC(C(=C21)C)=O)NCC1OCCC1)OC LXGOQSFYCHQTSH-UHFFFAOYSA-N 0.000 claims description 2
• WWZJXFLPJCGISX-UHFFFAOYSA-N 8,9-dimethoxy-4-(oxolan-2-ylmethylamino)-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound COC1=C(C=CC2=C1CCN1C(=CC(C=C21)=O)NCC1OCCC1)OC WWZJXFLPJCGISX-UHFFFAOYSA-N 0.000 claims description 2
• GFXKXMWNTIGCIE-ACBHZAAOSA-N 9,10-bis[(2,2-difluorocyclopropyl)methoxy]-2-[[(2S)-1,4-dioxan-2-yl]methoxy]-1-methyl-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound CC1=C2N(CCC3=C2C=C(OCC2CC2(F)F)C(OCC2CC2(F)F)=C3)C(=O)C=C1OC[C@@H]1COCCO1 GFXKXMWNTIGCIE-ACBHZAAOSA-N 0.000 claims description 2
• ZOXGEEPMOUAUJD-UHFFFAOYSA-N 9,10-dimethoxy-1-methyl-4-(oxolan-2-ylmethylamino)-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound COC1=CC2=C(C3=C(C(C=C(N3CC2)NCC2OCCC2)=O)C)C=C1OC ZOXGEEPMOUAUJD-UHFFFAOYSA-N 0.000 claims description 2
• KGCJLNPSAMAFIZ-UHFFFAOYSA-N 9-(2,2-difluoroethoxy)-1-ethyl-4-(oxolan-2-ylmethylamino)-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound FC(COC1=CC2=C(C3=C(C(C=C(N3CC2)NCC2OCCC2)=O)CC)C=C1)F KGCJLNPSAMAFIZ-UHFFFAOYSA-N 0.000 claims description 2
• WPLCARNFGBIXOQ-UHFFFAOYSA-N 9-(2,2-difluoroethoxy)-1-methyl-4-(oxan-2-ylmethylamino)-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound FC(COC1=CC2=C(C3=C(C(C=C(N3CC2)NCC2OCCCC2)=O)C)C=C1)F WPLCARNFGBIXOQ-UHFFFAOYSA-N 0.000 claims description 2
• KFUHBDCMBOZCKP-MRXNPFEDSA-N 9-(2,2-difluoroethoxy)-4-[[(2R)-1,4-dioxan-2-yl]methylamino]-1-methyl-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound FC(COC1=CC2=C(C3=C(C(C=C(N3CC2)NC[C@H]2OCCOC2)=O)C)C=C1)F KFUHBDCMBOZCKP-MRXNPFEDSA-N 0.000 claims description 2
• PRMBYLLJIFBSEH-KRWDZBQOSA-N 9-(3,3-difluoroazetidin-1-yl)-4-[[(2S)-1,4-dioxan-2-yl]methoxy]-1-methyl-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound FC1(CN(C1)C1=CC2=C(C3=C(C(C=C(N3CC2)OC[C@H]2OCCOC2)=O)C)C=C1)F PRMBYLLJIFBSEH-KRWDZBQOSA-N 0.000 claims description 2
• MTOVCOVHZRJMDX-IBGZPJMESA-N 9-(benzenesulfonyl)-4-[[(2S)-1,4-dioxan-2-yl]methoxy]-1-methyl-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound C1(=CC=CC=C1)S(=O)(=O)C1=CC2=C(C3=C(C(C=C(N3CC2)OC[C@H]2OCCOC2)=O)C)C=C1 MTOVCOVHZRJMDX-IBGZPJMESA-N 0.000 claims description 2
• WOKOLPPLCAGDLT-IBGZPJMESA-N 9-[(1-cyclopropyltetrazol-5-yl)methoxy]-2-[[(2S)-1,4-dioxan-2-yl]methoxy]-1-methyl-6,7-dihydrobenzo[a]quinolizin-4-one Chemical compound C1(CC1)N1N=NN=C1COC=1C=C2CCN3C(C2=CC=1)=C(C(=CC3=O)OC[C@H]1OCCOC1)C WOKOLPPLCAGDLT-IBGZPJMESA-N 0.000 claims description 2
• GNPXYYJVNCOJEQ-UHFFFAOYSA-N 9-[2-(dimethylamino)ethoxy]-1-methyl-4-(oxan-2-ylmethoxy)-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound CN(CCOC1=CC2=C(C3=C(C(C=C(N3CC2)OCC2OCCCC2)=O)C)C=C1)C GNPXYYJVNCOJEQ-UHFFFAOYSA-N 0.000 claims description 2
• OEZZIKUJXQGNMO-UHFFFAOYSA-N 9-[2-(dimethylamino)ethoxy]-1-methyl-4-(oxolan-2-ylmethoxy)-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound CN(CCOC1=CC2=C(C3=C(C(C=C(N3CC2)OCC2OCCC2)=O)C)C=C1)C OEZZIKUJXQGNMO-UHFFFAOYSA-N 0.000 claims description 2
• 102100033864 G-protein coupled receptor 84 Human genes 0.000 claims description 2
• 101001069589 Homo sapiens G-protein coupled receptor 84 Proteins 0.000 claims description 2
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 2
• 239000004202 carbamide Substances 0.000 claims description 2
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