AU2010206744B2 - Poly (ADP-ribose) polymerase (PARP) inhibitors - Google Patents

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Publication number

AU2010206744B2

AU2010206744B2 AU2010206744A AU2010206744A AU2010206744B2 AU 2010206744 B2 AU2010206744 B2 AU 2010206744B2 AU 2010206744 A AU2010206744 A AU 2010206744A AU 2010206744 A AU2010206744 A AU 2010206744A AU 2010206744 B2 AU2010206744 B2 AU 2010206744B2

Authority

AU

Australia

Prior art keywords

alkyl

hetero

methyl

pyrazin

piperazin

Prior art date

2009-01-23

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.)

Ceased

Links

• Espacenet
• Global Dossier
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• 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 title description 40
• 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 title description 40
• 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 title description 38
• 239000003112 inhibitor Substances 0.000 title description 9
• 150000001875 compounds Chemical class 0.000 claims abstract description 118
• 125000000217 alkyl group Chemical group 0.000 claims description 1757
• 125000005842 heteroatom Chemical group 0.000 claims description 1037
• 125000003118 aryl group Chemical group 0.000 claims description 478
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 472
• -1 cyano, thio, oxy, hydroxy, carbonyloxy Chemical group 0.000 claims description 300
• 150000001602 bicycloalkyls Chemical group 0.000 claims description 243
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 217
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 217
• 125000005843 halogen group Chemical group 0.000 claims description 205
• 125000004104 aryloxy group Chemical group 0.000 claims description 193
• 229910052739 hydrogen Inorganic materials 0.000 claims description 156
• 239000001257 hydrogen Substances 0.000 claims description 156
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 113
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 111
• 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 109
• 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 109
• 125000003282 alkyl amino group Chemical group 0.000 claims description 108
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 108
• 125000001841 imino group Chemical group [H]N=* 0.000 claims description 105
• 125000003545 alkoxy group Chemical group 0.000 claims description 102
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 96
• 125000003368 amide group Chemical group 0.000 claims description 80
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 79
• 125000005188 oxoalkyl group Chemical group 0.000 claims description 64
• 125000001424 substituent group Chemical group 0.000 claims description 53
• 125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 52
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 49
• 150000003839 salts Chemical class 0.000 claims description 47
• 125000004429 atom Chemical group 0.000 claims description 43
• KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 37
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 36
• 201000010099 disease Diseases 0.000 claims description 35
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 35
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 31
• 238000000034 method Methods 0.000 claims description 31
• 125000001072 heteroaryl group Chemical group 0.000 claims description 19
• DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 14
• 229910052757 nitrogen Inorganic materials 0.000 claims description 13
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 12
• 238000004519 manufacturing process Methods 0.000 claims description 11
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 9
• 239000003814 drug Substances 0.000 claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims description 8
• 235000005152 nicotinamide Nutrition 0.000 claims description 7
• 239000011570 nicotinamide Substances 0.000 claims description 7
• 229960003966 nicotinamide Drugs 0.000 claims description 7
• 235000001968 nicotinic acid Nutrition 0.000 claims description 7
• 239000011664 nicotinic acid Substances 0.000 claims description 7
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 6
• 206010028980 Neoplasm Diseases 0.000 claims description 6
• 206010063837 Reperfusion injury Diseases 0.000 claims description 6
• 230000000302 ischemic effect Effects 0.000 claims description 6
• 208000030159 metabolic disease Diseases 0.000 claims description 6
• 230000004770 neurodegeneration Effects 0.000 claims description 6
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 6
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
• 238000011282 treatment Methods 0.000 claims description 6
• 208000027866 inflammatory disease Diseases 0.000 claims description 5
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
• FZUFSEHGSIQODR-NRFANRHFSA-N (s)-ethyl 4-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1N1CCN(CC=2C=C3NC(=O)[C@@H]4CCCN4C3=NC=2)CC1 FZUFSEHGSIQODR-NRFANRHFSA-N 0.000 claims description 4
• XNKKOAUTBFSVRV-UHFFFAOYSA-N 1H-pyrazino[2,1-c][1,4]thiazin-6-one Chemical compound O=C1N2C=CSCC2=CN=C1 XNKKOAUTBFSVRV-UHFFFAOYSA-N 0.000 claims description 4
• WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 4
• 125000004076 pyridyl group Chemical group 0.000 claims description 4
• GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 claims description 3
• PGPPFIDIJMNDBJ-UHFFFAOYSA-N 6a,7,8,9-tetrahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-6(5h)-one Chemical compound O=C1NC2=CC=CN=C2N2C1CCC2 PGPPFIDIJMNDBJ-UHFFFAOYSA-N 0.000 claims description 3
• 239000005711 Benzoic acid Substances 0.000 claims description 3
• 235000010233 benzoic acid Nutrition 0.000 claims description 3
• PEKGQBRIPBJYKL-DEOSSOPVSA-N (6as)-3-[[4-(4-pyrazin-2-ylphenyl)piperazin-1-yl]methyl]-5,6a,7,8,9,10-hexahydrodipyrido[1,2-c:2',3'-f]pyrazin-6-one Chemical compound O=C([C@@H]1CCCCN1C1=NC=2)NC1=CC=2CN(CC1)CCN1C(C=C1)=CC=C1C1=CN=CC=N1 PEKGQBRIPBJYKL-DEOSSOPVSA-N 0.000 claims description 2
• NKKGGAZFAYKORV-VWLOTQADSA-N (6as)-3-[[4-(4-pyridin-3-ylphenyl)piperazin-1-yl]methyl]-5,6a,7,8,9,10-hexahydrodipyrido[1,2-c:2',3'-f]pyrazin-6-one Chemical compound O=C([C@@H]1CCCCN1C1=NC=2)NC1=CC=2CN(CC1)CCN1C(C=C1)=CC=C1C1=CC=CN=C1 NKKGGAZFAYKORV-VWLOTQADSA-N 0.000 claims description 2
• YMEXLMCPEWLIMU-DEOSSOPVSA-N (6as)-3-[[4-(4-pyrimidin-5-ylphenyl)piperazin-1-yl]methyl]-5,6a,7,8,9,10-hexahydrodipyrido[1,2-c:2',3'-f]pyrazin-6-one Chemical compound O=C([C@@H]1CCCCN1C1=NC=2)NC1=CC=2CN(CC1)CCN1C(C=C1)=CC=C1C1=CN=CN=C1 YMEXLMCPEWLIMU-DEOSSOPVSA-N 0.000 claims description 2
• PWQSVGZXVDVVLV-DEOSSOPVSA-N (6as)-3-[[4-(4-thiophen-3-ylphenyl)piperazin-1-yl]methyl]-5,6a,7,8,9,10-hexahydrodipyrido[1,2-c:2',3'-f]pyrazin-6-one Chemical compound O=C([C@@H]1CCCCN1C1=NC=2)NC1=CC=2CN(CC1)CCN1C(C=C1)=CC=C1C=1C=CSC=1 PWQSVGZXVDVVLV-DEOSSOPVSA-N 0.000 claims description 2
• KHIKTQUSCVHPBH-MHZLTWQESA-N (6as)-3-[[4-[4-(2-methylphenyl)phenyl]piperazin-1-yl]methyl]-5,6a,7,8,9,10-hexahydrodipyrido[1,2-c:2',3'-f]pyrazin-6-one Chemical compound CC1=CC=CC=C1C1=CC=C(N2CCN(CC=3C=C4NC(=O)[C@@H]5CCCCN5C4=NC=3)CC2)C=C1 KHIKTQUSCVHPBH-MHZLTWQESA-N 0.000 claims description 2
• PIMNAEQRVXQMJG-DEOSSOPVSA-N (6as)-3-[[4-[4-(6-aminopyridin-2-yl)phenyl]piperazin-1-yl]methyl]-5,6a,7,8,9,10-hexahydrodipyrido[1,2-c:2',3'-f]pyrazin-6-one Chemical compound NC1=CC=CC(C=2C=CC(=CC=2)N2CCN(CC=3C=C4NC(=O)[C@@H]5CCCCN5C4=NC=3)CC2)=N1 PIMNAEQRVXQMJG-DEOSSOPVSA-N 0.000 claims description 2
• WXCXFGAVUXTISL-QHCPKHFHSA-N (s)-3-((4-(4-(pyrrolidine-1-carbonyl)phenyl)piperazin-1-yl)methyl)-6a,7,8,9-tetrahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-6(5h)-one Chemical compound C=1C=C(N2CCN(CC=3C=C4NC(=O)[C@@H]5CCCN5C4=NC=3)CC2)C=CC=1C(=O)N1CCCC1 WXCXFGAVUXTISL-QHCPKHFHSA-N 0.000 claims description 2
• PPAJOMSDKOMGSS-IBGZPJMESA-N (s)-3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-6a,7,8,9-tetrahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-6(5h)-one Chemical compound C1=CC(Cl)=CC=C1N1CCN(CC=2C=C3NC(=O)[C@@H]4CCCN4C3=NC=2)CC1 PPAJOMSDKOMGSS-IBGZPJMESA-N 0.000 claims description 2
• JXLUEBGLWGRHIZ-FQEVSTJZSA-N (s)-3-chloro-4-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)benzonitrile Chemical compound ClC1=CC(C#N)=CC=C1N1CCN(CC=2C=C3NC(=O)[C@@H]4CCCN4C3=NC=2)CC1 JXLUEBGLWGRHIZ-FQEVSTJZSA-N 0.000 claims description 2
• MQNHZGGPZLIVLI-QFIPXVFZSA-N (s)-3-fluoro-n-isopropyl-4-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)benzamide Chemical compound FC1=CC(C(=O)NC(C)C)=CC=C1N1CCN(CC=2C=C3NC(=O)[C@@H]4CCCN4C3=NC=2)CC1 MQNHZGGPZLIVLI-QFIPXVFZSA-N 0.000 claims description 2
• WQKKUQDJDLOLIP-NRFANRHFSA-N (s)-3-methyl-4-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)benzonitrile Chemical compound CC1=CC(C#N)=CC=C1N1CCN(CC=2C=C3NC(=O)[C@@H]4CCCN4C3=NC=2)CC1 WQKKUQDJDLOLIP-NRFANRHFSA-N 0.000 claims description 2
• SVIWPAOOEMGLFF-QHCPKHFHSA-N (s)-n-cyclopropyl-3-methyl-4-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)b enzamide Chemical compound C=1C=C(N2CCN(CC=3C=C4NC(=O)[C@@H]5CCCN5C4=NC=3)CC2)C(C)=CC=1C(=O)NC1CC1 SVIWPAOOEMGLFF-QHCPKHFHSA-N 0.000 claims description 2
• JDXBBXHDCDMRAI-QFIPXVFZSA-N (s)-n-ethyl-3-methyl-4-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)benzamide Chemical compound CC1=CC(C(=O)NCC)=CC=C1N1CCN(CC=2C=C3NC(=O)[C@@H]4CCCN4C3=NC=2)CC1 JDXBBXHDCDMRAI-QFIPXVFZSA-N 0.000 claims description 2
• QWHQAPPPWWIOIF-IBGZPJMESA-N (s)-n-ethyl-6-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)nicotinamide Chemical compound N1=CC(C(=O)NCC)=CC=C1N1CCN(CC=2C=C3NC(=O)[C@@H]4CCCN4C3=NC=2)CC1 QWHQAPPPWWIOIF-IBGZPJMESA-N 0.000 claims description 2
• DXFWZZTUEGKQMI-FQEVSTJZSA-N (s)-n-isopropyl-6-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)nicotinamide Chemical compound N1=CC(C(=O)NC(C)C)=CC=C1N1CCN(CC=2C=C3NC(=O)[C@@H]4CCCN4C3=NC=2)CC1 DXFWZZTUEGKQMI-FQEVSTJZSA-N 0.000 claims description 2
• WBQJYGLXKWXXQU-FQEVSTJZSA-N (s)-n-methyl-4-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NC)=CC=C1N1CCN(CC=2C=C3NC(=O)[C@@H]4CCCN4C3=NC=2)CC1 WBQJYGLXKWXXQU-FQEVSTJZSA-N 0.000 claims description 2
• PVBIEGJRECSVFB-SFHVURJKSA-N (s)-n-methyl-6-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)nicotinamide Chemical compound N1=CC(C(=O)NC)=CC=C1N1CCN(CC=2C=C3NC(=O)[C@@H]4CCCN4C3=NC=2)CC1 PVBIEGJRECSVFB-SFHVURJKSA-N 0.000 claims description 2
• VMJNTFXCTXAXTC-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-5-carbonitrile Chemical group C1=C(C#N)C=C2OC(F)(F)OC2=C1 VMJNTFXCTXAXTC-UHFFFAOYSA-N 0.000 claims description 2
• FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 claims description 2
• QMLGFBXRJBLSKM-IBGZPJMESA-N 4-[4-[[(6ar)-6-oxo-6a,7,9,10-tetrahydro-5h-pyrido[1,2]pyrazino[4,6-a][1,4]thiazin-3-yl]methyl]piperazin-1-yl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1N1CCN(CC=2C=C3NC(=O)[C@@H]4CSCCN4C3=NC=2)CC1 QMLGFBXRJBLSKM-IBGZPJMESA-N 0.000 claims description 2
• LZNRFJNVVOWKJW-UHFFFAOYSA-N 6-[4-[(6-oxo-6a,7,9,10-tetrahydro-5h-pyrido[1,2]pyrazino[4,6-a][1,4]oxazin-3-yl)methyl]piperazin-1-yl]pyridine-3-carbonitrile Chemical compound C=1N=C2N3CCOCC3C(=O)NC2=CC=1CN(CC1)CCN1C1=CC=C(C#N)C=N1 LZNRFJNVVOWKJW-UHFFFAOYSA-N 0.000 claims description 2
• WIAZQDYZWUNBEI-UHFFFAOYSA-N C1=CC(C(=O)NCC)=CC=C1N1CCN(CC=2C=C3C(N4C=CC=C4C(=O)N3)=NC=2)CC1 Chemical compound C1=CC(C(=O)NCC)=CC=C1N1CCN(CC=2C=C3C(N4C=CC=C4C(=O)N3)=NC=2)CC1 WIAZQDYZWUNBEI-UHFFFAOYSA-N 0.000 claims description 2
• ILTFFEOFCFQLET-IBGZPJMESA-N O=C([C@@H]1CCCN1C1=NC=2)NC1=CC=2CN(CC1)CCN1C1=CC=C(C#N)N=C1 Chemical compound O=C([C@@H]1CCCN1C1=NC=2)NC1=CC=2CN(CC1)CCN1C1=CC=C(C#N)N=C1 ILTFFEOFCFQLET-IBGZPJMESA-N 0.000 claims description 2
• 239000013543 active substance Substances 0.000 claims description 2
• DWHFRZOTMVVCMV-NRFANRHFSA-N ethyl 4-[4-[[(6ar)-6-oxo-6a,7,9,10-tetrahydro-5h-pyrido[1,2]pyrazino[4,6-a][1,4]thiazin-3-yl]methyl]piperazin-1-yl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1N1CCN(CC=2C=C3NC(=O)[C@@H]4CSCCN4C3=NC=2)CC1 DWHFRZOTMVVCMV-NRFANRHFSA-N 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• 229910052727 yttrium Inorganic materials 0.000 claims description 2
• 150000002431 hydrogen Chemical class 0.000 claims 18
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 17
• WPYMKLBDIGXBTP-UHFFFAOYSA-M benzoate Chemical compound [O-]C(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-M 0.000 claims 2
• UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 claims 2
• 229960003512 nicotinic acid Drugs 0.000 claims 2
• AWKIAHXVBHQHPS-SANMLTNESA-N (6as)-3-[[4-[4-(4-methylpyridin-2-yl)phenyl]piperazin-1-yl]methyl]-5,6a,7,8,9,10-hexahydrodipyrido[1,2-c:2',3'-f]pyrazin-6-one Chemical compound CC1=CC=NC(C=2C=CC(=CC=2)N2CCN(CC=3C=C4NC(=O)[C@@H]5CCCCN5C4=NC=3)CC2)=C1 AWKIAHXVBHQHPS-SANMLTNESA-N 0.000 claims 1
• CKGPVOCSMDTBML-IBGZPJMESA-N (s)-4-(4-((6-oxo-6,6a,7,8-tetrahydro-5h-azeto[1,2-a]pyrido[3,2-e]pyrazin-3-yl)methyl)piperazin-1-yl)benzonitrile Chemical compound O=C([C@@H]1CCN1C1=NC=2)NC1=CC=2CN(CC1)CCN1C1=CC=C(C#N)C=C1 CKGPVOCSMDTBML-IBGZPJMESA-N 0.000 claims 1
• LBUIDXDGCKDDAL-IBGZPJMESA-N (s)-ethyl 6-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)nicotinate Chemical compound N1=CC(C(=O)OCC)=CC=C1N1CCN(CC=2C=C3NC(=O)[C@@H]4CCCN4C3=NC=2)CC1 LBUIDXDGCKDDAL-IBGZPJMESA-N 0.000 claims 1
• YHFQEXHSPMFQEW-NRFANRHFSA-N (s)-n,n-dimethyl-4-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)benzamide Chemical compound C1=CC(C(=O)N(C)C)=CC=C1N1CCN(CC=2C=C3NC(=O)[C@@H]4CCCN4C3=NC=2)CC1 YHFQEXHSPMFQEW-NRFANRHFSA-N 0.000 claims 1
• JCJXAMFPGJGHDE-NRFANRHFSA-N (s)-n-ethyl-4-(4-((6-oxo-5,6,6a,7,8,9-hexahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-3-yl)methyl)piperazin-1-yl)benzamide Chemical compound C1=CC(C(=O)NCC)=CC=C1N1CCN(CC=2C=C3NC(=O)[C@@H]4CCCN4C3=NC=2)CC1 JCJXAMFPGJGHDE-NRFANRHFSA-N 0.000 claims 1
• WYIZZTHRNWSIGO-IBGZPJMESA-N 2,5-difluoro-4-[4-[[(6S)-7-oxo-2,8,13-triazatricyclo[7.4.0.02,6]trideca-1(9),10,12-trien-11-yl]methyl]piperazin-1-yl]benzonitrile Chemical compound C1=C(C#N)C(F)=CC(N2CCN(CC=3C=C4NC(=O)[C@@H]5CCCN5C4=NC=3)CC2)=C1F WYIZZTHRNWSIGO-IBGZPJMESA-N 0.000 claims 1
• COYPKBHELNSTBR-NRFANRHFSA-N 4-[4-[[(6ar)-6-oxo-6a,7,9,10-tetrahydro-5h-pyrido[1,2]pyrazino[4,6-a][1,4]thiazin-3-yl]methyl]piperazin-1-yl]-n-ethylbenzamide Chemical compound C1=CC(C(=O)NCC)=CC=C1N1CCN(CC=2C=C3NC(=O)[C@@H]4CSCCN4C3=NC=2)CC1 COYPKBHELNSTBR-NRFANRHFSA-N 0.000 claims 1
• JZOZHLOLABSZBS-FQEVSTJZSA-N C1=CC(Cl)=CC=C1C(CC1)=CCN1CC1=CN=C(N2[C@@H](CCC2)C(=O)N2)C2=C1 Chemical compound C1=CC(Cl)=CC=C1C(CC1)=CCN1CC1=CN=C(N2[C@@H](CCC2)C(=O)N2)C2=C1 JZOZHLOLABSZBS-FQEVSTJZSA-N 0.000 claims 1
• WPYMKLBDIGXBTP-VQEHIDDOSA-N benzoic acid Chemical compound OC(=O)C1=CC=C[13CH]=C1 WPYMKLBDIGXBTP-VQEHIDDOSA-N 0.000 claims 1
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