BR112016030697B1 - Compostos inibidores de desmetilase-1 lisina-específica, composição farmacêutica e seus usos - Google Patents

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Publication number

BR112016030697B1

BR112016030697B1 BR112016030697-0A BR112016030697A BR112016030697B1 BR 112016030697 B1 BR112016030697 B1 BR 112016030697B1 BR 112016030697 A BR112016030697 A BR 112016030697A BR 112016030697 B1 BR112016030697 B1 BR 112016030697B1

Authority

BR

Brazil

Prior art keywords

oxo

methyl

benzonitrile

amino

optionally substituted

Prior art date

2014-06-27

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 243
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 10
• 239000003112 inhibitor Substances 0.000 title abstract description 10
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 50
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 29
• 201000011510 cancer Diseases 0.000 claims abstract description 15
• 206010005003 Bladder cancer Diseases 0.000 claims abstract description 5
• 206010006187 Breast cancer Diseases 0.000 claims abstract description 5
• 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 5
• 206010058467 Lung neoplasm malignant Diseases 0.000 claims abstract description 5
• 206010060862 Prostate cancer Diseases 0.000 claims abstract description 5
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims abstract description 5
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims abstract description 5
• 201000005202 lung cancer Diseases 0.000 claims abstract description 5
• 208000020816 lung neoplasm Diseases 0.000 claims abstract description 5
• 201000001441 melanoma Diseases 0.000 claims abstract description 5
• 201000005112 urinary bladder cancer Diseases 0.000 claims abstract description 5
• -1 4-aminopiperidinyl Chemical group 0.000 claims description 231
• 238000002360 preparation method Methods 0.000 claims description 111
• 229910052736 halogen Inorganic materials 0.000 claims description 89
• 150000003839 salts Chemical class 0.000 claims description 89
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 85
• 125000000217 alkyl group Chemical group 0.000 claims description 51
• 125000001072 heteroaryl group Chemical group 0.000 claims description 38
• 125000003118 aryl group Chemical group 0.000 claims description 23
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 23
• 229910052757 nitrogen Inorganic materials 0.000 claims description 21
• 239000001257 hydrogen Substances 0.000 claims description 20
• 229910052739 hydrogen Inorganic materials 0.000 claims description 20
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
• 125000005843 halogen group Chemical group 0.000 claims description 15
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 10
• 108090000623 proteins and genes Proteins 0.000 claims description 9
• 125000003545 alkoxy group Chemical group 0.000 claims description 8
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
• 125000005842 heteroatom Chemical group 0.000 claims description 8
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 6
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
• 125000004076 pyridyl group Chemical group 0.000 claims description 5
• 238000013518 transcription Methods 0.000 claims description 5
• 230000035897 transcription Effects 0.000 claims description 5
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 4
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 3
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
• BVMMSCHMTZVYRO-UHFFFAOYSA-N 2-[5-(4-aminopiperidin-1-yl)-3-(4-cyano-3-fluorophenyl)-2-(4-methoxyphenyl)-6-oxopyrazin-1-yl]acetamide Chemical compound COc1ccc(cc1)-c1c(nc(N2CCC(N)CC2)c(=O)n1CC(N)=O)-c1ccc(C#N)c(F)c1 BVMMSCHMTZVYRO-UHFFFAOYSA-N 0.000 claims description 2
• AMBKIZTVZPKPTQ-UHFFFAOYSA-N 2-fluoro-4-[2-(3-fluoro-4-methoxyphenyl)-1-methyl-5-[4-(methylamino)piperidin-1-yl]-6-oxopyridin-3-yl]benzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)C1=C(N(C(C(=C1)N1CCC(CC1)NC)=O)C)C1=CC(=C(C=C1)OC)F AMBKIZTVZPKPTQ-UHFFFAOYSA-N 0.000 claims description 2
• FKYGCMCSIKCVCF-UHFFFAOYSA-N 2-fluoro-4-[2-(4-methoxyphenyl)-1-methyl-5-[4-(methylamino)piperidin-1-yl]-6-oxopyridin-3-yl]benzonitrile Chemical compound CNC1CCN(CC1)C1=CC(C2=CC(F)=C(C=C2)C#N)=C(N(C)C1=O)C1=CC=C(OC)C=C1 FKYGCMCSIKCVCF-UHFFFAOYSA-N 0.000 claims description 2
• GNKYLQHFISWUOT-INIZCTEOSA-N 2-fluoro-4-[2-(4-methoxyphenyl)-1-methyl-6-oxo-5-[[(3S)-pyrrolidin-3-yl]methylamino]pyridin-3-yl]benzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)C1=C(N(C(C(=C1)NC[C@@H]1CNCC1)=O)C)C1=CC=C(C=C1)OC GNKYLQHFISWUOT-INIZCTEOSA-N 0.000 claims description 2
• HMNSDEAJDFBELC-HNNXBMFYSA-N 2-fluoro-4-[3-(4-methoxyphenyl)-4-methyl-5-oxo-6-[[(3S)-pyrrolidin-3-yl]methylamino]pyrazin-2-yl]benzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)C=1N=C(C(N(C=1C1=CC=C(C=C1)OC)C)=O)NC[C@@H]1CNCC1 HMNSDEAJDFBELC-HNNXBMFYSA-N 0.000 claims description 2
• AZBWVQOOBQSMEF-UHFFFAOYSA-N 2-fluoro-4-[4-(2-hydroxyethyl)-6-[4-(methylamino)piperidin-1-yl]-3-(4-methylphenyl)-5-oxopyrazin-2-yl]benzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)C=1N=C(C(N(C=1C1=CC=C(C=C1)C)CCO)=O)N1CCC(CC1)NC AZBWVQOOBQSMEF-UHFFFAOYSA-N 0.000 claims description 2
• VNAMIJQOOCNRAC-UHFFFAOYSA-N 2-fluoro-4-[4-(3-hydroxypropyl)-6-[4-(methylamino)piperidin-1-yl]-3-(4-methylphenyl)-5-oxopyrazin-2-yl]benzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)C=1N=C(C(N(C=1C1=CC=C(C=C1)C)CCCO)=O)N1CCC(CC1)NC VNAMIJQOOCNRAC-UHFFFAOYSA-N 0.000 claims description 2
• GXYJAMNVLXCFPP-AWEZNQCLSA-N 2-fluoro-4-[4-methyl-5-oxo-6-[[(3S)-pyrrolidin-3-yl]methylamino]-3-[4-(trifluoromethoxy)phenyl]pyrazin-2-yl]benzonitrile Chemical compound FC1=C(C#N)C=CC(=C1)C=1N=C(C(N(C=1C1=CC=C(C=C1)OC(F)(F)F)C)=O)NC[C@@H]1CNCC1 GXYJAMNVLXCFPP-AWEZNQCLSA-N 0.000 claims description 2
• RWNLXJGUOIZRKS-UHFFFAOYSA-N 3-[5-(4-aminopiperidin-1-yl)-3-(4-cyano-3-fluorophenyl)-2-(4-methoxyphenyl)-6-oxopyrazin-1-yl]propanamide Chemical compound COc1ccc(cc1)-c1c(nc(N2CCC(N)CC2)c(=O)n1CCC(N)=O)-c1ccc(C#N)c(F)c1 RWNLXJGUOIZRKS-UHFFFAOYSA-N 0.000 claims description 2
• TYZJQHVYGBCYAK-UHFFFAOYSA-N 4-[1-methyl-5-[4-(methylamino)piperidin-1-yl]-2-(4-methylphenyl)-6-oxopyridin-3-yl]benzonitrile Chemical compound CNC1CCN(CC1)C1=CC(C2=CC=C(C=C2)C#N)=C(N(C)C1=O)C1=CC=C(C)C=C1 TYZJQHVYGBCYAK-UHFFFAOYSA-N 0.000 claims description 2
• PIRBBOPADNXSKZ-KRWDZBQOSA-N 4-[2-(4-cyclopropylphenyl)-1-methyl-6-oxo-5-[[(3S)-pyrrolidin-3-yl]methylamino]pyridin-3-yl]-2-fluorobenzonitrile Chemical compound C1(CC1)C1=CC=C(C=C1)C=1N(C(C(=CC=1C1=CC(=C(C#N)C=C1)F)NC[C@@H]1CNCC1)=O)C PIRBBOPADNXSKZ-KRWDZBQOSA-N 0.000 claims description 2
• NGHZQIQVMRSJOS-SFHVURJKSA-N 4-[2-(4-ethylphenyl)-1-methyl-6-oxo-5-[[(3S)-pyrrolidin-3-yl]methylamino]pyridin-3-yl]-2-fluorobenzonitrile Chemical compound CCC1=CC=C(C=C1)C1=C(C=C(NC[C@H]2CCNC2)C(=O)N1C)C1=CC(F)=C(C=C1)C#N NGHZQIQVMRSJOS-SFHVURJKSA-N 0.000 claims description 2
• VOJZLWHSUQQPHK-UHFFFAOYSA-N 4-[2-(4-methoxyphenyl)-1-methyl-5-[4-(methylamino)piperidin-1-yl]-6-oxopyridin-3-yl]benzonitrile Chemical compound CNC1CCN(CC1)C1=CC(C2=CC=C(C=C2)C#N)=C(N(C)C1=O)C1=CC=C(OC)C=C1 VOJZLWHSUQQPHK-UHFFFAOYSA-N 0.000 claims description 2
• JJKHLYSGGIABCO-GOSISDBHSA-N 4-[3-(4-cyclopropylphenyl)-4-methyl-5-oxo-6-[[(3R)-pyrrolidin-3-yl]methylamino]pyrazin-2-yl]benzonitrile Chemical compound C1(CC1)C1=CC=C(C=C1)C1=C(N=C(C(N1C)=O)NC[C@H]1CNCC1)C1=CC=C(C#N)C=C1 JJKHLYSGGIABCO-GOSISDBHSA-N 0.000 claims description 2
• LQVUTYKLQHQKKD-INIZCTEOSA-N 4-[3-(4-cyclopropylphenyl)-4-methyl-5-oxo-6-[[(3S)-pyrrolidin-3-yl]methylamino]pyrazin-2-yl]-2-fluorobenzonitrile Chemical compound C1(CC1)C1=CC=C(C=C1)C1=C(N=C(C(N1C)=O)NC[C@@H]1CNCC1)C1=CC(=C(C#N)C=C1)F LQVUTYKLQHQKKD-INIZCTEOSA-N 0.000 claims description 2
• JJKHLYSGGIABCO-SFHVURJKSA-N 4-[3-(4-cyclopropylphenyl)-4-methyl-5-oxo-6-[[(3S)-pyrrolidin-3-yl]methylamino]pyrazin-2-yl]benzonitrile Chemical compound C1(CC1)C1=CC=C(C=C1)C1=C(N=C(C(N1C)=O)NC[C@@H]1CNCC1)C1=CC=C(C#N)C=C1 JJKHLYSGGIABCO-SFHVURJKSA-N 0.000 claims description 2
• JRLYEZIUSCNCGP-INIZCTEOSA-N 4-[3-(4-ethoxyphenyl)-4-methyl-5-oxo-6-[[(3S)-pyrrolidin-3-yl]methylamino]pyrazin-2-yl]-2-fluorobenzonitrile Chemical compound C(C)OC1=CC=C(C=C1)C1=C(N=C(C(N1C)=O)NC[C@@H]1CNCC1)C1=CC(=C(C#N)C=C1)F JRLYEZIUSCNCGP-INIZCTEOSA-N 0.000 claims description 2
• GMNOJUDCMFAXPA-LJQANCHMSA-N 4-[3-(4-ethylphenyl)-4-methyl-5-oxo-6-[[(3R)-pyrrolidin-3-yl]methylamino]pyrazin-2-yl]benzonitrile Chemical compound C(C)C1=CC=C(C=C1)C1=C(N=C(C(N1C)=O)NC[C@H]1CNCC1)C1=CC=C(C#N)C=C1 GMNOJUDCMFAXPA-LJQANCHMSA-N 0.000 claims description 2
• XMLPQBIHEWMCFM-KRWDZBQOSA-N 4-[3-(4-ethylphenyl)-4-methyl-5-oxo-6-[[(3S)-pyrrolidin-3-yl]methylamino]pyrazin-2-yl]-2-fluorobenzonitrile Chemical compound C(C)C1=CC=C(C=C1)C1=C(N=C(C(N1C)=O)NC[C@@H]1CNCC1)C1=CC(=C(C#N)C=C1)F XMLPQBIHEWMCFM-KRWDZBQOSA-N 0.000 claims description 2
• GMNOJUDCMFAXPA-IBGZPJMESA-N 4-[3-(4-ethylphenyl)-4-methyl-5-oxo-6-[[(3S)-pyrrolidin-3-yl]methylamino]pyrazin-2-yl]benzonitrile Chemical compound C(C)C1=CC=C(C=C1)C1=C(N=C(C(N1C)=O)NC[C@@H]1CNCC1)C1=CC=C(C#N)C=C1 GMNOJUDCMFAXPA-IBGZPJMESA-N 0.000 claims description 2
• IYUMXUWTJOXMFS-QGZVFWFLSA-N 4-[3-(4-methoxyphenyl)-4-methyl-5-oxo-6-[[(3R)-pyrrolidin-3-yl]methylamino]pyrazin-2-yl]benzonitrile Chemical compound COC1=CC=C(C=C1)C1=C(N=C(C(N1C)=O)NC[C@H]1CNCC1)C1=CC=C(C#N)C=C1 IYUMXUWTJOXMFS-QGZVFWFLSA-N 0.000 claims description 2
• IYUMXUWTJOXMFS-KRWDZBQOSA-N 4-[3-(4-methoxyphenyl)-4-methyl-5-oxo-6-[[(3S)-pyrrolidin-3-yl]methylamino]pyrazin-2-yl]benzonitrile Chemical compound COC1=CC=C(C=C1)C1=C(N=C(C(N1C)=O)NC[C@@H]1CNCC1)C1=CC=C(C#N)C=C1 IYUMXUWTJOXMFS-KRWDZBQOSA-N 0.000 claims description 2
• SQUOJCWNGIETBF-SFHVURJKSA-N 4-[3-[4-(cyclopropylmethoxy)phenyl]-4-methyl-5-oxo-6-[[(3S)-pyrrolidin-3-yl]methylamino]pyrazin-2-yl]-2-fluorobenzonitrile Chemical compound C1(CC1)COC1=CC=C(C=C1)C1=C(N=C(C(N1C)=O)NC[C@@H]1CNCC1)C1=CC(=C(C#N)C=C1)F SQUOJCWNGIETBF-SFHVURJKSA-N 0.000 claims description 2
• FNIJUSRGGUDIIM-GOSISDBHSA-N 4-[4-methyl-3-(4-methylphenyl)-5-oxo-6-[[(3R)-pyrrolidin-3-yl]methylamino]pyrazin-2-yl]benzonitrile Chemical compound CN1C(=C(N=C(C1=O)NC[C@H]1CNCC1)C1=CC=C(C#N)C=C1)C1=CC=C(C=C1)C FNIJUSRGGUDIIM-GOSISDBHSA-N 0.000 claims description 2
• FNIJUSRGGUDIIM-SFHVURJKSA-N 4-[4-methyl-3-(4-methylphenyl)-5-oxo-6-[[(3S)-pyrrolidin-3-yl]methylamino]pyrazin-2-yl]benzonitrile Chemical compound CN1C(=C(N=C(C1=O)NC[C@@H]1CNCC1)C1=CC=C(C#N)C=C1)C1=CC=C(C=C1)C FNIJUSRGGUDIIM-SFHVURJKSA-N 0.000 claims description 2
• JCGNLVXIPOIVDN-UHFFFAOYSA-N 4-[4-methyl-6-[4-(methylamino)piperidin-1-yl]-3-(4-methylphenyl)-5-oxopyrazin-2-yl]benzonitrile Chemical compound CN1C(=C(N=C(C1=O)N1CCC(CC1)NC)C1=CC=C(C#N)C=C1)C1=CC=C(C=C1)C JCGNLVXIPOIVDN-UHFFFAOYSA-N 0.000 claims description 2
• PCWSGEUEPJLWCJ-UHFFFAOYSA-N 4-[5-(4-aminopiperidin-1-yl)-1-(cyclopropylmethyl)-2-(4-methoxyphenyl)-6-oxopyridin-3-yl]-2-fluorobenzonitrile Chemical compound NC1CCN(CC1)C1=CC(=C(N(C1=O)CC1CC1)C1=CC=C(C=C1)OC)C1=CC(=C(C#N)C=C1)F PCWSGEUEPJLWCJ-UHFFFAOYSA-N 0.000 claims description 2
• GCPCWYIKDCPFJU-UHFFFAOYSA-N 4-[5-(4-aminopiperidin-1-yl)-1-(cyclopropylmethyl)-2-(4-methoxyphenyl)-6-oxopyridin-3-yl]benzonitrile Chemical compound NC1CCN(CC1)C1=CC(=C(N(C1=O)CC1CC1)C1=CC=C(C=C1)OC)C1=CC=C(C#N)C=C1 GCPCWYIKDCPFJU-UHFFFAOYSA-N 0.000 claims description 2
• KEFXVSWZJJSHAQ-UHFFFAOYSA-N 4-[5-(4-aminopiperidin-1-yl)-1-ethyl-2-(4-methoxyphenyl)-6-oxopyridin-3-yl]-2-fluorobenzonitrile Chemical compound NC1CCN(CC1)C1=CC(=C(N(C1=O)CC)C1=CC=C(C=C1)OC)C1=CC(=C(C#N)C=C1)F KEFXVSWZJJSHAQ-UHFFFAOYSA-N 0.000 claims description 2
• UAODWADQUMQWFF-UHFFFAOYSA-N 4-[5-(4-aminopiperidin-1-yl)-1-ethyl-2-(4-methoxyphenyl)-6-oxopyridin-3-yl]benzonitrile Chemical compound NC1CCN(CC1)C1=CC(=C(N(C1=O)CC)C1=CC=C(C=C1)OC)C1=CC=C(C#N)C=C1 UAODWADQUMQWFF-UHFFFAOYSA-N 0.000 claims description 2
• OHXOOCRRXDNMLR-UHFFFAOYSA-N 4-[5-(4-aminopiperidin-1-yl)-1-methyl-2-(4-methylphenyl)-6-oxopyridin-3-yl]-2-fluorobenzonitrile Chemical compound NC1CCN(CC1)C1=CC(=C(N(C1=O)C)C1=CC=C(C=C1)C)C1=CC(=C(C#N)C=C1)F OHXOOCRRXDNMLR-UHFFFAOYSA-N 0.000 claims description 2
• IZLXYASYOTWPIV-UHFFFAOYSA-N 4-[5-(4-aminopiperidin-1-yl)-1-methyl-2-(4-methylphenyl)-6-oxopyridin-3-yl]benzonitrile Chemical compound NC1CCN(CC1)C1=CC(=C(N(C1=O)C)C1=CC=C(C=C1)C)C1=CC=C(C#N)C=C1 IZLXYASYOTWPIV-UHFFFAOYSA-N 0.000 claims description 2
• CTWXOFMDXATANR-UHFFFAOYSA-N 4-[5-(4-aminopiperidin-1-yl)-2-(3-fluoro-4-methoxyphenyl)-1-methyl-6-oxopyridin-3-yl]-2-fluorobenzonitrile Chemical compound NC1CCN(CC1)C1=CC(=C(N(C1=O)C)C1=CC(=C(C=C1)OC)F)C1=CC(=C(C#N)C=C1)F CTWXOFMDXATANR-UHFFFAOYSA-N 0.000 claims description 2
• QFTURYYVMWHLTJ-UHFFFAOYSA-N 4-[5-(4-aminopiperidin-1-yl)-2-(3-fluoro-4-methoxyphenyl)-1-methyl-6-oxopyridin-3-yl]benzonitrile Chemical compound NC1CCN(CC1)C1=CC(=C(N(C1=O)C)C1=CC(=C(C=C1)OC)F)C1=CC=C(C#N)C=C1 QFTURYYVMWHLTJ-UHFFFAOYSA-N 0.000 claims description 2
• ZGPAIPTUZUSZIK-UHFFFAOYSA-N 4-[5-(4-aminopiperidin-1-yl)-2-(4-methoxyphenyl)-1-methyl-6-oxopyridin-3-yl]-2-fluorobenzonitrile Chemical compound NC1CCN(CC1)C1=CC(=C(N(C1=O)C)C1=CC=C(C=C1)OC)C1=CC(=C(C#N)C=C1)F ZGPAIPTUZUSZIK-UHFFFAOYSA-N 0.000 claims description 2
• WYXCJOHUPRUNNA-UHFFFAOYSA-N 4-[5-(4-aminopiperidin-1-yl)-2-(4-methoxyphenyl)-1-methyl-6-oxopyridin-3-yl]benzonitrile Chemical compound NC1CCN(CC1)C1=CC(=C(N(C1=O)C)C1=CC=C(C=C1)OC)C1=CC=C(C#N)C=C1 WYXCJOHUPRUNNA-UHFFFAOYSA-N 0.000 claims description 2
• OEJLBMDVHPTFDF-UHFFFAOYSA-N 4-[5-(4-aminopiperidin-1-yl)-3-(4-cyano-3-fluorophenyl)-2-(4-methoxyphenyl)-6-oxopyrazin-1-yl]butanamide Chemical compound COc1ccc(cc1)-c1c(nc(N2CCC(N)CC2)c(=O)n1CCCC(N)=O)-c1ccc(C#N)c(F)c1 OEJLBMDVHPTFDF-UHFFFAOYSA-N 0.000 claims description 2
• JKHMWVSHZWHZQX-UHFFFAOYSA-N 4-[6-(1,2,3,3a,4,6,7,7a-octahydropyrrolo[3,4-c]pyridin-5-yl)-4-methyl-3-(4-methylphenyl)-5-oxopyrazin-2-yl]benzonitrile Chemical compound CN1C(=C(N=C(C1=O)N1CC2C(CC1)CNC2)C1=CC=C(C#N)C=C1)C1=CC=C(C=C1)C JKHMWVSHZWHZQX-UHFFFAOYSA-N 0.000 claims description 2
• FUKABXYCAMJWMC-UHFFFAOYSA-N 4-[6-(2,3,3a,4,5,7,8,8a-octahydro-1H-pyrrolo[3,4-d]azepin-6-yl)-4-methyl-3-(4-methylphenyl)-5-oxopyrazin-2-yl]benzonitrile Chemical compound C1NCC2C1CCN(CC2)C=1C(N(C(=C(N=1)C1=CC=C(C#N)C=C1)C1=CC=C(C=C1)C)C)=O FUKABXYCAMJWMC-UHFFFAOYSA-N 0.000 claims description 2
• IHKIOZCQPHFFEP-UHFFFAOYSA-N 4-[6-(2,8-diazaspiro[4.5]decan-8-yl)-4-methyl-3-(4-methylphenyl)-5-oxopyrazin-2-yl]benzonitrile Chemical compound C1NCCC11CCN(CC1)C=1C(N(C(=C(N=1)C1=CC=C(C#N)C=C1)C1=CC=C(C=C1)C)C)=O IHKIOZCQPHFFEP-UHFFFAOYSA-N 0.000 claims description 2
• KUZLABBZFDJWSH-UHFFFAOYSA-N 4-[6-(3-aminopiperidin-1-yl)-4-methyl-3-(4-methylphenyl)-5-oxopyrazin-2-yl]benzonitrile Chemical compound NC1CN(CCC1)C=1C(N(C(=C(N=1)C1=CC=C(C#N)C=C1)C1=CC=C(C=C1)C)C)=O KUZLABBZFDJWSH-UHFFFAOYSA-N 0.000 claims description 2
• PUIOIFVTVNOUJL-UHFFFAOYSA-N 4-[6-(4-aminopiperidin-1-yl)-3-(4-cyclopropylphenyl)-4-(2-hydroxyethyl)-5-oxopyrazin-2-yl]benzonitrile Chemical compound NC1CCN(CC1)C=1C(N(C(=C(N=1)C1=CC=C(C#N)C=C1)C1=CC=C(C=C1)C1CC1)CCO)=O PUIOIFVTVNOUJL-UHFFFAOYSA-N 0.000 claims description 2
• RWFYTOFCBAGOBU-UHFFFAOYSA-N 4-[6-(4-aminopiperidin-1-yl)-3-(4-cyclopropylphenyl)-4-methyl-5-oxopyrazin-2-yl]-2-fluorobenzonitrile Chemical compound NC1CCN(CC1)C=1C(N(C(=C(N=1)C1=CC(=C(C#N)C=C1)F)C1=CC=C(C=C1)C1CC1)C)=O RWFYTOFCBAGOBU-UHFFFAOYSA-N 0.000 claims description 2
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