KR102438302B1 - 리신 특이적 데메틸라제-1의 억제제 - Google Patents
리신 특이적 데메틸라제-1의 억제제 Download PDFInfo
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- KR102438302B1 KR102438302B1 KR1020177000953A KR20177000953A KR102438302B1 KR 102438302 B1 KR102438302 B1 KR 102438302B1 KR 1020177000953 A KR1020177000953 A KR 1020177000953A KR 20177000953 A KR20177000953 A KR 20177000953A KR 102438302 B1 KR102438302 B1 KR 102438302B1
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- KR
- South Korea
- Prior art keywords
- oxo
- methyl
- benzonitrile
- amino
- optionally substituted
- Prior art date
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- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 239000004472 Lysine Substances 0.000 title claims abstract description 17
- 239000003112 inhibitor Substances 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 239
- -1 heterocycle derivative compound Chemical class 0.000 claims abstract description 218
- 238000000034 method Methods 0.000 claims abstract description 110
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 31
- 201000011510 cancer Diseases 0.000 claims abstract description 14
- 238000011282 treatment Methods 0.000 claims abstract description 11
- 239000008194 pharmaceutical composition Chemical class 0.000 claims abstract description 10
- 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
- 150000003839 salts Chemical class 0.000 claims description 93
- 229910052736 halogen Inorganic materials 0.000 claims description 89
- 150000002367 halogens Chemical group 0.000 claims description 85
- 125000000623 heterocyclic group Chemical group 0.000 claims description 55
- 125000000217 alkyl group Chemical group 0.000 claims description 51
- 125000001072 heteroaryl group Chemical group 0.000 claims description 37
- 150000003254 radicals Chemical class 0.000 claims description 35
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 24
- 239000001257 hydrogen Substances 0.000 claims description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 101000615488 Homo sapiens Methyl-CpG-binding domain protein 2 Proteins 0.000 claims description 20
- 102100021299 Methyl-CpG-binding domain protein 2 Human genes 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- 125000005843 halogen group Chemical group 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 230000000694 effects Effects 0.000 claims description 12
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 11
- 108090000623 proteins and genes Proteins 0.000 claims description 10
- 102000004190 Enzymes Human genes 0.000 claims description 9
- 108090000790 Enzymes Proteins 0.000 claims description 9
- 125000005842 heteroatom Chemical group 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 230000002401 inhibitory effect Effects 0.000 claims description 8
- 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
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 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
- 238000013518 transcription Methods 0.000 claims description 5
- 230000035897 transcription Effects 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
- 238000000338 in vitro Methods 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 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
- GFWMMMILHYKACP-KRWDZBQOSA-N 2-fluoro-4-[4-(2-hydroxyethyl)-3-(4-methylphenyl)-5-oxo-6-[[(3S)-pyrrolidin-3-yl]methylamino]pyrazin-2-yl]benzonitrile Chemical compound CC1=CC=C(C=C1)C1=C(N=C(NC[C@H]2CCNC2)C(=O)N1CCO)C1=CC(F)=C(C=C1)C#N GFWMMMILHYKACP-KRWDZBQOSA-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
- BUKAFMZJQWSLPI-SFHVURJKSA-N 2-fluoro-4-[4-(2-methoxyethyl)-3-(4-methylphenyl)-5-oxo-6-[[(3S)-pyrrolidin-3-yl]methylamino]pyrazin-2-yl]benzonitrile Chemical compound COCCN1C(=O)C(NC[C@H]2CCNC2)=NC(C2=CC(F)=C(C=C2)C#N)=C1C1=CC=C(C)C=C1 BUKAFMZJQWSLPI-SFHVURJKSA-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
- 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
- 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
- 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
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- ZFHBHZXQPJGRCR-UHFFFAOYSA-N tert-butyl N-[1-[6-(4-cyanophenyl)-4-methyl-5-(4-methylphenyl)-3-oxopyrazin-2-yl]piperidin-4-yl]carbamate Chemical compound CN1C(=O)C(=NC(C2=CC=C(C=C2)C#N)=C1C1=CC=C(C)C=C1)N1CCC(CC1)NC(=O)OC(C)(C)C ZFHBHZXQPJGRCR-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- 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
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- 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
- 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
- C07D401/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D405/14—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 three or more hetero rings
-
- 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
-
- 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
- C07D471/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
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- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Polyamides (AREA)
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| PL3160956T3 (pl) | 2014-06-27 | 2020-11-30 | Celgene Quanticel Research, Inc. | Inhibitory demetylazy-1 specyficznej dla lizyny |
| SMT202300205T1 (it) * | 2014-07-03 | 2023-09-06 | Celgene Quanticel Research Inc | Inibitori della demetilasi lisina-specifica-1 |
| ES3005884T3 (en) | 2015-02-12 | 2025-03-17 | Imago Biosciences Inc | A kdm1a inhibitor and its use in therapy |
| US20180284095A1 (en) | 2015-06-12 | 2018-10-04 | Oryzon Genomics, S.A. | Biomarkers associated with lsd1 inhibitors and uses thereof |
| WO2017013061A1 (en) | 2015-07-17 | 2017-01-26 | Oryzon Genomics, S.A. | Biomarkers associated with lsd1 inhibitors and uses thereof |
| CN120661674A (zh) | 2016-03-15 | 2025-09-19 | 奥莱松基因组股份有限公司 | 用于治疗实体瘤的lsd1抑制剂的组合 |
| US11034991B2 (en) | 2016-03-16 | 2021-06-15 | Oryzon Genomics S.A. | Methods to determine KDM1A target engagement and chemoprobes useful therefor |
| US10150754B2 (en) | 2016-04-19 | 2018-12-11 | Celgene Quanticel Research, Inc. | Histone demethylase inhibitors |
| WO2018035259A1 (en) | 2016-08-16 | 2018-02-22 | Imago Biosciences, Inc. | Methods and processes for the preparation of kdm1a inhibitors |
| WO2018083189A1 (en) | 2016-11-03 | 2018-05-11 | Oryzon Genomics, S.A. | Biomarkers for determining responsiveness to lsd1 inhibitors |
| JP7071962B2 (ja) * | 2017-04-10 | 2022-05-19 | 三井化学アグロ株式会社 | ピリドン化合物と有害生物防除剤を含有する有害生物防除組成物および有害生物の防除方法 |
| JP2020121925A (ja) * | 2017-04-10 | 2020-08-13 | 三井化学アグロ株式会社 | ピリドン化合物とキノリン系化合物を含有する有害生物防除組成物および有害生物の防除方法、ならびに新規キノリン系化合物 |
| WO2018190324A1 (ja) * | 2017-04-10 | 2018-10-18 | 三井化学アグロ株式会社 | ピリドン化合物を有効成分として含有する抗真菌剤およびその使用方法 |
| CA3071804A1 (en) | 2017-08-03 | 2019-02-07 | Oryzon Genomics, S.A. | Use of a kdm1a inhibitor in the treatment of behavior alterations |
| CN112368272B (zh) * | 2018-03-21 | 2023-04-21 | 苏州浦合医药科技有限公司 | Shp2抑制剂及其用途 |
| IL279260B2 (en) * | 2018-05-11 | 2024-10-01 | Imago Biosciences Inc | Kdm1a inhibitors for the treatment of disease |
| HRP20260110T1 (hr) | 2019-03-20 | 2026-03-13 | Oryzon Genomics, S.A. | Vafidemstat za liječenje neagresivnih simptoma graničnog poremećaja osobnosti |
| CN113631164A (zh) | 2019-03-20 | 2021-11-09 | 奥莱松基因组股份有限公司 | 使用kdm1a抑制剂如化合物伐菲德司他治疗注意缺陷多动症的方法 |
| JP2022546908A (ja) | 2019-07-05 | 2022-11-10 | オリゾン・ゲノミクス・ソシエダッド・アノニマ | Ｋｄｍ１ａ阻害剤を使用した小細胞肺がんの個別化された処置のためのバイオマーカーおよび方法 |
| MX2023011779A (es) | 2021-04-08 | 2023-11-22 | Oryzon Genomics Sa | Combinaciones de inhibidores de lsd1 para el tratamiento de canceres mieloides. |
| WO2022267495A1 (zh) * | 2021-06-22 | 2022-12-29 | 南昌弘益药业有限公司 | 含氮氧杂螺环类化合物及其应用 |
| WO2023069884A1 (en) * | 2021-10-18 | 2023-04-27 | Imago Biosciences, Inc. | Kdm1a inhibitors for the treatment of disease |
| CN119497613A (zh) | 2022-05-09 | 2025-02-21 | 奥莱松基因组股份有限公司 | 使用lsd1抑制剂治疗nf1-突变肿瘤的方法 |
| US20250275969A1 (en) | 2022-05-09 | 2025-09-04 | Oryzon Genomics, S.A. | Methods of treating malignant peripheral nerve sheath tumor (mpnst) using lsd1 inhibitors |
| CN120529900A (zh) | 2022-11-24 | 2025-08-22 | 奥莱松基因组股份有限公司 | 用于治疗癌症的LSD1抑制剂和Menin抑制剂的组合 |
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| JP2008533147A (ja) | 2005-03-14 | 2008-08-21 | メルク エンド カムパニー インコーポレーテッド | Ｃｇｒｐ受容体拮抗薬 |
| US20130012523A1 (en) | 2007-06-27 | 2013-01-10 | Stephen Brough | Pyrazinone derivatives, pharmaceutically acceptable salts thereof and their uses |
| US20130197013A1 (en) | 2010-07-29 | 2013-08-01 | Mathew Colin Thor Fyfe | Cyclopropylamine derivatives useful as lsd1 inhibitors |
| US20130331382A1 (en) | 2012-06-12 | 2013-12-12 | Abbvie Inc | Pyridinone and Pyridazinone Derivatives |
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| WO2007149448A2 (en) | 2006-06-21 | 2007-12-27 | E. I. Du Pont De Nemours And Company | Pyrazinones as cellular proliferation inhibitors |
| CL2008002793A1 (es) * | 2007-09-20 | 2009-09-04 | Cgi Pharmaceuticals Inc | Compuestos derivados de amidas sustituidas, inhibidores de la actividad de btk; composicion farmaceutica que los comprende; utiles en el tratamiento del cancer, trastornos oseos, enfermedades autoinmunes, entre otras |
| CA3161836A1 (en) * | 2013-12-11 | 2015-06-18 | Celgene Quanticel Research, Inc. | Inhibitors of lysine specific demethylase-1 |
| CN103804312B (zh) * | 2014-02-17 | 2016-04-20 | 四川百利药业有限责任公司 | 一类氮杂环化合物及其制备方法和用途 |
| PE20161438A1 (es) * | 2014-05-01 | 2017-01-18 | Celgene Quanticel Res Inc | Inhibidores de desmetilasa 1 especifica a lisina |
| PL3160956T3 (pl) | 2014-06-27 | 2020-11-30 | Celgene Quanticel Research, Inc. | Inhibitory demetylazy-1 specyficznej dla lizyny |
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| JP2008533147A (ja) | 2005-03-14 | 2008-08-21 | メルク エンド カムパニー インコーポレーテッド | Ｃｇｒｐ受容体拮抗薬 |
| US20130012523A1 (en) | 2007-06-27 | 2013-01-10 | Stephen Brough | Pyrazinone derivatives, pharmaceutically acceptable salts thereof and their uses |
| US20130197013A1 (en) | 2010-07-29 | 2013-08-01 | Mathew Colin Thor Fyfe | Cyclopropylamine derivatives useful as lsd1 inhibitors |
| US20130331382A1 (en) | 2012-06-12 | 2013-12-12 | Abbvie Inc | Pyridinone and Pyridazinone Derivatives |
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