IL279728B2 - Modified naphthyridinone compounds useful as t-cell activators - Google Patents
Modified naphthyridinone compounds useful as t-cell activatorsInfo
- Publication number
- IL279728B2 IL279728B2 IL279728A IL27972820A IL279728B2 IL 279728 B2 IL279728 B2 IL 279728B2 IL 279728 A IL279728 A IL 279728A IL 27972820 A IL27972820 A IL 27972820A IL 279728 B2 IL279728 B2 IL 279728B2
- Authority
- IL
- Israel
- Prior art keywords
- methyl
- dihydro
- oxo
- naphthyridine
- carbonitrile
- Prior art date
Links
- 229940126530 T cell activator Drugs 0.000 title 1
- VHSIAYLBCLUAFT-UHFFFAOYSA-N n-[3-acetyl-6-(4-chlorophenyl)-7-(2,4-dichlorophenyl)-1-methyl-2-oxo-1,8-naphthyridin-4-yl]acetamide Chemical class C=1C=C(Cl)C=CC=1C=1C=C2C(NC(=O)C)=C(C(C)=O)C(=O)N(C)C2=NC=1C1=CC=C(Cl)C=C1Cl VHSIAYLBCLUAFT-UHFFFAOYSA-N 0.000 title 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 331
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 162
- -1 cyanocyclopropyl Chemical group 0.000 claims 159
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 86
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 79
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims 52
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 38
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 30
- 125000000217 alkyl group Chemical group 0.000 claims 24
- 125000004093 cyano group Chemical group *C#N 0.000 claims 21
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 19
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims 19
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 19
- 150000001875 compounds Chemical class 0.000 claims 18
- 125000001424 substituent group Chemical group 0.000 claims 16
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 15
- 150000003839 salts Chemical class 0.000 claims 15
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 14
- 125000001207 fluorophenyl group Chemical group 0.000 claims 13
- 125000002757 morpholinyl group Chemical group 0.000 claims 12
- 125000004076 pyridyl group Chemical group 0.000 claims 12
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims 11
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 11
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims 11
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims 10
- 125000001544 thienyl group Chemical group 0.000 claims 10
- 125000001425 triazolyl group Chemical group 0.000 claims 10
- 125000000623 heterocyclic group Chemical group 0.000 claims 9
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 9
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 8
- 125000004122 cyclic group Chemical group 0.000 claims 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 8
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 8
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 7
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 7
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims 7
- JSSXHAMIXJGYCS-UHFFFAOYSA-N piperazin-4-ium-2-carboxylate Chemical compound OC(=O)C1CNCCN1 JSSXHAMIXJGYCS-UHFFFAOYSA-N 0.000 claims 7
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims 6
- 125000005605 benzo group Chemical group 0.000 claims 6
- 229910052799 carbon Inorganic materials 0.000 claims 6
- 125000001715 oxadiazolyl group Chemical group 0.000 claims 6
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 6
- 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 claims 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 5
- 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims 5
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims 5
- 125000001041 indolyl group Chemical group 0.000 claims 5
- 125000000842 isoxazolyl group Chemical group 0.000 claims 5
- 125000000335 thiazolyl group Chemical group 0.000 claims 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 4
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 4
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims 4
- 125000004802 cyanophenyl group Chemical group 0.000 claims 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims 4
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims 4
- 125000003709 fluoroalkyl group Chemical group 0.000 claims 4
- 125000002883 imidazolyl group Chemical group 0.000 claims 4
- 125000001786 isothiazolyl group Chemical group 0.000 claims 4
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims 4
- 125000002971 oxazolyl group Chemical group 0.000 claims 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims 4
- 125000002098 pyridazinyl group Chemical group 0.000 claims 4
- 125000003831 tetrazolyl group Chemical group 0.000 claims 4
- 125000001113 thiadiazolyl group Chemical group 0.000 claims 4
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims 3
- 125000003545 alkoxy group Chemical group 0.000 claims 3
- 125000002393 azetidinyl group Chemical group 0.000 claims 3
- 150000001721 carbon Chemical group 0.000 claims 3
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims 3
- BRYCUMKDWMEGMK-UHFFFAOYSA-N piperazine-2-carboxamide Chemical compound NC(=O)C1CNCCN1 BRYCUMKDWMEGMK-UHFFFAOYSA-N 0.000 claims 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 3
- WSEQXVZVJXJVFP-UHFFFAOYSA-N 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile Chemical compound O1CC2=CC(C#N)=CC=C2C1(CCCN(C)C)C1=CC=C(F)C=C1 WSEQXVZVJXJVFP-UHFFFAOYSA-N 0.000 claims 2
- MEXMKNJBCVRVOA-UHFFFAOYSA-N 1-[bis(4-fluorophenyl)methyl]-4-(3,6-dicyano-1-methyl-2-oxo-1,5-naphthyridin-4-yl)piperazine-2-carboxamide Chemical compound FC1=CC=C(C=C1)C(N1C(CN(CC1)C1=C(C(N(C2=CC=C(N=C12)C#N)C)=O)C#N)C(=O)N)C1=CC=C(C=C1)F MEXMKNJBCVRVOA-UHFFFAOYSA-N 0.000 claims 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 2
- QBTXPCPOQVQZOB-ZWKOTPCHSA-N 4-[(2R,5S)-4-[bis(4-fluorophenyl)methyl]-2,5-dimethylpiperazin-1-yl]-6-bromo-1-methyl-2-oxo-1,5-naphthyridine-3-carbonitrile Chemical compound FC1=CC=C(C=C1)C(N1C[C@H](N(C[C@@H]1C)C1=C(C(N(C2=CC=C(N=C12)Br)C)=O)C#N)C)C1=CC=C(C=C1)F QBTXPCPOQVQZOB-ZWKOTPCHSA-N 0.000 claims 2
- QBTXPCPOQVQZOB-MSOLQXFVSA-N 4-[(2S,5R)-4-[bis(4-fluorophenyl)methyl]-2,5-dimethylpiperazin-1-yl]-6-bromo-1-methyl-2-oxo-1,5-naphthyridine-3-carbonitrile Chemical compound FC1=CC=C(C=C1)C(N1C[C@@H](N(C[C@H]1C)C1=C(C(N(C2=CC=C(N=C12)Br)C)=O)C#N)C)C1=CC=C(C=C1)F QBTXPCPOQVQZOB-MSOLQXFVSA-N 0.000 claims 2
- MBYXQDFRAYIYHX-KRWDZBQOSA-N 4-[(3S)-4-[bis(4-fluorophenyl)methyl]-3-methylpiperazin-1-yl]-6-bromo-1-methyl-2-oxo-1,5-naphthyridine-3-carbonitrile Chemical compound FC1=CC=C(C=C1)C(N1[C@H](CN(CC1)C1=C(C(N(C2=CC=C(N=C12)Br)C)=O)C#N)C)C1=CC=C(C=C1)F MBYXQDFRAYIYHX-KRWDZBQOSA-N 0.000 claims 2
- MGGIIWNRRRSUHJ-UHFFFAOYSA-N 4-[4-[bis(4-fluorophenyl)methyl]-2-(hydroxymethyl)piperazin-1-yl]-6-bromo-1-methyl-2-oxo-1,5-naphthyridine-3-carbonitrile Chemical compound FC1=CC=C(C=C1)C(N1CC(N(CC1)C1=C(C(N(C2=CC=C(N=C12)Br)C)=O)C#N)CO)C1=CC=C(C=C1)F MGGIIWNRRRSUHJ-UHFFFAOYSA-N 0.000 claims 2
- CPIDLCMMNUSOMR-UHFFFAOYSA-N 4-[4-[bis(4-fluorophenyl)methyl]-3-(fluoromethyl)piperazin-1-yl]-6-bromo-1-methyl-2-oxo-1,5-naphthyridine-3-carbonitrile Chemical compound FC1=CC=C(C=C1)C(N1C(CN(CC1)C1=C(C(N(C2=CC=C(N=C12)Br)C)=O)C#N)CF)C1=CC=C(C=C1)F CPIDLCMMNUSOMR-UHFFFAOYSA-N 0.000 claims 2
- CPERRDVODQYEBJ-UHFFFAOYSA-N 4-[bis(4-fluorophenyl)methyl]-1-(6-cyano-1-methyl-2-oxo-1,5-naphthyridin-4-yl)-N-cyclopropylpiperazine-2-carboxamide Chemical compound FC1=CC=C(C=C1)C(N1CC(N(CC1)C1=CC(N(C2=CC=C(N=C12)C#N)C)=O)C(=O)NC1CC1)C1=CC=C(C=C1)F CPERRDVODQYEBJ-UHFFFAOYSA-N 0.000 claims 2
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 claims 2
- VXDFSJVJIQNMFY-OAHLLOKOSA-N 5-methyl-8-[(3R)-3-methyl-4-[[3-(trifluoromethyl)phenyl]methyl]piperazin-1-yl]-6-oxo-1,5-naphthyridine-2,7-dicarbonitrile Chemical compound CN1C=2C=CC(=NC=2C(=C(C1=O)C#N)N1C[C@H](N(CC1)CC1=CC(=CC=C1)C(F)(F)F)C)C#N VXDFSJVJIQNMFY-OAHLLOKOSA-N 0.000 claims 2
- KIRUNJRXOUVOAX-PHJFFFLHSA-N 6-bromo-4-[(2S,5R)-4-[(4-fluoro-2-methoxyphenyl)-(4-fluorophenyl)methyl]-2,5-dimethylpiperazin-1-yl]-1-methyl-2-oxo-1,5-naphthyridine-3-carbonitrile Chemical compound BrC=1N=C2C(=C(C(N(C2=CC=1)C)=O)C#N)N1[C@H](CN([C@@H](C1)C)C(C1=CC=C(C=C1)F)C1=C(C=C(C=C1)F)OC)C KIRUNJRXOUVOAX-PHJFFFLHSA-N 0.000 claims 2
- HVUHWYOOCVORCX-FARGSTTKSA-N 7-fluoro-8-[(2S,5R)-4-[(4-fluorophenyl)-(4-methylphenyl)methyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound FC=1C(N(C=2C=CC(=NC=2C=1N1[C@H](CN([C@@H](C1)C)C(C1=CC=C(C=C1)C)C1=CC=C(C=C1)F)C)C#N)C)=O HVUHWYOOCVORCX-FARGSTTKSA-N 0.000 claims 2
- GQLHFNHPEUITTI-HOYKHHGWSA-N 8-[(2R,5R)-4-[bis(4-fluorophenyl)methyl]-5-(hydroxymethyl)-2-methylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound FC1=CC=C(C=C1)C(N1C[C@H](N(C[C@@H]1CO)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C)C1=CC=C(C=C1)F GQLHFNHPEUITTI-HOYKHHGWSA-N 0.000 claims 2
- GZXHFTSLKAXNOA-LFPSWIHMSA-N 8-[(2S,5R)-2,5-dimethyl-4-[1-[4-[(2-methylpropan-2-yl)oxy]phenyl]ethyl]piperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound C(C)(C)(C)OC1=CC=C(C=C1)C(C)N1C[C@@H](N(C[C@H]1C)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C GZXHFTSLKAXNOA-LFPSWIHMSA-N 0.000 claims 2
- YVOQCCXTCWGDBU-CVEARBPZSA-N 8-[(2S,5R)-2,5-dimethyl-4-[[4-(trifluoromethoxy)phenyl]methyl]piperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound C[C@@H]1N(C[C@H](N(C1)CC1=CC=C(C=C1)OC(F)(F)F)C)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O YVOQCCXTCWGDBU-CVEARBPZSA-N 0.000 claims 2
- LNVCLHSXWJVWMA-YREILILBSA-N 8-[(2S,5R)-2-ethyl-4-[1-[3-fluoro-5-(trifluoromethoxy)phenyl]ethyl]-5-methylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound C(C)[C@@H]1N(C[C@H](N(C1)C(C)C1=CC(=CC(=C1)OC(F)(F)F)F)C)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O LNVCLHSXWJVWMA-YREILILBSA-N 0.000 claims 2
- LEODWIPLJQBCNZ-NYCGYEKWSA-N 8-[(2S,5R)-4-[(1,1-dioxothian-4-yl)-(4-fluorophenyl)methyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound O=S1(CCC(CC1)C(N1C[C@@H](N(C[C@H]1C)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C)C1=CC=C(C=C1)F)=O LEODWIPLJQBCNZ-NYCGYEKWSA-N 0.000 claims 2
- ULOYNRRHAMXBBH-NJNVLPOUSA-N 8-[(2S,5R)-4-[(1-tert-butyltetrazol-5-yl)-(4-fluorophenyl)methyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound C(C)(C)(C)N1N=NN=C1C(N1C[C@@H](N(C[C@H]1C)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C)C1=CC=C(C=C1)F ULOYNRRHAMXBBH-NJNVLPOUSA-N 0.000 claims 2
- QBLJMEHOKNLCLR-VQSPDULUSA-N 8-[(2S,5R)-4-[(2-fluorophenyl)-(4-fluorophenyl)methyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound FC1=C(C=CC=C1)C(N1C[C@@H](N(C[C@H]1C)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C)C1=CC=C(C=C1)F QBLJMEHOKNLCLR-VQSPDULUSA-N 0.000 claims 2
- CIFKXZYQLQJGCD-CVEARBPZSA-N 8-[(2S,5R)-4-[(2-fluorophenyl)methyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound FC1=C(C=CC=C1)CN1C[C@@H](N(C[C@H]1C)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C CIFKXZYQLQJGCD-CVEARBPZSA-N 0.000 claims 2
- HNJFAORLFWENCI-MSOLQXFVSA-N 8-[(2S,5R)-4-[(3-ethoxyphenyl)methyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound C(C)OC=1C=C(CN2C[C@@H](N(C[C@H]2C)C2=CC(N(C=3C=CC(=NC2=3)C#N)C)=O)C)C=CC=1 HNJFAORLFWENCI-MSOLQXFVSA-N 0.000 claims 2
- VJRRXJJIVVSBDA-ACKJMCFBSA-N 8-[(2S,5R)-4-[(4-chlorophenyl)-(4-fluorophenyl)methyl]-2,5-diethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound ClC1=CC=C(C=C1)C(N1C[C@@H](N(C[C@H]1CC)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)CC)C1=CC=C(C=C1)F VJRRXJJIVVSBDA-ACKJMCFBSA-N 0.000 claims 2
- HLCDYBNRYXVCFV-UWSFRVEYSA-N 8-[(2S,5R)-4-[(4-chlorophenyl)-(4-fluoropyridin-2-yl)methyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound ClC1=CC=C(C=C1)C(N1C[C@@H](N(C[C@H]1C)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C)C1=NC=CC(=C1)F HLCDYBNRYXVCFV-UWSFRVEYSA-N 0.000 claims 2
- LDWKVKLDMOPOEG-QIXCQHHOSA-N 8-[(2S,5R)-4-[(4-chlorophenyl)-(5-fluoropyridin-2-yl)methyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2,7-dicarbonitrile Chemical compound ClC1=CC=C(C=C1)C(N1C[C@@H](N(C[C@H]1C)C1=C(C(N(C=2C=CC(=NC1=2)C#N)C)=O)C#N)C)C1=NC=C(C=C1)F LDWKVKLDMOPOEG-QIXCQHHOSA-N 0.000 claims 2
- CIVOTAFHJFVZOK-XWZNDSGVSA-N 8-[(2S,5R)-4-[(4-chlorophenyl)-(6-methylpyridin-2-yl)methyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound ClC1=CC=C(C=C1)C(N1C[C@@H](N(C[C@H]1C)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C)C1=NC(=CC=C1)C CIVOTAFHJFVZOK-XWZNDSGVSA-N 0.000 claims 2
- RQNGLSXUPUPMPI-XWZNDSGVSA-N 8-[(2S,5R)-4-[(4-chlorophenyl)-phenylmethyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound ClC1=CC=C(C=C1)C(N1C[C@@H](N(C[C@H]1C)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C)C1=CC=CC=C1 RQNGLSXUPUPMPI-XWZNDSGVSA-N 0.000 claims 2
- QHZRVQJZFBNRBY-HZLHXKQSSA-N 8-[(2S,5R)-4-[(4-cyanophenyl)-(4-fluorophenyl)methyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2,7-dicarbonitrile Chemical compound C(#N)C1=CC=C(C=C1)C(N1C[C@@H](N(C[C@H]1C)C1=C(C(N(C=2C=CC(=NC1=2)C#N)C)=O)C#N)C)C1=CC=C(C=C1)F QHZRVQJZFBNRBY-HZLHXKQSSA-N 0.000 claims 2
- MMOZUOPQJMKDIT-WAPIFTKLSA-N 8-[(2S,5R)-4-[(4-fluorophenyl)-(1,3-oxazol-2-yl)methyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound FC1=CC=C(C=C1)C(N1C[C@@H](N(C[C@H]1C)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C)C=1OC=CN=1 MMOZUOPQJMKDIT-WAPIFTKLSA-N 0.000 claims 2
- YTOONUYMTBHCAX-RIGXQMBPSA-N 8-[(2S,5R)-4-[(4-fluorophenyl)-(1-methylpyrazol-4-yl)methyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound FC1=CC=C(C=C1)C(N1C[C@@H](N(C[C@H]1C)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C)C=1C=NN(C=1)C YTOONUYMTBHCAX-RIGXQMBPSA-N 0.000 claims 2
- MEBINTMEVREBQR-NYCGYEKWSA-N 8-[(2S,5R)-4-[(4-fluorophenyl)-(oxan-4-yl)methyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound FC1=CC=C(C=C1)C(N1C[C@@H](N(C[C@H]1C)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C)C1CCOCC1 MEBINTMEVREBQR-NYCGYEKWSA-N 0.000 claims 2
- GENCDMNMZDMOLF-XWZNDSGVSA-N 8-[(2S,5R)-4-[(5-fluoropyridin-2-yl)-(4-methylphenyl)methyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound FC=1C=CC(=NC=1)C(N1C[C@@H](N(C[C@H]1C)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C)C1=CC=C(C=C1)C GENCDMNMZDMOLF-XWZNDSGVSA-N 0.000 claims 2
- IOUXPOBFEDDMFT-XWZNDSGVSA-N 8-[(2S,5R)-4-[(5-fluoropyridin-3-yl)-(4-methylphenyl)methyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound FC=1C=C(C=NC=1)C(N1C[C@@H](N(C[C@H]1C)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C)C1=CC=C(C=C1)C IOUXPOBFEDDMFT-XWZNDSGVSA-N 0.000 claims 2
- BQLIVRVAEXPDQR-YSPPHNQVSA-N 8-[(2S,5R)-4-[1-(2,5-difluoro-4-methoxyphenyl)ethyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound FC1=C(C=C(C(=C1)OC)F)C(C)N1C[C@@H](N(C[C@H]1C)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C BQLIVRVAEXPDQR-YSPPHNQVSA-N 0.000 claims 2
- KGYOHRSEPGCAOK-ZQIYAJFXSA-N 8-[(2S,5R)-4-[1-(3,4-difluorophenyl)propyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound FC=1C=C(C=CC=1F)C(CC)N1C[C@@H](N(C[C@H]1C)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C KGYOHRSEPGCAOK-ZQIYAJFXSA-N 0.000 claims 2
- FZRFVBSHMKAVSO-GNXJLENFSA-N 8-[(2S,5R)-4-[1-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)ethyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2,7-dicarbonitrile Chemical compound C1(CC1)C1=NOC(=N1)C(C)N1C[C@@H](N(C[C@H]1C)C1=C(C(N(C=2C=CC(=NC1=2)C#N)C)=O)C#N)C FZRFVBSHMKAVSO-GNXJLENFSA-N 0.000 claims 2
- PFODHXRTZSTPRK-GARXDOFDSA-N 8-[(2S,5R)-4-[1-(4-cyano-2-fluorophenyl)ethyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound C(#N)C1=CC(=C(C=C1)C(C)N1C[C@@H](N(C[C@H]1C)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C)F PFODHXRTZSTPRK-GARXDOFDSA-N 0.000 claims 2
- QEQOHGCTCDZKCI-WLUWSMMMSA-N 8-[(2S,5R)-4-[1-[4-(2-cyclopropylethoxy)phenyl]propyl]-5-ethyl-2-methylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound C1(CC1)CCOC1=CC=C(C=C1)C(CC)N1C[C@@H](N(C[C@H]1CC)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C QEQOHGCTCDZKCI-WLUWSMMMSA-N 0.000 claims 2
- QKOGTWYGUBYUQM-HVUWCZLESA-N 8-[(2S,5R)-4-[1-[4-(2-hydroxy-2-methylpropoxy)phenyl]propyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound OC(COC1=CC=C(C=C1)C(CC)N1C[C@@H](N(C[C@H]1C)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C)(C)C QKOGTWYGUBYUQM-HVUWCZLESA-N 0.000 claims 2
- SKOPPPCMJOYYIC-YNHNLWNQSA-N 8-[(2S,5R)-4-[1-[4-(cyclopropylmethoxy)phenyl]propyl]-5-ethyl-2-methylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound C1(CC1)COC1=CC=C(C=C1)C(CC)N1C[C@@H](N(C[C@H]1CC)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C SKOPPPCMJOYYIC-YNHNLWNQSA-N 0.000 claims 2
- HRPORSZFIWTLNL-KAPBCSHCSA-N 8-[(2S,5R)-4-[1-deuterio-1-(4-fluorophenyl)ethyl]-2,5-dimethylpiperazin-1-yl]-7-fluoro-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound FC=1C(N(C=2C=CC(=NC=2C=1N1[C@H](CN([C@@H](C1)C)C(C)([2H])C1=CC=C(C=C1)F)C)C#N)C)=O HRPORSZFIWTLNL-KAPBCSHCSA-N 0.000 claims 2
- IWUWMIUSRCIVQK-SJORKVTESA-N 8-[(2S,5R)-4-[[2-(3-fluorophenyl)-5-methyl-1,3-oxazol-4-yl]methyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound FC=1C=C(C=CC=1)C=1OC(=C(N=1)CN1C[C@@H](N(C[C@H]1C)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C)C IWUWMIUSRCIVQK-SJORKVTESA-N 0.000 claims 2
- ZPTNEZWBFQNQJP-CABCVRRESA-N 8-[(2S,5R)-4-[[2-fluoro-4-(trifluoromethoxy)phenyl]methyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound FC1=C(C=CC(=C1)OC(F)(F)F)CN1C[C@@H](N(C[C@H]1C)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C ZPTNEZWBFQNQJP-CABCVRRESA-N 0.000 claims 2
- BLFDWYBHSLRILM-MOPGFXCFSA-N 8-[(2S,5R)-4-[bis(4-chlorophenyl)methyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2,7-dicarbonitrile Chemical compound ClC1=CC=C(C=C1)C(N1C[C@@H](N(C[C@H]1C)C1=C(C(N(C=2C=CC(=NC1=2)C#N)C)=O)C#N)C)C1=CC=C(C=C1)Cl BLFDWYBHSLRILM-MOPGFXCFSA-N 0.000 claims 2
- YCAYEAILNXOQOH-DFVYYXEXSA-N 8-[(2S,5R)-5-ethyl-2-methyl-4-[1-(4-propan-2-yloxyphenyl)propyl]piperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound C(C)[C@H]1N(C[C@@H](N(C1)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C)C(CC)C1=CC=C(C=C1)OC(C)C YCAYEAILNXOQOH-DFVYYXEXSA-N 0.000 claims 2
- QKKFEGOOSUEPSG-MAUKXSAKSA-N 8-[(2S,5R)-5-ethyl-4-[[2-fluoro-4-(trifluoromethoxy)phenyl]methyl]-2-methylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound C(C)[C@H]1N(C[C@@H](N(C1)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C)CC1=C(C=C(C=C1)OC(F)(F)F)F QKKFEGOOSUEPSG-MAUKXSAKSA-N 0.000 claims 2
- ZFGNOIVUPPAIIR-DFBJGRDBSA-N 8-[(2S,5S)-4-[bis(4-fluorophenyl)methyl]-5-(methoxymethyl)-2-methylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound FC1=CC=C(C=C1)C(N1C[C@@H](N(C[C@H]1COC)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C)C1=CC=C(C=C1)F ZFGNOIVUPPAIIR-DFBJGRDBSA-N 0.000 claims 2
- QUAZDSHOSFCRBC-GOSISDBHSA-N 8-[(3R)-4-[(3,5-dimethylphenyl)methyl]-3-methylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2,7-dicarbonitrile Chemical compound CC=1C=C(C=C(C=1)C)CN1[C@@H](CN(CC1)C1=C(C(N(C=2C=CC(=NC1=2)C#N)C)=O)C#N)C QUAZDSHOSFCRBC-GOSISDBHSA-N 0.000 claims 2
- DLJSUZMKDDXQSR-SIHBAMTISA-N 8-[(3R)-4-[(3-chlorophenyl)-(5-fluoropyridin-2-yl)methyl]-3-methylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2,7-dicarbonitrile Chemical compound ClC=1C=C(C=CC=1)C(N1[C@@H](CN(CC1)C1=C(C(N(C=2C=CC(=NC1=2)C#N)C)=O)C#N)C)C1=NC=C(C=C1)F DLJSUZMKDDXQSR-SIHBAMTISA-N 0.000 claims 2
- ONTRTSUXIUYRHY-HFLPEKOISA-N 8-[(3R)-4-[(4-chlorophenyl)-(4-methylphenyl)methyl]-3-methylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2,7-dicarbonitrile Chemical compound ClC1=CC=C(C=C1)C(N1[C@@H](CN(CC1)C1=C(C(N(C=2C=CC(=NC1=2)C#N)C)=O)C#N)C)C1=CC=C(C=C1)C ONTRTSUXIUYRHY-HFLPEKOISA-N 0.000 claims 2
- ANDTYZQSAKTEMK-SIHBAMTISA-N 8-[(3R)-4-[(4-chlorophenyl)-(5-chloropyridin-2-yl)methyl]-3-methylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2,7-dicarbonitrile Chemical compound ClC1=CC=C(C=C1)C(N1[C@@H](CN(CC1)C1=C(C(N(C=2C=CC(=NC1=2)C#N)C)=O)C#N)C)C1=NC=C(C=C1)Cl ANDTYZQSAKTEMK-SIHBAMTISA-N 0.000 claims 2
- DERMOPPXUJGXBT-SIHBAMTISA-N 8-[(3R)-4-[(4-chlorophenyl)-(5-fluoropyridin-2-yl)methyl]-3-methylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2,7-dicarbonitrile Chemical compound ClC1=CC=C(C=C1)C(N1[C@@H](CN(CC1)C1=C(C(N(C=2C=CC(=NC1=2)C#N)C)=O)C#N)C)C1=NC=C(C=C1)F DERMOPPXUJGXBT-SIHBAMTISA-N 0.000 claims 2
- DRBYZNZZCATSCU-GOSISDBHSA-N 8-[(3R)-4-[bis(4-chlorophenyl)methyl]-3-methylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound ClC1=CC=C(C=C1)C(N1[C@@H](CN(CC1)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C)C1=CC=C(C=C1)Cl DRBYZNZZCATSCU-GOSISDBHSA-N 0.000 claims 2
- LTJGKMKCEDICFU-UHFFFAOYSA-N 8-[4-[bis(4-fluorophenyl)methyl]-3-(difluoromethoxymethyl)piperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound FC1=CC=C(C=C1)C(N1C(CN(CC1)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)COC(F)F)C1=CC=C(C=C1)F LTJGKMKCEDICFU-UHFFFAOYSA-N 0.000 claims 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 2
- 108010062677 Diacylglycerol Kinase Proteins 0.000 claims 2
- 102100022735 Diacylglycerol kinase alpha Human genes 0.000 claims 2
- 101710181033 Diacylglycerol kinase alpha Proteins 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 101150052863 THY1 gene Proteins 0.000 claims 2
- 239000004305 biphenyl Substances 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 2
- IPZJQDSFZGZEOY-UHFFFAOYSA-N dimethylmethylene Chemical compound C[C]C IPZJQDSFZGZEOY-UHFFFAOYSA-N 0.000 claims 2
- 125000000597 dioxinyl group Chemical group 0.000 claims 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 2
- 125000001072 heteroaryl group Chemical group 0.000 claims 2
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims 2
- DFAADNXLVNGISM-DVKDBIPTSA-N methyl 3-[1-[(2R,5S)-4-(3,6-dicyano-1-methyl-2-oxo-1,5-naphthyridin-4-yl)-2,5-dimethylpiperazin-1-yl]ethyl]benzoate Chemical compound C(#N)C=1C(N(C2=CC=C(N=C2C=1N1C[C@H](N(C[C@@H]1C)C(C)C=1C=C(C(=O)OC)C=CC=1)C)C#N)C)=O DFAADNXLVNGISM-DVKDBIPTSA-N 0.000 claims 2
- ZXISXIRBOCLKQD-UHFFFAOYSA-N methyl 4-(6-cyano-1-methyl-2-oxo-1,5-naphthyridin-4-yl)-1-[(4-fluoro-2-methoxyphenyl)-(4-fluorophenyl)methyl]piperazine-2-carboxylate Chemical compound C(#N)C=1N=C2C(=CC(N(C2=CC=1)C)=O)N1CC(N(CC1)C(C1=CC=C(C=C1)F)C1=C(C=C(C=C1)F)OC)C(=O)OC ZXISXIRBOCLKQD-UHFFFAOYSA-N 0.000 claims 2
- CKMWEVDAAMCQDP-UHFFFAOYSA-N methyl 4-[bis(4-fluorophenyl)methyl]-1-(6-bromo-3-cyano-1-methyl-2-oxo-1,5-naphthyridin-4-yl)piperazine-2-carboxylate Chemical compound FC1=CC=C(C=C1)C(N1CC(N(CC1)C1=C(C(N(C2=CC=C(N=C12)Br)C)=O)C#N)C(=O)OC)C1=CC=C(C=C1)F CKMWEVDAAMCQDP-UHFFFAOYSA-N 0.000 claims 2
- ZYNOTIDUYQMMPY-UHFFFAOYSA-N methyl 4-[bis(4-fluorophenyl)methyl]-1-(6-cyano-1-methyl-2-oxo-1,5-naphthyridin-4-yl)piperazine-2-carboxylate Chemical compound FC1=CC=C(C=C1)C(N1CC(N(CC1)C1=CC(N(C2=CC=C(N=C12)C#N)C)=O)C(=O)OC)C1=CC=C(C=C1)F ZYNOTIDUYQMMPY-UHFFFAOYSA-N 0.000 claims 2
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 claims 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- 125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 claims 2
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- 125000006592 (C2-C3) alkenyl group Chemical group 0.000 claims 1
- 125000006593 (C2-C3) alkynyl group Chemical group 0.000 claims 1
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims 1
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 1
- OFWVYLFNBXIMET-DLBZAZTESA-N 8-[(2S,5R)-4-[1-(4-fluorophenyl)cyclopropyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile Chemical compound FC1=CC=C(C=C1)C1(CC1)N1C[C@@H](N(C[C@H]1C)C1=CC(N(C=2C=CC(=NC1=2)C#N)C)=O)C OFWVYLFNBXIMET-DLBZAZTESA-N 0.000 claims 1
- 239000005711 Benzoic acid Substances 0.000 claims 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims 1
- 206010008342 Cervix carcinoma Diseases 0.000 claims 1
- 102000011107 Diacylglycerol Kinase Human genes 0.000 claims 1
- 102100030220 Diacylglycerol kinase zeta Human genes 0.000 claims 1
- 101710192015 Diacylglycerol kinase zeta Proteins 0.000 claims 1
- 102100025027 E3 ubiquitin-protein ligase TRIM69 Human genes 0.000 claims 1
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims 1
- 108010081348 HRT1 protein Hairy Proteins 0.000 claims 1
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims 1
- 101000830203 Homo sapiens E3 ubiquitin-protein ligase TRIM69 Proteins 0.000 claims 1
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 206010025323 Lymphomas Diseases 0.000 claims 1
- 101150073096 NRAS gene Proteins 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 101150107341 RERE gene Proteins 0.000 claims 1
- 206010038389 Renal cancer Diseases 0.000 claims 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims 1
- 208000036142 Viral infection Diseases 0.000 claims 1
- WLYPBMBWKYALCG-UHFFFAOYSA-N [2,4-bis(trifluoromethyl)phenyl]boronic acid Chemical group OB(O)C1=CC=C(C(F)(F)F)C=C1C(F)(F)F WLYPBMBWKYALCG-UHFFFAOYSA-N 0.000 claims 1
- ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 claims 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 claims 1
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims 1
- 235000010233 benzoic acid Nutrition 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 201000010881 cervical cancer Diseases 0.000 claims 1
- 229960001653 citalopram Drugs 0.000 claims 1
- 208000029742 colonic neoplasm Diseases 0.000 claims 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical group F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 claims 1
- 125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 claims 1
- 201000010536 head and neck cancer Diseases 0.000 claims 1
- 208000014829 head and neck neoplasm Diseases 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 claims 1
- 201000010982 kidney cancer Diseases 0.000 claims 1
- 208000032839 leukemia Diseases 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 claims 1
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 claims 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims 1
- 125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 claims 1
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 claims 1
- 230000009385 viral infection Effects 0.000 claims 1
Classifications
-
- 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
-
- 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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862690439P | 2018-06-27 | 2018-06-27 | |
| US201962840459P | 2019-04-30 | 2019-04-30 | |
| PCT/US2019/039135 WO2020006018A1 (en) | 2018-06-27 | 2019-06-26 | Substituted naphthyridinone compounds useful as t cell activators |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| IL279728A IL279728A (en) | 2021-03-01 |
| IL279728B1 IL279728B1 (en) | 2023-03-01 |
| IL279728B2 true IL279728B2 (en) | 2023-07-01 |
Family
ID=67439335
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL279728A IL279728B2 (en) | 2018-06-27 | 2020-12-23 | Modified naphthyridinone compounds useful as t-cell activators |
Country Status (27)
| Country | Link |
|---|---|
| US (3) | US10669272B2 (enExample) |
| EP (1) | EP3814348B9 (enExample) |
| JP (1) | JP7432532B2 (enExample) |
| KR (1) | KR102767739B1 (enExample) |
| CN (1) | CN112654621B (enExample) |
| AU (1) | AU2019291794B2 (enExample) |
| BR (1) | BR112020026681A2 (enExample) |
| CA (1) | CA3104654A1 (enExample) |
| CL (1) | CL2020003260A1 (enExample) |
| DK (1) | DK3814348T3 (enExample) |
| ES (1) | ES2960754T3 (enExample) |
| FI (1) | FI3814348T3 (enExample) |
| HR (1) | HRP20231253T1 (enExample) |
| HU (1) | HUE064531T2 (enExample) |
| IL (1) | IL279728B2 (enExample) |
| LT (1) | LT3814348T (enExample) |
| MX (1) | MX2020013817A (enExample) |
| PE (1) | PE20210469A1 (enExample) |
| PL (1) | PL3814348T3 (enExample) |
| PT (1) | PT3814348T (enExample) |
| RS (1) | RS64641B1 (enExample) |
| SG (1) | SG11202012972YA (enExample) |
| SI (1) | SI3814348T1 (enExample) |
| SM (1) | SMT202300466T1 (enExample) |
| TW (1) | TW202019924A (enExample) |
| WO (1) | WO2020006018A1 (enExample) |
| ZA (1) | ZA202100555B (enExample) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111471059B (zh) * | 2019-01-23 | 2022-12-02 | 药捷安康(南京)科技股份有限公司 | Pde9抑制剂及其用途 |
| KR20220012244A (ko) | 2019-04-29 | 2022-02-03 | 솔렌트 테라퓨틱스, 엘엘씨 | Mrgx2의 억제제로서의 3-아미노-4h-벤조[e][1,2,4]티아디아진 1,1-디옥사이드 유도체 |
| AR119821A1 (es) | 2019-08-28 | 2022-01-12 | Bristol Myers Squibb Co | Compuestos de piridopirimidinonilo sustituidos útiles como activadores de células t |
| CN115210225A (zh) | 2019-11-28 | 2022-10-18 | 拜耳公司 | 取代的氨基喹诺酮类作为免疫激活的dgkalpha抑制剂 |
| CA3163107A1 (en) | 2019-11-28 | 2021-06-03 | Bayer Aktiengesellschaft | Substituted aminoquinolones as dgkalpha inhibitors for immune activation |
| GEP20247646B (en) | 2019-11-28 | 2024-07-25 | Bayer Ag | Substituted aminoquinolones as dgkalpha inhibitors for immune activation |
| WO2021127554A1 (en) * | 2019-12-19 | 2021-06-24 | Bristol-Myers Squibb Company | Combinations of dgk inhibitors and checkpoint antagonists |
| CA3162985A1 (en) | 2019-12-23 | 2021-07-01 | Upender Velaparthi | Substituted quinazolinyl compounds useful as t cell activators |
| WO2021133752A1 (en) * | 2019-12-23 | 2021-07-01 | Bristol-Myers Squibb Company | Substituted heteroaryl compounds useful as t cell activators |
| AR120823A1 (es) * | 2019-12-23 | 2022-03-23 | Bristol Myers Squibb Co | Compuestos bicíclicos sustituidos útiles como activadores de células t |
| MX2022007130A (es) * | 2019-12-23 | 2022-07-11 | Bristol Myers Squibb Co | Derivados de piperazina sustituidos utiles como activadores de celulas t. |
| ES2998500T3 (en) * | 2019-12-23 | 2025-02-20 | Bristol Myers Squibb Co | Substituted quinolinonyl piperazine compounds useful as t cell activators |
| MX2022007930A (es) | 2019-12-24 | 2022-08-08 | Carna Biosciences Inc | Compuestos moduladores de diacilglicerol quinasa. |
| AR120896A1 (es) * | 2019-12-25 | 2022-03-30 | Astellas Pharma Inc | COMPUESTO DE PIRIDAZINIL-TIAZOLCARBOXAMIDA COMO INHIBIDORES DE DGKz |
| CN120093741A (zh) * | 2020-04-24 | 2025-06-06 | 拜耳公司 | 作为dgkzeta抑制剂用于免疫活化的取代的氨基噻唑 |
| WO2021258010A1 (en) * | 2020-06-19 | 2021-12-23 | Gossamer Bio Services, Inc. | Oxime compounds useful as t cell activators |
| KR102682398B1 (ko) * | 2020-11-26 | 2024-07-05 | 주식회사 엘지화학 | 다이아실글리세롤 키나아제 저해제로서 헤테로사이클 화합물 및 이의 용도 |
| CR20230415A (es) * | 2020-11-30 | 2023-09-08 | Kotobuki Pharmaceutical Co Ltd | Compuesto de heteroarilcarboxamida |
| AU2021400725A1 (en) | 2020-12-16 | 2023-08-03 | Gossamer Bio Services, Inc. | Compounds useful as t cell activators |
| WO2022187406A1 (en) | 2021-03-03 | 2022-09-09 | Juno Therapeutics, Inc. | Combination of a t cell therapy and a dgk inhibitor |
| EP4359411A1 (en) | 2021-06-23 | 2024-05-01 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| MX2023014762A (es) * | 2021-06-23 | 2024-01-15 | Gilead Sciences Inc | Compuestos moduladores de diacilglicerol quinasa. |
| US11976072B2 (en) | 2021-06-23 | 2024-05-07 | Gilead Sciences, Inc. | Diacylglycerol kinase modulating compounds |
| EP4359413A1 (en) | 2021-06-23 | 2024-05-01 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| WO2023122777A1 (en) * | 2021-12-22 | 2023-06-29 | Gossamer Bio Services, Inc. | Oxime derivatives useful as t cell activators |
| EP4472963A1 (en) * | 2022-02-01 | 2024-12-11 | Arvinas Operations, Inc. | Dgk targeting compounds and uses thereof |
| TW202342477A (zh) | 2022-03-01 | 2023-11-01 | 香港商英矽智能科技知識產權有限公司 | 二醯基甘油激酶(DGK) α抑制劑及其用途 |
| WO2023165525A1 (en) * | 2022-03-01 | 2023-09-07 | Insilico Medicine Ip Limited | Diacylglycerol kinase (dgk) alpha inhibitors and uses thereof |
| AR128668A1 (es) * | 2022-03-01 | 2024-06-05 | Insilico Medicine Ip Ltd | INHIBIDORES DE DIACILGLICEROL CINASA (DGK) a Y USOS DE LOS MISMOS |
| WO2023178035A1 (en) | 2022-03-14 | 2023-09-21 | Slap Pharmaceuticals Llc | Multicyclic compounds |
| WO2023184327A1 (en) * | 2022-03-31 | 2023-10-05 | InventisBio Co., Ltd. | Kinase inhibitors, preparation methods and uses thereof |
| JP2025531850A (ja) | 2022-09-08 | 2025-09-25 | ジュノー セラピューティクス インコーポレイテッド | Ｔ細胞療法および継続的または間欠的ｄｇｋ阻害剤投薬の組合せ |
| CN120813352A (zh) | 2023-02-06 | 2025-10-17 | 拜耳公司 | Dgk（二酰基甘油激酶）抑制剂的组合 |
| CN116375654B (zh) * | 2023-03-22 | 2024-12-31 | 湖北三峡实验室 | 一种由双甘肽制备2,5-二酮哌嗪的方法 |
| CN119143715B (zh) * | 2024-11-12 | 2025-03-14 | 天津匠新致成科技有限公司 | 二芳基团甲基哌嗪类化合物及其制备方法、药物组合物和应用 |
Family Cites Families (67)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4324893A (en) | 1979-04-18 | 1982-04-13 | American Home Products Corporation | 4-Amino-3-carboxy or cyano-1,2-dihydro-2-oxo-1,8-naphthyridine derivatives |
| MY140679A (en) | 2001-05-24 | 2010-01-15 | Avanir Pharmaceuticals | Inhibitors of macrohage migration inhibitory factor and methods for identifying the same |
| JP2005537247A (ja) | 2002-06-27 | 2005-12-08 | シエーリング アクチエンゲゼルシャフト | 置換されたキノリンｃｃｒ５受容体アンタゴニスト |
| GB0230018D0 (en) | 2002-12-23 | 2003-01-29 | Syngenta Ltd | Fungicides |
| TW200418829A (en) | 2003-02-14 | 2004-10-01 | Avanir Pharmaceutics | Inhibitors of macrophage migration inhibitory factor and methods for identifying the same |
| WO2004087880A2 (en) | 2003-03-26 | 2004-10-14 | Bayer Pharmaceuticals Corporation | Compounds and their use to treat diabetes and related disorders |
| GB0316915D0 (en) | 2003-07-18 | 2003-08-20 | Glaxo Group Ltd | Compounds |
| WO2005009967A2 (en) | 2003-07-22 | 2005-02-03 | Janssen Pharmaceutica, N.V. | Quinolinone derivatives as inhibitors of c-fms kinase |
| MXJL06000006A (es) * | 2003-08-22 | 2006-05-04 | Avanir Pharmaceuticals | Derivados de naftiridina sustituidos como inhibidores del factor inhibidor de la migracion de macrofagos y su uso en el tratamiento de enfermedades en el hombre. |
| US7381401B2 (en) * | 2004-01-08 | 2008-06-03 | The University Of Chicago | T cell anergy is reversed by active Ras and regulated by diacylglycerol kinase |
| TWI309240B (en) | 2004-09-17 | 2009-05-01 | Hoffmann La Roche | Anti-ox40l antibodies |
| CA2602777C (en) | 2005-03-25 | 2018-12-11 | Tolerrx, Inc. | Gitr binding molecules and uses therefor |
| BR122020016659B8 (pt) | 2005-05-10 | 2021-07-27 | Incyte Holdings Corp | moduladores de 2,3-dioxigenase de indolamina e métodos de modulação de atividade de inibição e de imunossupressão |
| KR101888321B1 (ko) | 2005-07-01 | 2018-08-13 | 이. 알. 스퀴부 앤드 선즈, 엘.엘.씨. | 예정 사멸 리간드 1 (피디-엘1)에 대한 인간 모노클로날 항체 |
| ES2540561T3 (es) | 2005-12-20 | 2015-07-10 | Incyte Corporation | N-hidroxiamidinoheterociclos como moduladores de indolamina 2,3-dioxigenasa |
| GB0605689D0 (en) * | 2006-03-21 | 2006-05-03 | Novartis Ag | Organic compounds |
| JP2007308402A (ja) | 2006-05-17 | 2007-11-29 | Sumitomo Chemical Co Ltd | シンナモイル化合物及びその用途 |
| JP2007308441A (ja) | 2006-05-22 | 2007-11-29 | Sumitomo Chemical Co Ltd | 含複素環化合物及びその用途 |
| US20080125470A1 (en) | 2006-09-19 | 2008-05-29 | Incyte Corporation | N-hydroxyamidinoheterocycles as modulators of indoleamine 2,3-dioxygenase |
| CL2007002650A1 (es) | 2006-09-19 | 2008-02-08 | Incyte Corp | Compuestos derivados de heterociclo n-hidroxiamino; composicion farmaceutica, util para tratar cancer, infecciones virales y desordenes neurodegenerativos entre otras. |
| EP1987839A1 (en) | 2007-04-30 | 2008-11-05 | I.N.S.E.R.M. Institut National de la Sante et de la Recherche Medicale | Cytotoxic anti-LAG-3 monoclonal antibody and its use in the treatment or prevention of organ transplant rejection and autoimmune disease |
| DK2175884T3 (en) | 2007-07-12 | 2016-09-26 | Gitr Inc | Combination USING GITR BINDING MOLECULES |
| EP2044949A1 (en) | 2007-10-05 | 2009-04-08 | Immutep | Use of recombinant lag-3 or the derivatives thereof for eliciting monocyte immune response |
| WO2009073620A2 (en) | 2007-11-30 | 2009-06-11 | Newlink Genetics | Ido inhibitors |
| WO2009156652A1 (fr) | 2008-05-29 | 2009-12-30 | Saint-Gobain Centre De Recherches Et D'etudes Europeen | Structure en nid d'abeille a base de titanate d'aluminium |
| AR072999A1 (es) | 2008-08-11 | 2010-10-06 | Medarex Inc | Anticuerpos humanos que se unen al gen 3 de activacion linfocitaria (lag-3) y los usos de estos |
| WO2010042489A2 (en) | 2008-10-06 | 2010-04-15 | Emory University | Aminoquinoline derived heat shock protein 90 inhibitors, methods of preparing same, and methods for their use |
| US8217149B2 (en) | 2008-12-09 | 2012-07-10 | Genentech, Inc. | Anti-PD-L1 antibodies, compositions and articles of manufacture |
| WO2010088414A2 (en) | 2009-01-28 | 2010-08-05 | Emory University | Subunit selective nmda receptor potentiators for the treatment of neurological conditions |
| SG178991A1 (en) | 2009-09-03 | 2012-04-27 | Schering Corp | Anti-gitr antibodies |
| US8722720B2 (en) | 2009-10-28 | 2014-05-13 | Newlink Genetics Corporation | Imidazole derivatives as IDO inhibitors |
| SI2949670T1 (sl) | 2009-12-10 | 2019-05-31 | F. Hoffmann-La Roche Ag | Protitelesa, ki se preferenčno vežejo na zunajcelično domeno 4 človeškega CSF1R, in njihova uporaba |
| SG10201604336VA (en) | 2010-03-04 | 2016-07-28 | Macrogenics Inc | Antibodies Reactive With B7-H3, Immunologically Active Fragments Thereof And Uses Thereof |
| JP5989547B2 (ja) | 2010-03-05 | 2016-09-07 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | ヒトｃｓｆ−１ｒに対する抗体及びその使用 |
| MX2012010014A (es) | 2010-03-05 | 2012-09-21 | Hoffmann La Roche | Anticuerpos contra csf-1r humano y sus usos. |
| ES2706412T3 (es) | 2010-05-04 | 2019-03-28 | Five Prime Therapeutics Inc | Anticuerpos que se unen a CSF1R |
| US9050334B2 (en) | 2010-07-16 | 2015-06-09 | Innov88 Llc | MIF inhibitors and their uses |
| CA2810359C (en) | 2010-09-09 | 2021-06-22 | Pfizer Inc. | 4-1bb binding molecules |
| WO2012142498A2 (en) | 2011-04-13 | 2012-10-18 | Innovimmune Biotherapeutics, Inc. | Mif inhibitors and their uses |
| NO2694640T3 (enExample) | 2011-04-15 | 2018-03-17 | ||
| ES2669310T3 (es) | 2011-04-20 | 2018-05-24 | Medimmune, Llc | Anticuerpos y otras moléculas que se unen con B7-H1 y PD-1 |
| LT2785375T (lt) | 2011-11-28 | 2020-11-10 | Merck Patent Gmbh | Anti-pd-l1 antikūnai ir jų panaudojimas |
| MX356337B (es) | 2011-12-15 | 2018-05-23 | Hoffmann La Roche | Anticuerpos contra csf-1r humano y sus usos. |
| CN104093740B (zh) | 2012-02-06 | 2018-01-09 | 弗·哈夫曼-拉罗切有限公司 | 使用csf1r抑制剂的组合物和方法 |
| US9006257B2 (en) | 2012-02-09 | 2015-04-14 | Glenmark Pharmaceuticals S.A. | Bicyclic compounds as mPGES-1 inhibitors |
| AR090263A1 (es) | 2012-03-08 | 2014-10-29 | Hoffmann La Roche | Terapia combinada de anticuerpos contra el csf-1r humano y las utilizaciones de la misma |
| KR20150018533A (ko) | 2012-05-11 | 2015-02-23 | 파이브 프라임 테라퓨틱스, 인크. | 콜로니 자극 인자 1 수용체(csf1r)에 결속하는 항체들에 의한 질병 상태의 치료 방법 |
| UY34887A (es) | 2012-07-02 | 2013-12-31 | Bristol Myers Squibb Company Una Corporacion Del Estado De Delaware | Optimización de anticuerpos que se fijan al gen de activación de linfocitos 3 (lag-3) y sus usos |
| KR20150047593A (ko) | 2012-08-31 | 2015-05-04 | 파이브 프라임 테라퓨틱스, 인크. | 집락 자극 인자 1 수용체(csf1r)에 결합하는 항체로 질환을 치료하는 방법 |
| WO2014039513A2 (en) | 2012-09-04 | 2014-03-13 | The Trustees Of The University Of Pennsylvania | Inhibition of diacylglycerol kinase to augment adoptive t cell transfer |
| EA201792214A1 (ru) | 2015-04-10 | 2018-01-31 | Араксис Фарма Ллк | Соединения замещенного хиназолина |
| NZ742476A (en) | 2015-12-17 | 2022-09-30 | Merck Patent Gmbh | Polycyclic tlr7/8 antagonists and use thereof in the treatment of immune disorders |
| CN107216325B (zh) | 2016-03-22 | 2019-06-25 | 上海医药工业研究院 | 萘啶酮类化合物、及其制备方法和应用 |
| WO2017177037A1 (en) * | 2016-04-06 | 2017-10-12 | University Of Virginia Patent Foundation | Compositions and methods for treating cancer |
| SI3558955T1 (sl) | 2016-12-22 | 2021-12-31 | Amgen Inc., | Derivati benzizotiazola, izotiazola(3,4-b)piridina, kinazolina, ftalazina, pirido(2,3-d)piridazina in pirido(2,3-D)pirimidina, kot zaviralci KRAS G12C za zdravljenje pljučnega raka, raka trebušne slinavke ali kolorektalnega raka |
| WO2018134885A1 (ja) | 2017-01-17 | 2018-07-26 | 初実 田中 | 支援奨励システムおよび支援奨励方法 |
| GB201700814D0 (en) | 2017-01-17 | 2017-03-01 | Liverpool School Tropical Medicine | Compounds |
| JOP20190272A1 (ar) | 2017-05-22 | 2019-11-21 | Amgen Inc | مثبطات kras g12c وطرق لاستخدامها |
| WO2019005883A1 (en) | 2017-06-26 | 2019-01-03 | University Of Virginia Patent Foundation | COMPOSITIONS AND USES THEREOF |
| EP4509512A3 (en) | 2018-03-07 | 2025-04-09 | Pliant Therapeutics, Inc. | Amino acid compounds and methods of use |
| JP7312745B2 (ja) | 2018-06-07 | 2023-07-21 | 第一三共株式会社 | アゼチジン誘導体及びそのプロドラッグ |
| TWI833770B (zh) | 2018-06-27 | 2024-03-01 | 美商Ionis製藥公司 | 用於減少 lrrk2 表現之化合物及方法 |
| TWI841573B (zh) | 2018-06-27 | 2024-05-11 | 美商普萊恩醫療公司 | 具有未分支連接子之胺基酸化合物及使用方法 |
| MX2020013895A (es) | 2018-06-27 | 2021-07-21 | Biogen Ma Inc | Agentes inhibidores de ask1. |
| WO2020004594A1 (ja) | 2018-06-27 | 2020-01-02 | 株式会社リボルナバイオサイエンス | 脊髄性筋萎縮症の予防または治療剤 |
| MX2020013805A (es) | 2018-06-27 | 2021-03-09 | Oscotec Inc | Derivados de piridopirimidinona para uso como inhibidores de axl. |
| BR112020026580A2 (pt) | 2018-06-27 | 2021-03-23 | Proteostasis Therapeutics, Inc. (Fem) | Compostos, composição farmacêutica e métodos para tratar um paciente |
-
2019
- 2019-06-26 SG SG11202012972YA patent/SG11202012972YA/en unknown
- 2019-06-26 ES ES19744923T patent/ES2960754T3/es active Active
- 2019-06-26 SI SI201930609T patent/SI3814348T1/sl unknown
- 2019-06-26 HU HUE19744923A patent/HUE064531T2/hu unknown
- 2019-06-26 HR HRP20231253TT patent/HRP20231253T1/hr unknown
- 2019-06-26 PL PL19744923.4T patent/PL3814348T3/pl unknown
- 2019-06-26 PT PT197449234T patent/PT3814348T/pt unknown
- 2019-06-26 SM SM20230466T patent/SMT202300466T1/it unknown
- 2019-06-26 PE PE2020002111A patent/PE20210469A1/es unknown
- 2019-06-26 LT LTEPPCT/US2019/039135T patent/LT3814348T/lt unknown
- 2019-06-26 DK DK19744923.4T patent/DK3814348T3/da active
- 2019-06-26 WO PCT/US2019/039135 patent/WO2020006018A1/en not_active Ceased
- 2019-06-26 MX MX2020013817A patent/MX2020013817A/es unknown
- 2019-06-26 JP JP2020572691A patent/JP7432532B2/ja active Active
- 2019-06-26 AU AU2019291794A patent/AU2019291794B2/en active Active
- 2019-06-26 RS RS20230895A patent/RS64641B1/sr unknown
- 2019-06-26 EP EP19744923.4A patent/EP3814348B9/en active Active
- 2019-06-26 CA CA3104654A patent/CA3104654A1/en active Pending
- 2019-06-26 CN CN201980055715.8A patent/CN112654621B/zh active Active
- 2019-06-26 US US16/452,679 patent/US10669272B2/en active Active
- 2019-06-26 FI FIEP19744923.4T patent/FI3814348T3/fi active
- 2019-06-26 KR KR1020217002231A patent/KR102767739B1/ko active Active
- 2019-06-26 BR BR112020026681-7A patent/BR112020026681A2/pt unknown
- 2019-06-27 TW TW108122537A patent/TW202019924A/zh unknown
-
2020
- 2020-04-08 US US16/843,024 patent/US10954238B1/en active Active
- 2020-12-16 CL CL2020003260A patent/CL2020003260A1/es unknown
- 2020-12-23 IL IL279728A patent/IL279728B2/en unknown
-
2021
- 2021-01-26 ZA ZA2021/00555A patent/ZA202100555B/en unknown
- 2021-02-01 US US17/164,009 patent/US11713316B2/en active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| IL279728B2 (en) | Modified naphthyridinone compounds useful as t-cell activators | |
| JPWO2020006018A5 (enExample) | ||
| HRP20251203T1 (hr) | Supstituirani piridopirimidinonil spojevi korisni kao aktivatori t-stanica | |
| JP2019512482A5 (enExample) | ||
| ES2642586T3 (es) | Compuestos heterocíclicos condensados como moduladores de canales iónicos | |
| RU2014124953A (ru) | Производные аминопиридина в качестве модуляторов богатой лейцином повторной киназы 2 (lrrk2) | |
| CA2566609A1 (en) | Quinazolinones as inhibitors of human phosphatidylinositol 3-kinase delta | |
| US20130310340A1 (en) | Method of treating muscular degradation | |
| RU2013136542A (ru) | Конденсированные производные аминодигидротиазина | |
| HRP20211336T1 (hr) | Difluorometil-aminopiridini i difluorometil-aminopirimidini | |
| RU2014124639A (ru) | Производные 2-(фенил или пирид-3-ил)аминопиримидина в качестве модуляторов богатой лейцином повторной киназы 2 (lrrk2) для лечения болезни паркинсона | |
| RU2014152625A (ru) | Конденсированные с гетероарилкетонами азадекалины - модуляторы глюкокортикоидных рецепторов | |
| WO2004074270B1 (en) | Inhibitors of hepatitis c virus rna-dependent rna polymerase, and compositions and treatments using the same | |
| JP2015519307A5 (enExample) | ||
| RU2012131840A (ru) | Новое производное 3-гидрокси-5-арилизотиазола | |
| TWI825079B (zh) | 新穎的芳基或雜芳基三唑酮衍生物或其鹽或包含彼等之醫藥組合物 | |
| HRP20180371T1 (hr) | Novi derivati piridina | |
| JP2016523976A5 (enExample) | ||
| RU2014114120A (ru) | Производные бензойной кислоты в качестве ингибиторов эукариотического фактора инициации трансляции 4е | |
| RU2016111138A (ru) | Гетероциклические соединения и способы их применения | |
| RU2018133391A (ru) | 1,5-дигидро-4н-пиразоло[3,4-d]пиримидин-4-оны и 1,5-дигидро-4н-пиразоло[4,3-c]пиридин-4-оны в качестве ингибиторов pde1 | |
| JPWO2021041588A5 (enExample) | ||
| US20240158382A1 (en) | Agonists Of Free Fatty Acid Receptor 1 And Their Use In Diseases Associated With Said Receptor | |
| JPWO2020035052A5 (enExample) | ||
| RU2014133738A (ru) | Замещенное производное фенилазола |