JP2018528192A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2018528192A5 JP2018528192A5 JP2018508715A JP2018508715A JP2018528192A5 JP 2018528192 A5 JP2018528192 A5 JP 2018528192A5 JP 2018508715 A JP2018508715 A JP 2018508715A JP 2018508715 A JP2018508715 A JP 2018508715A JP 2018528192 A5 JP2018528192 A5 JP 2018528192A5
- Authority
- JP
- Japan
- Prior art keywords
- formula
- pharmaceutical composition
- composition according
- motomeko
- alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 239000008194 pharmaceutical composition Substances 0.000 claims description 41
- 125000000217 alkyl group Chemical group 0.000 claims description 38
- 150000003839 salts Chemical class 0.000 claims description 38
- -1 C 1 -C 3 alkoxy Chemical group 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 22
- 150000001875 compounds Chemical class 0.000 claims description 18
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 15
- 239000012828 PI3K inhibitor Substances 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 14
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims description 12
- 229940121372 histone deacetylase inhibitor Drugs 0.000 claims description 12
- 239000003276 histone deacetylase inhibitor Substances 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 206010028980 Neoplasm Diseases 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 238000002560 therapeutic procedure Methods 0.000 claims description 6
- 125000006832 (C1-C10) alkylene group Chemical group 0.000 claims description 4
- YUXMAKUNSXIEKN-BTJKTKAUSA-N BGT226 Chemical compound OC(=O)\C=C/C(O)=O.C1=NC(OC)=CC=C1C1=CC=C(N=CC2=C3N(C=4C=C(C(N5CCNCC5)=CC=4)C(F)(F)F)C(=O)N2C)C3=C1 YUXMAKUNSXIEKN-BTJKTKAUSA-N 0.000 claims description 4
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 4
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 4
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000004450 alkenylene group Chemical group 0.000 claims description 3
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 3
- 125000004419 alkynylene group Chemical group 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- HBPXWEPKNBHKAX-NSHDSACASA-N (2S)-N1-[5-(2-tert-butyl-4-thiazolyl)-4-methyl-2-thiazolyl]pyrrolidine-1,2-dicarboxamide Chemical compound S1C(C=2N=C(SC=2)C(C)(C)C)=C(C)N=C1NC(=O)N1CCC[C@H]1C(N)=O HBPXWEPKNBHKAX-NSHDSACASA-N 0.000 claims description 2
- SQWZFLMPDUSYGV-POHAHGRESA-N (5Z)-5-(quinoxalin-6-ylmethylidene)-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)\C1=C\C1=CC=C(N=CC=N2)C2=C1 SQWZFLMPDUSYGV-POHAHGRESA-N 0.000 claims description 2
- SRLVNYDXMUGOFI-YWEYNIOJSA-N (5e)-5-[(2,2-difluoro-1,3-benzodioxol-5-yl)methylene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C2OC(F)(F)OC2=CC=C1\C=C1/SC(=O)NC1=O SRLVNYDXMUGOFI-YWEYNIOJSA-N 0.000 claims description 2
- UFBTYTGRUBUUIL-KPKJPENVSA-N (5e)-5-[[5-(4-fluorophenyl)furan-2-yl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=CC(F)=CC=C1C(O1)=CC=C1\C=C\1C(=O)NC(=O)S/1 UFBTYTGRUBUUIL-KPKJPENVSA-N 0.000 claims description 2
- OYYVWNDMOQPMGE-SDQBBNPISA-N (5z)-5-[[5-(4-fluoro-2-hydroxyphenyl)furan-2-yl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound OC1=CC(F)=CC=C1C(O1)=CC=C1\C=C/1C(=O)NC(=O)S\1 OYYVWNDMOQPMGE-SDQBBNPISA-N 0.000 claims description 2
- 125000006697 (C1-C3) aminoalkyl group Chemical group 0.000 claims description 2
- 125000006677 (C1-C3) haloalkoxy group Chemical group 0.000 claims description 2
- 125000006699 (C1-C3) hydroxyalkyl group Chemical group 0.000 claims description 2
- LAMIXXKAWNLXOC-INIZCTEOSA-N (S)-HDAC-42 Chemical compound O=C([C@@H](C(C)C)C=1C=CC=CC=1)NC1=CC=C(C(=O)NO)C=C1 LAMIXXKAWNLXOC-INIZCTEOSA-N 0.000 claims description 2
- BLVQHYHDYFTPDV-VCABWLAWSA-N (e)-n-(2-amino-4-fluorophenyl)-3-[1-[(e)-3-phenylprop-2-enyl]pyrazol-4-yl]prop-2-enamide Chemical compound NC1=CC(F)=CC=C1NC(=O)\C=C\C1=CN(C\C=C\C=2C=CC=CC=2)N=C1 BLVQHYHDYFTPDV-VCABWLAWSA-N 0.000 claims description 2
- PRXXYMVLYKJITB-IZZDOVSWSA-N (e)-n-(2-aminophenyl)-3-[1-[4-(1-methylpyrazol-4-yl)phenyl]sulfonylpyrrol-3-yl]prop-2-enamide Chemical compound C1=NN(C)C=C1C1=CC=C(S(=O)(=O)N2C=C(\C=C\C(=O)NC=3C(=CC=CC=3)N)C=C2)C=C1 PRXXYMVLYKJITB-IZZDOVSWSA-N 0.000 claims description 2
- QRGHOAATPOLDPF-BYICEURKSA-N 2-[(1r,5s)-6-[(6-fluoroquinolin-2-yl)methylamino]-3-azabicyclo[3.1.0]hexan-3-yl]-n-hydroxypyrimidine-5-carboxamide Chemical compound N1=CC(C(=O)NO)=CN=C1N1C[C@@H](C2NCC=3N=C4C=CC(F)=CC4=CC=3)[C@@H]2C1 QRGHOAATPOLDPF-BYICEURKSA-N 0.000 claims description 2
- UAXHPOBBKRWJGA-ZDUSSCGKSA-N 2-[2-[(2s)-2-methyl-2,3-dihydroindol-1-yl]-2-oxoethyl]-6-morpholin-4-yl-1h-pyrimidin-4-one Chemical compound C([C@@H]1C)C2=CC=CC=C2N1C(=O)CC(NC(=O)C=1)=NC=1N1CCOCC1 UAXHPOBBKRWJGA-ZDUSSCGKSA-N 0.000 claims description 2
- IRTDIKMSKMREGO-OAHLLOKOSA-N 2-[[(1R)-1-[7-methyl-2-(4-morpholinyl)-4-oxo-9-pyrido[1,2-a]pyrimidinyl]ethyl]amino]benzoic acid Chemical compound N([C@H](C)C=1C=2N(C(C=C(N=2)N2CCOCC2)=O)C=C(C)C=1)C1=CC=CC=C1C(O)=O IRTDIKMSKMREGO-OAHLLOKOSA-N 0.000 claims description 2
- XDLYKKIQACFMJG-UHFFFAOYSA-N 2-amino-8-[4-(2-hydroxyethoxy)cyclohexyl]-6-(6-methoxypyridin-3-yl)-4-methylpyrido[2,3-d]pyrimidin-7-one Chemical compound C1=NC(OC)=CC=C1C(C1=O)=CC2=C(C)N=C(N)N=C2N1C1CCC(OCCO)CC1 XDLYKKIQACFMJG-UHFFFAOYSA-N 0.000 claims description 2
- RGHYDLZMTYDBDT-UHFFFAOYSA-N 2-amino-8-ethyl-4-methyl-6-(1H-pyrazol-5-yl)-7-pyrido[2,3-d]pyrimidinone Chemical compound O=C1N(CC)C2=NC(N)=NC(C)=C2C=C1C=1C=CNN=1 RGHYDLZMTYDBDT-UHFFFAOYSA-N 0.000 claims description 2
- BEUQXVWXFDOSAQ-UHFFFAOYSA-N 2-methyl-2-[4-[2-(5-methyl-2-propan-2-yl-1,2,4-triazol-3-yl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]pyrazol-1-yl]propanamide Chemical compound CC(C)N1N=C(C)N=C1C1=CN(CCOC=2C3=CC=C(C=2)C2=CN(N=C2)C(C)(C)C(N)=O)C3=N1 BEUQXVWXFDOSAQ-UHFFFAOYSA-N 0.000 claims description 2
- MAUCONCHVWBMHK-UHFFFAOYSA-N 3-[(dimethylamino)methyl]-N-[2-[4-[(hydroxyamino)-oxomethyl]phenoxy]ethyl]-2-benzofurancarboxamide Chemical compound O1C2=CC=CC=C2C(CN(C)C)=C1C(=O)NCCOC1=CC=C(C(=O)NO)C=C1 MAUCONCHVWBMHK-UHFFFAOYSA-N 0.000 claims description 2
- RXRZPHQBTHQXSV-UHFFFAOYSA-N 5-(2-amino-8-fluoro-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-n-tert-butylpyridine-3-sulfonamide Chemical compound CC(C)(C)NS(=O)(=O)C1=CN=CC(C2=CN3N=C(N)N=C3C(F)=C2)=C1 RXRZPHQBTHQXSV-UHFFFAOYSA-N 0.000 claims description 2
- JEGHXKRHKHPBJD-UHFFFAOYSA-N 5-(7-methylsulfonyl-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-4-yl)pyrimidin-2-amine Chemical compound CS(=O)(=O)N1CCC2=C1N=C(N1CCOCC1)N=C2C1=CN=C(N)N=C1 JEGHXKRHKHPBJD-UHFFFAOYSA-N 0.000 claims description 2
- XOZLHJMDLKDZAL-UHFFFAOYSA-N 5-[6-(3-methoxyoxetan-3-yl)-7-methyl-4-morpholin-4-ylthieno[3,2-d]pyrimidin-2-yl]pyrimidin-2-amine Chemical compound S1C2=C(N3CCOCC3)N=C(C=3C=NC(N)=NC=3)N=C2C(C)=C1C1(OC)COC1 XOZLHJMDLKDZAL-UHFFFAOYSA-N 0.000 claims description 2
- JTDYUFSDZATMKU-UHFFFAOYSA-N 6-(1,3-dioxo-2-benzo[de]isoquinolinyl)-N-hydroxyhexanamide Chemical compound C1=CC(C(N(CCCCCC(=O)NO)C2=O)=O)=C3C2=CC=CC3=C1 JTDYUFSDZATMKU-UHFFFAOYSA-N 0.000 claims description 2
- DOCINCLJNAXZQF-LBPRGKRZSA-N 6-fluoro-3-phenyl-2-[(1s)-1-(7h-purin-6-ylamino)ethyl]quinazolin-4-one Chemical compound C1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)=NC2=CC=C(F)C=C2C(=O)N1C1=CC=CC=C1 DOCINCLJNAXZQF-LBPRGKRZSA-N 0.000 claims description 2
- LMJFJIDLEAWOQJ-CQSZACIVSA-N 8-[(1r)-1-(3,5-difluoroanilino)ethyl]-n,n-dimethyl-2-morpholin-4-yl-4-oxochromene-6-carboxamide Chemical compound N([C@H](C)C=1C2=C(C(C=C(O2)N2CCOCC2)=O)C=C(C=1)C(=O)N(C)C)C1=CC(F)=CC(F)=C1 LMJFJIDLEAWOQJ-CQSZACIVSA-N 0.000 claims description 2
- CPRAGQJXBLMUEL-UHFFFAOYSA-N 9-(1-anilinoethyl)-7-methyl-2-(4-morpholinyl)-4-pyrido[1,2-a]pyrimidinone Chemical compound C=1C(C)=CN(C(C=C(N=2)N3CCOCC3)=O)C=2C=1C(C)NC1=CC=CC=C1 CPRAGQJXBLMUEL-UHFFFAOYSA-N 0.000 claims description 2
- 229960005531 AMG 319 Drugs 0.000 claims description 2
- GNWHRHGTIBRNSM-UHFFFAOYSA-N IC-87114 Chemical compound CC1=CC=CC=C1N1C(=O)C2=C(C)C=CC=C2N=C1CN1C2=NC=NC(N)=C2N=C1 GNWHRHGTIBRNSM-UHFFFAOYSA-N 0.000 claims description 2
- QQDIFLSJMFDTCQ-UHFFFAOYSA-N MC1568 Chemical compound CN1C(C=CC(=O)NO)=CC=C1C=CC(=O)C1=CC=CC(F)=C1 QQDIFLSJMFDTCQ-UHFFFAOYSA-N 0.000 claims description 2
- FCKJZIRDZMVDEM-UHFFFAOYSA-N N-(7,8-dimethoxy-2,3-dihydro-1H-imidazo[1,2-c]quinazolin-5-ylidene)pyridine-3-carboxamide Chemical compound COC1=C(C2=NC(=NC(=O)C3=CN=CC=C3)N4CCNC4=C2C=C1)OC FCKJZIRDZMVDEM-UHFFFAOYSA-N 0.000 claims description 2
- BHUZLJOUHMBZQY-YXQOSMAKSA-N N-[4-[(2R,4R,6S)-4-[[(4,5-diphenyl-2-oxazolyl)thio]methyl]-6-[4-(hydroxymethyl)phenyl]-1,3-dioxan-2-yl]phenyl]-N'-hydroxyoctanediamide Chemical compound C1=CC(CO)=CC=C1[C@H]1O[C@@H](C=2C=CC(NC(=O)CCCCCCC(=O)NO)=CC=2)O[C@@H](CSC=2OC(=C(N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)C1 BHUZLJOUHMBZQY-YXQOSMAKSA-N 0.000 claims description 2
- WWGBHDIHIVGYLZ-UHFFFAOYSA-N N-[4-[3-[[[7-(hydroxyamino)-7-oxoheptyl]amino]-oxomethyl]-5-isoxazolyl]phenyl]carbamic acid tert-butyl ester Chemical compound C1=CC(NC(=O)OC(C)(C)C)=CC=C1C1=CC(C(=O)NCCCCCCC(=O)NO)=NO1 WWGBHDIHIVGYLZ-UHFFFAOYSA-N 0.000 claims description 2
- QGZYDVAGYRLSKP-UHFFFAOYSA-N N-[7-(hydroxyamino)-7-oxoheptyl]-2-(N-phenylanilino)-5-pyrimidinecarboxamide Chemical compound N1=CC(C(=O)NCCCCCCC(=O)NO)=CN=C1N(C=1C=CC=CC=1)C1=CC=CC=C1 QGZYDVAGYRLSKP-UHFFFAOYSA-N 0.000 claims description 2
- AJRGHIGYPXNABY-UHFFFAOYSA-N N-hydroxy-1-[(4-methoxyphenyl)methyl]-6-indolecarboxamide Chemical compound C1=CC(OC)=CC=C1CN1C2=CC(C(=O)NO)=CC=C2C=C1 AJRGHIGYPXNABY-UHFFFAOYSA-N 0.000 claims description 2
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 claims description 2
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 claims description 2
- QIUASFSNWYMDFS-NILGECQDSA-N PX-866 Chemical compound CC(=O)O[C@@H]1C[C@]2(C)C(=O)CC[C@H]2C2=C1[C@@]1(C)[C@@H](COC)OC(=O)\C(=C\N(CC=C)CC=C)C1=C(O)C2=O QIUASFSNWYMDFS-NILGECQDSA-N 0.000 claims description 2
- RTKIYFITIVXBLE-UHFFFAOYSA-N Trichostatin A Natural products ONC(=O)C=CC(C)=CC(C)C(=O)C1=CC=C(N(C)C)C=C1 RTKIYFITIVXBLE-UHFFFAOYSA-N 0.000 claims description 2
- HGVNLRPZOWWDKD-UHFFFAOYSA-N ZSTK-474 Chemical compound FC(F)C1=NC2=CC=CC=C2N1C(N=1)=NC(N2CCOCC2)=NC=1N1CCOCC1 HGVNLRPZOWWDKD-UHFFFAOYSA-N 0.000 claims description 2
- 229950008805 abexinostat Drugs 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 2
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 2
- 230000003409 anti-rejection Effects 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- NCNRHFGMJRPRSK-MDZDMXLPSA-N belinostat Chemical compound ONC(=O)\C=C\C1=CC=CC(S(=O)(=O)NC=2C=CC=CC=2)=C1 NCNRHFGMJRPRSK-MDZDMXLPSA-N 0.000 claims description 2
- 229960003094 belinostat Drugs 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- GLNWREBYRLDPQP-MHZLTWQESA-N cyclopentyl (2s)-2-[[4-[[8-(hydroxyamino)-8-oxooctanoyl]amino]phenyl]methylamino]-2-phenylacetate Chemical compound C1=CC(NC(=O)CCCCCCC(=O)NO)=CC=C1CN[C@@H](C=1C=CC=CC=1)C(=O)OC1CCCC1 GLNWREBYRLDPQP-MHZLTWQESA-N 0.000 claims description 2
- INVTYAOGFAGBOE-UHFFFAOYSA-N entinostat Chemical compound NC1=CC=CC=C1NC(=O)C(C=C1)=CC=C1CNC(=O)OCC1=CC=CN=C1 INVTYAOGFAGBOE-UHFFFAOYSA-N 0.000 claims description 2
- 229950005837 entinostat Drugs 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 208000026278 immune system disease Diseases 0.000 claims description 2
- 208000027866 inflammatory disease Diseases 0.000 claims description 2
- 208000032839 leukemia Diseases 0.000 claims description 2
- KWRYMZHCQIOOEB-LBPRGKRZSA-N n-[(1s)-1-(7-fluoro-2-pyridin-2-ylquinolin-3-yl)ethyl]-7h-purin-6-amine Chemical compound C1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)=CC2=CC=C(F)C=C2N=C1C1=CC=CC=N1 KWRYMZHCQIOOEB-LBPRGKRZSA-N 0.000 claims description 2
- QTHCAAFKVUWAFI-DJKKODMXSA-N n-[(e)-(6-bromoimidazo[1,2-a]pyridin-3-yl)methylideneamino]-n,2-dimethyl-5-nitrobenzenesulfonamide Chemical compound C=1N=C2C=CC(Br)=CN2C=1/C=N/N(C)S(=O)(=O)C1=CC([N+]([O-])=O)=CC=C1C QTHCAAFKVUWAFI-DJKKODMXSA-N 0.000 claims description 2
- JFVNFXCESCXMBC-UHFFFAOYSA-N n-[5-[4-chloro-3-(2-hydroxyethylsulfamoyl)phenyl]-4-methyl-1,3-thiazol-2-yl]acetamide Chemical compound S1C(=N/C(=O)C)\NC(C)=C1C1=CC=C(Cl)C(S(=O)(=O)NCCO)=C1 JFVNFXCESCXMBC-UHFFFAOYSA-N 0.000 claims description 2
- VRYZCEONIWEUAV-UHFFFAOYSA-N n-[6-(hydroxyamino)-6-oxohexoxy]-3,5-dimethylbenzamide Chemical compound CC1=CC(C)=CC(C(=O)NOCCCCCC(=O)NO)=C1 VRYZCEONIWEUAV-UHFFFAOYSA-N 0.000 claims description 2
- HORXBWNTEDOVKN-UHFFFAOYSA-N n-[[4-(4-phenyl-1,3-thiazol-2-yl)oxan-4-yl]methyl]-3-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide Chemical compound O1C(C(F)(F)F)=NC(C=2C=C(C=CC=2)C(=O)NCC2(CCOCC2)C=2SC=C(N=2)C=2C=CC=CC=2)=N1 HORXBWNTEDOVKN-UHFFFAOYSA-N 0.000 claims description 2
- JOWXJLIFIIOYMS-UHFFFAOYSA-N n-hydroxy-2-[[2-(6-methoxypyridin-3-yl)-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl-methylamino]pyrimidine-5-carboxamide Chemical compound C1=NC(OC)=CC=C1C1=NC(N2CCOCC2)=C(SC(CN(C)C=2N=CC(=CN=2)C(=O)NO)=C2)C2=N1 JOWXJLIFIIOYMS-UHFFFAOYSA-N 0.000 claims description 2
- RFAZNTABYJYOAR-UHFFFAOYSA-N n-hydroxy-4-[2-[n-(2-hydroxyethyl)anilino]-2-oxoethyl]benzamide Chemical compound C=1C=CC=CC=1N(CCO)C(=O)CC1=CC=C(C(=O)NO)C=C1 RFAZNTABYJYOAR-UHFFFAOYSA-N 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 210000000056 organ Anatomy 0.000 claims description 2
- 229960005184 panobinostat Drugs 0.000 claims description 2
- FWZRWHZDXBDTFK-ZHACJKMWSA-N panobinostat Chemical compound CC1=NC2=CC=C[CH]C2=C1CCNCC1=CC=C(\C=C\C(=O)NO)C=C1 FWZRWHZDXBDTFK-ZHACJKMWSA-N 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- JHDKZFFAIZKUCU-ZRDIBKRKSA-N pracinostat Chemical compound ONC(=O)/C=C/C1=CC=C2N(CCN(CC)CC)C(CCCC)=NC2=C1 JHDKZFFAIZKUCU-ZRDIBKRKSA-N 0.000 claims description 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- FECGNJPYVFEKOD-VMPITWQZSA-N resminostat Chemical compound C1=CC(CN(C)C)=CC=C1S(=O)(=O)N1C=C(\C=C\C(=O)NO)C=C1 FECGNJPYVFEKOD-VMPITWQZSA-N 0.000 claims description 2
- 229950002821 resminostat Drugs 0.000 claims description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
- 229950006743 ricolinostat Drugs 0.000 claims description 2
- OHRURASPPZQGQM-GCCNXGTGSA-N romidepsin Chemical compound O1C(=O)[C@H](C(C)C)NC(=O)C(=C/C)/NC(=O)[C@H]2CSSCC\C=C\[C@@H]1CC(=O)N[C@H](C(C)C)C(=O)N2 OHRURASPPZQGQM-GCCNXGTGSA-N 0.000 claims description 2
- 229960003452 romidepsin Drugs 0.000 claims description 2
- OHRURASPPZQGQM-UHFFFAOYSA-N romidepsin Natural products O1C(=O)C(C(C)C)NC(=O)C(=CC)NC(=O)C2CSSCCC=CC1CC(=O)NC(C(C)C)C(=O)N2 OHRURASPPZQGQM-UHFFFAOYSA-N 0.000 claims description 2
- 108010091666 romidepsin Proteins 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- BLGWHBSBBJNKJO-UHFFFAOYSA-N serabelisib Chemical compound C=1C=C2OC(N)=NC2=CC=1C(=CN12)C=CC1=NC=C2C(=O)N1CCOCC1 BLGWHBSBBJNKJO-UHFFFAOYSA-N 0.000 claims description 2
- 229960002232 sodium phenylbutyrate Drugs 0.000 claims description 2
- AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- VAZAPHZUAVEOMC-UHFFFAOYSA-N tacedinaline Chemical compound C1=CC(NC(=O)C)=CC=C1C(=O)NC1=CC=CC=C1N VAZAPHZUAVEOMC-UHFFFAOYSA-N 0.000 claims description 2
- 229950001269 taselisib Drugs 0.000 claims description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 2
- 238000002054 transplantation Methods 0.000 claims description 2
- RTKIYFITIVXBLE-QEQCGCAPSA-N trichostatin A Chemical compound ONC(=O)/C=C/C(/C)=C/[C@@H](C)C(=O)C1=CC=C(N(C)C)C=C1 RTKIYFITIVXBLE-QEQCGCAPSA-N 0.000 claims description 2
- GOVYBPLHWIEHEJ-UHFFFAOYSA-N tubastatin A Chemical compound C1N(C)CCC2=C1C1=CC=CC=C1N2CC1=CC=C(C(=O)NO)C=C1 GOVYBPLHWIEHEJ-UHFFFAOYSA-N 0.000 claims description 2
- 229960000237 vorinostat Drugs 0.000 claims description 2
- WAEXFXRVDQXREF-UHFFFAOYSA-N vorinostat Chemical compound ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1 WAEXFXRVDQXREF-UHFFFAOYSA-N 0.000 claims description 2
- QDLHCMPXEPAAMD-QAIWCSMKSA-N wortmannin Chemical compound C1([C@]2(C)C3=C(C4=O)OC=C3C(=O)O[C@@H]2COC)=C4[C@@H]2CCC(=O)[C@@]2(C)C[C@H]1OC(C)=O QDLHCMPXEPAAMD-QAIWCSMKSA-N 0.000 claims description 2
- QDLHCMPXEPAAMD-UHFFFAOYSA-N wortmannin Natural products COCC1OC(=O)C2=COC(C3=O)=C2C1(C)C1=C3C2CCC(=O)C2(C)CC1OC(C)=O QDLHCMPXEPAAMD-UHFFFAOYSA-N 0.000 claims description 2
- 230000004572 zinc-binding Effects 0.000 claims description 2
- 239000013066 combination product Substances 0.000 claims 1
- 229940127555 combination product Drugs 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 37
- 238000000034 method Methods 0.000 description 34
- 241001465754 Metazoa Species 0.000 description 2
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- HIHJTEJYORZWIL-ZVAWYAOSSA-N C(c(cn1)cc2c1[o]c1c2nc(-c2c(cc[nH]3)c3ccc2)nc1N1CCOCC1)N1C(C2)CO[C@@H]2C1 Chemical compound C(c(cn1)cc2c1[o]c1c2nc(-c2c(cc[nH]3)c3ccc2)nc1N1CCOCC1)N1C(C2)CO[C@@H]2C1 HIHJTEJYORZWIL-ZVAWYAOSSA-N 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1514756.4 | 2015-08-19 | ||
| GBGB1514756.4A GB201514756D0 (en) | 2015-08-19 | 2015-08-19 | Compound and method of use |
| PCT/GB2016/052571 WO2017029514A1 (en) | 2015-08-19 | 2016-08-19 | Compositions comprising a pi3k inhibitor and an hdac inhibitor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2018528192A JP2018528192A (ja) | 2018-09-27 |
| JP2018528192A5 true JP2018528192A5 (enExample) | 2019-09-26 |
Family
ID=54258855
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018508715A Withdrawn JP2018528192A (ja) | 2015-08-19 | 2016-08-19 | Ｐｉ３ｋ阻害剤およびｈｄａｃ阻害剤を含む組成物 |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US20180243317A1 (enExample) |
| EP (2) | EP3337484A1 (enExample) |
| JP (1) | JP2018528192A (enExample) |
| KR (1) | KR20180069788A (enExample) |
| CN (1) | CN108348523A (enExample) |
| AU (1) | AU2016307882A1 (enExample) |
| BR (1) | BR112018003026A2 (enExample) |
| CA (1) | CA2995991A1 (enExample) |
| GB (1) | GB201514756D0 (enExample) |
| HK (1) | HK1251466A1 (enExample) |
| IL (1) | IL257521A (enExample) |
| MX (1) | MX2018001990A (enExample) |
| SG (1) | SG10201913619XA (enExample) |
| WO (1) | WO2017029514A1 (enExample) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2012002059A (es) | 2009-08-20 | 2012-04-19 | Karus Therapeutics Ltd | Compestos heterociclicos triciclicos como inhibidores de fosfoionositida 3-quinasa. |
| GB201204125D0 (en) | 2012-03-08 | 2012-04-25 | Karus Therapeutics Ltd | Compounds |
| PT2994465T (pt) | 2013-05-10 | 2018-10-25 | Karus Therapeutics Ltd | Novos inibidores de histona desacetilase |
| GB201402431D0 (en) | 2014-02-12 | 2014-03-26 | Karus Therapeutics Ltd | Compounds |
| GB201514760D0 (en) | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Compounds and method of use |
| GB201514754D0 (en) | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Compounds |
| GB201514751D0 (en) | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Compounds |
| GB201514758D0 (en) | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Formulation |
| TWI808055B (zh) | 2016-05-11 | 2023-07-11 | 美商滬亞生物國際有限公司 | Hdac 抑制劑與 pd-1 抑制劑之組合治療 |
| TWI794171B (zh) | 2016-05-11 | 2023-03-01 | 美商滬亞生物國際有限公司 | Ｈｄａｃ抑制劑與ｐｄ-ｌ１抑制劑之組合治療 |
| WO2018165520A1 (en) | 2017-03-10 | 2018-09-13 | Vps-3, Inc. | Metalloenzyme inhibitor compounds |
| EP3737362B1 (en) | 2018-01-12 | 2025-10-15 | Kdac Therapeutics, Inc. | Combination of a selective histone deacetylase 3 (hdac3) inhibitor and an immunotherapy agent for the treatment of cancer |
| EP3826998A4 (en) * | 2018-07-23 | 2022-06-01 | The Regents of the University of California | COMPOSITIONS AND METHODS OF TREATING AN EPIGENETIC DISEASE |
| KR102162744B1 (ko) * | 2018-09-18 | 2020-10-07 | 인제대학교산학협력단 | 프라시노스타트를 포함하는 염증성 장질환 치료용 약학 조성물 |
| GB201909468D0 (en) * | 2019-07-01 | 2019-08-14 | Karus Therapeutics Ltd | Compounds for treating cancer |
| AU2020321955A1 (en) | 2019-07-30 | 2022-03-17 | Eikonizo Therapapeutics, Inc. | HDAC6 inhibitors and uses thereof |
| GB201913121D0 (en) * | 2019-09-11 | 2019-10-23 | Seald As | Compositions and methods for treatment of cholangiocarcinoma |
| WO2021113401A2 (en) * | 2019-12-02 | 2021-06-10 | The Regents Of The University Of Colorado, A Body Corporate | Histone deacytlase 6 modulation of titin protein mediated cardiac tissue stiffness and method for same |
| TW202134245A (zh) | 2019-12-05 | 2021-09-16 | 美商邊際分析公司 | 稠合三環雜環化合物及其用途 |
| MX2022007376A (es) | 2019-12-20 | 2022-09-02 | Tenaya Therapeutics Inc | Fluoroalqull-oxadiazoles y sus usos. |
| CN111686097A (zh) * | 2020-07-31 | 2020-09-22 | 上海交通大学医学院附属第九人民医院 | Lmk235在抑制瘢痕形成的药物中的应用 |
| WO2022169882A1 (en) | 2021-02-03 | 2022-08-11 | Verge Analytics, Inc. | Methods and treatment of viral infection caused by sars-cov-2 |
| US20240252502A1 (en) | 2021-05-04 | 2024-08-01 | Tenaya Therapeutics, Inc. | Hdac6 inhibitors for treatment of metabolic disease and hfpef |
| TW202345813A (zh) | 2022-04-08 | 2023-12-01 | 美商艾科尼佐療法股份有限公司 | 㗁二唑ｈｄａｃ６抑制劑及其用途 |
| CN114890989B (zh) * | 2022-05-25 | 2024-03-22 | 广东晨康生物科技有限公司 | 一种含氮衍生物为Linker的HDAC8降解剂其制备方法和应用 |
| AU2024231699A1 (en) * | 2023-03-03 | 2025-09-11 | Ionctura Sa | Combination of roginolisib and hdac inhibitor in the treatment of haematological malignancy |
| CN116987073B (zh) * | 2023-08-03 | 2025-12-30 | 嘉兴大学 | 一种PI3Kα/HDAC6亚型选择性双重抑制剂及其应用 |
| CN118750492A (zh) * | 2024-07-15 | 2024-10-11 | 中日友好医院(中日友好临床医学研究所) | 一种hdac6高选择抑制剂cay10603的应用 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6905669B2 (en) | 2001-04-24 | 2005-06-14 | Supergen, Inc. | Compositions and methods for reestablishing gene transcription through inhibition of DNA methylation and histone deacetylase |
| EP2120909A2 (en) * | 2006-12-15 | 2009-11-25 | Ordway Research Institute | Treatments of therapy-resistant diseases comprising drug combinations |
| MX2012002059A (es) | 2009-08-20 | 2012-04-19 | Karus Therapeutics Ltd | Compestos heterociclicos triciclicos como inhibidores de fosfoionositida 3-quinasa. |
| PT2994465T (pt) * | 2013-05-10 | 2018-10-25 | Karus Therapeutics Ltd | Novos inibidores de histona desacetilase |
| WO2015054099A1 (en) * | 2013-10-08 | 2015-04-16 | Acetylon Pharmaceuticals, Inc. | Combinations of histone deacetylase inhibitors and either her2 inhibitors or pi3k inhibitors |
| ES2818933T3 (es) | 2013-10-10 | 2021-04-14 | Acetylon Pharmaceuticals Inc | Inhibidores de la HDAC en combinación con los inhibidores de la pi3k, para el tratamiento del linfoma no Hodgkin |
| GB201402431D0 (en) * | 2014-02-12 | 2014-03-26 | Karus Therapeutics Ltd | Compounds |
-
2015
- 2015-08-19 GB GBGB1514756.4A patent/GB201514756D0/en not_active Ceased
-
2016
- 2016-08-19 WO PCT/GB2016/052571 patent/WO2017029514A1/en not_active Ceased
- 2016-08-19 EP EP16756762.7A patent/EP3337484A1/en not_active Withdrawn
- 2016-08-19 SG SG10201913619XA patent/SG10201913619XA/en unknown
- 2016-08-19 MX MX2018001990A patent/MX2018001990A/es unknown
- 2016-08-19 CA CA2995991A patent/CA2995991A1/en not_active Abandoned
- 2016-08-19 AU AU2016307882A patent/AU2016307882A1/en not_active Abandoned
- 2016-08-19 US US15/753,356 patent/US20180243317A1/en not_active Abandoned
- 2016-08-19 JP JP2018508715A patent/JP2018528192A/ja not_active Withdrawn
- 2016-08-19 HK HK18110946.4A patent/HK1251466A1/zh unknown
- 2016-08-19 EP EP18202398.6A patent/EP3456355A1/en not_active Withdrawn
- 2016-08-19 CN CN201680058695.6A patent/CN108348523A/zh active Pending
- 2016-08-19 KR KR1020187007811A patent/KR20180069788A/ko not_active Withdrawn
- 2016-08-19 BR BR112018003026A patent/BR112018003026A2/pt not_active IP Right Cessation
-
2018
- 2018-02-14 IL IL257521A patent/IL257521A/en unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2018528192A5 (enExample) | ||
| CL2023000196A1 (es) | Compuestos de tetrahidropirazolo-pirazinil-dihidroimidazolona o tetrahidropirazolo-piridinil-dihidroimidazolona y métodos de uso de los mismos | |
| MX2021000887A (es) | Compuestos espiroheterociclicos y metodos de uso de los mismos para el tratamiento de cancer. | |
| MX2021005924A (es) | Compuestos y metodos de uso de los mismos para el tratamiento del cancer. | |
| MX2019013954A (es) | Inhibidores covalentes de kras. | |
| AR122783A2 (es) | Inhibidores de kras g12c y métodos para su uso | |
| MX2022003102A (es) | Degradadores bifuncionales de brd9 y sus metodos de uso. | |
| PH12019502245A1 (en) | Compounds that inhibit mcl-1 protein | |
| NZ777871A (en) | Small molecule modulators of il-17 | |
| JP2019521988A5 (enExample) | ||
| AR072442A1 (es) | Metodo para la terapia del cancer, uso, kit | |
| EA201101507A1 (ru) | Способы лечения солидных опухолей | |
| MX2019002212A (es) | Compuestos de amino-pirrolo-pirimidinona y metodos de uso de los mismos. | |
| MX2020006599A (es) | Composiciones y metodos para el tratamiento de trastornos en el sistema nervioso central. | |
| MX380928B (es) | Inhibidores de kras g12c. | |
| EA201692267A1 (ru) | Ингибиторы фосфатидилинозитол-3-киназы | |
| PE20160550A1 (es) | Formulaciones de (s)-3-(4-((4-(morfolinometil)bencil)oxi)-1-oxoisoindolin-2-il)piperidin-2,6-diona | |
| EA201892746A1 (ru) | Лечение гематологической злокачественной опухоли с помощью 2-(4-хлорфенил)-n-((2-(2,6-диоксопиперидин-3-ил)-1-оксоизоиндолин-5-ил)метил)-2,2-дифторацетамида | |
| EA201891931A1 (ru) | Новые ингибиторы фосфатидилинозитол-3-киназы гамма | |
| RU2016138676A (ru) | Ингибиторы усилителя zeste гомолога 2 | |
| RU2013136861A (ru) | Новое производное индола или индазола или его соль | |
| EA202090959A1 (ru) | Аминзамещенные гетероциклические соединения в качестве ингибиторов ehmt2, их соли и способы их синтеза | |
| MX2021015447A (es) | Métodos de tratamiento del cáncer dirigidos a tumores fríos. | |
| BR112021006318A2 (pt) | terapia de combinação para o tratamento de câncer | |
| JP2016515550A5 (enExample) |