JP2012532854A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2012532854A5 JP2012532854A5 JP2012519055A JP2012519055A JP2012532854A5 JP 2012532854 A5 JP2012532854 A5 JP 2012532854A5 JP 2012519055 A JP2012519055 A JP 2012519055A JP 2012519055 A JP2012519055 A JP 2012519055A JP 2012532854 A5 JP2012532854 A5 JP 2012532854A5
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- thiadiazol
- formula
- compound
- oxo
- 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.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 claims description 52
- 229910052736 halogen Inorganic materials 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 18
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 11
- -1 4H- [1,2,4] -triazolyl Chemical group 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims 27
- 230000000144 pharmacologic effect Effects 0.000 claims 26
- 239000012453 solvate Substances 0.000 claims 25
- 125000003118 aryl group Chemical group 0.000 claims 14
- 206010028980 Neoplasm Diseases 0.000 claims 13
- 201000011510 cancer Diseases 0.000 claims 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 9
- 125000001072 heteroaryl group Chemical group 0.000 claims 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 8
- 125000004429 atom Chemical group 0.000 claims 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims 7
- 239000003814 drug Substances 0.000 claims 7
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 6
- 229910052799 carbon Inorganic materials 0.000 claims 6
- 229910052757 nitrogen Inorganic materials 0.000 claims 6
- 125000006574 non-aromatic ring group Chemical group 0.000 claims 6
- 125000001424 substituent group Chemical group 0.000 claims 6
- 239000002671 adjuvant Substances 0.000 claims 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims 5
- 125000005843 halogen group Chemical group 0.000 claims 5
- 229910052760 oxygen Inorganic materials 0.000 claims 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims 5
- 239000000047 product Substances 0.000 claims 5
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 claims 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims 4
- 125000000217 alkyl group Chemical group 0.000 claims 4
- 239000013066 combination product Substances 0.000 claims 4
- 229940127555 combination product Drugs 0.000 claims 4
- 125000005842 heteroatom Chemical group 0.000 claims 4
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims 4
- 229940124597 therapeutic agent Drugs 0.000 claims 4
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims 3
- 229910052739 hydrogen Inorganic materials 0.000 claims 3
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 claims 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 2
- NOTGFIUVDGNKRI-UUOKFMHZSA-N AICA ribonucleotide Chemical compound NC1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(O)=O)O1 NOTGFIUVDGNKRI-UUOKFMHZSA-N 0.000 claims 2
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 claims 2
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 claims 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 claims 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 2
- 206010012601 diabetes mellitus Diseases 0.000 claims 2
- 208000019691 hematopoietic and lymphoid cell neoplasm Diseases 0.000 claims 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 2
- MNULEGDCPYONBU-WMBHJXFZSA-N (1r,4s,5e,5'r,6'r,7e,10s,11r,12s,14r,15s,16s,18r,19s,20r,21e,25s,26r,27s,29s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-[(2s)-2-hydroxypropyl]-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trio Polymers O([C@@H]1CC[C@@H](/C=C/C=C/C[C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)/C=C/C(=O)O[C@H]([C@H]2C)[C@H]1C)CC)[C@]12CC[C@@H](C)[C@@H](C[C@H](C)O)O1 MNULEGDCPYONBU-WMBHJXFZSA-N 0.000 claims 1
- MNULEGDCPYONBU-DJRUDOHVSA-N (1s,4r,5z,5'r,6'r,7e,10s,11r,12s,14r,15s,18r,19r,20s,21e,26r,27s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-(2-hydroxypropyl)-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers O([C@H]1CC[C@H](\C=C/C=C/C[C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@H](C)[C@@H](O)C(C)C(=O)[C@H](C)[C@H](O)[C@@H](C)/C=C/C(=O)OC([C@H]2C)C1C)CC)[C@]12CC[C@@H](C)[C@@H](CC(C)O)O1 MNULEGDCPYONBU-DJRUDOHVSA-N 0.000 claims 1
- VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 claims 1
- MNULEGDCPYONBU-YNZHUHFTSA-N (4Z,18Z,20Z)-22-ethyl-7,11,14,15-tetrahydroxy-6'-(2-hydroxypropyl)-5',6,8,10,12,14,16,28,29-nonamethylspiro[2,26-dioxabicyclo[23.3.1]nonacosa-4,18,20-triene-27,2'-oxane]-3,9,13-trione Polymers CC1C(C2C)OC(=O)\C=C/C(C)C(O)C(C)C(=O)C(C)C(O)C(C)C(=O)C(C)(O)C(O)C(C)C\C=C/C=C\C(CC)CCC2OC21CCC(C)C(CC(C)O)O2 MNULEGDCPYONBU-YNZHUHFTSA-N 0.000 claims 1
- MNULEGDCPYONBU-VVXVDZGXSA-N (5e,5'r,7e,10s,11r,12s,14s,15r,16r,18r,19s,20r,21e,26r,29s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-[(2s)-2-hydroxypropyl]-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers C([C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@@H](C)[C@H](O)[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)/C=C/C(=O)OC([C@H]1C)[C@H]2C)\C=C\C=C\C(CC)CCC2OC21CC[C@@H](C)C(C[C@H](C)O)O2 MNULEGDCPYONBU-VVXVDZGXSA-N 0.000 claims 1
- 125000001894 2,4,6-trinitrophenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1[N+]([O-])=O)[N+]([O-])=O)[N+]([O-])=O 0.000 claims 1
- QPEXDGNCMPBSAR-UHFFFAOYSA-N 2,4-dichloro-n-[2-[(4-fluorophenyl)methyl]-3-oxo-1,2,4-thiadiazol-5-yl]benzamide Chemical compound C1=CC(F)=CC=C1CN1C(=O)N=C(NC(=O)C=2C(=CC(Cl)=CC=2)Cl)S1 QPEXDGNCMPBSAR-UHFFFAOYSA-N 0.000 claims 1
- FUXNPGYQRLEJOH-UHFFFAOYSA-N 2,6-dichloro-n-[2-[(4-fluorophenyl)methyl]-3-oxo-1,2,4-thiadiazol-5-yl]benzamide Chemical compound C1=CC(F)=CC=C1CN1C(=O)N=C(NC(=O)C=2C(=CC=CC=2Cl)Cl)S1 FUXNPGYQRLEJOH-UHFFFAOYSA-N 0.000 claims 1
- LKOHEZNWJKGELG-UHFFFAOYSA-N 2-(2-phenylethyl)-5-[4-(trifluoromethoxy)anilino]-1,2,4-thiadiazol-3-one Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC(S1)=NC(=O)N1CCC1=CC=CC=C1 LKOHEZNWJKGELG-UHFFFAOYSA-N 0.000 claims 1
- HGTKLMBPGLDIFR-UHFFFAOYSA-N 2-(2-phenylethyl)-5-[4-(trifluoromethyl)anilino]-1,2,4-thiadiazol-3-one Chemical compound C1=CC(C(F)(F)F)=CC=C1NC(S1)=NC(=O)N1CCC1=CC=CC=C1 HGTKLMBPGLDIFR-UHFFFAOYSA-N 0.000 claims 1
- GWIUBVYZRHTBHY-UHFFFAOYSA-N 2-(4-fluorophenyl)-n-[3-oxo-2-[[3-(trifluoromethyl)phenyl]methyl]-1,2,4-thiadiazol-5-yl]acetamide Chemical compound C1=CC(F)=CC=C1CC(=O)NC(S1)=NC(=O)N1CC1=CC=CC(C(F)(F)F)=C1 GWIUBVYZRHTBHY-UHFFFAOYSA-N 0.000 claims 1
- HNGKUGUJMPSSGY-UHFFFAOYSA-N 2-[(3,4-difluorophenyl)methyl]-5-[4-(trifluoromethoxy)anilino]-1,2,4-thiadiazol-3-one Chemical compound C1=C(F)C(F)=CC=C1CN1C(=O)N=C(NC=2C=CC(OC(F)(F)F)=CC=2)S1 HNGKUGUJMPSSGY-UHFFFAOYSA-N 0.000 claims 1
- XJTWKJIKTOVTGK-UHFFFAOYSA-N 2-[(3,4-difluorophenyl)methyl]-5-[4-(trifluoromethyl)anilino]-1,2,4-thiadiazol-3-one Chemical compound C1=C(F)C(F)=CC=C1CN1C(=O)N=C(NC=2C=CC(=CC=2)C(F)(F)F)S1 XJTWKJIKTOVTGK-UHFFFAOYSA-N 0.000 claims 1
- RJZSSMHOEKAAPX-UHFFFAOYSA-N 2-[(3-fluorophenyl)methyl]-5-[4-(trifluoromethoxy)anilino]-1,2,4-thiadiazol-3-one Chemical compound FC1=CC=CC(CN2C(N=C(NC=3C=CC(OC(F)(F)F)=CC=3)S2)=O)=C1 RJZSSMHOEKAAPX-UHFFFAOYSA-N 0.000 claims 1
- LZADXQXNWDOMDY-UHFFFAOYSA-N 2-[(3-fluorophenyl)methyl]-5-[4-(trifluoromethyl)anilino]-1,2,4-thiadiazol-3-one Chemical compound FC1=CC=CC(CN2C(N=C(NC=3C=CC(=CC=3)C(F)(F)F)S2)=O)=C1 LZADXQXNWDOMDY-UHFFFAOYSA-N 0.000 claims 1
- AMUWSZXTELUHFX-UHFFFAOYSA-N 2-[(4-chlorophenyl)methyl]-5-[4-(trifluoromethoxy)anilino]-1,2,4-thiadiazol-3-one Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC(S1)=NC(=O)N1CC1=CC=C(Cl)C=C1 AMUWSZXTELUHFX-UHFFFAOYSA-N 0.000 claims 1
- ZNNXRHUTYUXTHC-UHFFFAOYSA-N 2-[(4-chlorophenyl)methyl]-5-[4-(trifluoromethyl)anilino]-1,2,4-thiadiazol-3-one Chemical compound C1=CC(C(F)(F)F)=CC=C1NC(S1)=NC(=O)N1CC1=CC=C(Cl)C=C1 ZNNXRHUTYUXTHC-UHFFFAOYSA-N 0.000 claims 1
- RFZWGFCULXKUMF-UHFFFAOYSA-N 2-[(4-methoxyphenyl)methyl]-5-[4-(trifluoromethoxy)anilino]-1,2,4-thiadiazol-3-one Chemical compound C1=CC(OC)=CC=C1CN1C(=O)N=C(NC=2C=CC(OC(F)(F)F)=CC=2)S1 RFZWGFCULXKUMF-UHFFFAOYSA-N 0.000 claims 1
- WYBNVXBKQQMPFJ-UHFFFAOYSA-N 2-[(4-methoxyphenyl)methyl]-5-[4-(trifluoromethyl)anilino]-1,2,4-thiadiazol-3-one Chemical compound C1=CC(OC)=CC=C1CN1C(=O)N=C(NC=2C=CC(=CC=2)C(F)(F)F)S1 WYBNVXBKQQMPFJ-UHFFFAOYSA-N 0.000 claims 1
- NHYKNGYFZCJBDR-UHFFFAOYSA-N 2-[2-(4-chloro-n-methylanilino)ethyl]-5-(3,4-dichloroanilino)-1,2,4-thiadiazol-3-one Chemical compound C=1C=C(Cl)C=CC=1N(C)CCN(C(N=1)=O)SC=1NC1=CC=C(Cl)C(Cl)=C1 NHYKNGYFZCJBDR-UHFFFAOYSA-N 0.000 claims 1
- UQVPZZXWWFWQNN-UHFFFAOYSA-N 2-[2-(4-chlorophenyl)sulfanylethyl]-5-(3,4-dichloroanilino)-1,2,4-thiadiazol-3-one Chemical compound C1=CC(Cl)=CC=C1SCCN1C(=O)N=C(NC=2C=C(Cl)C(Cl)=CC=2)S1 UQVPZZXWWFWQNN-UHFFFAOYSA-N 0.000 claims 1
- YPPMKZRGLLMSDM-UHFFFAOYSA-N 2-chloro-6-fluoro-n-[2-[(4-fluorophenyl)methyl]-3-oxo-1,2,4-thiadiazol-5-yl]benzamide Chemical compound C1=CC(F)=CC=C1CN1C(=O)N=C(NC(=O)C=2C(=CC=CC=2F)Cl)S1 YPPMKZRGLLMSDM-UHFFFAOYSA-N 0.000 claims 1
- FSHRXYMLLSKYGV-UHFFFAOYSA-N 3,4-dichloro-n-[2-[(4-fluorophenyl)methyl]-3-oxo-1,2,4-thiadiazol-5-yl]benzamide Chemical compound C1=CC(F)=CC=C1CN1C(=O)N=C(NC(=O)C=2C=C(Cl)C(Cl)=CC=2)S1 FSHRXYMLLSKYGV-UHFFFAOYSA-N 0.000 claims 1
- NDEIURVSGKHEAW-UHFFFAOYSA-N 3,4-dichloro-n-[2-[1-(4-fluorophenyl)cyclopropyl]-3-oxo-1,2,4-thiadiazol-5-yl]benzamide Chemical compound C1=CC(F)=CC=C1C1(N2C(N=C(NC(=O)C=3C=C(Cl)C(Cl)=CC=3)S2)=O)CC1 NDEIURVSGKHEAW-UHFFFAOYSA-N 0.000 claims 1
- HWOJETIWOGVVBU-UHFFFAOYSA-N 3,4-difluoro-n-[2-[(4-fluorophenyl)methyl]-3-oxo-1,2,4-thiadiazol-5-yl]benzamide Chemical compound C1=CC(F)=CC=C1CN1C(=O)N=C(NC(=O)C=2C=C(F)C(F)=CC=2)S1 HWOJETIWOGVVBU-UHFFFAOYSA-N 0.000 claims 1
- FMPOTICVEOAYQK-UHFFFAOYSA-N 3,5-difluoro-n-[2-[(4-fluorophenyl)methyl]-3-oxo-1,2,4-thiadiazol-5-yl]benzamide Chemical compound C1=CC(F)=CC=C1CN1C(=O)N=C(NC(=O)C=2C=C(F)C=C(F)C=2)S1 FMPOTICVEOAYQK-UHFFFAOYSA-N 0.000 claims 1
- UMWQWADVYZQVBY-UHFFFAOYSA-N 3-[[5-(4-chloroanilino)-3-oxo-1,2,4-thiadiazol-2-yl]methyl]-n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC(CN2C(N=C(NC=3C=CC(Cl)=CC=3)S2)=O)=C1 UMWQWADVYZQVBY-UHFFFAOYSA-N 0.000 claims 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims 1
- DEIHGKFXCGHEGK-UHFFFAOYSA-N 4-[(4-chlorophenyl)methyl]-5-(3,4-dichlorophenyl)imino-1,2,4-thiadiazolidin-3-one Chemical compound C1=CC(Cl)=CC=C1CN(C(=O)NS1)C1=NC1=CC=C(Cl)C(Cl)=C1 DEIHGKFXCGHEGK-UHFFFAOYSA-N 0.000 claims 1
- QGGKZABFKBNKLA-UHFFFAOYSA-N 4-[1-(4-chlorophenyl)cyclopropyl]-5-(4-chlorophenyl)imino-1,2,4-thiadiazolidin-3-one Chemical compound C1=CC(Cl)=CC=C1N=C1N(C2(CC2)C=2C=CC(Cl)=CC=2)C(=O)NS1 QGGKZABFKBNKLA-UHFFFAOYSA-N 0.000 claims 1
- PESMVTAMUPTUQX-UHFFFAOYSA-N 4-[2-(4-chloro-N-methylanilino)ethyl]-5-(3,4-dichlorophenyl)-1-imino-1,2,4-thiadiazolidin-3-one Chemical compound ClC1=CC=C(C=C1)N(CCN1C(NS(C1C1=CC(=C(C=C1)Cl)Cl)=N)=O)C PESMVTAMUPTUQX-UHFFFAOYSA-N 0.000 claims 1
- LVDORRLYOXNORK-UHFFFAOYSA-N 4-[2-(4-chlorophenyl)sulfanylethyl]-5-(3,4-dichlorophenyl)imino-1,2,4-thiadiazolidin-3-one Chemical compound C1=CC(Cl)=CC=C1SCCN(C(=O)NS1)C1=NC1=CC=C(Cl)C(Cl)=C1 LVDORRLYOXNORK-UHFFFAOYSA-N 0.000 claims 1
- OQCAQPYSSFQACS-UHFFFAOYSA-N 4-[[2-[(3,4-difluorophenyl)methyl]-3-oxo-1,2,4-thiadiazol-5-yl]amino]benzonitrile Chemical compound C1=C(F)C(F)=CC=C1CN1C(=O)N=C(NC=2C=CC(=CC=2)C#N)S1 OQCAQPYSSFQACS-UHFFFAOYSA-N 0.000 claims 1
- XKILBXRPFVVUBB-UHFFFAOYSA-N 4-[[4-[(3,4-difluorophenyl)methyl]-3-oxo-1,2,4-thiadiazolidin-5-ylidene]amino]benzonitrile Chemical compound C1=C(F)C(F)=CC=C1CN(C(=O)NS1)C1=NC1=CC=C(C#N)C=C1 XKILBXRPFVVUBB-UHFFFAOYSA-N 0.000 claims 1
- HYYOUTIDAKSXEU-UHFFFAOYSA-N 4-benzhydryl-5-(3,4-dichlorophenyl)imino-1,2,4-thiadiazolidin-3-one Chemical compound C1=C(Cl)C(Cl)=CC=C1N=C1N(C(C=2C=CC=CC=2)C=2C=CC=CC=2)C(=O)NS1 HYYOUTIDAKSXEU-UHFFFAOYSA-N 0.000 claims 1
- KVQYNKBQULGFLP-UHFFFAOYSA-N 4-chloro-n-[2-[(3,4-difluorophenyl)methyl]-3-oxo-1,2,4-thiadiazol-5-yl]benzamide Chemical compound C1=C(F)C(F)=CC=C1CN1C(=O)N=C(NC(=O)C=2C=CC(Cl)=CC=2)S1 KVQYNKBQULGFLP-UHFFFAOYSA-N 0.000 claims 1
- WEDWLYRQKUTOAX-UHFFFAOYSA-N 4-chloro-n-[2-[(4-chlorophenyl)methyl]-3-oxo-1,2,4-thiadiazol-5-yl]benzamide Chemical compound C1=CC(Cl)=CC=C1CN1C(=O)N=C(NC(=O)C=2C=CC(Cl)=CC=2)S1 WEDWLYRQKUTOAX-UHFFFAOYSA-N 0.000 claims 1
- WWKBAXKETBKLRJ-UHFFFAOYSA-N 4-chloro-n-[2-[(4-fluorophenyl)methyl]-3-oxo-1,2,4-thiadiazol-5-yl]benzamide Chemical compound C1=CC(F)=CC=C1CN1C(=O)N=C(NC(=O)C=2C=CC(Cl)=CC=2)S1 WWKBAXKETBKLRJ-UHFFFAOYSA-N 0.000 claims 1
- ZUHLQVQSIGNCJR-UHFFFAOYSA-N 4-chloro-n-[2-[2-(4-chlorophenyl)sulfanylethyl]-3-oxo-1,2,4-thiadiazol-5-yl]benzamide Chemical compound C1=CC(Cl)=CC=C1SCCN1C(=O)N=C(NC(=O)C=2C=CC(Cl)=CC=2)S1 ZUHLQVQSIGNCJR-UHFFFAOYSA-N 0.000 claims 1
- VFZXNINYXOCKCV-UHFFFAOYSA-N 4-chloro-n-[3-oxo-4-[[3-(trifluoromethyl)phenyl]methyl]-1,2,4-thiadiazolidin-5-ylidene]benzamide Chemical compound FC(F)(F)C1=CC=CC(CN2C(SNC2=O)=NC(=O)C=2C=CC(Cl)=CC=2)=C1 VFZXNINYXOCKCV-UHFFFAOYSA-N 0.000 claims 1
- MNULEGDCPYONBU-UHFFFAOYSA-N 4-ethyl-11,12,15,19-tetrahydroxy-6'-(2-hydroxypropyl)-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers CC1C(C2C)OC(=O)C=CC(C)C(O)C(C)C(=O)C(C)C(O)C(C)C(=O)C(C)(O)C(O)C(C)CC=CC=CC(CC)CCC2OC21CCC(C)C(CC(C)O)O2 MNULEGDCPYONBU-UHFFFAOYSA-N 0.000 claims 1
- IHAHDANKRDSQDI-UHFFFAOYSA-N 4-fluoro-n-[3-oxo-2-[[3-(trifluoromethyl)phenyl]methyl]-1,2,4-thiadiazol-5-yl]benzamide Chemical compound C1=CC(F)=CC=C1C(=O)NC(S1)=NC(=O)N1CC1=CC=CC(C(F)(F)F)=C1 IHAHDANKRDSQDI-UHFFFAOYSA-N 0.000 claims 1
- CQPHWPNJPUDZJN-UHFFFAOYSA-N 5-(3,4-dichloroanilino)-2-(2-phenoxyethyl)-1,2,4-thiadiazol-3-one Chemical compound C1=C(Cl)C(Cl)=CC=C1NC(S1)=NC(=O)N1CCOC1=CC=CC=C1 CQPHWPNJPUDZJN-UHFFFAOYSA-N 0.000 claims 1
- CSDMWFUBTUQLEJ-UHFFFAOYSA-N 5-(3,4-dichloroanilino)-2-[(3-fluorophenyl)methyl]-1,2,4-thiadiazol-3-one Chemical compound FC1=CC=CC(CN2C(N=C(NC=3C=C(Cl)C(Cl)=CC=3)S2)=O)=C1 CSDMWFUBTUQLEJ-UHFFFAOYSA-N 0.000 claims 1
- HXIOAMUSVHJFJR-UHFFFAOYSA-N 5-(3,4-dichlorophenyl)imino-4-(2-phenoxyethyl)-1,2,4-thiadiazolidin-3-one Chemical compound C1=C(Cl)C(Cl)=CC=C1N=C1N(CCOC=2C=CC=CC=2)C(=O)NS1 HXIOAMUSVHJFJR-UHFFFAOYSA-N 0.000 claims 1
- LYSHPGVDISUMCS-UHFFFAOYSA-N 5-(3,4-dichlorophenyl)imino-4-[(3,4-difluorophenyl)methyl]-1,2,4-thiadiazolidin-3-one Chemical compound C1=C(F)C(F)=CC=C1CN(C(=O)NS1)C1=NC1=CC=C(Cl)C(Cl)=C1 LYSHPGVDISUMCS-UHFFFAOYSA-N 0.000 claims 1
- AJVQFHMIZQIECE-UHFFFAOYSA-N 5-(3,4-dichlorophenyl)imino-4-[(3-fluorophenyl)methyl]-1,2,4-thiadiazolidin-3-one Chemical compound FC1=CC=CC(CN2C(SNC2=O)=NC=2C=C(Cl)C(Cl)=CC=2)=C1 AJVQFHMIZQIECE-UHFFFAOYSA-N 0.000 claims 1
- MQVDUIHSNWIVBM-UHFFFAOYSA-N 5-(3,4-dichlorophenyl)imino-4-[(4-methoxyphenyl)methyl]-1,2,4-thiadiazolidin-3-one Chemical compound C1=CC(OC)=CC=C1CN(C(=O)NS1)C1=NC1=CC=C(Cl)C(Cl)=C1 MQVDUIHSNWIVBM-UHFFFAOYSA-N 0.000 claims 1
- AZQPOQDQXYPOTD-UHFFFAOYSA-N 5-(3,4-dichlorophenyl)imino-4-[[3-(trifluoromethyl)phenyl]methyl]-1,2,4-thiadiazolidin-3-one Chemical compound FC(F)(F)C1=CC=CC(CN2C(SNC2=O)=NC=2C=C(Cl)C(Cl)=CC=2)=C1 AZQPOQDQXYPOTD-UHFFFAOYSA-N 0.000 claims 1
- HMDIBJPBXYGKBE-UHFFFAOYSA-N 5-(3,4-dichlorophenyl)imino-4-[[4-(1,2,4-triazol-1-yl)phenyl]methyl]-1,2,4-thiadiazolidin-3-one Chemical compound C1=C(Cl)C(Cl)=CC=C1N=C1N(CC=2C=CC(=CC=2)N2N=CN=C2)C(=O)NS1 HMDIBJPBXYGKBE-UHFFFAOYSA-N 0.000 claims 1
- YHLFAOGONXFOMA-UHFFFAOYSA-N 5-(4-chloroanilino)-2-[1-(4-chlorophenyl)cyclopropyl]-1,2,4-thiadiazol-3-one Chemical compound C1=CC(Cl)=CC=C1NC1=NC(=O)N(C2(CC2)C=2C=CC(Cl)=CC=2)S1 YHLFAOGONXFOMA-UHFFFAOYSA-N 0.000 claims 1
- DUARHOWRVABIDW-UHFFFAOYSA-N 5-(6-chloropyridin-3-yl)imino-4-[(3,4-difluorophenyl)methyl]-1,2,4-thiadiazolidin-3-one Chemical compound C1=C(F)C(F)=CC=C1CN(C(=O)NS1)C1=NC1=CC=C(Cl)N=C1 DUARHOWRVABIDW-UHFFFAOYSA-N 0.000 claims 1
- YEGKCBNUIOQIOQ-UHFFFAOYSA-N 5-[(3,4-dichlorophenyl)methylamino]-2-[(3,4-difluorophenyl)methyl]-1,2,4-thiadiazol-3-one Chemical compound C1=C(F)C(F)=CC=C1CN1C(=O)N=C(NCC=2C=C(Cl)C(Cl)=CC=2)S1 YEGKCBNUIOQIOQ-UHFFFAOYSA-N 0.000 claims 1
- SDNFEWYUYLJMFS-UHFFFAOYSA-N 5-[(4-chlorophenyl)methylimino]-4-[(3,4-difluorophenyl)methyl]-1,2,4-thiadiazolidin-3-one Chemical compound C1=C(F)C(F)=CC=C1CN(C(=O)NS1)C1=NCC1=CC=C(Cl)C=C1 SDNFEWYUYLJMFS-UHFFFAOYSA-N 0.000 claims 1
- NKOHRVBBQISBSB-UHFFFAOYSA-N 5-[(4-hydroxyphenyl)methyl]-1,3-thiazolidine-2,4-dione Chemical compound C1=CC(O)=CC=C1CC1C(=O)NC(=O)S1 NKOHRVBBQISBSB-UHFFFAOYSA-N 0.000 claims 1
- QCCSDJVVSABTKP-UHFFFAOYSA-N 5-[(6-chloropyridin-3-yl)amino]-2-[(3,4-difluorophenyl)methyl]-1,2,4-thiadiazol-3-one Chemical compound C1=C(F)C(F)=CC=C1CN1C(=O)N=C(NC=2C=NC(Cl)=CC=2)S1 QCCSDJVVSABTKP-UHFFFAOYSA-N 0.000 claims 1
- MPLLLQUZNJSVTK-UHFFFAOYSA-N 5-[3-[4-[2-(4-fluorophenyl)ethoxy]phenyl]propyl]furan-2-carboxylic acid Chemical compound O1C(C(=O)O)=CC=C1CCCC(C=C1)=CC=C1OCCC1=CC=C(F)C=C1 MPLLLQUZNJSVTK-UHFFFAOYSA-N 0.000 claims 1
- MODAULMVTKWLKJ-UHFFFAOYSA-N 5-amino-1,2,4-thiadiazol-3-one Chemical compound NC1=NC(=O)NS1 MODAULMVTKWLKJ-UHFFFAOYSA-N 0.000 claims 1
- 229940122815 Aromatase inhibitor Drugs 0.000 claims 1
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 claims 1
- 229940123208 Biguanide Drugs 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- BGLFFOQHDZARCZ-UHFFFAOYSA-N CN1C(=O)NC(S1=N)C2=CC=C(C=C2)C(F)(F)F Chemical compound CN1C(=O)NC(S1=N)C2=CC=C(C=C2)C(F)(F)F BGLFFOQHDZARCZ-UHFFFAOYSA-N 0.000 claims 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims 1
- ZFKQCQMIXKQUND-UHFFFAOYSA-N N=C(CN(C(C(C=C1)=CC(Cl)=C1Cl)SN1)C1=O)C1=CC=CC=C1 Chemical compound N=C(CN(C(C(C=C1)=CC(Cl)=C1Cl)SN1)C1=O)C1=CC=CC=C1 ZFKQCQMIXKQUND-UHFFFAOYSA-N 0.000 claims 1
- ONFKIPLQQJNDCW-UHFFFAOYSA-O O=C1N=C(NC(C=C2)=CC(Cl)=C2Cl)[S+](CCC2=CC=CC=C2)N1 Chemical compound O=C1N=C(NC(C=C2)=CC(Cl)=C2Cl)[S+](CCC2=CC=CC=C2)N1 ONFKIPLQQJNDCW-UHFFFAOYSA-O 0.000 claims 1
- 229940126033 PPAR agonist Drugs 0.000 claims 1
- ILRCGYURZSFMEG-UHFFFAOYSA-N Salidroside Natural products OC1C(O)C(O)C(CO)OC1OCCC1=CC=C(O)C=C1 ILRCGYURZSFMEG-UHFFFAOYSA-N 0.000 claims 1
- 102000000344 Sirtuin 1 Human genes 0.000 claims 1
- 108010041191 Sirtuin 1 Proteins 0.000 claims 1
- 239000012190 activator Substances 0.000 claims 1
- 239000004037 angiogenesis inhibitor Substances 0.000 claims 1
- 229940121369 angiogenesis inhibitor Drugs 0.000 claims 1
- 239000003886 aromatase inhibitor Substances 0.000 claims 1
- 210000000481 breast Anatomy 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 238000011260 co-administration Methods 0.000 claims 1
- 210000001072 colon Anatomy 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 claims 1
- 239000000824 cytostatic agent Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 201000005787 hematologic cancer Diseases 0.000 claims 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims 1
- 229940022353 herceptin Drugs 0.000 claims 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims 1
- 239000004615 ingredient Substances 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 208000032839 leukemia Diseases 0.000 claims 1
- WSJCPQGBELBKIE-UHFFFAOYSA-N n-[2-[(4-fluorophenyl)methyl]-3-oxo-1,2,4-thiadiazol-5-yl]-3,5-bis(trifluoromethyl)benzamide Chemical compound C1=CC(F)=CC=C1CN1C(=O)N=C(NC(=O)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)S1 WSJCPQGBELBKIE-UHFFFAOYSA-N 0.000 claims 1
- AGHYVPGSDQFGIP-UHFFFAOYSA-N n-[2-[(4-fluorophenyl)methyl]-3-oxo-1,2,4-thiadiazol-5-yl]-4-(trifluoromethoxy)benzamide Chemical compound C1=CC(F)=CC=C1CN1C(=O)N=C(NC(=O)C=2C=CC(OC(F)(F)F)=CC=2)S1 AGHYVPGSDQFGIP-UHFFFAOYSA-N 0.000 claims 1
- JWCZVGWBEPZJLO-UHFFFAOYSA-N n-[2-[(4-fluorophenyl)methyl]-3-oxo-1,2,4-thiadiazol-5-yl]-4-methoxybenzamide Chemical compound C1=CC(OC)=CC=C1C(=O)NC(S1)=NC(=O)N1CC1=CC=C(F)C=C1 JWCZVGWBEPZJLO-UHFFFAOYSA-N 0.000 claims 1
- WMOWRZATFPXDAS-UHFFFAOYSA-N n-[3-oxo-2-[[3-(trifluoromethyl)phenyl]methyl]-1,2,4-thiadiazol-5-yl]benzamide Chemical compound FC(F)(F)C1=CC=CC(CN2C(N=C(NC(=O)C=3C=CC=CC=3)S2)=O)=C1 WMOWRZATFPXDAS-UHFFFAOYSA-N 0.000 claims 1
- KIDIYOSDZIEFKU-UHFFFAOYSA-N n-[4-[(3,4-dichlorophenyl)methyl]-3-oxo-1,2,4-thiadiazolidin-5-ylidene]-3,4-difluorobenzamide Chemical compound C1=C(F)C(F)=CC=C1C(=O)N=C1N(CC=2C=C(Cl)C(Cl)=CC=2)C(=O)NS1 KIDIYOSDZIEFKU-UHFFFAOYSA-N 0.000 claims 1
- ZIPZCMQFNYAKGX-UHFFFAOYSA-N n-[4-[(3-fluorophenyl)methyl]-3-oxo-1,2,4-thiadiazolidin-5-ylidene]-4-(trifluoromethyl)benzamide Chemical compound FC1=CC=CC(CN2C(SNC2=O)=NC(=O)C=2C=CC(=CC=2)C(F)(F)F)=C1 ZIPZCMQFNYAKGX-UHFFFAOYSA-N 0.000 claims 1
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
- 229930191479 oligomycin Natural products 0.000 claims 1
- MNULEGDCPYONBU-AWJDAWNUSA-N oligomycin A Polymers O([C@H]1CC[C@H](/C=C/C=C/C[C@@H](C)[C@H](O)[C@@](C)(O)C(=O)[C@@H](C)[C@H](O)[C@@H](C)C(=O)[C@@H](C)[C@H](O)[C@@H](C)/C=C/C(=O)O[C@@H]([C@@H]2C)[C@@H]1C)CC)[C@@]12CC[C@H](C)[C@H](C[C@@H](C)O)O1 MNULEGDCPYONBU-AWJDAWNUSA-N 0.000 claims 1
- 239000002831 pharmacologic agent Substances 0.000 claims 1
- 210000002307 prostate Anatomy 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 1
- ILRCGYURZSFMEG-RQICVUQASA-N salidroside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)OC1OCCC1=CC=C(O)C=C1 ILRCGYURZSFMEG-RQICVUQASA-N 0.000 claims 1
- 229960001603 tamoxifen Drugs 0.000 claims 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims 1
- 229960000575 trastuzumab Drugs 0.000 claims 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 claims 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 claims 1
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 claims 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
- 0 CN(*)NC(SN1)=NC1=O Chemical compound CN(*)NC(SN1)=NC1=O 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 239000003444 phase transfer catalyst Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- AZYTZQYCOBXDGY-UHFFFAOYSA-N 2-pyrrolidin-1-ylpyridine Chemical compound C1CCCN1C1=CC=CC=N1 AZYTZQYCOBXDGY-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 101150003085 Pdcl gene Proteins 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- KACBNBQMSXQASC-UHFFFAOYSA-J [O-]C(F)=O.[O-]C(F)=O.[O-]C(F)=O.[O-]C(F)=O.C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1.C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1.C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1.C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 Chemical compound [O-]C(F)=O.[O-]C(F)=O.[O-]C(F)=O.[O-]C(F)=O.C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1.C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1.C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1.C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 KACBNBQMSXQASC-UHFFFAOYSA-J 0.000 description 1
- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 1
- PFYXSUNOLOJMDX-UHFFFAOYSA-N bis(2,5-dioxopyrrolidin-1-yl) carbonate Chemical compound O=C1CCC(=O)N1OC(=O)ON1C(=O)CCC1=O PFYXSUNOLOJMDX-UHFFFAOYSA-N 0.000 description 1
- SBGUYEPUJPATFD-UHFFFAOYSA-N bromo(tripyrrolidin-1-yl)phosphanium Chemical compound C1CCCN1[P+](N1CCCC1)(Br)N1CCCC1 SBGUYEPUJPATFD-UHFFFAOYSA-N 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- JCIVHYBIFRUGKO-UHFFFAOYSA-N lithium;2,2,6,6-tetramethylpiperidine Chemical compound [Li].CC1(C)CCCC(C)(C)N1 JCIVHYBIFRUGKO-UHFFFAOYSA-N 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- 125000005441 o-toluyl group Chemical group [H]C1=C([H])C(C(*)=O)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US21373509P | 2009-07-08 | 2009-07-08 | |
| US61/213,735 | 2009-07-08 | ||
| PCT/GB2010/001315 WO2011004162A2 (en) | 2009-07-08 | 2010-07-08 | Compounds useful as medicaments |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2012532854A JP2012532854A (ja) | 2012-12-20 |
| JP2012532854A5 true JP2012532854A5 (https=) | 2013-08-15 |
| JP5982281B2 JP5982281B2 (ja) | 2016-08-31 |
Family
ID=43086401
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012519055A Active JP5982281B2 (ja) | 2009-07-08 | 2010-07-08 | 医薬として有用な化合物 |
Country Status (24)
| Country | Link |
|---|---|
| US (2) | US9162994B2 (https=) |
| EP (1) | EP2451794B1 (https=) |
| JP (1) | JP5982281B2 (https=) |
| KR (1) | KR101765957B1 (https=) |
| CN (1) | CN102596923B (https=) |
| AU (1) | AU2010270030B2 (https=) |
| BR (1) | BR112012000370B1 (https=) |
| CA (1) | CA2767291C (https=) |
| DK (1) | DK2451794T3 (https=) |
| EA (1) | EA026674B1 (https=) |
| ES (1) | ES2567753T3 (https=) |
| HR (1) | HRP20160353T1 (https=) |
| HU (1) | HUE027263T2 (https=) |
| IL (1) | IL216723A (https=) |
| ME (1) | ME02443B (https=) |
| MX (1) | MX337516B (https=) |
| NZ (1) | NZ597075A (https=) |
| PL (1) | PL2451794T3 (https=) |
| RS (1) | RS54718B1 (https=) |
| SG (1) | SG177558A1 (https=) |
| SI (1) | SI2451794T1 (https=) |
| SM (1) | SMT201600225B (https=) |
| WO (1) | WO2011004162A2 (https=) |
| ZA (1) | ZA201108901B (https=) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100931145B1 (ko) * | 2008-07-04 | 2009-12-10 | 현대자동차주식회사 | 조정식 킥 다운 스위치의 조작기구 |
| WO2013108026A1 (en) | 2012-01-17 | 2013-07-25 | Baltic Bio Ab | Thiadiazolone derivatives useful in the treatment of diabetes |
| US8889730B2 (en) | 2012-04-10 | 2014-11-18 | Pfizer Inc. | Indole and indazole compounds that activate AMPK |
| JP6064062B2 (ja) | 2013-03-15 | 2017-01-18 | ファイザー・インク | Ａｍｐｋを活性化させるインダゾール化合物 |
| GB201308325D0 (en) * | 2013-05-09 | 2013-06-19 | Immodulon Therapeutics Ltd | Cancer Therapy |
| AU2017275657B2 (en) | 2016-06-02 | 2021-08-19 | Novartis Ag | Potassium channel modulators |
| EA202092441A1 (ru) | 2016-06-07 | 2021-05-21 | Джакобио Фармасьютикалс Ко., Лтд. | Новые гетероциклические производные, применимые в качестве ингибиторов shp2 |
| PL3571193T3 (pl) | 2017-01-23 | 2022-04-25 | Cadent Therapeutics, Inc. | Modulatory kanału potasowego |
| KR20240026521A (ko) | 2017-03-23 | 2024-02-28 | 자코바이오 파마슈티칼스 컴퍼니 리미티드 | Shp2 억제제로서 유용한 신규한 헤테로환형 유도체 |
| CN112839935A (zh) | 2018-09-26 | 2021-05-25 | 北京加科思新药研发有限公司 | 可用作shp2抑制剂的新型杂环衍生物 |
| EP3870291A1 (en) | 2018-10-22 | 2021-09-01 | Cadent Therapeutics, Inc. | Crystalline forms of potassium channel modulators |
| WO2020095010A1 (en) | 2018-11-05 | 2020-05-14 | Balticgruppen Bio Ab | Methods of treating diabetes in severe insulin-resistant diabetic subjects |
| CN109879808B (zh) * | 2019-03-05 | 2020-10-16 | 北京工业大学 | 一种含五元唑类杂环基查尔酮类衍生物及制备方法和医药用途 |
| GB201910092D0 (en) | 2019-07-15 | 2019-08-28 | Balticgruppen Bio Ab | New formulations |
| GB201910093D0 (en) | 2019-07-15 | 2019-08-28 | Balticgruppen Bio Ab | New formulations |
| US11691954B2 (en) | 2019-10-18 | 2023-07-04 | Betagenon Ab | Formulations |
| GB201915094D0 (en) * | 2019-10-18 | 2019-12-04 | Balticgruppen Bio Ab | New formulations |
| GB202015585D0 (en) * | 2020-10-01 | 2020-11-18 | Betagenon Bio Ab | New compounds |
| GB202100352D0 (en) * | 2021-01-12 | 2021-02-24 | Balticgruppen Bio Ab | New methods |
| GB202112529D0 (en) | 2021-09-02 | 2021-10-20 | Betagenon Bio Ab | New compounds |
| WO2025017194A1 (en) | 2023-07-20 | 2025-01-23 | Betagenon Ab | Methods for regulating blood glucose levels using a dual ampk activator and mitochondrial uncoupler |
| WO2025017193A1 (en) | 2023-07-20 | 2025-01-23 | Betagenon Ab | Methods of treating cardiomyopathy induced by metabolic inflexibility |
| WO2025027205A1 (en) | 2023-08-03 | 2025-02-06 | Betagenon Ab | Treatment of cancer with the pdk inhibitor 4-chloro-n-(2-(4-chlorobenzyl)-3-oxo-2,3-dihydro-1,2,4-thiadiazol-5-yl)benzamide |
| WO2025252672A1 (en) | 2024-06-03 | 2025-12-11 | Betagenon Ab | Use of tryptophan and metabolites thereof as biomarkers for treatment methods |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4093624A (en) | 1977-01-31 | 1978-06-06 | Icn Pharmaceuticals, Inc. | 1,2,4-Thiadiazolidine-3,5-dione |
| MXPA02011079A (es) | 2000-05-11 | 2004-08-19 | Consejo Superior Investigacion | Inhibidores heterociclicos de quinasa de sintasa de glucogeno gsk3. |
| ES2166328B1 (es) * | 2000-05-11 | 2003-09-16 | Consejo Superior Investigacion | Inhibidores heterociclicos del enzima gsk 3 utiles en el tratamiento de procesos neurodegenerativos e hiperproliferativos |
| WO2006045581A1 (en) | 2004-10-21 | 2006-05-04 | Neuropharma, S.A. | The use of 1, 2, 4-thiadiazolidine-3, 5-diones as ppar activators |
| US20090156644A1 (en) | 2005-07-21 | 2009-06-18 | Jacob Westman | Use of thiazole derivatives and analogues in the treatment of cancer |
| WO2008090356A1 (en) * | 2007-01-25 | 2008-07-31 | Betagenon Ab | Thiazolidinone derivatives useful in the treatment of cancer and disorders caused by excess adiposity |
-
2010
- 2010-07-08 AU AU2010270030A patent/AU2010270030B2/en active Active
- 2010-07-08 SI SI201031157A patent/SI2451794T1/sl unknown
- 2010-07-08 DK DK10759940.9T patent/DK2451794T3/en active
- 2010-07-08 PL PL10759940T patent/PL2451794T3/pl unknown
- 2010-07-08 RS RS20160255A patent/RS54718B1/sr unknown
- 2010-07-08 SG SG2012001236A patent/SG177558A1/en unknown
- 2010-07-08 EA EA201200102A patent/EA026674B1/ru not_active IP Right Cessation
- 2010-07-08 HU HUE10759940A patent/HUE027263T2/en unknown
- 2010-07-08 JP JP2012519055A patent/JP5982281B2/ja active Active
- 2010-07-08 MX MX2012000441A patent/MX337516B/es active IP Right Grant
- 2010-07-08 CN CN201080030894.9A patent/CN102596923B/zh active Active
- 2010-07-08 NZ NZ597075A patent/NZ597075A/xx unknown
- 2010-07-08 ES ES10759940.9T patent/ES2567753T3/es active Active
- 2010-07-08 HR HRP20160353TT patent/HRP20160353T1/hr unknown
- 2010-07-08 US US13/381,426 patent/US9162994B2/en active Active
- 2010-07-08 BR BR112012000370-4A patent/BR112012000370B1/pt active IP Right Grant
- 2010-07-08 ME MEP-2016-66A patent/ME02443B/me unknown
- 2010-07-08 KR KR1020117030830A patent/KR101765957B1/ko active Active
- 2010-07-08 EP EP10759940.9A patent/EP2451794B1/en active Active
- 2010-07-08 WO PCT/GB2010/001315 patent/WO2011004162A2/en not_active Ceased
- 2010-07-08 CA CA2767291A patent/CA2767291C/en active Active
-
2011
- 2011-12-01 IL IL216723A patent/IL216723A/en active IP Right Grant
- 2011-12-05 ZA ZA2011/08901A patent/ZA201108901B/en unknown
-
2015
- 2015-10-14 US US14/883,190 patent/US9675596B2/en active Active
-
2016
- 2016-07-12 SM SM201600225T patent/SMT201600225B/it unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2012532854A5 (https=) | ||
| JP5982281B2 (ja) | 医薬として有用な化合物 | |
| US5399566A (en) | Pyridine derivatives having angiotensin II antagonism | |
| JP3298641B2 (ja) | イミダゾール誘導体およびそのサイトカイン阻害剤としての使用 | |
| US20100311748A1 (en) | Heterocyclic amides useful for the treatment of cancer and psoriasis | |
| US20050203153A1 (en) | Phthalimide carboxylic acid derivatives | |
| KR20110091865A (ko) | ２ｈ-크로멘 화합물 및 그의 유도체 | |
| RU2442777C2 (ru) | Ингибиторы киназ и способы их применения | |
| EP1836173A4 (en) | ANTI-INFLAMMATORY DRUGS | |
| JP2006528193A (ja) | Ｃ−ｆｍｓキナーゼの阻害剤としてのキノリノン誘導体 | |
| AU2009200478A1 (en) | Metabotropic glutamate receptor-5 modulators | |
| SK242590A3 (en) | Substituted n-(aryloxyalkyl)heteroaryl piperidines and -piperazines, method for their preparation and pharmaceutical compositions containing same | |
| AU2005270132A1 (en) | Anti-inflammatory medicaments | |
| PL203771B1 (pl) | Pochodna bifenylosulfonamidu jako dualny antagonista receptorów angiotensyny i endoteliny, sposób jej wytwarzania i jej zastosowanie oraz pochodna bifenylu i pochodna benzenu | |
| JP2005539000A (ja) | Ａｌｋ５阻害剤としての２−フェニルピリジン−４−イル誘導体 | |
| JP2017502057A (ja) | ブロモドメイン阻害剤としての二環式複素環誘導体 | |
| JP2008266295A (ja) | キナーセ゛阻害活性を有する新規チアシ゛アソ゛ール誘導体 | |
| AU2002238855B2 (en) | N-phenylarylsulfonamide compound, drug containing the compound as active ingredient, intermediate for the compound, and processes for producing the same | |
| CA2803880C (en) | Compounds for the inhibition of cellular proliferation | |
| CA3136725A1 (en) | Inhibitors of cd40-cd154 binding | |
| WO2001058880A1 (en) | Novel triazole derivatives | |
| RU2287529C2 (ru) | Новые гетероциклические производные и их медицинское использование | |
| KR20070116876A (ko) | 피리미딘 카르복실산 유도체 및 그의 용도 | |
| KR20150012289A (ko) | 항바이러스 활성을 가진 메탄티온 화합물 | |
| AU2004262482A1 (en) | 2-`4(phenylamino)-piperidin-1-yl-n-phenyl-acetamine derivatives and related compounds as neuropeptide Y5 (NPY5) ligands for the treatement of obesity |