CA2881996A1 - 2,3-benzodiazepines - Google Patents
2,3-benzodiazepines Download PDFInfo
- Publication number
- CA2881996A1 CA2881996A1 CA2881996A CA2881996A CA2881996A1 CA 2881996 A1 CA2881996 A1 CA 2881996A1 CA 2881996 A CA2881996 A CA 2881996A CA 2881996 A CA2881996 A CA 2881996A CA 2881996 A1 CA2881996 A1 CA 2881996A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- dihydro
- benzodiazepine
- carboxamide
- alkoxy
- 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.)
- Abandoned
Links
- RPBDCDQMCRHNLM-UHFFFAOYSA-N C1=NNC=C2C=CC=CC2=C1 Chemical class C1=NNC=C2C=CC=CC2=C1 RPBDCDQMCRHNLM-UHFFFAOYSA-N 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 103
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 24
- 208000035475 disorder Diseases 0.000 claims abstract description 24
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 13
- 230000003143 atherosclerotic effect Effects 0.000 claims abstract description 7
- 208000036142 Viral infection Diseases 0.000 claims abstract description 6
- 230000009385 viral infection Effects 0.000 claims abstract description 6
- 230000035558 fertility Effects 0.000 claims abstract description 5
- 230000003463 hyperproliferative effect Effects 0.000 claims abstract description 5
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 5
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 3
- 206010040047 Sepsis Diseases 0.000 claims abstract description 3
- 206010020718 hyperplasia Diseases 0.000 claims abstract description 3
- 208000019553 vascular disease Diseases 0.000 claims abstract description 3
- 239000000543 intermediate Substances 0.000 claims abstract 4
- -1 cyano, carboxyl Chemical group 0.000 claims description 1008
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 851
- 125000006413 ring segment Chemical group 0.000 claims description 451
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 377
- 229910052736 halogen Inorganic materials 0.000 claims description 321
- 150000002367 halogens Chemical class 0.000 claims description 314
- 125000001424 substituent group Chemical group 0.000 claims description 285
- 229910052739 hydrogen Inorganic materials 0.000 claims description 250
- 239000001257 hydrogen Substances 0.000 claims description 250
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 235
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 229
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 218
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 181
- 239000000460 chlorine Substances 0.000 claims description 162
- 229910052801 chlorine Inorganic materials 0.000 claims description 162
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 161
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 151
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 143
- 239000011737 fluorine Substances 0.000 claims description 120
- 229910052731 fluorine Inorganic materials 0.000 claims description 120
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 118
- 125000004076 pyridyl group Chemical group 0.000 claims description 115
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 90
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 90
- 229910052794 bromium Inorganic materials 0.000 claims description 90
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 90
- 150000003839 salts Chemical class 0.000 claims description 90
- 239000012453 solvate Substances 0.000 claims description 89
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 85
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical group [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 85
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 81
- 125000004043 oxo group Chemical group O=* 0.000 claims description 73
- 125000004193 piperazinyl group Chemical group 0.000 claims description 73
- 125000002757 morpholinyl group Chemical group 0.000 claims description 72
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 61
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 60
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 48
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 46
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 45
- 125000003386 piperidinyl group Chemical group 0.000 claims description 44
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 43
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 40
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 35
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 32
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 32
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 32
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 30
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 28
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 28
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 125000004432 carbon atom Chemical group C* 0.000 claims description 24
- 125000005059 halophenyl group Chemical group 0.000 claims description 21
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 21
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 20
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 20
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 19
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 16
- 125000006379 fluoropyridyl group Chemical group 0.000 claims description 16
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 16
- 125000000160 oxazolidinyl group Chemical group 0.000 claims description 16
- 125000001425 triazolyl group Chemical group 0.000 claims description 15
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 14
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 14
- 125000002393 azetidinyl group Chemical group 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 125000001544 thienyl group Chemical group 0.000 claims description 13
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
- 125000003310 benzodiazepinyl group Chemical group N1N=C(C=CC2=C1C=CC=C2)* 0.000 claims description 12
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 11
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 11
- 125000003282 alkyl amino group Chemical group 0.000 claims description 10
- 125000005959 diazepanyl group Chemical group 0.000 claims description 10
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 10
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 9
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
- 125000006317 cyclopropyl amino group Chemical group 0.000 claims description 9
- 125000002883 imidazolyl group Chemical group 0.000 claims description 9
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 9
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 9
- 125000000335 thiazolyl group Chemical group 0.000 claims description 9
- SESYXUWPTXSJBV-UHFFFAOYSA-N [amino(hydroxy)-lambda3-chloranyl]formonitrile Chemical compound NCl(O)C#N SESYXUWPTXSJBV-UHFFFAOYSA-N 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 239000001301 oxygen Substances 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 238000002560 therapeutic procedure Methods 0.000 claims description 8
- 125000001984 thiazolidinyl group Chemical group 0.000 claims description 8
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 7
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 7
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 7
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- PJOUURZOYJMYPA-UHFFFAOYSA-N OClC#N Chemical compound OClC#N PJOUURZOYJMYPA-UHFFFAOYSA-N 0.000 claims description 6
- 125000006001 difluoroethyl group Chemical group 0.000 claims description 6
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 6
- 238000011321 prophylaxis Methods 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 5
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 5
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 3
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 2
- 208000032839 leukemia Diseases 0.000 claims description 2
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 28
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 25
- KUXDMRAONOYXDM-FUBQLUNQSA-N 1-[4-[(3s)-3-hydroxypyrrolidin-1-yl]phenyl]-7,8-dimethoxy-n,4-dimethyl-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound C12=CC(OC)=C(OC)C=C2CC(C)N(C(=O)NC)N=C1C(C=C1)=CC=C1N1CC[C@H](O)C1 KUXDMRAONOYXDM-FUBQLUNQSA-N 0.000 claims 2
- MVAHTFLZMOQYDC-LLVKDONJSA-N (4R)-1-(4-chlorophenyl)-N,4-dimethyl-8-(trifluoromethoxy)-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound ClC1=CC=C(C=C1)C1=NN([C@@H](CC2=C1C=C(C=C2)OC(F)(F)F)C)C(=O)NC MVAHTFLZMOQYDC-LLVKDONJSA-N 0.000 claims 1
- JAPYRZRQVTWQPV-OAHLLOKOSA-N (4R)-1-(4-chlorophenyl)-N,4-dimethyl-8-morpholin-4-yl-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound ClC1=CC=C(C=C1)C1=NN([C@@H](CC2=C1C=C(C=C2)N2CCOCC2)C)C(=O)NC JAPYRZRQVTWQPV-OAHLLOKOSA-N 0.000 claims 1
- LVOZKSSVIPZABA-CQSZACIVSA-N (4R)-1-[4-(2,4-dimethyl-1,3-thiazol-5-yl)phenyl]-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound CC=1SC(=C(N1)C)C1=CC=C(C=C1)C1=NN([C@@H](CC2=C1C=C(C(=C2)OC)OC)C)C(=O)NC LVOZKSSVIPZABA-CQSZACIVSA-N 0.000 claims 1
- LUFRZKPVUCTMLL-CQSZACIVSA-N (4R)-1-[4-(3,5-dimethyl-1,2-oxazol-4-yl)phenyl]-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound CC1=NOC(=C1C1=CC=C(C=C1)C1=NN([C@@H](CC2=C1C=C(C(=C2)OC)OC)C)C(=O)NC)C LUFRZKPVUCTMLL-CQSZACIVSA-N 0.000 claims 1
- ZDRURUMITWYFTN-CQSZACIVSA-N (4R)-1-[4-(3-fluoroazetidin-1-yl)phenyl]-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound FC1CN(C1)C1=CC=C(C=C1)C1=NN([C@@H](CC2=C1C=C(C(=C2)OC)OC)C)C(=O)NC ZDRURUMITWYFTN-CQSZACIVSA-N 0.000 claims 1
- IZYRNJVZGWEGHB-QGZVFWFLSA-N (4R)-1-[4-(4-acetylpiperazin-1-yl)phenyl]-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound C(C)(=O)N1CCN(CC1)C1=CC=C(C=C1)C1=NN([C@@H](CC2=C1C=C(C(=C2)OC)OC)C)C(=O)NC IZYRNJVZGWEGHB-QGZVFWFLSA-N 0.000 claims 1
- SRUSJOIHVSHPAK-OAHLLOKOSA-N (4R)-1-[4-(azetidin-1-yl)phenyl]-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound N1(CCC1)C1=CC=C(C=C1)C1=NN([C@@H](CC2=C1C=C(C(=C2)OC)OC)C)C(=O)NC SRUSJOIHVSHPAK-OAHLLOKOSA-N 0.000 claims 1
- NPQSRNGURRYZDG-MRXNPFEDSA-N (4R)-7,8-dimethoxy-N,4-dimethyl-1-(4-morpholin-4-ylphenyl)-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound COC=1C(=CC2=C(C[C@H](N(N=C2C2=CC=C(C=C2)N2CCOCC2)C(=O)NC)C)C1)OC NPQSRNGURRYZDG-MRXNPFEDSA-N 0.000 claims 1
- JGCATJICLCFSEV-MRXNPFEDSA-N (4R)-7,8-dimethoxy-N,4-dimethyl-1-[4-(4-methyl-2-oxopiperazin-1-yl)phenyl]-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound COC=1C(=CC2=C(C[C@H](N(N=C2C2=CC=C(C=C2)N2C(CN(CC2)C)=O)C(=O)NC)C)C1)OC JGCATJICLCFSEV-MRXNPFEDSA-N 0.000 claims 1
- QQENNSOEIIPWGC-CYBMUJFWSA-N (4R)-7-(difluoromethoxy)-1-[4-(3,5-dimethyl-1,2-oxazol-4-yl)phenyl]-8-methoxy-N,4-dimethyl-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound FC(OC=1C(=CC2=C(C[C@H](N(N=C2C2=CC=C(C=C2)C=2C(=NOC2C)C)C(=O)NC)C)C1)OC)F QQENNSOEIIPWGC-CYBMUJFWSA-N 0.000 claims 1
- CSDIIHOAJVAHHD-MRXNPFEDSA-N (4R)-7-(difluoromethoxy)-8-methoxy-N,4-dimethyl-1-[4-(4-methylpiperazin-1-yl)phenyl]-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound FC(OC=1C(=CC2=C(C[C@H](N(N=C2C2=CC=C(C=C2)N2CCN(CC2)C)C(=O)NC)C)C1)OC)F CSDIIHOAJVAHHD-MRXNPFEDSA-N 0.000 claims 1
- RJFPYIZAIZXRQR-GFCCVEGCSA-N (4R)-7-chloro-1-[4-(3,5-dimethyl-1,2-oxazol-4-yl)phenyl]-N,4-dimethyl-8-(trifluoromethoxy)-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound ClC=1C(=CC2=C(C[C@H](N(N=C2C2=CC=C(C=C2)C=2C(=NOC2C)C)C(=O)NC)C)C1)OC(F)(F)F RJFPYIZAIZXRQR-GFCCVEGCSA-N 0.000 claims 1
- VVMJEFWIDBTRQV-LLVKDONJSA-N (4R)-8-chloro-1-(4-chlorophenyl)-7-methoxy-N,4-dimethyl-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound CNC(=O)N1N=C(c2ccc(Cl)cc2)c2cc(Cl)c(OC)cc2C[C@H]1C VVMJEFWIDBTRQV-LLVKDONJSA-N 0.000 claims 1
- RHZBQXXNYNUUAA-CYBMUJFWSA-N (4R)-8-chloro-1-[4-(3,5-dimethyl-1,2-oxazol-4-yl)phenyl]-7-methoxy-N,4-dimethyl-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound ClC1=CC2=C(C[C@H](N(N=C2C2=CC=C(C=C2)C=2C(=NOC2C)C)C(=O)NC)C)C=C1OC RHZBQXXNYNUUAA-CYBMUJFWSA-N 0.000 claims 1
- VEIXXVJKOAJEOO-LBPRGKRZSA-N (4S)-1-(4-bromophenyl)-8-methoxy-N,4-dimethyl-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound CNC(=O)N1N=C(c2ccc(Br)cc2)c2cc(OC)ccc2C[C@@H]1C VEIXXVJKOAJEOO-LBPRGKRZSA-N 0.000 claims 1
- MVAHTFLZMOQYDC-NSHDSACASA-N (4S)-1-(4-chlorophenyl)-N,4-dimethyl-8-(trifluoromethoxy)-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound ClC1=CC=C(C=C1)C1=NN([C@H](CC2=C1C=C(C=C2)OC(F)(F)F)C)C(=O)NC MVAHTFLZMOQYDC-NSHDSACASA-N 0.000 claims 1
- LVOZKSSVIPZABA-AWEZNQCLSA-N (4S)-1-[4-(2,4-dimethyl-1,3-thiazol-5-yl)phenyl]-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound CC=1SC(=C(N1)C)C1=CC=C(C=C1)C1=NN([C@H](CC2=C1C=C(C(=C2)OC)OC)C)C(=O)NC LVOZKSSVIPZABA-AWEZNQCLSA-N 0.000 claims 1
- ZDRURUMITWYFTN-AWEZNQCLSA-N (4S)-1-[4-(3-fluoroazetidin-1-yl)phenyl]-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound FC1CN(C1)C1=CC=C(C=C1)C1=NN([C@H](CC2=C1C=C(C(=C2)OC)OC)C)C(=O)NC ZDRURUMITWYFTN-AWEZNQCLSA-N 0.000 claims 1
- VRRWTCUDSZFECD-HNNXBMFYSA-N (4S)-1-[4-(3-hydroxy-3-methylazetidin-1-yl)phenyl]-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound OC1(CN(C1)C1=CC=C(C=C1)C1=NN([C@H](CC2=C1C=C(C(=C2)OC)OC)C)C(=O)NC)C VRRWTCUDSZFECD-HNNXBMFYSA-N 0.000 claims 1
- IZYRNJVZGWEGHB-KRWDZBQOSA-N (4S)-1-[4-(4-acetylpiperazin-1-yl)phenyl]-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound C(C)(=O)N1CCN(CC1)C1=CC=C(C=C1)C1=NN([C@H](CC2=C1C=C(C(=C2)OC)OC)C)C(=O)NC IZYRNJVZGWEGHB-KRWDZBQOSA-N 0.000 claims 1
- DVCONRPRRZVNNC-INIZCTEOSA-N (4S)-1-[4-(4-hydroxypiperidin-1-yl)phenyl]-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound OC1CCN(CC1)C1=CC=C(C=C1)C1=NN([C@H](CC2=C1C=C(C(=C2)OC)OC)C)C(=O)NC DVCONRPRRZVNNC-INIZCTEOSA-N 0.000 claims 1
- NAMYBRJRBNIRIQ-FQEVSTJZSA-N (4S)-1-[4-(5-cyclopropyl-3-phenylpyrazol-1-yl)phenyl]-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound C1(CC1)C1=CC(=NN1C1=CC=C(C=C1)C1=NN([C@H](CC2=C1C=C(C(=C2)OC)OC)C)C(=O)NC)C2=CC=CC=C2 NAMYBRJRBNIRIQ-FQEVSTJZSA-N 0.000 claims 1
- SRUSJOIHVSHPAK-HNNXBMFYSA-N (4S)-1-[4-(azetidin-1-yl)phenyl]-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound N1(CCC1)C1=CC=C(C=C1)C1=NN([C@H](CC2=C1C=C(C(=C2)OC)OC)C)C(=O)NC SRUSJOIHVSHPAK-HNNXBMFYSA-N 0.000 claims 1
- ONNQNUAUYFRDQK-SFHVURJKSA-N (4S)-1-[4-[3-(4-fluorophenyl)pyrazol-1-yl]phenyl]-7,8-dimethoxy-N,4-dimethyl-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound FC1=CC=C(C=C1)C1=NN(C=C1)C1=CC=C(C=C1)C1=NN([C@H](CC2=C1C=C(C(=C2)OC)OC)C)C(=O)NC ONNQNUAUYFRDQK-SFHVURJKSA-N 0.000 claims 1
- GTCPNBUMUTYGMM-IBGZPJMESA-N (4S)-4-ethyl-7,8-dimethoxy-N-methyl-1-(4-morpholin-4-ylphenyl)-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound CC[C@H]1Cc2cc(OC)c(OC)cc2C(=NN1C(=O)NC)c1ccc(cc1)N1CCOCC1 GTCPNBUMUTYGMM-IBGZPJMESA-N 0.000 claims 1
- VGSXYJZOCNNOPB-KRWDZBQOSA-N (4S)-7,8-dimethoxy-1-[4-(4-methoxypiperidin-1-yl)phenyl]-N,4-dimethyl-4,5-dihydro-2,3-benzodiazepine-3-carboxamide Chemical compound COC=1C(=CC2=C(C[C@@H](N(N=C2C2=CC=C(C=C2)N2CCC(CC2)OC)C(=O)NC)C)C1)OC VGSXYJZOCNNOPB-KRWDZBQOSA-N 0.000 claims 1
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| GB0919426D0 (en) | 2009-11-05 | 2009-12-23 | Glaxosmithkline Llc | Novel compounds |
| EP2902030B1 (en) * | 2010-05-14 | 2016-09-14 | Dana-Farber Cancer Institute, Inc. | Thienotriazolodiazepine compounds for treating neoplasia |
| US9249161B2 (en) | 2010-12-02 | 2016-02-02 | Constellation Pharmaceuticals, Inc. | Bromodomain inhibitors and uses thereof |
| AR084070A1 (es) * | 2010-12-02 | 2013-04-17 | Constellation Pharmaceuticals Inc | Inhibidores del bromodominio y usos de los mismos |
-
2013
- 2013-08-13 KR KR20157003659A patent/KR20150041787A/ko not_active Withdrawn
- 2013-08-13 WO PCT/EP2013/066931 patent/WO2014026997A1/de not_active Ceased
- 2013-08-13 EA EA201590356A patent/EA201590356A1/ru unknown
- 2013-08-13 JP JP2015526970A patent/JP6333251B2/ja not_active Expired - Fee Related
- 2013-08-13 CA CA2881996A patent/CA2881996A1/en not_active Abandoned
- 2013-08-13 AU AU2013304146A patent/AU2013304146A1/en not_active Abandoned
- 2013-08-13 MX MX2015001880A patent/MX2015001880A/es unknown
- 2013-08-13 PE PE2015000185A patent/PE20150729A1/es not_active Application Discontinuation
- 2013-08-13 CN CN201380053739.2A patent/CN104755473B/zh not_active Expired - Fee Related
- 2013-08-13 US US14/421,994 patent/US9890147B2/en not_active Expired - Fee Related
- 2013-08-13 ES ES13748072T patent/ES2628005T3/es active Active
- 2013-08-13 EP EP13748072.9A patent/EP2885286B1/de not_active Not-in-force
- 2013-08-14 UY UY0001034977A patent/UY34977A/es not_active Application Discontinuation
- 2013-08-14 AR ARP130102888A patent/AR092129A1/es unknown
- 2013-08-15 TW TW102129344A patent/TW201408651A/zh unknown
-
2015
- 2015-01-25 IL IL236898A patent/IL236898A0/en unknown
- 2015-02-06 DO DO2015000022A patent/DOP2015000022A/es unknown
- 2015-02-10 CR CR20150066A patent/CR20150066A/es unknown
- 2015-02-12 CL CL2015000337A patent/CL2015000337A1/es unknown
- 2015-02-12 EC ECIEPI20155376A patent/ECSP15005376A/es unknown
- 2015-02-13 PH PH12015500323A patent/PH12015500323A1/en unknown
- 2015-02-13 TN TNP2015000051A patent/TN2015000051A1/fr unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR20150041787A (ko) | 2015-04-17 |
| JP6333251B2 (ja) | 2018-05-30 |
| ECSP15005376A (es) | 2015-12-31 |
| IL236898A0 (en) | 2015-03-31 |
| EP2885286B1 (de) | 2017-03-22 |
| CN104755473B (zh) | 2017-03-08 |
| WO2014026997A1 (de) | 2014-02-20 |
| TW201408651A (zh) | 2014-03-01 |
| CL2015000337A1 (es) | 2015-05-04 |
| AU2013304146A1 (en) | 2015-02-26 |
| PE20150729A1 (es) | 2015-06-14 |
| EA201590356A1 (ru) | 2015-07-30 |
| EP2885286A1 (de) | 2015-06-24 |
| HK1208443A1 (en) | 2016-03-04 |
| TN2015000051A1 (en) | 2016-06-29 |
| ES2628005T3 (es) | 2017-08-01 |
| PH12015500323A1 (en) | 2015-03-30 |
| CN104755473A (zh) | 2015-07-01 |
| CR20150066A (es) | 2015-04-17 |
| AR092129A1 (es) | 2015-03-25 |
| JP2015529192A (ja) | 2015-10-05 |
| UY34977A (es) | 2014-03-31 |
| DOP2015000022A (es) | 2015-09-15 |
| US9890147B2 (en) | 2018-02-13 |
| MX2015001880A (es) | 2015-05-11 |
| US20150203483A1 (en) | 2015-07-23 |
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Legal Events
| Date | Code | Title | Description |
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| EEER | Examination request |
Effective date: 20180809 |
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| FZDE | Discontinued |
Effective date: 20210831 |