JP2018534270A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2018534270A5 JP2018534270A5 JP2018517286A JP2018517286A JP2018534270A5 JP 2018534270 A5 JP2018534270 A5 JP 2018534270A5 JP 2018517286 A JP2018517286 A JP 2018517286A JP 2018517286 A JP2018517286 A JP 2018517286A JP 2018534270 A5 JP2018534270 A5 JP 2018534270A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- halo
- optionally substituted
- alkoxy
- aryl
- 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- Withdrawn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
- 125000000217 alkyl group Chemical group 0.000 claims description 467
- 125000003545 alkoxy group Chemical group 0.000 claims description 181
- 125000003118 aryl group Chemical group 0.000 claims description 170
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 114
- 125000005843 halogen group Chemical group 0.000 claims description 112
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 108
- -1 nitro, amino Chemical group 0.000 claims description 100
- 229910052739 hydrogen Inorganic materials 0.000 claims description 90
- 239000001257 hydrogen Substances 0.000 claims description 80
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 78
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 74
- 125000000623 heterocyclic group Chemical group 0.000 claims description 71
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 69
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 65
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 64
- 150000001875 compounds Chemical class 0.000 claims description 64
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 63
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 62
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 54
- 235000010290 biphenyl Nutrition 0.000 claims description 54
- 239000004305 biphenyl Substances 0.000 claims description 54
- 125000001072 heteroaryl group Chemical group 0.000 claims description 54
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 47
- 239000000203 mixture Substances 0.000 claims description 40
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 38
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 35
- 150000003839 salts Chemical class 0.000 claims description 32
- 125000006413 ring segment Chemical group 0.000 claims description 31
- 239000012453 solvate Substances 0.000 claims description 28
- 125000004429 atom Chemical group 0.000 claims description 19
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 18
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 16
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 14
- 125000002619 bicyclic group Chemical group 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 13
- 229920006395 saturated elastomer Polymers 0.000 claims description 13
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 208000002193 Pain Diseases 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 7
- 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 description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 102000016913 Voltage-Gated Sodium Channels Human genes 0.000 claims description 4
- 108010053752 Voltage-Gated Sodium Channels Proteins 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 3
- 206010058019 Cancer Pain Diseases 0.000 claims description 2
- 208000023890 Complex Regional Pain Syndromes Diseases 0.000 claims description 2
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 2
- 201000009273 Endometriosis Diseases 0.000 claims description 2
- 208000001640 Fibromyalgia Diseases 0.000 claims description 2
- 208000010412 Glaucoma Diseases 0.000 claims description 2
- 206010019233 Headaches Diseases 0.000 claims description 2
- 208000019695 Migraine disease Diseases 0.000 claims description 2
- 208000019022 Mood disease Diseases 0.000 claims description 2
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 2
- 208000018737 Parkinson disease Diseases 0.000 claims description 2
- 206010036376 Postherpetic Neuralgia Diseases 0.000 claims description 2
- 208000004550 Postoperative Pain Diseases 0.000 claims description 2
- 208000028017 Psychotic disease Diseases 0.000 claims description 2
- 208000008765 Sciatica Diseases 0.000 claims description 2
- 208000027520 Somatoform disease Diseases 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims description 2
- 230000000996 additive effect Effects 0.000 claims description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 2
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 2
- 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 206010015037 epilepsy Diseases 0.000 claims description 2
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 2
- 231100000869 headache Toxicity 0.000 claims description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 208000028867 ischemia Diseases 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 206010027599 migraine Diseases 0.000 claims description 2
- 201000006417 multiple sclerosis Diseases 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 claims description 2
- 208000027753 pain disease Diseases 0.000 claims description 2
- 230000001314 paroxysmal effect Effects 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 230000001568 sexual effect Effects 0.000 claims description 2
- 230000001148 spastic effect Effects 0.000 claims description 2
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 2
- 206010044652 trigeminal neuralgia Diseases 0.000 claims description 2
- UTQNKKSJPHTPBS-UHFFFAOYSA-N 2,2,2-trichloroethanone Chemical group ClC(Cl)(Cl)[C]=O UTQNKKSJPHTPBS-UHFFFAOYSA-N 0.000 claims 2
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 claims 1
- 150000004677 hydrates Chemical class 0.000 claims 1
- 230000036571 hydration Effects 0.000 claims 1
- 238000006703 hydration reaction Methods 0.000 claims 1
- 238000003419 tautomerization reaction Methods 0.000 claims 1
- 0 CC(C(*)CN1C(N[C@@](CN(*)C(*)=O)C2=NC3=[N+])=[N+])([C@@]12N3O)O Chemical compound CC(C(*)CN1C(N[C@@](CN(*)C(*)=O)C2=NC3=[N+])=[N+])([C@@]12N3O)O 0.000 description 80
- KYEACNNYFNZCST-UHFFFAOYSA-N CN(C(CC1)=O)C1=O Chemical compound CN(C(CC1)=O)C1=O KYEACNNYFNZCST-UHFFFAOYSA-N 0.000 description 11
- KZNICNPSHKQLFF-UHFFFAOYSA-N O=C(CC1)NC1=O Chemical compound O=C(CC1)NC1=O KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 10
- TTZJVVZTHPDUIB-UHFFFAOYSA-O N=C(NCC1N2)N(CCC3(O)O)C13NC2=[NH2+] Chemical compound N=C(NCC1N2)N(CCC3(O)O)C13NC2=[NH2+] TTZJVVZTHPDUIB-UHFFFAOYSA-O 0.000 description 4
- GRWXJRHEMNQLLE-UHFFFAOYSA-N NC(c1c(CCCC2)c2ccc1)=O Chemical compound NC(c1c(CCCC2)c2ccc1)=O GRWXJRHEMNQLLE-UHFFFAOYSA-N 0.000 description 4
- 238000009833 condensation Methods 0.000 description 4
- 230000005494 condensation Effects 0.000 description 4
- CIHJZKMEIJKCIE-VGZKRQLQSA-O N=C(NCC1N2)N(CC[C@H]3O)C13NC2=[NH2+] Chemical compound N=C(NCC1N2)N(CC[C@H]3O)C13NC2=[NH2+] CIHJZKMEIJKCIE-VGZKRQLQSA-O 0.000 description 3
- HXZZHYZJJLFSKL-UHFFFAOYSA-N NC(c1c(CCC2)c2ccc1)=O Chemical compound NC(c1c(CCC2)c2ccc1)=O HXZZHYZJJLFSKL-UHFFFAOYSA-N 0.000 description 3
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 description 3
- PGHYPCPNTBGZLQ-UHFFFAOYSA-N CN(C(C1C2CCCC1)=O)C2=O Chemical compound CN(C(C1C2CCCC1)=O)C2=O PGHYPCPNTBGZLQ-UHFFFAOYSA-N 0.000 description 2
- RHYBFKMFHLPQPH-UHFFFAOYSA-N CN(CC(N1)=O)C1=O Chemical compound CN(CC(N1)=O)C1=O RHYBFKMFHLPQPH-UHFFFAOYSA-N 0.000 description 2
- RFTORHYUCZJHDO-UHFFFAOYSA-N CN(CC(N1C)=O)C1=O Chemical compound CN(CC(N1C)=O)C1=O RFTORHYUCZJHDO-UHFFFAOYSA-N 0.000 description 2
- JHMBTUMIVBSJFS-UHFFFAOYSA-N CN(Cc1ccccc11)C1=O Chemical compound CN(Cc1ccccc11)C1=O JHMBTUMIVBSJFS-UHFFFAOYSA-N 0.000 description 2
- BBETZVGADODUNX-XIRUVYRFSA-O N=C(NCC1N2)N(C[C@@H](C3(O)O)OC(c4cc(C(F)(F)F)ccc4C(F)(F)F)=O)C13NC2=[NH2+] Chemical compound N=C(NCC1N2)N(C[C@@H](C3(O)O)OC(c4cc(C(F)(F)F)ccc4C(F)(F)F)=O)C13NC2=[NH2+] BBETZVGADODUNX-XIRUVYRFSA-O 0.000 description 2
- DXBQJUMPQKYUJH-MLGTYFKZSA-O N=C(N[C@@H](CN(C(CC1)=O)C1=O)C1N2)N(CCC3(O)O)C13NC2=[NH2+] Chemical compound N=C(N[C@@H](CN(C(CC1)=O)C1=O)C1N2)N(CCC3(O)O)C13NC2=[NH2+] DXBQJUMPQKYUJH-MLGTYFKZSA-O 0.000 description 2
- RPQXVSUAYFXFJA-HGRQIUPRSA-N saxitoxin Chemical class NC(=O)OC[C@@H]1N=C(N)N2CCC(O)(O)[C@@]22N=C(N)N[C@@H]12 RPQXVSUAYFXFJA-HGRQIUPRSA-N 0.000 description 2
- ZUKVOFZWPKIFJM-KOULWWPBSA-O C#C[C@@](C(C1)NC(c(cccc2O3)c2OC3(F)F)=O)([C@@](C(C(CN(C(CC2)=O)C2=O)N2)N3)(NC3=[NH2+])N1C2=N)O Chemical compound C#C[C@@](C(C1)NC(c(cccc2O3)c2OC3(F)F)=O)([C@@](C(C(CN(C(CC2)=O)C2=O)N2)N3)(NC3=[NH2+])N1C2=N)O ZUKVOFZWPKIFJM-KOULWWPBSA-O 0.000 description 1
- SSALFBQYYAZQKA-UHFFFAOYSA-O C#[O]CC(C(CN1)N2)(NC2=[NH2+])N(CCNC(c2cc(OC(F)(F)F)ccc2)=O)C1=N Chemical compound C#[O]CC(C(CN1)N2)(NC2=[NH2+])N(CCNC(c2cc(OC(F)(F)F)ccc2)=O)C1=N SSALFBQYYAZQKA-UHFFFAOYSA-O 0.000 description 1
- IAUWHMJFQSXYQQ-SDUBBSOGSA-O C#[O][C@H](CC1)C(C([C@H](CN(C(CC2)=O)C2=O)N2)N3)(NC3=[NH2+])N1C2=N Chemical compound C#[O][C@H](CC1)C(C([C@H](CN(C(CC2)=O)C2=O)N2)N3)(NC3=[NH2+])N1C2=N IAUWHMJFQSXYQQ-SDUBBSOGSA-O 0.000 description 1
- HEAFHLROVZMBSI-DSHYYTJWSA-O C#[O][C@H]([C@H](C1)OC(NCC(c2ccccc2)c2ccccc2)=O)C(C(C(CN(C(CC2)=O)C2=O)N2)N3)(NC3=[NH2+])N1C2=N Chemical compound C#[O][C@H]([C@H](C1)OC(NCC(c2ccccc2)c2ccccc2)=O)C(C(C(CN(C(CC2)=O)C2=O)N2)N3)(NC3=[NH2+])N1C2=N HEAFHLROVZMBSI-DSHYYTJWSA-O 0.000 description 1
- HMAGPILRACXBOF-ZCXPMMKJSA-O CC(C)(C)c1cc(C(NC(CN(C2(C([C@H](CN(C(CC3)=O)C3=O)N3)N4)NC4=[NH2+])C3=N)C2(O)O)=O)cc(C(C)(C)C)c1 Chemical compound CC(C)(C)c1cc(C(NC(CN(C2(C([C@H](CN(C(CC3)=O)C3=O)N3)N4)NC4=[NH2+])C3=N)C2(O)O)=O)cc(C(C)(C)C)c1 HMAGPILRACXBOF-ZCXPMMKJSA-O 0.000 description 1
- AVCGCMDLFOTMQA-SMCLFLENSA-O CC(C)(CC(N1C[C@@H](C(C(C2(O)O)(N3)N4C[C@@H]2OC(c2ccccc2)=O)NC3=[NH2+])NC4=N)=O)C1=O Chemical compound CC(C)(CC(N1C[C@@H](C(C(C2(O)O)(N3)N4C[C@@H]2OC(c2ccccc2)=O)NC3=[NH2+])NC4=N)=O)C1=O AVCGCMDLFOTMQA-SMCLFLENSA-O 0.000 description 1
- OTDPHUVUEVYGSU-OUCOXNFUSA-O CC(C)c1cccc(C(N[C@@H](CN(C2(C([C@H](CN(C(CC3)=O)C3=O)N3)N4)NC4=[NH2+])C3=N)[C@H]2O)=O)c1 Chemical compound CC(C)c1cccc(C(N[C@@H](CN(C2(C([C@H](CN(C(CC3)=O)C3=O)N3)N4)NC4=[NH2+])C3=N)[C@H]2O)=O)c1 OTDPHUVUEVYGSU-OUCOXNFUSA-O 0.000 description 1
- LAJVBLKQJDLAMY-HSOUVSANSA-P CC(CC(N1CC([C@@H](C2(N3)N4CC[C@]2(O)O/[O]=C(/c2c(C(F)(F)F)ccc(C(F)(F)F)c2)\O)NC3=[NH2+])NC4=[NH2+])=O)C1=O Chemical compound CC(CC(N1CC([C@@H](C2(N3)N4CC[C@]2(O)O/[O]=C(/c2c(C(F)(F)F)ccc(C(F)(F)F)c2)\O)NC3=[NH2+])NC4=[NH2+])=O)C1=O LAJVBLKQJDLAMY-HSOUVSANSA-P 0.000 description 1
- HTOLDSVVWKWNPI-YHDGPQDUSA-O CC(CCC1)CN1C(O[C@@H](CN(C1([C@H](C(CN(C(CC2)=O)C2=O)N2)N3)NC3=[NH2+])C2=N)[C@H]1O)=O Chemical compound CC(CCC1)CN1C(O[C@@H](CN(C1([C@H](C(CN(C(CC2)=O)C2=O)N2)N3)NC3=[NH2+])C2=N)[C@H]1O)=O HTOLDSVVWKWNPI-YHDGPQDUSA-O 0.000 description 1
- RFDKBGHPJVMBIU-UHFFFAOYSA-O CC(CN(C1(C)C(CN2)NC(N)=[NH2+])C2=N)C1O Chemical compound CC(CN(C1(C)C(CN2)NC(N)=[NH2+])C2=N)C1O RFDKBGHPJVMBIU-UHFFFAOYSA-O 0.000 description 1
- ZNQFZPCFVNOXJQ-UHFFFAOYSA-N CC(N(C)C(C)=O)=O Chemical compound CC(N(C)C(C)=O)=O ZNQFZPCFVNOXJQ-UHFFFAOYSA-N 0.000 description 1
- PXBITQXVPUBFIX-DHBPRGKBSA-O CC(N(C[C@@H]([C@@H](C(C1(O)O)(N2)N3CC1NC(c1ccccc1)=O)NC2=[NH2+])NC3=N)C(c1ccccc1)=O)=O Chemical compound CC(N(C[C@@H]([C@@H](C(C1(O)O)(N2)N3CC1NC(c1ccccc1)=O)NC2=[NH2+])NC3=N)C(c1ccccc1)=O)=O PXBITQXVPUBFIX-DHBPRGKBSA-O 0.000 description 1
- LLVXVUDZJDQCAS-MWZJOOGASA-P CC(NC(CN(C1([C@H](C(CN(C(CC2)=O)C2=O)N2)N3)NC3=[NH2+])C2=[NH2+])C1(O)O)=O Chemical compound CC(NC(CN(C1([C@H](C(CN(C(CC2)=O)C2=O)N2)N3)NC3=[NH2+])C2=[NH2+])C1(O)O)=O LLVXVUDZJDQCAS-MWZJOOGASA-P 0.000 description 1
- VRDCQUCPNHPHEG-WZUVNVEFSA-O CC/C=C(/N[C@@H](CN(C(CC1)=O)C1=O)C1N2)\N(CC([C@H]3O)NC(Nc4cccc5c4cccc5)=O)C13NC2=[NH2+] Chemical compound CC/C=C(/N[C@@H](CN(C(CC1)=O)C1=O)C1N2)\N(CC([C@H]3O)NC(Nc4cccc5c4cccc5)=O)C13NC2=[NH2+] VRDCQUCPNHPHEG-WZUVNVEFSA-O 0.000 description 1
- QMZKVJHECYMVFH-UHFFFAOYSA-P CCN(C(C)(C(CN1)N2)NC2=[NH2+])C1=[NH2+] Chemical compound CCN(C(C)(C(CN1)N2)NC2=[NH2+])C1=[NH2+] QMZKVJHECYMVFH-UHFFFAOYSA-P 0.000 description 1
- PTNJCSMQSBNPGH-GQPBQNEESA-P CCc1cccc(C(NC(CN(C2(C([C@H](CN(C(CC3)=O)C3=O)N3)N4)NC4=[NH2+])C3=[NH2+])C2(O)O)=O)c1 Chemical compound CCc1cccc(C(NC(CN(C2(C([C@H](CN(C(CC3)=O)C3=O)N3)N4)NC4=[NH2+])C3=[NH2+])C2(O)O)=O)c1 PTNJCSMQSBNPGH-GQPBQNEESA-P 0.000 description 1
- NXDUJHLJBYWAKW-ORLHQXTGSA-P CN(C(C(O)O/[O]=C(/NCCc1cc(C(F)(F)F)ccc1)\O)([C@H]([C@H](CN(C(CC1)=O)C1=O)N1)N2)NC2=[NH2+])C1=[NH2+] Chemical compound CN(C(C(O)O/[O]=C(/NCCc1cc(C(F)(F)F)ccc1)\O)([C@H]([C@H](CN(C(CC1)=O)C1=O)N1)N2)NC2=[NH2+])C1=[NH2+] NXDUJHLJBYWAKW-ORLHQXTGSA-P 0.000 description 1
- UJUFDBPRRGYWRS-UHFFFAOYSA-N CN(C(CC(CC1)CC1C1)=O)C1=O Chemical compound CN(C(CC(CC1)CC1C1)=O)C1=O UJUFDBPRRGYWRS-UHFFFAOYSA-N 0.000 description 1
- LAOTUIUQSXGKEW-UHFFFAOYSA-N CN(C1CCCCC1)C(O)=O Chemical compound CN(C1CCCCC1)C(O)=O LAOTUIUQSXGKEW-UHFFFAOYSA-N 0.000 description 1
- DNELHPKXBIWNTM-AHBRZUODSA-O CN(CC(N1CC(C(C([C@@H]2[O]#C)(N3)N4CC2NC(c2c(CCCC5)c5ccc2)=O)NC3=[NH2+])NC4=N)=O)C1=O Chemical compound CN(CC(N1CC(C(C([C@@H]2[O]#C)(N3)N4CC2NC(c2c(CCCC5)c5ccc2)=O)NC3=[NH2+])NC4=N)=O)C1=O DNELHPKXBIWNTM-AHBRZUODSA-O 0.000 description 1
- MFJPDINHYXJFNN-BNBIOPAKSA-O CN(CC(N1C[C@@H]([C@@H](C([C@@H]2O)(N3)N4C[C@@H]2NC(N2CCCCC2)=O)NC3=[NH2+])NC4=N)=O)C1=O Chemical compound CN(CC(N1C[C@@H]([C@@H](C([C@@H]2O)(N3)N4C[C@@H]2NC(N2CCCCC2)=O)NC3=[NH2+])NC4=N)=O)C1=O MFJPDINHYXJFNN-BNBIOPAKSA-O 0.000 description 1
- WJCLFPOCCNKXKW-OLMXLDPFSA-O CN(Cc1cc(C(F)(F)F)ccc1)C(O[C@@H](CN(C1(C([C@H](CN(C(CC2)=O)C2=O)N2)N3)NC3=[NH2+])C2=N)[C@H]1O)=O Chemical compound CN(Cc1cc(C(F)(F)F)ccc1)C(O[C@@H](CN(C1(C([C@H](CN(C(CC2)=O)C2=O)N2)N3)NC3=[NH2+])C2=N)[C@H]1O)=O WJCLFPOCCNKXKW-OLMXLDPFSA-O 0.000 description 1
- DGVORXWMCNREFA-UHFFFAOYSA-N CN1OCCC1=O Chemical compound CN1OCCC1=O DGVORXWMCNREFA-UHFFFAOYSA-N 0.000 description 1
- QHUSCPKRXNACNA-UHFFFAOYSA-N CNC(c1c(CCCC2)c2ccc1)=O Chemical compound CNC(c1c(CCCC2)c2ccc1)=O QHUSCPKRXNACNA-UHFFFAOYSA-N 0.000 description 1
- HBWIUWXBHRQLRT-VQLJEYIZSA-O COC(N(C[C@@H](C(C(C1(O)O)(N2)N3C[C@@H]1NC(c1ccccc1)=O)NC2=[NH2+])NC3=N)C(c1ccccc1)=O)=O Chemical compound COC(N(C[C@@H](C(C(C1(O)O)(N2)N3C[C@@H]1NC(c1ccccc1)=O)NC2=[NH2+])NC3=N)C(c1ccccc1)=O)=O HBWIUWXBHRQLRT-VQLJEYIZSA-O 0.000 description 1
- MAXIYKZRNRKFBU-XSQOWPIBSA-P COc(cc(cc1OC)C(NC(CN(C2([C@H]([C@H](CN(C(CC3)=O)C3=O)N3)N4)NC4=[NH2+])C3=[NH2+])C2(O)O)=O)c1OC Chemical compound COc(cc(cc1OC)C(NC(CN(C2([C@H]([C@H](CN(C(CC3)=O)C3=O)N3)N4)NC4=[NH2+])C3=[NH2+])C2(O)O)=O)c1OC MAXIYKZRNRKFBU-XSQOWPIBSA-P 0.000 description 1
- GZWGJJRNCLYUIL-UHFFFAOYSA-N COc1ccc(cccc2)c2c1C(N)=O Chemical compound COc1ccc(cccc2)c2c1C(N)=O GZWGJJRNCLYUIL-UHFFFAOYSA-N 0.000 description 1
- VKPLPDIMEREJJF-UHFFFAOYSA-N COc1cccc(C(N)=O)c1 Chemical compound COc1cccc(C(N)=O)c1 VKPLPDIMEREJJF-UHFFFAOYSA-N 0.000 description 1
- PBIRKPBECSMYMB-XAICZQMXSA-O CS(c1cccc(C(NC(CN(C2(C([C@H](CN(C(CC3)=O)C3=O)N3)N4)NC4=[NH2+])C3=N)C2(O)O)=O)c1)(=O)=O Chemical compound CS(c1cccc(C(NC(CN(C2(C([C@H](CN(C(CC3)=O)C3=O)N3)N4)NC4=[NH2+])C3=N)C2(O)O)=O)c1)(=O)=O PBIRKPBECSMYMB-XAICZQMXSA-O 0.000 description 1
- XNPWVUYTYCPKHM-PJBUOPRJSA-P C[C@](C([C@H](CN(C(CC1)=O)C1=O)N1)NC(N)=[NH2+])(C([C@H](C2)NC(C3(CC3)C(F)(F)F)=O)(O)O)N2C1=[NH2+] Chemical compound C[C@](C([C@H](CN(C(CC1)=O)C1=O)N1)NC(N)=[NH2+])(C([C@H](C2)NC(C3(CC3)C(F)(F)F)=O)(O)O)N2C1=[NH2+] XNPWVUYTYCPKHM-PJBUOPRJSA-P 0.000 description 1
- ZQFRBASISPVGMX-PGUXBMHVSA-O C[C@]([C@H](CN1)NC(N)=[NH2+])(C([C@H](C2)OC(c3c(C(F)(F)F)ccc(C(F)(F)F)c3)=O)(O)O)N2C1=N Chemical compound C[C@]([C@H](CN1)NC(N)=[NH2+])(C([C@H](C2)OC(c3c(C(F)(F)F)ccc(C(F)(F)F)c3)=O)(O)O)N2C1=N ZQFRBASISPVGMX-PGUXBMHVSA-O 0.000 description 1
- RMOWPPKQWGDSSA-NAPDUAICSA-O Cc(c(C(F)(F)F)ccc1)c1C(NC(CN(C1(C([C@H](CN(C(CC2)=O)C2=O)N2)N3)NC3=[NH2+])C2=N)[C@H]1O)=O Chemical compound Cc(c(C(F)(F)F)ccc1)c1C(NC(CN(C1(C([C@H](CN(C(CC2)=O)C2=O)N2)N3)NC3=[NH2+])C2=N)[C@H]1O)=O RMOWPPKQWGDSSA-NAPDUAICSA-O 0.000 description 1
- LGGSZFXAVKKLAO-PWGIXOLCSA-O N=C(NC(CN(C(C1C2CCCC1)=O)C2=O)[C@@H]1N2)N(C[C@@H](C3(O)O)OC(c4cc(C(F)(F)F)ccc4C(F)(F)F)=O)C13NC2=[NH2+] Chemical compound N=C(NC(CN(C(C1C2CCCC1)=O)C2=O)[C@@H]1N2)N(C[C@@H](C3(O)O)OC(c4cc(C(F)(F)F)ccc4C(F)(F)F)=O)C13NC2=[NH2+] LGGSZFXAVKKLAO-PWGIXOLCSA-O 0.000 description 1
- PISSTCUUROPBQO-UHFFFAOYSA-O N=C(NC(CN(C(CC1)=O)C1=O)C1N2)N(CC(C3(O)O)NC(Cc4cc(C(F)(F)F)cc(C(F)(F)F)c4)=O)C13NC2=[NH2+] Chemical compound N=C(NC(CN(C(CC1)=O)C1=O)C1N2)N(CC(C3(O)O)NC(Cc4cc(C(F)(F)F)cc(C(F)(F)F)c4)=O)C13NC2=[NH2+] PISSTCUUROPBQO-UHFFFAOYSA-O 0.000 description 1
- YGFUZKZAWIFLSO-UHFFFAOYSA-O N=C(NC(CN(C(CC1)=O)C1=O)C1N2)N(CC(C3(O)O)NC(c(cc4)ccc4-c4c(C(F)(F)F)cccc4)=O)C13NC2=[NH2+] Chemical compound N=C(NC(CN(C(CC1)=O)C1=O)C1N2)N(CC(C3(O)O)NC(c(cc4)ccc4-c4c(C(F)(F)F)cccc4)=O)C13NC2=[NH2+] YGFUZKZAWIFLSO-UHFFFAOYSA-O 0.000 description 1
- XGQXGFBRKHJKRM-BDLDAZCMSA-O N=C(NC(CN(C(CC1)=O)C1=O)C1N2)N(C[C@@H](C3(O)O)O)C13NC2=[NH2+] Chemical compound N=C(NC(CN(C(CC1)=O)C1=O)C1N2)N(C[C@@H](C3(O)O)O)C13NC2=[NH2+] XGQXGFBRKHJKRM-BDLDAZCMSA-O 0.000 description 1
- XKMKMEHJQZSJLZ-DWNKDTBLSA-O N=C(NC(CN(C(CC1)=O)C1=O)C1N2)N(C[C@@H]([C@H]3O)NC(c(cccc4Cl)c4Cl)=O)C13NC2=[NH2+] Chemical compound N=C(NC(CN(C(CC1)=O)C1=O)C1N2)N(C[C@@H]([C@H]3O)NC(c(cccc4Cl)c4Cl)=O)C13NC2=[NH2+] XKMKMEHJQZSJLZ-DWNKDTBLSA-O 0.000 description 1
- PKWJJPXHSWRFMX-BSZXCEGUSA-O N=C(NC(CN(C(CC1)=O)C1=O)C1N2)N(C[C@@H]([C@H]3O)NC(c4ccc(C(F)(F)F)[o]4)=O)C13NC2=[NH2+] Chemical compound N=C(NC(CN(C(CC1)=O)C1=O)C1N2)N(C[C@@H]([C@H]3O)NC(c4ccc(C(F)(F)F)[o]4)=O)C13NC2=[NH2+] PKWJJPXHSWRFMX-BSZXCEGUSA-O 0.000 description 1
- DLVFHYRFWFEATP-JUOWWRIMSA-O N=C(NC(CN(C(CC1)=O)C1=O)C1N2)N(C[C@@H]([C@H]3O)OC(N(CC4)CCC4c4ccccc4)=O)C13NC2=[NH2+] Chemical compound N=C(NC(CN(C(CC1)=O)C1=O)C1N2)N(C[C@@H]([C@H]3O)OC(N(CC4)CCC4c4ccccc4)=O)C13NC2=[NH2+] DLVFHYRFWFEATP-JUOWWRIMSA-O 0.000 description 1
- ANHNEYJSFPJYAJ-IBDFYSOUSA-O N=C(NC(CN(C(CN1c2ccccc2)=O)C1=O)C1N2)N(CC[C@]3(O)O/[O]=C(/c4cc(C(F)(F)F)ccc4C(F)(F)F)\O)C13NC2=[NH2+] Chemical compound N=C(NC(CN(C(CN1c2ccccc2)=O)C1=O)C1N2)N(CC[C@]3(O)O/[O]=C(/c4cc(C(F)(F)F)ccc4C(F)(F)F)\O)C13NC2=[NH2+] ANHNEYJSFPJYAJ-IBDFYSOUSA-O 0.000 description 1
- XSUZYHKRUXVIGG-CVUFBCLXSA-O N=C(NC(CN(C(CN1c2ccccc2)=O)C1=O)C1N2)N(C[C@@H](C3(O)O)O)[C@@]13NC2=[NH2+] Chemical compound N=C(NC(CN(C(CN1c2ccccc2)=O)C1=O)C1N2)N(C[C@@H](C3(O)O)O)[C@@]13NC2=[NH2+] XSUZYHKRUXVIGG-CVUFBCLXSA-O 0.000 description 1
- WFZYIFOKHABMNM-UHFFFAOYSA-O N=C(NCC1N2)N(CC(C3(O)O)NC(c4cc(C(F)(F)F)cc(F)c4)=O)C13NC2=[NH2+] Chemical compound N=C(NCC1N2)N(CC(C3(O)O)NC(c4cc(C(F)(F)F)cc(F)c4)=O)C13NC2=[NH2+] WFZYIFOKHABMNM-UHFFFAOYSA-O 0.000 description 1
- CIHJZKMEIJKCIE-UHFFFAOYSA-O N=C(NCC1N2)N(CCC3O)C13NC2=[NH2+] Chemical compound N=C(NCC1N2)N(CCC3O)C13NC2=[NH2+] CIHJZKMEIJKCIE-UHFFFAOYSA-O 0.000 description 1
- KMXGNKGXVYNPQX-CUMGRINNSA-O N=C(NCC1N2)N(CC[C@]3(O)O/[O]=C(/c4c(C(F)(F)F)ccc(C(F)(F)F)c4)\O)C13NC2=[NH2+] Chemical compound N=C(NCC1N2)N(CC[C@]3(O)O/[O]=C(/c4c(C(F)(F)F)ccc(C(F)(F)F)c4)\O)C13NC2=[NH2+] KMXGNKGXVYNPQX-CUMGRINNSA-O 0.000 description 1
- PTJNCQVIXFNFMA-XIRUVYRFSA-O N=C(NCC1N2)N(C[C@@H](C3(O)O)NC(c4cc(C(F)(F)F)ccc4C(F)(F)F)=O)C13NC2=[NH2+] Chemical compound N=C(NCC1N2)N(C[C@@H](C3(O)O)NC(c4cc(C(F)(F)F)ccc4C(F)(F)F)=O)C13NC2=[NH2+] PTJNCQVIXFNFMA-XIRUVYRFSA-O 0.000 description 1
- NASIRFSMYXVMBZ-YRYTWGTQSA-O N=C(N[C@@H](CN(C(CC1)=O)C1=O)C1N2)N(CC[C@H]3O)[C@@]13NC2=[NH2+] Chemical compound N=C(N[C@@H](CN(C(CC1)=O)C1=O)C1N2)N(CC[C@H]3O)[C@@]13NC2=[NH2+] NASIRFSMYXVMBZ-YRYTWGTQSA-O 0.000 description 1
- UERBXKMHAZOYPH-PVLFBTKPSA-O N=C(N[C@@H](CN(C(CC1)=O)C1=O)C1N2)N(C[C@@H](C3(O)O)NC(c4c(Cc5ccccc5-5)c-5ccc4)=O)C13NC2=[NH2+] Chemical compound N=C(N[C@@H](CN(C(CC1)=O)C1=O)C1N2)N(C[C@@H](C3(O)O)NC(c4c(Cc5ccccc5-5)c-5ccc4)=O)C13NC2=[NH2+] UERBXKMHAZOYPH-PVLFBTKPSA-O 0.000 description 1
- UIKVTAQNLSTGEK-LTFJVWCCSA-O N=C(N[C@@H](CN(C(CC1)=O)C1=O)C1N2)N(C[C@@H]([C@H]3O)NC(CCc4cc(C(F)(F)F)ccc4)=O)C13NC2=[NH2+] Chemical compound N=C(N[C@@H](CN(C(CC1)=O)C1=O)C1N2)N(C[C@@H]([C@H]3O)NC(CCc4cc(C(F)(F)F)ccc4)=O)C13NC2=[NH2+] UIKVTAQNLSTGEK-LTFJVWCCSA-O 0.000 description 1
- GIPJYYBNKPXOMF-WSNFYNDHSA-O N=C(N[C@@H](CN(C(CC1)=O)C1=O)C1N2)N(C[C@@H]([C@H]3O)OC(NC(c4ccccc4)c4ccccc4)=O)C13NC2=[NH2+] Chemical compound N=C(N[C@@H](CN(C(CC1)=O)C1=O)C1N2)N(C[C@@H]([C@H]3O)OC(NC(c4ccccc4)c4ccccc4)=O)C13NC2=[NH2+] GIPJYYBNKPXOMF-WSNFYNDHSA-O 0.000 description 1
- DVXASLZOYKIDIN-TUWRHPFVSA-O N=C(N[C@@H](CN(C(CC1)=O)C1=O)[C@@H]1N2)N(CC([C@H]3O)NC(c4c(cccc5)c5ccc4)=O)C13NC2=[NH2+] Chemical compound N=C(N[C@@H](CN(C(CC1)=O)C1=O)[C@@H]1N2)N(CC([C@H]3O)NC(c4c(cccc5)c5ccc4)=O)C13NC2=[NH2+] DVXASLZOYKIDIN-TUWRHPFVSA-O 0.000 description 1
- UGRNAJRRSZPMND-DIXCMASTSA-O N=C(N[C@@H](CN(C(CN1c2ccccc2)=O)C1=O)C1N2)N(CC(C3(O)O)NC(c(cccc4F)c4F)=O)C13NC2=[NH2+] Chemical compound N=C(N[C@@H](CN(C(CN1c2ccccc2)=O)C1=O)C1N2)N(CC(C3(O)O)NC(c(cccc4F)c4F)=O)C13NC2=[NH2+] UGRNAJRRSZPMND-DIXCMASTSA-O 0.000 description 1
- FBSIZUQQBLGICW-UOVGYUOHSA-O N=C(N[C@@H](CN(C(CN1c2ccccc2)=O)C1=O)C1N2)N(CC(C3[O]=O)NC(c4cccc-5c4Cc4ccccc-54)=O)C13NC2=[NH2+] Chemical compound N=C(N[C@@H](CN(C(CN1c2ccccc2)=O)C1=O)C1N2)N(CC(C3[O]=O)NC(c4cccc-5c4Cc4ccccc-54)=O)C13NC2=[NH2+] FBSIZUQQBLGICW-UOVGYUOHSA-O 0.000 description 1
- UQQYHEBDLNGYRE-TWDOJJHJSA-O N=C(N[C@@H](CN(C(CN1c2ccccc2)=O)C1=O)[C@@H]1N2)N(C[C@@H](C3(O)O)NC(C4(CC4)C(F)(F)F)=O)C13NC2=[NH2+] Chemical compound N=C(N[C@@H](CN(C(CN1c2ccccc2)=O)C1=O)[C@@H]1N2)N(C[C@@H](C3(O)O)NC(C4(CC4)C(F)(F)F)=O)C13NC2=[NH2+] UQQYHEBDLNGYRE-TWDOJJHJSA-O 0.000 description 1
- CKBZJTAMRPPVSR-UHFFFAOYSA-N NC(C1(CC(C2)C3)CC3CC2C1)=O Chemical compound NC(C1(CC(C2)C3)CC3CC2C1)=O CKBZJTAMRPPVSR-UHFFFAOYSA-N 0.000 description 1
- YXORDBZLZWAHBB-UHFFFAOYSA-N NC(Cc1cccc(C(F)(F)F)c1)=O Chemical compound NC(Cc1cccc(C(F)(F)F)c1)=O YXORDBZLZWAHBB-UHFFFAOYSA-N 0.000 description 1
- IDIXWLCRJFBQJA-UHFFFAOYSA-N NC(c(cc1)ccc1OC(F)(F)F)=O Chemical compound NC(c(cc1)ccc1OC(F)(F)F)=O IDIXWLCRJFBQJA-UHFFFAOYSA-N 0.000 description 1
- QBAYIBZITZBSFO-UHFFFAOYSA-N NC(c1c(C(F)(F)F)cccc1)=O Chemical compound NC(c1c(C(F)(F)F)cccc1)=O QBAYIBZITZBSFO-UHFFFAOYSA-N 0.000 description 1
- FTFHZWLNIADXOA-UHFFFAOYSA-N NC(c1c2-c3ccccc3Cc2ccc1)=O Chemical compound NC(c1c2-c3ccccc3Cc2ccc1)=O FTFHZWLNIADXOA-UHFFFAOYSA-N 0.000 description 1
- WJVVPYVGCDWJKB-UHFFFAOYSA-N NC(c1c2OCCc2ccc1)=O Chemical compound NC(c1c2OCCc2ccc1)=O WJVVPYVGCDWJKB-UHFFFAOYSA-N 0.000 description 1
- YNOPIKHMZIOWHS-UHFFFAOYSA-N NC(c1cc(C(F)(F)F)cc(C(F)(F)F)c1)=O Chemical compound NC(c1cc(C(F)(F)F)cc(C(F)(F)F)c1)=O YNOPIKHMZIOWHS-UHFFFAOYSA-N 0.000 description 1
- XBGXGCOLWCMVOI-UHFFFAOYSA-N NC(c1cc(C(F)(F)F)ccc1)=O Chemical compound NC(c1cc(C(F)(F)F)ccc1)=O XBGXGCOLWCMVOI-UHFFFAOYSA-N 0.000 description 1
- ZWPCLQQKRKZJAH-UHFFFAOYSA-N NC(c1cc(C(F)(F)F)cnc1)=O Chemical compound NC(c1cc(C(F)(F)F)cnc1)=O ZWPCLQQKRKZJAH-UHFFFAOYSA-N 0.000 description 1
- BJKWHAILFUUIRT-UHFFFAOYSA-N NC(c1cc(F)ccc1F)=O Chemical compound NC(c1cc(F)ccc1F)=O BJKWHAILFUUIRT-UHFFFAOYSA-N 0.000 description 1
- WEJHBEDHLLBJFW-UHFFFAOYSA-N NC(c1ccc(C(F)(F)F)cc1)=O Chemical compound NC(c1ccc(C(F)(F)F)cc1)=O WEJHBEDHLLBJFW-UHFFFAOYSA-N 0.000 description 1
- KXDAEFPNCMNJSK-UHFFFAOYSA-N NC(c1ccccc1)=O Chemical compound NC(c1ccccc1)=O KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 1
- MYYNOLXKTUIFJA-UHFFFAOYSA-N NC(c1cnc(C(F)(F)F)[nH]1)=O Chemical compound NC(c1cnc(C(F)(F)F)[nH]1)=O MYYNOLXKTUIFJA-UHFFFAOYSA-N 0.000 description 1
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N Nc1ncccn1 Chemical compound Nc1ncccn1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 1
- WJRBRSLFGCUECM-UHFFFAOYSA-N O=C(CN1)NC1=O Chemical compound O=C(CN1)NC1=O WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 1
- MPAFAYXEPQCBPP-UHFFFAOYSA-N O=C(CN1c2ccccc2)NC1=O Chemical compound O=C(CN1c2ccccc2)NC1=O MPAFAYXEPQCBPP-UHFFFAOYSA-N 0.000 description 1
- ZOBPZXTWZATXDG-UHFFFAOYSA-N O=C(CS1)NC1=O Chemical compound O=C(CS1)NC1=O ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 description 1
- KAADYLCSXGRGRX-UHFFFAOYSA-N OC(N(CCC1)C1c1ccccc1)=O Chemical compound OC(N(CCC1)C1c1ccccc1)=O KAADYLCSXGRGRX-UHFFFAOYSA-N 0.000 description 1
- NYCVCXMSZNOGDH-UHFFFAOYSA-N OC(N1CCCC1)=O Chemical compound OC(N1CCCC1)=O NYCVCXMSZNOGDH-UHFFFAOYSA-N 0.000 description 1
- TWVMOBWHILUBSS-UHFFFAOYSA-N OC(NC(c1ccccc1)=O)=O Chemical compound OC(NC(c1ccccc1)=O)=O TWVMOBWHILUBSS-UHFFFAOYSA-N 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N OC(c1ccccc1)=O Chemical compound OC(c1ccccc1)=O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- AGUQCSWVGOURPG-UHFFFAOYSA-P [NH2+]=C(NC1CN2)NC1(C(C(C1)NC(c3cc(C(F)(F)F)ccc3)=O)(O)O)N1C2=[NH2+] Chemical compound [NH2+]=C(NC1CN2)NC1(C(C(C1)NC(c3cc(C(F)(F)F)ccc3)=O)(O)O)N1C2=[NH2+] AGUQCSWVGOURPG-UHFFFAOYSA-P 0.000 description 1
- TTZJVVZTHPDUIB-UHFFFAOYSA-P [NH2+]=C(NC1CN2)NC1(C(CC1)(O)O)N1C2=[NH2+] Chemical compound [NH2+]=C(NC1CN2)NC1(C(CC1)(O)O)N1C2=[NH2+] TTZJVVZTHPDUIB-UHFFFAOYSA-P 0.000 description 1
- RUEZTUNCFBFEHZ-KWBRXMNFSA-P [NH2+]=C(NC1CN2)NC1([C@@H](C(C1)NC(N3c4ccccc4CC3)=O)O)N1C2=[NH2+] Chemical compound [NH2+]=C(NC1CN2)NC1([C@@H](C(C1)NC(N3c4ccccc4CC3)=O)O)N1C2=[NH2+] RUEZTUNCFBFEHZ-KWBRXMNFSA-P 0.000 description 1
- HMCCCZUWWFJVBT-FOEZSWGGSA-P [NH2+]=C(NC1CN2)N[C@]1(C(C(C1)NC(c3nc(C(F)(F)F)ncc3)=O)(O)O)N1C2=[NH2+] Chemical compound [NH2+]=C(NC1CN2)N[C@]1(C(C(C1)NC(c3nc(C(F)(F)F)ncc3)=O)(O)O)N1C2=[NH2+] HMCCCZUWWFJVBT-FOEZSWGGSA-P 0.000 description 1
- DXBQJUMPQKYUJH-MLGTYFKZSA-P [NH2+]=C(NC1[C@H](CN(C(CC2)=O)C2=O)N2)NC1(C(CC1)(O)O)N1C2=[NH2+] Chemical compound [NH2+]=C(NC1[C@H](CN(C(CC2)=O)C2=O)N2)NC1(C(CC1)(O)O)N1C2=[NH2+] DXBQJUMPQKYUJH-MLGTYFKZSA-P 0.000 description 1
- HOXYOZOHZZCYDZ-OUCOXNFUSA-P [NH2+]=C(NC1[C@H](CN(C(CC2)=O)C2=O)N2)NC1([C@@H]([C@H](C1)OC(NCCCc3cc(C(F)(F)F)ccc3)=O)O)N1C2=[NH2+] Chemical compound [NH2+]=C(NC1[C@H](CN(C(CC2)=O)C2=O)N2)NC1([C@@H]([C@H](C1)OC(NCCCc3cc(C(F)(F)F)ccc3)=O)O)N1C2=[NH2+] HOXYOZOHZZCYDZ-OUCOXNFUSA-P 0.000 description 1
- ZUKCOBLSFAJDMX-INKXHZSESA-P [NH2+]=C(N[C@@H](CN(C(CC1)=O)C1=O)C1N2)N(C[C@@H]([C@H]3O)OC(N(CCC4)CC4c4ccccc4)=O)C13N/C2=[NH+]/C1CCC1 Chemical compound [NH2+]=C(N[C@@H](CN(C(CC1)=O)C1=O)C1N2)N(C[C@@H]([C@H]3O)OC(N(CCC4)CC4c4ccccc4)=O)C13N/C2=[NH+]/C1CCC1 ZUKCOBLSFAJDMX-INKXHZSESA-P 0.000 description 1
- BPYAJZDYKUYMFL-GZKPAXRCSA-P [NH2+]=C(N[C@H]1[C@H](CN(C(CC2)=O)C2=O)N2)NC1([C@@H]([C@H](C1)OC(NCCC(c3ccccc3)c3ccccc3)=O)O)N1C2=[NH2+] Chemical compound [NH2+]=C(N[C@H]1[C@H](CN(C(CC2)=O)C2=O)N2)NC1([C@@H]([C@H](C1)OC(NCCC(c3ccccc3)c3ccccc3)=O)O)N1C2=[NH2+] BPYAJZDYKUYMFL-GZKPAXRCSA-P 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562235412P | 2015-09-30 | 2015-09-30 | |
| US62/235,412 | 2015-09-30 | ||
| PCT/US2016/055050 WO2017059385A1 (en) | 2015-09-30 | 2016-09-30 | 11,13-modified saxitoxins for the treatment of pain |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2018534270A JP2018534270A (ja) | 2018-11-22 |
| JP2018534270A5 true JP2018534270A5 (enExample) | 2019-11-07 |
Family
ID=57200084
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018517286A Withdrawn JP2018534270A (ja) | 2015-09-30 | 2016-09-30 | 疼痛の治療のための１１，１３−修飾サキシトキシン |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US10112953B2 (enExample) |
| EP (1) | EP3356370B1 (enExample) |
| JP (1) | JP2018534270A (enExample) |
| CN (1) | CN108473503A (enExample) |
| AU (1) | AU2016329201A1 (enExample) |
| CA (1) | CA3000708A1 (enExample) |
| ES (1) | ES2895155T3 (enExample) |
| IL (1) | IL258471A (enExample) |
| WO (1) | WO2017059385A1 (enExample) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2015243437B2 (en) | 2014-04-09 | 2019-08-29 | Siteone Therapeutics, Inc. | 10',11'-modified saxitoxins useful for the treatment of pain |
| WO2018183782A1 (en) | 2017-03-29 | 2018-10-04 | Siteone Therapeutics, Inc. | 11,13-modified saxitoxins for the treatment of pain |
| KR20200012833A (ko) * | 2017-03-29 | 2020-02-05 | 사이트원 테라퓨틱스, 인코포레이티드 | 통증 치료용 11,13-개질된 색시톡신 |
| WO2020072835A1 (en) * | 2018-10-03 | 2020-04-09 | Siteone Therapeutics, Inc. | 11,13-modified saxitoxins for the treatment of pain |
| DK4069691T3 (da) | 2019-12-06 | 2024-10-28 | Vertex Pharma | Substituerede tetrahydrofuraner som modulatorer af natriumkanaler |
| MX2023001741A (es) * | 2020-08-14 | 2023-04-25 | Siteone Therapeutics Inc | Inhibidores de cetonas no hidratadas de nav1.7 para el tratamiento de dolor. |
| JP2024520649A (ja) | 2021-06-04 | 2024-05-24 | バーテックス ファーマシューティカルズ インコーポレイテッド | （２ｒ，３ｓ，４ｓ，５ｒ）－４－［［３－（３，４－ジフルオロ－２－メトキシ－フェニル）－４，５－ジメチル－５－（トリフルオロメチル）テトラヒドロフラン－２－カルボニル］アミノ］ピリジン－２－カルボキサミドを含む固体剤形及び投与レジメン |
| CA3221939A1 (en) | 2021-06-04 | 2022-12-08 | Vertex Pharmaceuticals Incorporated | N-(hydroxyalkyl (hetero)aryl) tetrahydrofuran carboxamide analogs as modulators of sodium channels |
| CN117794918A (zh) | 2021-06-04 | 2024-03-29 | 沃泰克斯药物股份有限公司 | 经取代的四氢呋喃类似物作为钠通道调节剂 |
| JP2024520648A (ja) | 2021-06-04 | 2024-05-24 | バーテックス ファーマシューティカルズ インコーポレイテッド | ナトリウムチャネルの調節因子としての置換テトラヒドロフラン－２－カルボキサミド |
| EP4347033A1 (en) | 2021-06-04 | 2024-04-10 | Vertex Pharmaceuticals Incorporated | Hydroxy and (halo)alkoxy substituted tetrahydrofurans as modulators of sodium channels |
| MA64853B1 (fr) | 2021-06-04 | 2025-11-28 | Vertex Pharmaceuticals Incorporated | N-(hydroxyalkyl (hétéro)aryl) tétrahydrofuran carboxamides utilisés en tant que modulateurs de canaux sodiques |
| CN113943243B (zh) * | 2021-10-14 | 2023-08-01 | 南开大学 | 一种用于同时鉴定和定量氨基酸的氟探针的制备与应用 |
| JP2025513452A (ja) | 2022-04-22 | 2025-04-24 | バーテックス ファーマシューティカルズ インコーポレイテッド | 疼痛の治療のためのヘテロアリール化合物 |
| JP2025513455A (ja) | 2022-04-22 | 2025-04-24 | バーテックス ファーマシューティカルズ インコーポレイテッド | 疼痛の治療のためのヘテロアリール化合物 |
| EP4511115A1 (en) | 2022-04-22 | 2025-02-26 | Vertex Pharmaceuticals Incorporated | Heteroaryl compounds for the treatment of pain |
| AU2023255771A1 (en) | 2022-04-22 | 2024-10-31 | Vertex Pharmaceuticals Incorporated | Heteroaryl compounds for the treatment of pain |
| EP4630405A1 (en) | 2022-12-06 | 2025-10-15 | Vertex Pharmaceuticals Incorporated | Process for the synthesis of substituted tetrahydrofuran modulators of sodium channels |
| WO2025090511A1 (en) | 2023-10-23 | 2025-05-01 | Vertex Pharmaceuticals Incorporated | Methods of preparing modulators of sodium channels and solid forms of the same for treating pain |
| WO2025090516A1 (en) | 2023-10-23 | 2025-05-01 | Vertex Pharmaceuticals Incorporated | Methods of preparing compounds for treating pain and solid forms thereof |
| WO2025090465A1 (en) | 2023-10-23 | 2025-05-01 | Vertex Pharmaceuticals Incorporated | Heteroaryl compounds for the treatment of pain |
| WO2025122953A1 (en) | 2023-12-07 | 2025-06-12 | Vertex Pharmaceuticals Incorporated | Dosing regimens and formulations of suzetrigine for use in the treatment of acute and chronic pain |
| US20260001877A1 (en) | 2024-06-28 | 2026-01-01 | Vertex Pharmaceuticals Incorporated | Heteroaryl compounds for the treatment of pain |
| WO2026013449A2 (en) | 2024-07-11 | 2026-01-15 | Sea4Us - Biotecnologia E Recursos Marinhos, Sa | Oxazolidone-derived compounds and their use in the treatment of chronic and acute pain |
| WO2026030525A1 (en) | 2024-07-31 | 2026-02-05 | Vertex Pharmaceuticals Incorporated | Zilvetrigine dosage forms and dosing regimens for treating pain |
Family Cites Families (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3536809A (en) | 1969-02-17 | 1970-10-27 | Alza Corp | Medication method |
| US3598123A (en) | 1969-04-01 | 1971-08-10 | Alza Corp | Bandage for administering drugs |
| US3957996A (en) | 1971-12-08 | 1976-05-18 | Astra Pharmaceutical Products, Inc. | Pharmaceutical local anesthetic compositions |
| US3845770A (en) | 1972-06-05 | 1974-11-05 | Alza Corp | Osmatic dispensing device for releasing beneficial agent |
| US3916899A (en) | 1973-04-25 | 1975-11-04 | Alza Corp | Osmotic dispensing device with maximum and minimum sizes for the passageway |
| US4008719A (en) | 1976-02-02 | 1977-02-22 | Alza Corporation | Osmotic system having laminar arrangement for programming delivery of active agent |
| ES8702440A1 (es) | 1984-10-04 | 1986-12-16 | Monsanto Co | Un procedimiento para la preparacion de una composicion de polipeptido inyectable sustancialmente no acuosa. |
| IE58110B1 (en) | 1984-10-30 | 1993-07-14 | Elan Corp Plc | Controlled release powder and process for its preparation |
| US5073543A (en) | 1988-07-21 | 1991-12-17 | G. D. Searle & Co. | Controlled release formulations of trophic factors in ganglioside-lipsome vehicle |
| IT1229203B (it) | 1989-03-22 | 1991-07-25 | Bioresearch Spa | Impiego di acido 5 metiltetraidrofolico, di acido 5 formiltetraidrofolico e dei loro sali farmaceuticamente accettabili per la preparazione di composizioni farmaceutiche in forma a rilascio controllato attive nella terapia dei disturbi mentali organici e composizioni farmaceutiche relative. |
| PH30995A (en) | 1989-07-07 | 1997-12-23 | Novartis Inc | Sustained release formulations of water soluble peptides. |
| US5120548A (en) | 1989-11-07 | 1992-06-09 | Merck & Co., Inc. | Swelling modulated polymeric drug delivery device |
| US5733566A (en) | 1990-05-15 | 1998-03-31 | Alkermes Controlled Therapeutics Inc. Ii | Controlled release of antiparasitic agents in animals |
| US5580578A (en) | 1992-01-27 | 1996-12-03 | Euro-Celtique, S.A. | Controlled release formulations coated with aqueous dispersions of acrylic polymers |
| TW333456B (en) | 1992-12-07 | 1998-06-11 | Takeda Pharm Ind Co Ltd | A pharmaceutical composition of sustained-release preparation the invention relates to a pharmaceutical composition of sustained-release preparation which comprises a physiologically active peptide. |
| US5591767A (en) | 1993-01-25 | 1997-01-07 | Pharmetrix Corporation | Liquid reservoir transdermal patch for the administration of ketorolac |
| US6087324A (en) | 1993-06-24 | 2000-07-11 | Takeda Chemical Industries, Ltd. | Sustained-release preparation |
| IT1270594B (it) | 1994-07-07 | 1997-05-07 | Recordati Chem Pharm | Composizione farmaceutica a rilascio controllato di moguisteina in sospensione liquida |
| WO1997001331A2 (en) | 1995-06-27 | 1997-01-16 | Takeda Chemical Industries, Ltd. | Method of producing sustained-release preparation |
| TW448055B (en) | 1995-09-04 | 2001-08-01 | Takeda Chemical Industries Ltd | Method of production of sustained-release preparation |
| JP2909418B2 (ja) | 1995-09-18 | 1999-06-23 | 株式会社資生堂 | 薬物の遅延放出型マイクロスフイア |
| US5980945A (en) | 1996-01-16 | 1999-11-09 | Societe De Conseils De Recherches Et D'applications Scientifique S.A. | Sustained release drug formulations |
| US6264970B1 (en) | 1996-06-26 | 2001-07-24 | Takeda Chemical Industries, Ltd. | Sustained-release preparation |
| US6419961B1 (en) | 1996-08-29 | 2002-07-16 | Takeda Chemical Industries, Ltd. | Sustained release microcapsules of a bioactive substance and a biodegradable polymer |
| CA2217134A1 (en) | 1996-10-09 | 1998-04-09 | Sumitomo Pharmaceuticals Co., Ltd. | Sustained release formulation |
| EP0839525B1 (en) | 1996-10-31 | 2004-08-04 | Takeda Chemical Industries, Ltd. | Sustained-release preparation |
| DE69719367T2 (de) | 1996-12-20 | 2003-10-16 | Takeda Chemical Industries, Ltd. | Verfahren zur herstellung einer zusammensetzung mit verzoegerter abgabe |
| EP0857972A1 (en) | 1997-01-24 | 1998-08-12 | Tepual, S.A. | Immunoassay for the detection and quantitation of toxins causing paralytic shellfish poisoning |
| US5891474A (en) | 1997-01-29 | 1999-04-06 | Poli Industria Chimica, S.P.A. | Time-specific controlled release dosage formulations and method of preparing same |
| CN1081034C (zh) | 1997-03-07 | 2002-03-20 | 潘心富 | 一种双胍基氢化嘌呤环类化合物的戒毒药 |
| US6030974A (en) | 1997-04-02 | 2000-02-29 | The Regents Of The University Of California | Method of anesthesia |
| AU7389098A (en) | 1997-05-16 | 1998-12-08 | Brigham And Women's Hospital | Local anesthetic formulations |
| US6613358B2 (en) | 1998-03-18 | 2003-09-02 | Theodore W. Randolph | Sustained-release composition including amorphous polymer |
| KR19990085365A (ko) | 1998-05-16 | 1999-12-06 | 허영섭 | 지속적으로 약물 조절방출이 가능한 생분해성 고분자 미립구 및그 제조방법 |
| US6248363B1 (en) | 1999-11-23 | 2001-06-19 | Lipocine, Inc. | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
| CN1382443A (zh) | 2001-04-25 | 2002-12-04 | 威克斯医疗仪器有限公司 | 钠离子通道阻断剂在制备用于局部神经麻醉或镇痛的药物中的应用 |
| JP2003012699A (ja) | 2001-07-04 | 2003-01-15 | Japan Science & Technology Corp | 抗麻酔性貝毒抗体の製法、新規抗体、該抗体を用いるｅｌｉｓａ測定キット、該製法による系標識毒標品 |
| CN1194693C (zh) | 2002-01-11 | 2005-03-30 | 中国科学院海洋研究所 | 麻痹性贝毒毒素作为制备疗治疼痛病症药物的应用 |
| US20050202093A1 (en) | 2002-12-02 | 2005-09-15 | Kohane Daniel S. | Prolonged suppression of electrical activity in excitable tissues |
| AU2003901897A0 (en) | 2003-02-12 | 2003-05-08 | Australian Institute Of Marine Science | Conjugate |
| US20050137177A1 (en) | 2003-12-18 | 2005-06-23 | Shafer Steven L. | Ester combination local anesthetic |
| MXPA06012960A (es) | 2004-05-07 | 2007-06-12 | Phytotox Ltd | Administracion transdermal de ficotoxinas. |
| CA2606530C (en) | 2004-05-07 | 2014-01-07 | Phytotox Limited | Phycotoxins and uses thereof |
| RU2277097C1 (ru) | 2004-12-27 | 2006-05-27 | Институт Молекулярной Генетики Российской Академии Наук (Имг Ран) | Высокомеченный тритием дигидрохлорид [3h]сакситоксина |
| CN101513408A (zh) | 2008-02-19 | 2009-08-26 | 熊平 | 双胍基嘌呤环类衍生物制备提高抗癌药药效的新应用 |
| AU2009281732A1 (en) | 2008-08-15 | 2010-02-18 | Georgetown University | Na channels, disease, and related assays and compositions |
| CN102459273A (zh) * | 2009-05-07 | 2012-05-16 | 里兰斯坦福初级大学理事会 | 用于研究、成像以及治疗疼痛的方法和组合物 |
| WO2011098539A1 (en) * | 2010-02-10 | 2011-08-18 | Phytotox Limited | Treatment of loss of sense of touch with saxitoxin derivatives |
| EP3009427B1 (en) * | 2011-03-03 | 2019-12-18 | Zalicus Pharmaceuticals Ltd. | Benzimidazole inhibitors of the sodium channel |
| AU2015243437B2 (en) | 2014-04-09 | 2019-08-29 | Siteone Therapeutics, Inc. | 10',11'-modified saxitoxins useful for the treatment of pain |
-
2016
- 2016-09-30 EP EP16785597.2A patent/EP3356370B1/en active Active
- 2016-09-30 CA CA3000708A patent/CA3000708A1/en not_active Abandoned
- 2016-09-30 CN CN201680068998.6A patent/CN108473503A/zh active Pending
- 2016-09-30 JP JP2018517286A patent/JP2018534270A/ja not_active Withdrawn
- 2016-09-30 ES ES16785597T patent/ES2895155T3/es active Active
- 2016-09-30 US US15/283,187 patent/US10112953B2/en active Active
- 2016-09-30 AU AU2016329201A patent/AU2016329201A1/en not_active Abandoned
- 2016-09-30 WO PCT/US2016/055050 patent/WO2017059385A1/en not_active Ceased
-
2018
- 2018-03-29 IL IL258471A patent/IL258471A/en unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2018534270A5 (enExample) | ||
| JP6690543B2 (ja) | 置換ジヒドロピロロピラゾール化合物 | |
| JP2020515610A5 (enExample) | ||
| CN110088107B (zh) | 化合物、组合物及其用途 | |
| EP2098526B1 (en) | Nitrogen-containing bicyclic compounds active on chronic pain conditions | |
| JP6637954B2 (ja) | フラバグリン誘導体 | |
| RU2765718C1 (ru) | Замещенное производное дигидропирролопиразола | |
| RU2639153C2 (ru) | Трициклическое бензоксабороловое соединение, способ его получения и его применение | |
| JP2017519754A5 (enExample) | ||
| WO2013033093A1 (en) | Heterocyclic compounds as janus kinase inhibitors | |
| WO2011150356A1 (en) | Heterocyclic compounds as janus kinase inhibitors | |
| Soliman et al. | Synthesis and biological activity of dihydroimidazole and 3, 4-dihydrobenzo [4, 5] imidazo [1, 2-a][1, 3, 5] triazins | |
| WO2020100944A1 (ja) | ジヒドロピロロピラゾール誘導体 | |
| JP2024033009A (ja) | インフルエンザを処置するためのオルソミクソウイルス複製の阻害剤としての１０－（ジ（フェニル）メチル）－４－ヒドロキシ－８，９，９ａ，１０－テトラヒドロ－７Ｈ－ピロロ［１’，２’：４，５］ピラジノ［１，２－ｂ］ピリダジン－３，５－ジオン誘導体および関連化合物 | |
| JP2017137323A (ja) | 新規抗がん剤 | |
| EP4032890A1 (en) | Heterocyclic amide compound, pharmaceutically acceptable salt thereof, and preparation method therefor and use thereof | |
| AU2014370124A1 (en) | Crystalline forms of a macrocyclic HCV NS3 inhibiting tripeptide | |
| JP7101176B2 (ja) | 新規ＪＡＫキナーゼ阻害剤としての５－（７Ｈ－ピロロ［２，３－ｄ］ピリミジン－４－イル）－５－アザスピロ［２．５］オクタン－８－カルボン酸誘導体 | |
| TWI537280B (zh) | 抗組蛋白去乙醯酶及３－羥－３－甲基戊二輔酶ａ還原酶之雙重作用抑制劑 | |
| WO2022187804A9 (en) | Benzoxazolone inhibitors of inflammasomes | |
| JPH05222040A (ja) | トリアザスピロデカノン−メチルクロマン類 | |
| KR102031334B1 (ko) | 통증 및 기타 장애의 치료용의 감마-아미노뷰티르산(gaba) 유사체 | |
| CN115397815A (zh) | 稠合二环类衍生物、其制备方法及其在医药上的应用 | |
| WO2023040810A1 (en) | Methods of cancer treatment using a combination of btk inhibitors and pi3 kinase inhibitors | |
| JP2019112305A (ja) | アトピー性皮膚炎の治療または予防のための医薬組成物 |