ES2821529T3 - Derivados de 4,6-diamino-pirimidina como inhibidores de Bmi-1 para el tratamiento del cáncer - Google Patents
Derivados de 4,6-diamino-pirimidina como inhibidores de Bmi-1 para el tratamiento del cáncer Download PDFInfo
- Publication number
- ES2821529T3 ES2821529T3 ES13857326T ES13857326T ES2821529T3 ES 2821529 T3 ES2821529 T3 ES 2821529T3 ES 13857326 T ES13857326 T ES 13857326T ES 13857326 T ES13857326 T ES 13857326T ES 2821529 T3 ES2821529 T3 ES 2821529T3
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- ES
- Spain
- Prior art keywords
- diamine
- fluoro
- benzoimidazol
- alkyl
- methyl
- 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.)
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- 206010028980 Neoplasm Diseases 0.000 title claims description 188
- 101100058550 Mus musculus Bmi1 gene Proteins 0.000 title claims description 184
- 201000011510 cancer Diseases 0.000 title claims description 118
- 238000011282 treatment Methods 0.000 title claims description 20
- 239000003112 inhibitor Substances 0.000 title description 25
- MISVBCMQSJUHMH-UHFFFAOYSA-N pyrimidine-4,6-diamine Chemical class NC1=CC(N)=NC=N1 MISVBCMQSJUHMH-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 414
- -1 cyano, hydroxyl Chemical group 0.000 claims abstract description 350
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 231
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 79
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 76
- 125000005843 halogen group Chemical group 0.000 claims abstract description 48
- 150000003839 salts Chemical class 0.000 claims abstract description 48
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 47
- 125000003118 aryl group Chemical group 0.000 claims abstract description 44
- 125000001424 substituent group Chemical group 0.000 claims abstract description 40
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 30
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 27
- 239000002253 acid Substances 0.000 claims abstract description 25
- 239000012453 solvate Substances 0.000 claims abstract description 25
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 23
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims abstract description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 20
- 239000001257 hydrogen Chemical group 0.000 claims abstract description 20
- 150000002148 esters Chemical class 0.000 claims abstract description 18
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 17
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 16
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 14
- 125000001769 aryl amino group Chemical group 0.000 claims abstract description 13
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims abstract description 12
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 12
- 239000012458 free base Substances 0.000 claims abstract description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 9
- 239000013522 chelant Substances 0.000 claims abstract description 8
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 7
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 6
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 5
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims abstract description 5
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims abstract description 5
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 5
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims abstract description 4
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims abstract description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract 5
- 210000004027 cell Anatomy 0.000 claims description 73
- 238000000034 method Methods 0.000 claims description 66
- 239000003795 chemical substances by application Substances 0.000 claims description 52
- 230000001404 mediated effect Effects 0.000 claims description 50
- 210000000130 stem cell Anatomy 0.000 claims description 49
- 125000004076 pyridyl group Chemical group 0.000 claims description 26
- 239000008194 pharmaceutical composition Substances 0.000 claims description 23
- 210000004881 tumor cell Anatomy 0.000 claims description 18
- 239000002246 antineoplastic agent Substances 0.000 claims description 16
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 16
- 125000003342 alkenyl group Chemical group 0.000 claims description 15
- 125000000304 alkynyl group Chemical group 0.000 claims description 15
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 13
- 229940127089 cytotoxic agent Drugs 0.000 claims description 12
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 12
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 11
- 230000001028 anti-proliverative effect Effects 0.000 claims description 10
- 239000003242 anti bacterial agent Substances 0.000 claims description 8
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 8
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 8
- 238000001959 radiotherapy Methods 0.000 claims description 8
- 239000004037 angiogenesis inhibitor Substances 0.000 claims description 7
- 230000002519 immonomodulatory effect Effects 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 7
- 239000000556 agonist Substances 0.000 claims description 6
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 6
- AMVNCIDWFCDCNE-UHFFFAOYSA-N 2-(2-methylpyrazolo[1,5-a]pyridin-3-yl)-4-n-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine Chemical compound CC1=NN2C=CC=CC2=C1C(N=1)=NC(N)=CC=1NC1=CC=C(C(F)(F)F)C=C1 AMVNCIDWFCDCNE-UHFFFAOYSA-N 0.000 claims description 5
- KFNZRUUAZRCHAP-UHFFFAOYSA-N 2-(6-fluoro-2-methylbenzimidazol-1-yl)-4-n-(4-methoxyphenyl)pyrimidine-4,6-diamine Chemical compound C1=CC(OC)=CC=C1NC1=CC(N)=NC(N2C3=CC(F)=CC=C3N=C2C)=N1 KFNZRUUAZRCHAP-UHFFFAOYSA-N 0.000 claims description 5
- 229940088710 antibiotic agent Drugs 0.000 claims description 5
- 230000003637 steroidlike Effects 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 229940100198 alkylating agent Drugs 0.000 claims description 4
- 239000002168 alkylating agent Substances 0.000 claims description 4
- 229940034982 antineoplastic agent Drugs 0.000 claims description 4
- 239000003443 antiviral agent Substances 0.000 claims description 4
- 239000011230 binding agent Substances 0.000 claims description 4
- 239000000812 cholinergic antagonist Substances 0.000 claims description 4
- 239000003862 glucocorticoid Substances 0.000 claims description 4
- 125000001188 haloalkyl group Chemical group 0.000 claims description 4
- JZEFXPLZEMNPKI-UHFFFAOYSA-N 1-[4-amino-5-fluoro-6-(4-methylanilino)pyrimidin-2-yl]-2-methylbenzimidazole-5-carbonitrile Chemical compound CC1=NC2=CC(C#N)=CC=C2N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(C)C=C1 JZEFXPLZEMNPKI-UHFFFAOYSA-N 0.000 claims description 3
- QWNRBKAXMKABIG-UHFFFAOYSA-N 1-[4-amino-5-fluoro-6-[4-(trifluoromethyl)anilino]pyrimidin-2-yl]-2-methylbenzimidazole-5-carbonitrile Chemical compound CC1=NC2=CC(C#N)=CC=C2N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(C(F)(F)F)C=C1 QWNRBKAXMKABIG-UHFFFAOYSA-N 0.000 claims description 3
- WKKKIRDLPBGOBE-UHFFFAOYSA-N 2-(2-cyclopropyl-4-fluorobenzimidazol-1-yl)-5-fluoro-4-n-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine Chemical compound FC=1C(N)=NC(N2C3=CC=CC(F)=C3N=C2C2CC2)=NC=1NC1=CC=C(C(F)(F)F)C=C1 WKKKIRDLPBGOBE-UHFFFAOYSA-N 0.000 claims description 3
- SGTURXOUZJDSMP-UHFFFAOYSA-N 2-(2-cyclopropyl-6-fluorobenzimidazol-1-yl)-4-n-[4-(difluoromethoxy)phenyl]pyrimidine-4,6-diamine Chemical compound N=1C(N2C3=CC(F)=CC=C3N=C2C2CC2)=NC(N)=CC=1NC1=CC=C(OC(F)F)C=C1 SGTURXOUZJDSMP-UHFFFAOYSA-N 0.000 claims description 3
- QMRUWLFJRUMHQQ-UHFFFAOYSA-N 2-(2-cyclopropyl-6-fluoroimidazo[4,5-b]pyridin-1-yl)-4-n-[4-(difluoromethoxy)phenyl]-5-fluoropyrimidine-4,6-diamine Chemical compound FC=1C(N)=NC(N2C3=CC(F)=CN=C3N=C2C2CC2)=NC=1NC1=CC=C(OC(F)F)C=C1 QMRUWLFJRUMHQQ-UHFFFAOYSA-N 0.000 claims description 3
- MJFMGIUOZPWGKF-UHFFFAOYSA-N 2-(2-ethyl-6-fluorobenzimidazol-1-yl)-5-fluoro-4-n-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine Chemical compound CCC1=NC2=CC=C(F)C=C2N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(C(F)(F)F)C=C1 MJFMGIUOZPWGKF-UHFFFAOYSA-N 0.000 claims description 3
- IMFIKEVUZDKFCK-UHFFFAOYSA-N 2-(4,6-difluoro-2-methylbenzimidazol-1-yl)-5-fluoro-4-n-(4-methoxyphenyl)pyrimidine-4,6-diamine Chemical compound C1=CC(OC)=CC=C1NC1=NC(N2C3=CC(F)=CC(F)=C3N=C2C)=NC(N)=C1F IMFIKEVUZDKFCK-UHFFFAOYSA-N 0.000 claims description 3
- IKOHBXWYJCAUPJ-UHFFFAOYSA-N 2-(4,6-difluoro-2-methylbenzimidazol-1-yl)-5-fluoro-4-n-(4-methylphenyl)pyrimidine-4,6-diamine Chemical compound CC1=NC2=C(F)C=C(F)C=C2N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(C)C=C1 IKOHBXWYJCAUPJ-UHFFFAOYSA-N 0.000 claims description 3
- HVXYQSYBMZNXQV-UHFFFAOYSA-N 2-(4,6-difluoro-2-methylbenzimidazol-1-yl)-5-fluoro-4-n-[4-(trifluoromethoxy)phenyl]pyrimidine-4,6-diamine Chemical compound CC1=NC2=C(F)C=C(F)C=C2N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(OC(F)(F)F)C=C1 HVXYQSYBMZNXQV-UHFFFAOYSA-N 0.000 claims description 3
- USGPPZYVPLYVHZ-UHFFFAOYSA-N 2-(5,6-difluoro-2-methylbenzimidazol-1-yl)-5-fluoro-4-n-(4-methoxyphenyl)pyrimidine-4,6-diamine Chemical compound C1=CC(OC)=CC=C1NC1=NC(N2C3=CC(F)=C(F)C=C3N=C2C)=NC(N)=C1F USGPPZYVPLYVHZ-UHFFFAOYSA-N 0.000 claims description 3
- CUOWJRCANYJXAW-UHFFFAOYSA-N 2-(5,7-difluoro-2-methylbenzimidazol-1-yl)-5-fluoro-4-n-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine Chemical compound CC1=NC2=CC(F)=CC(F)=C2N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(C(F)(F)F)C=C1 CUOWJRCANYJXAW-UHFFFAOYSA-N 0.000 claims description 3
- GSLHLSQSTNAUDI-UHFFFAOYSA-N 2-(5-chloro-2-methylbenzimidazol-1-yl)-4-n-[4-(difluoromethoxy)phenyl]-5-fluoropyrimidine-4,6-diamine Chemical compound CC1=NC2=CC(Cl)=CC=C2N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(OC(F)F)C=C1 GSLHLSQSTNAUDI-UHFFFAOYSA-N 0.000 claims description 3
- WDCLEYPIKDXQQR-UHFFFAOYSA-N 2-(5-chloro-2-methylbenzimidazol-1-yl)-5-fluoro-4-n-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine Chemical compound CC1=NC2=CC(Cl)=CC=C2N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(C(F)(F)F)C=C1 WDCLEYPIKDXQQR-UHFFFAOYSA-N 0.000 claims description 3
- QEKISZCIPMIENB-UHFFFAOYSA-N 2-(6-amino-2-methylbenzimidazol-1-yl)-4-n-[4-(difluoromethoxy)phenyl]-5-fluoropyrimidine-4,6-diamine Chemical compound CC1=NC2=CC=C(N)C=C2N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(OC(F)F)C=C1 QEKISZCIPMIENB-UHFFFAOYSA-N 0.000 claims description 3
- LAVGTIUAJZMRJB-UHFFFAOYSA-N 2-(6-chloro-2-methylbenzimidazol-1-yl)-4-n-[4-(difluoromethoxy)phenyl]-5-fluoropyrimidine-4,6-diamine Chemical compound CC1=NC2=CC=C(Cl)C=C2N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(OC(F)F)C=C1 LAVGTIUAJZMRJB-UHFFFAOYSA-N 0.000 claims description 3
- WRFKCROHHVRHNR-UHFFFAOYSA-N 2-(6-fluoro-2-methylbenzimidazol-1-yl)-4-n-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine Chemical compound CC1=NC2=CC=C(F)C=C2N1C(N=1)=NC(N)=CC=1NC1=CC=C(C(F)(F)F)C=C1 WRFKCROHHVRHNR-UHFFFAOYSA-N 0.000 claims description 3
- GIQXAVZXTSGXKG-UHFFFAOYSA-N 2-(6-fluoro-2-methylimidazo[1,2-a]pyridin-3-yl)-4-n-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine Chemical compound CC=1N=C2C=CC(F)=CN2C=1C(N=1)=NC(N)=CC=1NC1=CC=C(C(F)(F)F)C=C1 GIQXAVZXTSGXKG-UHFFFAOYSA-N 0.000 claims description 3
- IQQSHMVVOXOAFZ-UHFFFAOYSA-N 3-[4-amino-5-fluoro-6-(4-methylanilino)pyrimidin-2-yl]-2-methylbenzimidazole-5-carbonitrile Chemical compound CC1=NC2=CC=C(C#N)C=C2N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(C)C=C1 IQQSHMVVOXOAFZ-UHFFFAOYSA-N 0.000 claims description 3
- JNYJIRDGMLJAQG-UHFFFAOYSA-N 3-[4-amino-5-fluoro-6-[4-(trifluoromethyl)anilino]pyrimidin-2-yl]-2-methylbenzimidazole-5-carbonitrile Chemical compound CC1=NC2=CC=C(C#N)C=C2N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(C(F)(F)F)C=C1 JNYJIRDGMLJAQG-UHFFFAOYSA-N 0.000 claims description 3
- QJVLZNRNFLBQHK-UHFFFAOYSA-N 3-[4-amino-6-[4-(difluoromethoxy)anilino]-5-fluoropyrimidin-2-yl]-2-methylbenzimidazole-5-carbonitrile Chemical compound CC1=NC2=CC=C(C#N)C=C2N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(OC(F)F)C=C1 QJVLZNRNFLBQHK-UHFFFAOYSA-N 0.000 claims description 3
- XCINULITTUKURC-UHFFFAOYSA-N 4-n-[4-(difluoromethoxy)-3-fluorophenyl]-5-fluoro-2-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidine-4,6-diamine Chemical compound CC=1N=C2C=CC=CN2C=1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(OC(F)F)C(F)=C1 XCINULITTUKURC-UHFFFAOYSA-N 0.000 claims description 3
- MXQGLUIZBAUBGA-UHFFFAOYSA-N 4-n-[4-(difluoromethoxy)-3-fluorophenyl]-5-fluoro-2-(2-methylimidazo[4,5-b]pyridin-1-yl)pyrimidine-4,6-diamine Chemical compound CC1=NC2=NC=CC=C2N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(OC(F)F)C(F)=C1 MXQGLUIZBAUBGA-UHFFFAOYSA-N 0.000 claims description 3
- QPORTJYLGOENII-UHFFFAOYSA-N 4-n-[4-(difluoromethoxy)-3-fluorophenyl]-5-fluoro-2-(4-fluoro-2-methylbenzimidazol-1-yl)pyrimidine-4,6-diamine Chemical compound CC1=NC2=C(F)C=CC=C2N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(OC(F)F)C(F)=C1 QPORTJYLGOENII-UHFFFAOYSA-N 0.000 claims description 3
- OSFIPAFSHUOLIS-UHFFFAOYSA-N 4-n-[4-(difluoromethoxy)phenyl]-2-(2-ethyl-4,6-difluorobenzimidazol-1-yl)-5-fluoropyrimidine-4,6-diamine Chemical compound CCC1=NC2=C(F)C=C(F)C=C2N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(OC(F)F)C=C1 OSFIPAFSHUOLIS-UHFFFAOYSA-N 0.000 claims description 3
- SXBFUXDGQDHUKU-UHFFFAOYSA-N 4-n-[4-(difluoromethoxy)phenyl]-2-(2-ethyl-5-fluorobenzimidazol-1-yl)-5-fluoropyrimidine-4,6-diamine Chemical compound CCC1=NC2=CC(F)=CC=C2N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(OC(F)F)C=C1 SXBFUXDGQDHUKU-UHFFFAOYSA-N 0.000 claims description 3
- VKYQYDNTFBKTAN-UHFFFAOYSA-N 4-n-[4-(difluoromethoxy)phenyl]-2-(2-ethyl-5-fluoropyrazolo[1,5-a]pyridin-3-yl)-5-fluoropyrimidine-4,6-diamine Chemical compound CCC1=NN2C=CC(F)=CC2=C1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(OC(F)F)C=C1 VKYQYDNTFBKTAN-UHFFFAOYSA-N 0.000 claims description 3
- YEGULBHTVJTZKW-UHFFFAOYSA-N 4-n-[4-(difluoromethoxy)phenyl]-2-(2-ethyl-6-fluorobenzimidazol-1-yl)-5-fluoropyrimidine-4,6-diamine Chemical compound CCC1=NC2=CC=C(F)C=C2N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(OC(F)F)C=C1 YEGULBHTVJTZKW-UHFFFAOYSA-N 0.000 claims description 3
- RVJAJAQKQAHBAM-UHFFFAOYSA-N 4-n-[4-(difluoromethoxy)phenyl]-2-(5,6-difluoro-2-methylbenzimidazol-1-yl)-5-fluoropyrimidine-4,6-diamine Chemical compound CC1=NC2=CC(F)=C(F)C=C2N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(OC(F)F)C=C1 RVJAJAQKQAHBAM-UHFFFAOYSA-N 0.000 claims description 3
- KOIXIABGYDXHCE-UHFFFAOYSA-N 4-n-[4-(difluoromethoxy)phenyl]-2-[2-(1-methylcyclopropyl)benzimidazol-1-yl]pyrimidine-4,6-diamine Chemical compound N=1C2=CC=CC=C2N(C=2N=C(NC=3C=CC(OC(F)F)=CC=3)C=C(N)N=2)C=1C1(C)CC1 KOIXIABGYDXHCE-UHFFFAOYSA-N 0.000 claims description 3
- LZDVUNDJVSINAM-UHFFFAOYSA-N 4-n-[4-(difluoromethoxy)phenyl]-2-[2-(difluoromethyl)-6-fluorobenzimidazol-1-yl]pyrimidine-4,6-diamine Chemical compound N=1C(N2C3=CC(F)=CC=C3N=C2C(F)F)=NC(N)=CC=1NC1=CC=C(OC(F)F)C=C1 LZDVUNDJVSINAM-UHFFFAOYSA-N 0.000 claims description 3
- HSDFCHLVPYNTMT-UHFFFAOYSA-N 4-n-[4-(difluoromethoxy)phenyl]-5-fluoro-2-(2-methyl-6-nitrobenzimidazol-1-yl)pyrimidine-4,6-diamine Chemical compound CC1=NC2=CC=C([N+]([O-])=O)C=C2N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(OC(F)F)C=C1 HSDFCHLVPYNTMT-UHFFFAOYSA-N 0.000 claims description 3
- JNQCJNFMFPUFIV-UHFFFAOYSA-N 4-n-[4-(difluoromethoxy)phenyl]-5-fluoro-2-(6-methoxy-2-methylbenzimidazol-1-yl)pyrimidine-4,6-diamine Chemical compound C12=CC(OC)=CC=C2N=C(C)N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(OC(F)F)C=C1 JNQCJNFMFPUFIV-UHFFFAOYSA-N 0.000 claims description 3
- ZRZOQIFKQBPEII-UHFFFAOYSA-N 5-fluoro-2-(2-methyl-6-nitrobenzimidazol-1-yl)-4-n-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine Chemical compound CC1=NC2=CC=C([N+]([O-])=O)C=C2N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(C(F)(F)F)C=C1 ZRZOQIFKQBPEII-UHFFFAOYSA-N 0.000 claims description 3
- SPJWHRBEQIAYCD-UHFFFAOYSA-N 5-fluoro-2-(2-methylimidazo[1,2-a]pyridin-3-yl)-4-n-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine Chemical compound CC=1N=C2C=CC=CN2C=1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(C(F)(F)F)C=C1 SPJWHRBEQIAYCD-UHFFFAOYSA-N 0.000 claims description 3
- MSZOYFDDFLTOHW-UHFFFAOYSA-N 5-fluoro-2-(4-fluoro-2-methylbenzimidazol-1-yl)-4-n-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine Chemical compound CC1=NC2=C(F)C=CC=C2N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(C(F)(F)F)C=C1 MSZOYFDDFLTOHW-UHFFFAOYSA-N 0.000 claims description 3
- LOOYMJVHKCMLCS-UHFFFAOYSA-N 5-fluoro-2-(6-fluoro-2-methylbenzimidazol-1-yl)-4-n-[4-(trifluoromethoxy)phenyl]pyrimidine-4,6-diamine Chemical compound CC1=NC2=CC=C(F)C=C2N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(OC(F)(F)F)C=C1 LOOYMJVHKCMLCS-UHFFFAOYSA-N 0.000 claims description 3
- TWLWOOPCEXYVBE-UHFFFAOYSA-N 5-fluoro-2-(6-fluoro-2-methylbenzimidazol-1-yl)-4-n-[4-(trifluoromethyl)phenyl]pyrimidine-4,6-diamine Chemical compound CC1=NC2=CC=C(F)C=C2N1C(N=1)=NC(N)=C(F)C=1NC1=CC=C(C(F)(F)F)C=C1 TWLWOOPCEXYVBE-UHFFFAOYSA-N 0.000 claims description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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