PT2493876E - Derivados de imidazol como inibidores de caseína cinase - Google Patents

Info

Publication number

PT2493876E

PT2493876E PT107742827T PT10774282T PT2493876E PT 2493876 E PT2493876 E PT 2493876E PT 107742827 T PT107742827 T PT 107742827T PT 10774282 T PT10774282 T PT 10774282T PT 2493876 E PT2493876 E PT 2493876E

Authority

PT

Portugal

Prior art keywords

imidazol

fluorophenyl

pyrimidine

alkyl

quot

Prior art date

2009-10-28

Links

• Espacenet
• Global Dossier
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• 150000002460 imidazoles Chemical class 0.000 title description 3
• 102000005403 Casein Kinases Human genes 0.000 title description 2
• 108010031425 Casein Kinases Proteins 0.000 title 1
• 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 title 1
• 229940043355 kinase inhibitor Drugs 0.000 title 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 title 1
• -1 2-methylpyridin-4-yl Chemical group 0.000 claims description 171
• 150000001875 compounds Chemical class 0.000 claims description 149
• 125000001424 substituent group Chemical group 0.000 claims description 98
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 78
• 239000001257 hydrogen Substances 0.000 claims description 64
• 229910052739 hydrogen Inorganic materials 0.000 claims description 64
• 150000003839 salts Chemical class 0.000 claims description 51
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 44
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 42
• 229910052736 halogen Inorganic materials 0.000 claims description 33
• 125000005842 heteroatom Chemical group 0.000 claims description 28
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 26
• 125000001072 heteroaryl group Chemical group 0.000 claims description 24
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
• 150000002367 halogens Chemical class 0.000 claims description 16
• 125000000217 alkyl group Chemical group 0.000 claims description 13
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 12
• 208000035475 disorder Diseases 0.000 claims description 12
• 125000001153 fluoro group Chemical group F* 0.000 claims description 11
• 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 9
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 9
• 208000020925 Bipolar disease Diseases 0.000 claims description 8
• 208000019022 Mood disease Diseases 0.000 claims description 8
• 230000000694 effects Effects 0.000 claims description 8
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims description 8
• 208000019116 sleep disease Diseases 0.000 claims description 8
• 208000012902 Nervous system disease Diseases 0.000 claims description 7
• 208000025966 Neurological disease Diseases 0.000 claims description 7
• 230000000926 neurological effect Effects 0.000 claims description 7
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 7
• 208000020016 psychiatric disease Diseases 0.000 claims description 7
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
• 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 6
• 201000010099 disease Diseases 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
• 208000020685 sleep-wake disease Diseases 0.000 claims description 6
• YOWNAAWVSZSZSY-UHFFFAOYSA-N 4-[5-(4-fluorophenyl)-3-[1-(pyrimidin-2-ylmethyl)piperidin-4-yl]imidazol-4-yl]pyrimidin-2-amine Chemical compound NC1=NC=CC(C=2N(C=NC=2C=2C=CC(F)=CC=2)C2CCN(CC=3N=CC=CN=3)CC2)=N1 YOWNAAWVSZSZSY-UHFFFAOYSA-N 0.000 claims description 5
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
• YLKRIZZCCGCJKZ-UHFFFAOYSA-N n-methyl-4-[5-phenyl-3-[1-(pyrimidin-2-ylmethyl)piperidin-4-yl]imidazol-4-yl]pyrimidin-2-amine Chemical compound CNC1=NC=CC(C=2N(C=NC=2C=2C=CC=CC=2)C2CCN(CC=3N=CC=CN=3)CC2)=N1 YLKRIZZCCGCJKZ-UHFFFAOYSA-N 0.000 claims description 5
• QLMXTWLZXLSYPY-UHFFFAOYSA-N 2-[[4-(4-phenyl-5-pyrimidin-4-ylimidazol-1-yl)piperidin-1-yl]methyl]pyrimidine Chemical compound N=1C=CC=NC=1CN(CC1)CCC1N1C=NC(C=2C=CC=CC=2)=C1C1=CC=NC=N1 QLMXTWLZXLSYPY-UHFFFAOYSA-N 0.000 claims description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
• 230000027288 circadian rhythm Effects 0.000 claims description 4
• 230000002401 inhibitory effect Effects 0.000 claims description 4
• 230000005764 inhibitory process Effects 0.000 claims description 4
• 208000020401 Depressive disease Diseases 0.000 claims description 3
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 2
• VZAXDQKRESHTGW-UHFFFAOYSA-N 3-[[4-[4-(4-fluorophenyl)-5-pyrimidin-4-ylimidazol-1-yl]piperidin-1-yl]methyl]-1,2-oxazole Chemical compound C1=CC(F)=CC=C1C1=C(C=2N=CN=CC=2)N(C2CCN(CC3=NOC=C3)CC2)C=N1 VZAXDQKRESHTGW-UHFFFAOYSA-N 0.000 claims description 2
• ZJCNTDISYRIDDQ-UHFFFAOYSA-N 4-[3-[1-(1,2-oxazol-3-ylmethyl)piperidin-4-yl]-5-phenylimidazol-4-yl]pyrimidin-2-amine Chemical compound NC1=NC=CC(C=2N(C=NC=2C=2C=CC=CC=2)C2CCN(CC3=NOC=C3)CC2)=N1 ZJCNTDISYRIDDQ-UHFFFAOYSA-N 0.000 claims description 2
• RXNQNOUVAKIMHA-UHFFFAOYSA-N 4-[5-(4-fluorophenyl)-3-[1-(1,2-oxazol-3-ylmethyl)piperidin-4-yl]imidazol-4-yl]-n-methylpyrimidin-2-amine Chemical compound CNC1=NC=CC(C=2N(C=NC=2C=2C=CC(F)=CC=2)C2CCN(CC3=NOC=C3)CC2)=N1 RXNQNOUVAKIMHA-UHFFFAOYSA-N 0.000 claims description 2
• SMYILHSDBTWVCE-UHFFFAOYSA-N 4-[5-(4-fluorophenyl)-3-[1-(1,2-oxazol-3-ylmethyl)pyrrolidin-3-yl]imidazol-4-yl]pyrimidin-2-amine Chemical compound NC1=NC=CC(C=2N(C=NC=2C=2C=CC(F)=CC=2)C2CN(CC3=NOC=C3)CC2)=N1 SMYILHSDBTWVCE-UHFFFAOYSA-N 0.000 claims description 2
• BEPDMFYDDOZELL-UHFFFAOYSA-N 4-[5-(4-fluorophenyl)-3-[1-[(2-methylpyrimidin-5-yl)methyl]piperidin-4-yl]imidazol-4-yl]pyrimidin-2-amine Chemical compound C1=NC(C)=NC=C1CN1CCC(N2C(=C(N=C2)C=2C=CC(F)=CC=2)C=2N=C(N)N=CC=2)CC1 BEPDMFYDDOZELL-UHFFFAOYSA-N 0.000 claims description 2
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
• XPWHRQHBPRSUAW-UHFFFAOYSA-N 4-[5-(4-fluorophenyl)-3-[1-(1,2-oxazol-3-ylmethyl)piperidin-4-yl]imidazol-4-yl]pyrimidin-2-amine Chemical compound NC1=NC=CC(C=2N(C=NC=2C=2C=CC(F)=CC=2)C2CCN(CC3=NOC=C3)CC2)=N1 XPWHRQHBPRSUAW-UHFFFAOYSA-N 0.000 claims 1
• LNSKPRAKVGLVRO-UHFFFAOYSA-N 4-[5-(4-fluorophenyl)-3-[1-(1,3-thiazol-5-ylmethyl)piperidin-4-yl]imidazol-4-yl]pyrimidin-2-amine Chemical compound NC1=NC=CC(C=2N(C=NC=2C=2C=CC(F)=CC=2)C2CCN(CC=3SC=NC=3)CC2)=N1 LNSKPRAKVGLVRO-UHFFFAOYSA-N 0.000 claims 1
• 125000006163 5-membered heteroaryl group Chemical group 0.000 claims 1
• 150000002431 hydrogen Chemical class 0.000 claims 1
• PNZSCTKQBAZEQU-UHFFFAOYSA-N n-methyl-4-[3-[1-(1,2-oxazol-3-ylmethyl)piperidin-4-yl]-5-phenylimidazol-4-yl]pyrimidin-2-amine Chemical compound CNC1=NC=CC(C=2N(C=NC=2C=2C=CC=CC=2)C2CCN(CC3=NOC=C3)CC2)=N1 PNZSCTKQBAZEQU-UHFFFAOYSA-N 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 132
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 69
• 239000000203 mixture Substances 0.000 description 68
• 238000000034 method Methods 0.000 description 59
• 239000007787 solid Substances 0.000 description 55
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
• 239000000047 product Substances 0.000 description 47
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
• 239000000243 solution Substances 0.000 description 43
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 40
• 238000005481 NMR spectroscopy Methods 0.000 description 34
• 125000001624 naphthyl group Chemical group 0.000 description 34
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 33
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
• 229910052799 carbon Inorganic materials 0.000 description 29
• 238000006243 chemical reaction Methods 0.000 description 26
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
• 125000004432 carbon atom Chemical group C* 0.000 description 23
• 239000011541 reaction mixture Substances 0.000 description 23
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
• 125000003118 aryl group Chemical group 0.000 description 22
• 239000012044 organic layer Substances 0.000 description 22
• 238000003786 synthesis reaction Methods 0.000 description 22
• 239000002904 solvent Substances 0.000 description 21
• 230000015572 biosynthetic process Effects 0.000 description 20
• 206010028980 Neoplasm Diseases 0.000 description 19
• 125000005843 halogen group Chemical group 0.000 description 19
• 229910052757 nitrogen Inorganic materials 0.000 description 19
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 18
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
• 239000012071 phase Substances 0.000 description 18
• 239000003480 eluent Substances 0.000 description 17
• RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical class C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 16
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 16
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
• VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 15
• 241000124008 Mammalia Species 0.000 description 14
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 14
• 239000003921 oil Substances 0.000 description 14
• 150000001721 carbon Chemical group 0.000 description 13
• 239000010410 layer Substances 0.000 description 13
• 229920006395 saturated elastomer Polymers 0.000 description 13
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 12
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
• 238000010898 silica gel chromatography Methods 0.000 description 12
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
• 150000001299 aldehydes Chemical class 0.000 description 11
• 238000000065 atmospheric pressure chemical ionisation Methods 0.000 description 11
• 125000004429 atom Chemical group 0.000 description 11
• 125000000753 cycloalkyl group Chemical group 0.000 description 11
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 11
• 235000019341 magnesium sulphate Nutrition 0.000 description 11
• 230000002829 reductive effect Effects 0.000 description 11
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
• 208000002193 Pain Diseases 0.000 description 10
• 239000003814 drug Substances 0.000 description 10
• 238000004128 high performance liquid chromatography Methods 0.000 description 10
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 10
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 9
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
• 239000002585 base Substances 0.000 description 9
• 238000001914 filtration Methods 0.000 description 9
• 238000009472 formulation Methods 0.000 description 9
• 125000000623 heterocyclic group Chemical group 0.000 description 9
• 239000003112 inhibitor Substances 0.000 description 9
• 238000002360 preparation method Methods 0.000 description 9
• 125000006413 ring segment Chemical group 0.000 description 9
• 238000003756 stirring Methods 0.000 description 9
• 238000005160 1H NMR spectroscopy Methods 0.000 description 8
• 206010039491 Sarcoma Diseases 0.000 description 8
• 208000009956 adenocarcinoma Diseases 0.000 description 8
• 239000007864 aqueous solution Substances 0.000 description 8
• 239000003153 chemical reaction reagent Substances 0.000 description 8
• 150000002500 ions Chemical class 0.000 description 8
• 238000000746 purification Methods 0.000 description 8
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 7
• 206010025323 Lymphomas Diseases 0.000 description 7
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 7
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
• 239000002246 antineoplastic agent Substances 0.000 description 7
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
• 238000001819 mass spectrum Methods 0.000 description 7
• 239000001301 oxygen Substances 0.000 description 7
• 229910052760 oxygen Inorganic materials 0.000 description 7
• 125000006239 protecting group Chemical group 0.000 description 7
• 229910052938 sodium sulfate Inorganic materials 0.000 description 7
• 235000011152 sodium sulphate Nutrition 0.000 description 7
• WNVZOHNNPDZYFN-UHFFFAOYSA-N 1,2-oxazole-3-carbaldehyde Chemical compound O=CC=1C=CON=1 WNVZOHNNPDZYFN-UHFFFAOYSA-N 0.000 description 6
• DEBZZOLMKVPGDM-UHFFFAOYSA-N 4-[5-(4-fluorophenyl)-3-piperidin-4-ylimidazol-4-yl]pyrimidine Chemical compound C1=CC(F)=CC=C1C1=C(C=2N=CN=CC=2)N(C2CCNCC2)C=N1 DEBZZOLMKVPGDM-UHFFFAOYSA-N 0.000 description 6
• CNPURSDMOWDNOQ-UHFFFAOYSA-N 4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound COC1=NC(N)=NC2=C1C=CN2 CNPURSDMOWDNOQ-UHFFFAOYSA-N 0.000 description 6
• 206010012289 Dementia Diseases 0.000 description 6
• 101000975474 Homo sapiens Keratin, type I cytoskeletal 10 Proteins 0.000 description 6
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
• 102100023970 Keratin, type I cytoskeletal 10 Human genes 0.000 description 6
• 208000010877 cognitive disease Diseases 0.000 description 6
• 238000001816 cooling Methods 0.000 description 6
• 239000002552 dosage form Substances 0.000 description 6
• 239000000463 material Substances 0.000 description 6
• 150000007524 organic acids Chemical class 0.000 description 6
• 229910000027 potassium carbonate Inorganic materials 0.000 description 6
• 238000010992 reflux Methods 0.000 description 6
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
• 235000017557 sodium bicarbonate Nutrition 0.000 description 6
• 239000003826 tablet Substances 0.000 description 6
• UXCQPEDHCCJBNL-UHFFFAOYSA-N 1-[(4-fluorophenyl)-isocyanomethyl]sulfonyl-4-methylbenzene Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C([N+]#[C-])C1=CC=C(F)C=C1 UXCQPEDHCCJBNL-UHFFFAOYSA-N 0.000 description 5
• ICNSLEJMOHSUIQ-UHFFFAOYSA-N 4-[5-(4-fluorophenyl)-3-pyrrolidin-3-ylimidazol-4-yl]pyrimidin-2-amine Chemical compound NC1=NC=CC(C=2N(C=NC=2C=2C=CC(F)=CC=2)C2CNCC2)=N1 ICNSLEJMOHSUIQ-UHFFFAOYSA-N 0.000 description 5
• 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 description 5
• 201000009030 Carcinoma Diseases 0.000 description 5
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• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
• 239000002253 acid Substances 0.000 description 5
• 230000001154 acute effect Effects 0.000 description 5
• 201000011510 cancer Diseases 0.000 description 5
• 125000002837 carbocyclic group Chemical group 0.000 description 5
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 5
• 210000003169 central nervous system Anatomy 0.000 description 5
• 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 5
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
• 210000000214 mouth Anatomy 0.000 description 5
• 235000005985 organic acids Nutrition 0.000 description 5
• 239000000843 powder Substances 0.000 description 5
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
• 125000003226 pyrazolyl group Chemical group 0.000 description 5
• 125000004076 pyridyl group Chemical group 0.000 description 5
• OKULHRWWYCFJAB-UHFFFAOYSA-N pyrimidine-4-carbaldehyde Chemical compound O=CC1=CC=NC=N1 OKULHRWWYCFJAB-UHFFFAOYSA-N 0.000 description 5
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• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 5
• 201000000980 schizophrenia Diseases 0.000 description 5
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• 239000012453 solvate Substances 0.000 description 5
• 206010041823 squamous cell carcinoma Diseases 0.000 description 5
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• 229910052717 sulfur Chemical group 0.000 description 5
• 239000011593 sulfur Chemical group 0.000 description 5
• 239000003643 water by type Substances 0.000 description 5
• 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 description 4
• DFZIBCAWOSFLFR-AATRIKPKSA-N (e)-4-(dimethylamino)-1,1-dimethoxybut-3-en-2-one Chemical compound COC(OC)C(=O)\C=C\N(C)C DFZIBCAWOSFLFR-AATRIKPKSA-N 0.000 description 4
• HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 4
• CSHYVNHEYCETSG-MRXNPFEDSA-N 3-[(1r)-1-[4-[4-(4-fluorophenyl)-5-pyrimidin-4-ylimidazol-1-yl]piperidin-1-yl]ethyl]-1,2-oxazole Chemical compound C1CN([C@H](C)C2=NOC=C2)CCC1N1C=NC(C=2C=CC(F)=CC=2)=C1C1=CC=NC=N1 CSHYVNHEYCETSG-MRXNPFEDSA-N 0.000 description 4
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