ES2665421T3 - Compuestos de pirimidina y su uso como moduladores de la gamma secretasa - Google Patents

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Publication number

ES2665421T3

ES2665421T3 ES14727562.2T ES14727562T ES2665421T3 ES 2665421 T3 ES2665421 T3 ES 2665421T3 ES 14727562 T ES14727562 T ES 14727562T ES 2665421 T3 ES2665421 T3 ES 2665421T3

Authority

ES

Spain

Prior art keywords

methyl

methoxy

mmol

imidazol

trifluoroethoxy

Prior art date

2013-06-04

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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• 150000003230 pyrimidines Chemical class 0.000 title description 3
• VHNYOQKVZQVBLC-RTCGXNAVSA-N (4r,7e,9as)-7-[[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]methylidene]-4-(3,4,5-trifluorophenyl)-1,3,4,8,9,9a-hexahydropyrido[2,1-c][1,4]oxazin-6-one Chemical compound C1([C@@H]2COC[C@@H]3CC\C(C(N32)=O)=C/C=2C=C(C(=CC=2)N2C=C(C)N=C2)OC)=CC(F)=C(F)C(F)=C1 VHNYOQKVZQVBLC-RTCGXNAVSA-N 0.000 title 1
• 229940124648 γ-Secretase Modulator Drugs 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 295
• 150000003839 salts Chemical class 0.000 claims abstract description 41
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 34
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 30
• 239000001257 hydrogen Substances 0.000 claims abstract description 29
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 29
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 25
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 17
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 15
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 9
• 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 8
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 8
• 150000002431 hydrogen Chemical class 0.000 claims abstract description 8
• 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 8
• 125000001424 substituent group Chemical group 0.000 claims abstract description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 7
• 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 4
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 3
• -1 cyanomethyl Chemical group 0.000 claims description 135
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 77
• ZZLCFHIKESPLTH-UHFFFAOYSA-N 4-Methylbiphenyl Chemical compound C1=CC(C)=CC=C1C1=CC=CC=C1 ZZLCFHIKESPLTH-UHFFFAOYSA-N 0.000 claims description 39
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 34
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 31
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 19
• 208000024827 Alzheimer disease Diseases 0.000 claims description 18
• 238000011282 treatment Methods 0.000 claims description 15
• 239000003795 chemical substances by application Substances 0.000 claims description 14
• 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims description 12
• ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 claims description 12
• 239000008194 pharmaceutical composition Substances 0.000 claims description 12
• 238000002560 therapeutic procedure Methods 0.000 claims description 12
• KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 claims description 10
• 230000002265 prevention Effects 0.000 claims description 9
• 239000003085 diluting agent Substances 0.000 claims description 8
• 229960005017 olanzapine Drugs 0.000 claims description 8
• 206010012289 Dementia Diseases 0.000 claims description 7
• 239000003937 drug carrier Substances 0.000 claims description 7
• 230000007170 pathology Effects 0.000 claims description 7
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
• 230000003389 potentiating effect Effects 0.000 claims description 7
• OBYVIVUJQDGTKI-RIUYPTKQSA-N 2-[[(2R,3S,4S,5R,6R)-3,5-dihydroxy-2-(hydroxymethyl)-6-methoxyoxan-4-yl]oxymethyl]quinoline-7-carboxylic acid Chemical compound CO[C@H]1[C@@H]([C@H]([C@H]([C@H](O1)CO)O)OCC2=NC3=C(C=CC(=C3)C(=O)O)C=C2)O OBYVIVUJQDGTKI-RIUYPTKQSA-N 0.000 claims description 6
• CEUORZQYGODEFX-UHFFFAOYSA-N Aripirazole Chemical compound ClC1=CC=CC(N2CCN(CCCCOC=3C=C4NC(=O)CCC4=CC=3)CC2)=C1Cl CEUORZQYGODEFX-UHFFFAOYSA-N 0.000 claims description 6
• XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 claims description 6
• 239000003693 atypical antipsychotic agent Substances 0.000 claims description 6
• QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 claims description 6
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
• 229960004640 memantine Drugs 0.000 claims description 6
• RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 claims description 6
• 229960001685 tacrine Drugs 0.000 claims description 6
• YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 claims description 6
• MVWVFYHBGMAFLY-UHFFFAOYSA-N ziprasidone Chemical compound C1=CC=C2C(N3CCN(CC3)CCC3=CC=4CC(=O)NC=4C=C3Cl)=NSC2=C1 MVWVFYHBGMAFLY-UHFFFAOYSA-N 0.000 claims description 6
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 5
• 239000003814 drug Substances 0.000 claims description 5
• 229960004431 quetiapine Drugs 0.000 claims description 5
• URKOMYMAXPYINW-UHFFFAOYSA-N quetiapine Chemical compound C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 URKOMYMAXPYINW-UHFFFAOYSA-N 0.000 claims description 5
• RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 claims description 4
• 229960004372 aripiprazole Drugs 0.000 claims description 4
• BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 claims description 4
• 239000000544 cholinesterase inhibitor Substances 0.000 claims description 4
• 229960004170 clozapine Drugs 0.000 claims description 4
• 208000010877 cognitive disease Diseases 0.000 claims description 4
• 230000001149 cognitive effect Effects 0.000 claims description 4
• 201000010099 disease Diseases 0.000 claims description 4
• 229960002464 fluoxetine Drugs 0.000 claims description 4
• 229960003980 galantamine Drugs 0.000 claims description 4
• ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 claims description 4
• 229960001534 risperidone Drugs 0.000 claims description 4
• 229960004136 rivastigmine Drugs 0.000 claims description 4
• 229960000607 ziprasidone Drugs 0.000 claims description 4
• 208000000044 Amnesia Diseases 0.000 claims description 3
• 208000026139 Memory disease Diseases 0.000 claims description 3
• 229940121363 anti-inflammatory agent Drugs 0.000 claims description 3
• 239000002260 anti-inflammatory agent Substances 0.000 claims description 3
• 230000006984 memory degeneration Effects 0.000 claims description 3
• 208000023060 memory loss Diseases 0.000 claims description 3
• 208000024891 symptom Diseases 0.000 claims description 3
• 125000006661 (C4-C6) heterocyclic group Chemical group 0.000 claims description 2
• YJQWOLFZVCPXGK-UHFFFAOYSA-N 1-[2-[3-methoxy-4-(4-methoxyimidazol-1-yl)anilino]-6-(2,2,2-trifluoroethoxymethyl)pyrimidin-4-yl]ethanol Chemical compound C1=NC(OC)=CN1C(C(=C1)OC)=CC=C1NC1=NC(COCC(F)(F)F)=CC(C(C)O)=N1 YJQWOLFZVCPXGK-UHFFFAOYSA-N 0.000 claims description 2
• XAOCKFGTPHMXGH-UHFFFAOYSA-N 1-[2-[3-methoxy-4-(4-methylimidazol-1-yl)anilino]-6-(2,2,2-trifluoroethoxymethyl)pyrimidin-4-yl]-2-methylpropan-1-ol Chemical compound C=1C=C(N2C=C(C)N=C2)C(OC)=CC=1NC1=NC(COCC(F)(F)F)=CC(C(O)C(C)C)=N1 XAOCKFGTPHMXGH-UHFFFAOYSA-N 0.000 claims description 2
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
• BYADJZYDNFDSFF-UHFFFAOYSA-N 2-[2-[3-methoxy-4-(4-methoxyimidazol-1-yl)anilino]-6-(2,2,2-trifluoroethoxymethyl)pyrimidin-4-yl]propan-2-ol Chemical compound C1=NC(OC)=CN1C(C(=C1)OC)=CC=C1NC1=NC(COCC(F)(F)F)=CC(C(C)(C)O)=N1 BYADJZYDNFDSFF-UHFFFAOYSA-N 0.000 claims description 2
• HWFMQHNCLUXIHR-UHFFFAOYSA-N 2-[2-[3-methoxy-4-(4-methylimidazol-1-yl)anilino]-6-(2,2,2-trifluoroethoxymethyl)pyrimidin-4-yl]propan-2-ol Chemical compound C=1C=C(N2C=C(C)N=C2)C(OC)=CC=1NC1=NC(COCC(F)(F)F)=CC(C(C)(C)O)=N1 HWFMQHNCLUXIHR-UHFFFAOYSA-N 0.000 claims description 2
• FGEODWQZAMQRTK-UHFFFAOYSA-N 2-[2-[3-methoxy-4-(4-methylimidazol-1-yl)anilino]-6-(3,3,3-trifluoropropoxymethyl)pyrimidin-4-yl]propan-2-ol Chemical compound C=1C=C(N2C=C(C)N=C2)C(OC)=CC=1NC1=NC(COCCC(F)(F)F)=CC(C(C)(C)O)=N1 FGEODWQZAMQRTK-UHFFFAOYSA-N 0.000 claims description 2
• XEDJVNXJZMYHAN-UHFFFAOYSA-N 2-[2-[3-methoxy-4-(4-methylimidazol-1-yl)anilino]-6-[1-(2,2,2-trifluoroethoxy)ethyl]pyrimidin-4-yl]propan-2-ol Chemical compound C=1C=C(N2C=C(C)N=C2)C(OC)=CC=1NC1=NC(C(C)OCC(F)(F)F)=CC(C(C)(C)O)=N1 XEDJVNXJZMYHAN-UHFFFAOYSA-N 0.000 claims description 2
• KNWHEQXEAMCNQN-UHFFFAOYSA-N 2-[6-(cyclopropylmethoxymethyl)-2-[3-methoxy-4-(4-methylimidazol-1-yl)anilino]pyrimidin-4-yl]propan-2-ol Chemical compound C=1C=C(N2C=C(C)N=C2)C(OC)=CC=1NC(N=C(C=1)C(C)(C)O)=NC=1COCC1CC1 KNWHEQXEAMCNQN-UHFFFAOYSA-N 0.000 claims description 2
• FLZQJRMOJZCNRP-UHFFFAOYSA-N 2-[6-[(3,3-difluorocyclobutyl)methoxymethyl]-2-[3-methoxy-4-(4-methylimidazol-1-yl)anilino]pyrimidin-4-yl]propan-2-ol Chemical compound C=1C=C(N2C=C(C)N=C2)C(OC)=CC=1NC(N=C(C=1)C(C)(C)O)=NC=1COCC1CC(F)(F)C1 FLZQJRMOJZCNRP-UHFFFAOYSA-N 0.000 claims description 2
• CALAULRNFVARAH-UHFFFAOYSA-N 2-n-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]-4-n-(oxetan-3-yl)-6-(2,2,2-trifluoroethoxymethyl)pyrimidine-2,4-diamine Chemical compound C=1C=C(N2C=C(C)N=C2)C(OC)=CC=1NC(N=1)=NC(COCC(F)(F)F)=CC=1NC1COC1 CALAULRNFVARAH-UHFFFAOYSA-N 0.000 claims description 2
• DEJAIXXXUVLLBV-UHFFFAOYSA-N 2-n-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]-4-n-methyl-6-(2,2,2-trifluoroethoxymethyl)pyrimidine-2,4-diamine Chemical compound CNC1=CC(COCC(F)(F)F)=NC(NC=2C=C(OC)C(=CC=2)N2C=C(C)N=C2)=N1 DEJAIXXXUVLLBV-UHFFFAOYSA-N 0.000 claims description 2
• OGINPTXCWGPOJG-UHFFFAOYSA-N 2-n-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]-4-n-propan-2-yl-6-(2,2,2-trifluoroethoxymethyl)pyrimidine-2,4-diamine Chemical compound C=1C=C(N2C=C(C)N=C2)C(OC)=CC=1NC1=NC(COCC(F)(F)F)=CC(NC(C)C)=N1 OGINPTXCWGPOJG-UHFFFAOYSA-N 0.000 claims description 2
• ZNSHPICMEBTIDG-UHFFFAOYSA-N 3-[[2-[3-methoxy-4-(4-methylimidazol-1-yl)anilino]-6-(2,2,2-trifluoroethoxymethyl)pyrimidin-4-yl]amino]propanenitrile Chemical compound C=1C=C(N2C=C(C)N=C2)C(OC)=CC=1NC1=NC(COCC(F)(F)F)=CC(NCCC#N)=N1 ZNSHPICMEBTIDG-UHFFFAOYSA-N 0.000 claims description 2
• WETTXVVWUDYFEV-UHFFFAOYSA-N 4-(azetidin-1-yl)-n-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]-6-(2,2,2-trifluoroethoxymethyl)pyrimidin-2-amine Chemical compound C=1C=C(N2C=C(C)N=C2)C(OC)=CC=1NC(N=1)=NC(COCC(F)(F)F)=CC=1N1CCC1 WETTXVVWUDYFEV-UHFFFAOYSA-N 0.000 claims description 2
• MYGVFZNIOCVSMR-UHFFFAOYSA-N 4-[(3-fluoroazetidin-1-yl)methyl]-n-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]-6-(2,2,2-trifluoroethoxymethyl)pyrimidin-2-amine Chemical compound C=1C=C(N2C=C(C)N=C2)C(OC)=CC=1NC(N=1)=NC(COCC(F)(F)F)=CC=1CN1CC(F)C1 MYGVFZNIOCVSMR-UHFFFAOYSA-N 0.000 claims description 2
• HEYWBCWIRSVHLW-UHFFFAOYSA-N 4-[(dimethylamino)methyl]-n-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]-6-(2,2,2-trifluoroethoxymethyl)pyrimidin-2-amine Chemical compound C=1C=C(N2C=C(C)N=C2)C(OC)=CC=1NC1=NC(COCC(F)(F)F)=CC(CN(C)C)=N1 HEYWBCWIRSVHLW-UHFFFAOYSA-N 0.000 claims description 2
• DYFFZRKOCOIEBK-UHFFFAOYSA-N 4-[1-(3-fluoroazetidin-1-yl)ethyl]-n-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]-6-(2,2,2-trifluoroethoxymethyl)pyrimidin-2-amine Chemical compound C=1C=C(N2C=C(C)N=C2)C(OC)=CC=1NC(N=1)=NC(COCC(F)(F)F)=CC=1C(C)N1CC(F)C1 DYFFZRKOCOIEBK-UHFFFAOYSA-N 0.000 claims description 2
• NXIJKQAXXRFXRS-UHFFFAOYSA-N 4-n-(2-methoxyethyl)-2-n-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]-6-(2,2,2-trifluoroethoxymethyl)pyrimidine-2,4-diamine Chemical compound COCCNC1=CC(COCC(F)(F)F)=NC(NC=2C=C(OC)C(=CC=2)N2C=C(C)N=C2)=N1 NXIJKQAXXRFXRS-UHFFFAOYSA-N 0.000 claims description 2
• UKVGHGDIWOCDFC-UHFFFAOYSA-N 4-n-(cyclopropylmethyl)-2-n-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]-6-(2,2,2-trifluoroethoxymethyl)pyrimidine-2,4-diamine Chemical compound C=1C=C(N2C=C(C)N=C2)C(OC)=CC=1NC(N=1)=NC(COCC(F)(F)F)=CC=1NCC1CC1 UKVGHGDIWOCDFC-UHFFFAOYSA-N 0.000 claims description 2
• MXANQQONSNDYOB-UHFFFAOYSA-N 4-n-benzyl-2-n-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]-4-n-methyl-6-(2,2,2-trifluoroethoxymethyl)pyrimidine-2,4-diamine Chemical compound C=1C=C(N2C=C(C)N=C2)C(OC)=CC=1NC(N=1)=NC(COCC(F)(F)F)=CC=1N(C)CC1=CC=CC=C1 MXANQQONSNDYOB-UHFFFAOYSA-N 0.000 claims description 2
• NWAZCFKNPYIPFM-UHFFFAOYSA-N 4-n-cyclopropyl-2-n-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]-6-(2,2,2-trifluoroethoxymethyl)pyrimidine-2,4-diamine Chemical compound C=1C=C(N2C=C(C)N=C2)C(OC)=CC=1NC(N=1)=NC(COCC(F)(F)F)=CC=1NC1CC1 NWAZCFKNPYIPFM-UHFFFAOYSA-N 0.000 claims description 2
• OOFOLNCXBGEMHJ-UHFFFAOYSA-N 6-(cyclopropylmethoxymethyl)-2-n-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]-4-n-methylpyrimidine-2,4-diamine Chemical compound N=1C(NC=2C=C(OC)C(=CC=2)N2C=C(C)N=C2)=NC(NC)=CC=1COCC1CC1 OOFOLNCXBGEMHJ-UHFFFAOYSA-N 0.000 claims description 2
• 206010059245 Angiopathy Diseases 0.000 claims description 2
• 208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims description 2
• 206010008111 Cerebral haemorrhage Diseases 0.000 claims description 2
• 208000028698 Cognitive impairment Diseases 0.000 claims description 2
• 208000011990 Corticobasal Degeneration Diseases 0.000 claims description 2
• 206010033799 Paralysis Diseases 0.000 claims description 2
• 208000018737 Parkinson disease Diseases 0.000 claims description 2
• 206010036631 Presenile dementia Diseases 0.000 claims description 2
• 206010039966 Senile dementia Diseases 0.000 claims description 2
• RIZAICBTGSFMNQ-UHFFFAOYSA-N [2-[3-methoxy-4-(4-methylimidazol-1-yl)anilino]-6-(2,2,2-trifluoroethoxymethyl)pyrimidin-4-yl]methanol Chemical compound C=1C=C(N2C=C(C)N=C2)C(OC)=CC=1NC1=NC(CO)=CC(COCC(F)(F)F)=N1 RIZAICBTGSFMNQ-UHFFFAOYSA-N 0.000 claims description 2
• 125000002393 azetidinyl group Chemical group 0.000 claims description 2
• BKARZTSOFHUZDW-UHFFFAOYSA-N cyclopropyl-[2-[3-methoxy-4-(4-methylimidazol-1-yl)anilino]-6-(2,2,2-trifluoroethoxymethyl)pyrimidin-4-yl]methanol Chemical compound C=1C=C(N2C=C(C)N=C2)C(OC)=CC=1NC(N=1)=NC(COCC(F)(F)F)=CC=1C(O)C1CC1 BKARZTSOFHUZDW-UHFFFAOYSA-N 0.000 claims description 2
• 230000006735 deficit Effects 0.000 claims description 2
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• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
• 208000027061 mild cognitive impairment Diseases 0.000 claims description 2
• 230000004770 neurodegeneration Effects 0.000 claims description 2
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• 229940124597 therapeutic agent Drugs 0.000 claims description 2
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
• 230000002792 vascular Effects 0.000 claims description 2
• CDUINTDPTHLEDE-UHFFFAOYSA-N 1-[[2-[3-methoxy-4-(4-methylimidazol-1-yl)anilino]-6-(2,2,2-trifluoroethoxymethyl)pyrimidin-4-yl]amino]-2-methylpropan-2-ol Chemical compound C=1C=C(N2C=C(C)N=C2)C(OC)=CC=1NC1=NC(COCC(F)(F)F)=CC(NCC(C)(C)O)=N1 CDUINTDPTHLEDE-UHFFFAOYSA-N 0.000 claims 1
• UZWNEPMLUIEMIH-UHFFFAOYSA-N 2,2,2-trifluoro-1-[2-[3-methoxy-4-(4-methylimidazol-1-yl)anilino]-6-(2,2,2-trifluoroethoxymethyl)pyrimidin-4-yl]ethanol Chemical compound C=1C=C(N2C=C(C)N=C2)C(OC)=CC=1NC1=NC(COCC(F)(F)F)=CC(C(O)C(F)(F)F)=N1 UZWNEPMLUIEMIH-UHFFFAOYSA-N 0.000 claims 1
• YZOYNABHGIGZHM-UHFFFAOYSA-N 2-[2-[3-methoxy-4-(4-methylimidazol-1-yl)anilino]-6-(2,2,2-trifluoroethoxymethyl)pyrimidin-4-yl]acetonitrile Chemical compound C=1C=C(N2C=C(C)N=C2)C(OC)=CC=1NC1=NC(COCC(F)(F)F)=CC(CC#N)=N1 YZOYNABHGIGZHM-UHFFFAOYSA-N 0.000 claims 1
• IOBDVBVNPMCPMC-UHFFFAOYSA-N 2-[6-(methoxymethyl)-2-[3-methoxy-4-(4-methylimidazol-1-yl)anilino]pyrimidin-4-yl]propan-2-ol Chemical compound COCC1=CC(C(C)(C)O)=NC(NC=2C=C(OC)C(=CC=2)N2C=C(C)N=C2)=N1 IOBDVBVNPMCPMC-UHFFFAOYSA-N 0.000 claims 1
• POSYWZHCDBDIBZ-UHFFFAOYSA-N 4-(4,4-difluoropiperidin-1-yl)-n-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]-6-(2,2,2-trifluoroethoxymethyl)pyrimidin-2-amine Chemical compound C=1C=C(N2C=C(C)N=C2)C(OC)=CC=1NC(N=1)=NC(COCC(F)(F)F)=CC=1N1CCC(F)(F)CC1 POSYWZHCDBDIBZ-UHFFFAOYSA-N 0.000 claims 1
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