AU2006297890B2 - New pyrimidine derivatives and their use in therapy as well as the use of pyrimidine derivatives in the manufacture of a medicament for prevention and/or treatment of Alzheimer's disease - Google Patents

Info

Publication number

AU2006297890B2

AU2006297890B2 AU2006297890A AU2006297890A AU2006297890B2 AU 2006297890 B2 AU2006297890 B2 AU 2006297890B2 AU 2006297890 A AU2006297890 A AU 2006297890A AU 2006297890 A AU2006297890 A AU 2006297890A AU 2006297890 B2 AU2006297890 B2 AU 2006297890B2

Authority

AU

Australia

Prior art keywords

imidazol

methyl

fluoro

pyrimidin

alkyl

Prior art date

2005-10-03

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.)

Ceased

Links

• Espacenet
• Global Dossier
• Discuss

• 230000002265 prevention Effects 0.000 title claims description 27
• 208000024827 Alzheimer disease Diseases 0.000 title claims description 25
• 238000004519 manufacturing process Methods 0.000 title claims description 16
• 239000003814 drug Substances 0.000 title claims description 15
• 238000002560 therapeutic procedure Methods 0.000 title claims description 6
• 150000003230 pyrimidines Chemical class 0.000 title description 7
• 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 4
• 150000001875 compounds Chemical class 0.000 claims description 446
• 125000000217 alkyl group Chemical group 0.000 claims description 323
• 125000001188 haloalkyl group Chemical group 0.000 claims description 232
• 125000000623 heterocyclic group Chemical group 0.000 claims description 168
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 161
• 229910052739 hydrogen Inorganic materials 0.000 claims description 159
• 239000001257 hydrogen Substances 0.000 claims description 157
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 146
• 125000005843 halogen group Chemical group 0.000 claims description 118
• LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 claims description 116
• 150000002431 hydrogen Chemical group 0.000 claims description 112
• -1 cyano, methanesulphonyl- Chemical group 0.000 claims description 92
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 91
• 150000003839 salts Chemical class 0.000 claims description 71
• 125000001072 heteroaryl group Chemical group 0.000 claims description 69
• 238000000034 method Methods 0.000 claims description 68
• 125000003118 aryl group Chemical group 0.000 claims description 63
• 125000003545 alkoxy group Chemical group 0.000 claims description 55
• 125000004429 atom Chemical group 0.000 claims description 54
• 239000012453 solvate Substances 0.000 claims description 47
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 38
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 37
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 36
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 35
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 33
• 238000006243 chemical reaction Methods 0.000 claims description 33
• 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 claims description 30
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 29
• 125000005842 heteroatom Chemical group 0.000 claims description 28
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 26
• 239000012458 free base Substances 0.000 claims description 26
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 25
• 206010012289 Dementia Diseases 0.000 claims description 24
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 21
• MPVDXIMFBOLMNW-UHFFFAOYSA-N chembl1615565 Chemical compound OC1=CC=C2C=C(S(O)(=O)=O)C=C(S(O)(=O)=O)C2=C1N=NC1=CC=CC=C1 MPVDXIMFBOLMNW-UHFFFAOYSA-N 0.000 claims description 20
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 19
• 230000008569 process Effects 0.000 claims description 19
• 201000010099 disease Diseases 0.000 claims description 17
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 16
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
• 201000011240 Frontotemporal dementia Diseases 0.000 claims description 15
• 208000010877 cognitive disease Diseases 0.000 claims description 14
• 125000006239 protecting group Chemical group 0.000 claims description 13
• 229910052717 sulfur Inorganic materials 0.000 claims description 13
• 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 9
• 208000020925 Bipolar disease Diseases 0.000 claims description 9
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 9
• 208000017004 dementia pugilistica Diseases 0.000 claims description 9
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
• 230000007170 pathology Effects 0.000 claims description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims description 9
• 125000001963 4 membered heterocyclic group Chemical group 0.000 claims description 8
• RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 claims description 8
• 208000018737 Parkinson disease Diseases 0.000 claims description 8
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 8
• 206010012601 diabetes mellitus Diseases 0.000 claims description 8
• 208000035475 disorder Diseases 0.000 claims description 8
• 125000001153 fluoro group Chemical group F* 0.000 claims description 8
• 206010027175 memory impairment Diseases 0.000 claims description 8
• 125000004043 oxo group Chemical group O=* 0.000 claims description 8
• 241000124008 Mammalia Species 0.000 claims description 7
• 208000037658 Parkinson-dementia complex of Guam Diseases 0.000 claims description 7
• 108010011222 cyclo(Arg-Pro) Proteins 0.000 claims description 7
• 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 7
• 201000000980 schizophrenia Diseases 0.000 claims description 7
• CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 claims description 6
• 201000004384 Alopecia Diseases 0.000 claims description 6
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 6
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 6
• LTHSGGMHLKBAIG-UHFFFAOYSA-N methyl 3-[[4-(2,3-dimethylimidazol-4-yl)-5-fluoropyrimidin-2-yl]amino]benzoate Chemical compound COC(=O)C1=CC=CC(NC=2N=C(C(F)=CN=2)C=2N(C(C)=NC=2)C)=C1 LTHSGGMHLKBAIG-UHFFFAOYSA-N 0.000 claims description 6
• 230000004770 neurodegeneration Effects 0.000 claims description 6
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 6
• KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 5
• 208000028698 Cognitive impairment Diseases 0.000 claims description 5
• 206010019196 Head injury Diseases 0.000 claims description 5
• 208000027089 Parkinsonian disease Diseases 0.000 claims description 5
• 206010034010 Parkinsonism Diseases 0.000 claims description 5
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 5
• BUQKKNYYABDKOK-UHFFFAOYSA-N [4-[[5-fluoro-4-[2-methyl-3-(oxan-4-yl)imidazol-4-yl]pyrimidin-2-yl]amino]-2-methoxyphenyl]-(4-methylpiperazin-1-yl)methanone;hydrochloride Chemical compound Cl.C=1C=C(C(=O)N2CCN(C)CC2)C(OC)=CC=1NC(N=1)=NC=C(F)C=1C1=CN=C(C)N1C1CCOCC1 BUQKKNYYABDKOK-UHFFFAOYSA-N 0.000 claims description 5
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 5
• SNIABFMMCKVXSY-UHFFFAOYSA-N benzoylazanium;chloride Chemical compound Cl.NC(=O)C1=CC=CC=C1 SNIABFMMCKVXSY-UHFFFAOYSA-N 0.000 claims description 5
• 210000000988 bone and bone Anatomy 0.000 claims description 5
• 230000001684 chronic effect Effects 0.000 claims description 5
• 239000003085 diluting agent Substances 0.000 claims description 5
• 150000002148 esters Chemical class 0.000 claims description 5
• 238000001727 in vivo Methods 0.000 claims description 5
• ADLMNARJRRPSOT-UHFFFAOYSA-N 3-[[5-fluoro-4-[2-methyl-3-(oxan-4-yl)imidazol-4-yl]pyrimidin-2-yl]amino]benzonitrile;hydrochloride Chemical compound Cl.C1COCCC1N1C(C)=NC=C1C(C(=CN=1)F)=NC=1NC1=CC=CC(C#N)=C1 ADLMNARJRRPSOT-UHFFFAOYSA-N 0.000 claims description 4
• BCPCWRAHMRSSBP-UHFFFAOYSA-N 5-fluoro-4-[2-methyl-3-(oxan-4-yl)imidazol-4-yl]-n-[4-(trifluoromethyl)phenyl]pyrimidin-2-amine;hydrochloride Chemical compound Cl.C1COCCC1N1C(C)=NC=C1C(C(=CN=1)F)=NC=1NC1=CC=C(C(F)(F)F)C=C1 BCPCWRAHMRSSBP-UHFFFAOYSA-N 0.000 claims description 4
• 208000011990 Corticobasal Degeneration Diseases 0.000 claims description 4
• 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 4
• 201000010374 Down Syndrome Diseases 0.000 claims description 4
• 101100379081 Emericella variicolor andC gene Proteins 0.000 claims description 4
• 208000023105 Huntington disease Diseases 0.000 claims description 4
• 208000019022 Mood disease Diseases 0.000 claims description 4
• 208000014060 Niemann-Pick disease Diseases 0.000 claims description 4
• 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 4
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 4
• 230000006999 cognitive decline Effects 0.000 claims description 4
• WYAYYHGIYLDBPQ-UHFFFAOYSA-N n-(3,5-dichlorophenyl)-4-(2,3-dimethylimidazol-4-yl)-5-fluoropyrimidin-2-amine Chemical compound CN1C(C)=NC=C1C1=NC(NC=2C=C(Cl)C=C(Cl)C=2)=NC=C1F WYAYYHGIYLDBPQ-UHFFFAOYSA-N 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• 201000002212 progressive supranuclear palsy Diseases 0.000 claims description 4
• 150000003527 tetrahydropyrans Chemical group 0.000 claims description 4
• PXBFMLJZNCDSMP-UHFFFAOYSA-N 2-Aminobenzamide Chemical compound NC(=O)C1=CC=CC=C1N PXBFMLJZNCDSMP-UHFFFAOYSA-N 0.000 claims description 3
• BDXZIUJTKUIELX-UHFFFAOYSA-N 4-[[5-fluoro-4-[2-methyl-3-(oxan-4-yl)imidazol-4-yl]pyrimidin-2-yl]amino]benzonitrile;hydrochloride Chemical compound Cl.C1COCCC1N1C(C)=NC=C1C(C(=CN=1)F)=NC=1NC1=CC=C(C#N)C=C1 BDXZIUJTKUIELX-UHFFFAOYSA-N 0.000 claims description 3
• PEYBMQWFUHAKRT-UHFFFAOYSA-N 5-fluoro-4-[2-methyl-3-(oxan-4-yl)imidazol-4-yl]-n-[4-(morpholin-4-ylmethyl)phenyl]pyrimidin-2-amine;hydrochloride Chemical compound Cl.C1COCCC1N1C(C)=NC=C1C(C(=CN=1)F)=NC=1NC(C=C1)=CC=C1CN1CCOCC1 PEYBMQWFUHAKRT-UHFFFAOYSA-N 0.000 claims description 3
• ZCNYDSWSOIKGPQ-UHFFFAOYSA-N 5-fluoro-4-[2-methyl-3-(oxan-4-yl)imidazol-4-yl]-n-[4-methylsulfonyl-3-(trifluoromethyl)phenyl]pyrimidin-2-amine;hydrochloride Chemical compound Cl.C1COCCC1N1C(C)=NC=C1C(C(=CN=1)F)=NC=1NC1=CC=C(S(C)(=O)=O)C(C(F)(F)F)=C1 ZCNYDSWSOIKGPQ-UHFFFAOYSA-N 0.000 claims description 3
• KWPKLLKLLVEXEJ-UHFFFAOYSA-N 5-fluoro-n-[4-(4-methylpiperazin-1-yl)sulfonylphenyl]-4-[3-(oxan-4-yl)imidazol-4-yl]pyrimidin-2-amine Chemical compound C1CN(C)CCN1S(=O)(=O)C(C=C1)=CC=C1NC1=NC=C(F)C(C=2N(C=NC=2)C2CCOCC2)=N1 KWPKLLKLLVEXEJ-UHFFFAOYSA-N 0.000 claims description 3
• 206010067889 Dementia with Lewy bodies Diseases 0.000 claims description 3
• 201000002832 Lewy body dementia Diseases 0.000 claims description 3
• 208000006011 Stroke Diseases 0.000 claims description 3
• 201000004810 Vascular dementia Diseases 0.000 claims description 3
• QQWXTLWDLGRYRU-UHFFFAOYSA-N [4-[[5-fluoro-4-[2-methyl-3-(1-methylpiperidin-4-yl)imidazol-4-yl]pyrimidin-2-yl]amino]phenyl]-(4-methylpiperazin-1-yl)methanone;hydrochloride Chemical compound Cl.C1CN(C)CCC1N1C(C=2C(=CN=C(NC=3C=CC(=CC=3)C(=O)N3CCN(C)CC3)N=2)F)=CN=C1C QQWXTLWDLGRYRU-UHFFFAOYSA-N 0.000 claims description 3
• WNVLQYNNHQWMHM-UHFFFAOYSA-N [4-[[5-fluoro-4-[2-methyl-3-(oxan-4-yl)imidazol-4-yl]pyrimidin-2-yl]amino]phenyl]-(4-methylpiperazin-1-yl)methanone;hydrochloride Chemical compound Cl.C1CN(C)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=C(F)C(C=2N(C(C)=NC=2)C2CCOCC2)=N1 WNVLQYNNHQWMHM-UHFFFAOYSA-N 0.000 claims description 3
• 239000004480 active ingredient Substances 0.000 claims description 3
• 230000007000 age related cognitive decline Effects 0.000 claims description 3
• 206010068168 androgenetic alopecia Diseases 0.000 claims description 3
• 201000002996 androgenic alopecia Diseases 0.000 claims description 3
• 230000007423 decrease Effects 0.000 claims description 3
• UHDXDZQXNNJWDY-UHFFFAOYSA-N (3,3-difluoropyrrolidin-1-yl)-[4-[[5-fluoro-4-[2-methyl-3-(oxan-4-yl)imidazol-4-yl]pyrimidin-2-yl]amino]phenyl]methanone;hydrochloride Chemical compound Cl.C1COCCC1N1C(C)=NC=C1C(C(=CN=1)F)=NC=1NC(C=C1)=CC=C1C(=O)N1CCC(F)(F)C1 UHDXDZQXNNJWDY-UHFFFAOYSA-N 0.000 claims description 2
• LBKLDMQKYYVRHT-UHFFFAOYSA-N 2-(oxolan-3-yl)benzamide hydrochloride Chemical compound Cl.O1CC(CC1)C1=C(C(=O)N)C=CC=C1 LBKLDMQKYYVRHT-UHFFFAOYSA-N 0.000 claims description 2
• DCDIEFUKOHCORY-UHFFFAOYSA-N 2-[4-[[5-fluoro-4-[2-methyl-3-(oxan-4-yl)imidazol-4-yl]pyrimidin-2-yl]amino]phenyl]sulfonylethanol Chemical compound C1COCCC1N1C(C)=NC=C1C(C(=CN=1)F)=NC=1NC1=CC=C(S(=O)(=O)CCO)C=C1 DCDIEFUKOHCORY-UHFFFAOYSA-N 0.000 claims description 2
• OTGRAAUTGFNVIC-UHFFFAOYSA-N 5-fluoro-4-[2-methyl-3-(oxan-4-yl)imidazol-4-yl]-n-[4-(4-methylpiperazin-1-yl)sulfonylphenyl]pyrimidin-2-amine;hydrochloride Chemical compound Cl.C1CN(C)CCN1S(=O)(=O)C(C=C1)=CC=C1NC1=NC=C(F)C(C=2N(C(C)=NC=2)C2CCOCC2)=N1 OTGRAAUTGFNVIC-UHFFFAOYSA-N 0.000 claims description 2
• 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 2
• YQZMQENIWNFASN-UHFFFAOYSA-N Cl.O1CCC(CC1)C1=C(C(=O)N)C=CC=C1 Chemical compound Cl.O1CCC(CC1)C1=C(C(=O)N)C=CC=C1 YQZMQENIWNFASN-UHFFFAOYSA-N 0.000 claims description 2
• SINAKXHPXDZHGA-UHFFFAOYSA-N [3-[[4-(2,3-dimethylimidazol-4-yl)-5-fluoropyrimidin-2-yl]amino]phenyl]-[3-(hydroxymethyl)piperidin-1-yl]methanone Chemical compound CN1C(C)=NC=C1C1=NC(NC=2C=C(C=CC=2)C(=O)N2CC(CO)CCC2)=NC=C1F SINAKXHPXDZHGA-UHFFFAOYSA-N 0.000 claims description 2
• MXUBUUIXLWLCRF-UHFFFAOYSA-N [4-[[4-(2,3-dimethylimidazol-4-yl)-5-fluoropyrimidin-2-yl]amino]-2-(trifluoromethoxy)phenyl]-(4-methylpiperazin-1-yl)methanone;hydrochloride Chemical compound Cl.C1CN(C)CCN1C(=O)C(C(=C1)OC(F)(F)F)=CC=C1NC1=NC=C(F)C(C=2N(C(C)=NC=2)C)=N1 MXUBUUIXLWLCRF-UHFFFAOYSA-N 0.000 claims description 2
• BIRUVOFPJATQLL-UHFFFAOYSA-N [4-[[4-(2,3-dimethylimidazol-4-yl)-5-fluoropyrimidin-2-yl]amino]phenyl]-phenylmethanone Chemical compound CN1C(C)=NC=C1C1=NC(NC=2C=CC(=CC=2)C(=O)C=2C=CC=CC=2)=NC=C1F BIRUVOFPJATQLL-UHFFFAOYSA-N 0.000 claims description 2
• RSYKUWQLLZMBSK-UHFFFAOYSA-N [4-[[5-fluoro-4-[2-methyl-3-(oxan-4-yl)imidazol-4-yl]pyrimidin-2-yl]amino]phenyl]-(3-hydroxypyrrolidin-1-yl)methanone;hydrochloride Chemical compound Cl.C1COCCC1N1C(C)=NC=C1C(C(=CN=1)F)=NC=1NC(C=C1)=CC=C1C(=O)N1CCC(O)C1 RSYKUWQLLZMBSK-UHFFFAOYSA-N 0.000 claims description 2
• UOYZAQZJEFUCIP-UHFFFAOYSA-N [4-[[5-fluoro-4-[3-(oxan-4-yl)-2-(trifluoromethyl)imidazol-4-yl]pyrimidin-2-yl]amino]phenyl]-(4-methylpiperazin-1-yl)methanone;hydrochloride Chemical compound Cl.C1CN(C)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=C(F)C(C=2N(C(=NC=2)C(F)(F)F)C2CCOCC2)=N1 UOYZAQZJEFUCIP-UHFFFAOYSA-N 0.000 claims description 2
• MOOUYDFWJLJXCM-UHFFFAOYSA-N [4-[[5-fluoro-4-[3-methyl-2-(trifluoromethyl)imidazol-4-yl]pyrimidin-2-yl]amino]phenyl]-(4-methylpiperazin-1-yl)methanone;hydrochloride Chemical compound Cl.C1CN(C)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=C(F)C(C=2N(C(=NC=2)C(F)(F)F)C)=N1 MOOUYDFWJLJXCM-UHFFFAOYSA-N 0.000 claims description 2
• 230000001149 cognitive effect Effects 0.000 claims description 2
• 208000027061 mild cognitive impairment Diseases 0.000 claims description 2
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 2
• SHNUBALDGXWUJI-UHFFFAOYSA-N pyridin-2-ylmethanol Chemical compound OCC1=CC=CC=N1 SHNUBALDGXWUJI-UHFFFAOYSA-N 0.000 claims description 2
• 229910052701 rubidium Inorganic materials 0.000 claims description 2
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 11
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 2
• FWVSZXYNCFXKRT-UHFFFAOYSA-N 3,4-dihydro-2h-thiochromen-4-ol Chemical compound C1=CC=C2C(O)CCSC2=C1 FWVSZXYNCFXKRT-UHFFFAOYSA-N 0.000 claims 2
• HPWNIPMSABCNAE-UHFFFAOYSA-N 5-fluoro-4-[2-methyl-3-(oxan-4-yl)imidazol-4-yl]-n-[4-(oxan-2-ylmethylsulfonyl)phenyl]pyrimidin-2-amine Chemical compound C1COCCC1N1C(C)=NC=C1C(C(=CN=1)F)=NC=1NC(C=C1)=CC=C1S(=O)(=O)CC1CCCCO1 HPWNIPMSABCNAE-UHFFFAOYSA-N 0.000 claims 2
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 2
• MJCZCHGQXQZPRH-UHFFFAOYSA-N [4-[[5-fluoro-4-[2-methyl-3-(oxan-4-yl)imidazol-4-yl]pyrimidin-2-yl]amino]phenyl]-(4-propan-2-ylpiperazin-1-yl)methanone;hydrochloride Chemical compound Cl.C1CN(C(C)C)CCN1C(=O)C(C=C1)=CC=C1NC1=NC=C(F)C(C=2N(C(C)=NC=2)C2CCOCC2)=N1 MJCZCHGQXQZPRH-UHFFFAOYSA-N 0.000 claims 2
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 1
• IWTFTXAHVPOGGS-UHFFFAOYSA-N 3-[[4-(2,3-dimethylimidazol-4-yl)-5-fluoropyrimidin-2-yl]amino]-n-(3-methoxypropyl)benzamide;hydrochloride Chemical compound Cl.COCCCNC(=O)C1=CC=CC(NC=2N=C(C(F)=CN=2)C=2N(C(C)=NC=2)C)=C1 IWTFTXAHVPOGGS-UHFFFAOYSA-N 0.000 claims 1
• LXZBSHXSXUNDAQ-UHFFFAOYSA-N 4-[[5-fluoro-4-[2-methyl-3-(oxan-4-yl)imidazol-4-yl]pyrimidin-2-yl]amino]-n-(2-morpholin-4-ylethyl)benzamide;hydrochloride Chemical compound Cl.C1COCCC1N1C(C)=NC=C1C(C(=CN=1)F)=NC=1NC(C=C1)=CC=C1C(=O)NCCN1CCOCC1 LXZBSHXSXUNDAQ-UHFFFAOYSA-N 0.000 claims 1
• JHHGIBQYWIETCQ-UHFFFAOYSA-N 4-[[5-fluoro-4-[2-methyl-3-(oxan-4-yl)imidazol-4-yl]pyrimidin-2-yl]amino]-n-(2-piperidin-1-ylethyl)benzamide;hydrochloride Chemical compound Cl.C1COCCC1N1C(C)=NC=C1C(C(=CN=1)F)=NC=1NC(C=C1)=CC=C1C(=O)NCCN1CCCCC1 JHHGIBQYWIETCQ-UHFFFAOYSA-N 0.000 claims 1
• JOVUROKJGTYMBQ-UHFFFAOYSA-N 4-[[5-fluoro-4-[2-methyl-3-(oxan-4-yl)imidazol-4-yl]pyrimidin-2-yl]amino]-n-(3-methoxypropyl)benzamide;hydrochloride Chemical compound Cl.C1=CC(C(=O)NCCCOC)=CC=C1NC1=NC=C(F)C(C=2N(C(C)=NC=2)C2CCOCC2)=N1 JOVUROKJGTYMBQ-UHFFFAOYSA-N 0.000 claims 1
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