IL269152B2 - Bruton's tyrosine kinase inhibitors - Google Patents

Info

Publication number

IL269152B2

IL269152B2 IL269152A IL26915219A IL269152B2 IL 269152 B2 IL269152 B2 IL 269152B2 IL 269152 A IL269152 A IL 269152A IL 26915219 A IL26915219 A IL 26915219A IL 269152 B2 IL269152 B2 IL 269152B2

Authority

IL

Israel

Prior art keywords

pyrazin

phenyl

imidazo

pyrrolidin

fluoro

Prior art date

2017-03-22

Links

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• Global Dossier
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• 108091000080 Phosphotransferase Proteins 0.000 title description 5
• 102000020233 phosphotransferase Human genes 0.000 title description 5
• 150000001875 compounds Chemical class 0.000 claims description 91
• 206010028980 Neoplasm Diseases 0.000 claims description 7
• 208000023275 Autoimmune disease Diseases 0.000 claims description 6
• 229940002612 prodrug Drugs 0.000 claims description 6
• 239000000651 prodrug Substances 0.000 claims description 6
• 201000010099 disease Diseases 0.000 claims description 5
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
• 239000008194 pharmaceutical composition Substances 0.000 claims description 5
• 208000027866 inflammatory disease Diseases 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• 230000001404 mediated effect Effects 0.000 claims description 3
• 239000012453 solvate Substances 0.000 claims description 3
• 125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 183
• 239000000203 mixture Substances 0.000 description 111
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 84
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 71
• 239000000243 solution Substances 0.000 description 70
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 68
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 49
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 47
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 43
• LVOICKNPHXSSQM-UHFFFAOYSA-N prop-2-en-1-one Chemical compound C=C[C]=O LVOICKNPHXSSQM-UHFFFAOYSA-N 0.000 description 43
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 42
• 239000012044 organic layer Substances 0.000 description 41
• 239000012267 brine Substances 0.000 description 37
• RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 37
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 37
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
• 229910052938 sodium sulfate Inorganic materials 0.000 description 36
• 235000011152 sodium sulphate Nutrition 0.000 description 36
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 32
• -1 methoxyphenoxy Chemical group 0.000 description 31
• 101150041968 CDC13 gene Proteins 0.000 description 29
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 29
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
• 238000000034 method Methods 0.000 description 24
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 24
• 239000002904 solvent Substances 0.000 description 22
• 238000005160 1H NMR spectroscopy Methods 0.000 description 21
• 238000004809 thin layer chromatography Methods 0.000 description 21
• 239000000047 product Substances 0.000 description 20
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
• 125000000217 alkyl group Chemical group 0.000 description 15
• 239000011541 reaction mixture Substances 0.000 description 15
• 238000010898 silica gel chromatography Methods 0.000 description 15
• GWWWKCOHKLXZME-UHFFFAOYSA-N 6-[2-[(3-chloropyrazin-2-yl)amino]acetyl]-2,5,6,7,8,8a-hexahydro-1H-indolizin-3-one Chemical compound ClC=1C(=NC=CN=1)NCC(=O)C1CN2C(CCC2CC1)=O GWWWKCOHKLXZME-UHFFFAOYSA-N 0.000 description 14
• 230000000694 effects Effects 0.000 description 14
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 13
• 238000000746 purification Methods 0.000 description 13
• 238000006243 chemical reaction Methods 0.000 description 12
• 229910000027 potassium carbonate Inorganic materials 0.000 description 12
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
• 235000011181 potassium carbonates Nutrition 0.000 description 11
• 235000019000 fluorine Nutrition 0.000 description 10
• 229910052739 hydrogen Inorganic materials 0.000 description 10
• 239000001257 hydrogen Substances 0.000 description 10
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 9
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
• 238000003556 assay Methods 0.000 description 9
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
• 125000001153 fluoro group Chemical group F* 0.000 description 9
• IYZLDMUWHYPROV-UHFFFAOYSA-N methyl 6-[2-[(2,4-dimethoxyphenyl)methylamino]ethyl]piperidine-3-carboxylate Chemical compound N1CC(C(=O)OC)CCC1CCNCC1=CC=C(OC)C=C1OC IYZLDMUWHYPROV-UHFFFAOYSA-N 0.000 description 9
• 229910052757 nitrogen Inorganic materials 0.000 description 9
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 8
• 239000007821 HATU Substances 0.000 description 8
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
• NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 8
• 150000002367 halogens Chemical group 0.000 description 8
• 125000001072 heteroaryl group Chemical group 0.000 description 8
• 150000002431 hydrogen Chemical class 0.000 description 8
• 229910052760 oxygen Inorganic materials 0.000 description 8
• 239000000741 silica gel Substances 0.000 description 8
• 229910002027 silica gel Inorganic materials 0.000 description 8
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 7
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 7
• 125000003118 aryl group Chemical group 0.000 description 7
• 125000004429 atom Chemical group 0.000 description 7
• 239000000543 intermediate Substances 0.000 description 7
• 125000006239 protecting group Chemical group 0.000 description 7
• 238000010992 reflux Methods 0.000 description 7
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 7
• 229940124291 BTK inhibitor Drugs 0.000 description 6
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
• 102100029823 Tyrosine-protein kinase BTK Human genes 0.000 description 6
• 239000000460 chlorine Substances 0.000 description 6
• 239000012043 crude product Substances 0.000 description 6
• 229910052736 halogen Inorganic materials 0.000 description 6
• 125000005842 heteroatom Chemical group 0.000 description 6
• 125000000623 heterocyclic group Chemical group 0.000 description 6
• 229920006395 saturated elastomer Polymers 0.000 description 6
• 229910052717 sulfur Chemical group 0.000 description 6
• IZKATSCDUREBRD-UHFFFAOYSA-N 2,5,6,7,8,8a-hexahydro-1h-indolizin-3-one Chemical compound C1CCCN2C(=O)CCC21 IZKATSCDUREBRD-UHFFFAOYSA-N 0.000 description 5
• 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 5
• UBWXANWHFAYIOY-UHFFFAOYSA-N [4-(2-fluoro-3-methoxyphenoxy)phenyl]boronic acid Chemical compound FC1=C(OC2=CC=C(C=C2)B(O)O)C=CC=C1OC UBWXANWHFAYIOY-UHFFFAOYSA-N 0.000 description 5
• HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 description 5
• 239000008346 aqueous phase Substances 0.000 description 5
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
• 239000003153 chemical reaction reagent Substances 0.000 description 5
• 229940125904 compound 1 Drugs 0.000 description 5
• 238000001514 detection method Methods 0.000 description 5
• 239000003814 drug Substances 0.000 description 5
• 150000002148 esters Chemical class 0.000 description 5
• 238000003818 flash chromatography Methods 0.000 description 5
• 125000000524 functional group Chemical group 0.000 description 5
• UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 description 5
• 230000005764 inhibitory process Effects 0.000 description 5
• 238000001819 mass spectrum Methods 0.000 description 5
• 239000001301 oxygen Chemical group 0.000 description 5
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
• 239000007858 starting material Substances 0.000 description 5
• 238000003786 synthesis reaction Methods 0.000 description 5
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
• MLMBONPOGVHSAB-NRFANRHFSA-N 4-[3-[(2S)-1-but-2-ynoylpyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl]-N-(2-fluoro-3-methoxyphenyl)benzamide Chemical compound C(C#CC)(=O)N1[C@@H](CCC1)C1=NC(=C2N1C=CN=C2)C1=CC=C(C(=O)NC2=C(C(=CC=C2)OC)F)C=C1 MLMBONPOGVHSAB-NRFANRHFSA-N 0.000 description 4
• HZNWZCMJVCMITA-UHFFFAOYSA-N 7-(1-bromoimidazo[1,5-a]pyrazin-3-yl)-2-methyl-4,4a,5,6,7,8-hexahydro-3H-pyrido[1,2-c]pyrimidin-1-one Chemical compound C1CC(C=2N3C=CN=CC3=C(N=2)Br)CN2C1CCN(C)C2=O HZNWZCMJVCMITA-UHFFFAOYSA-N 0.000 description 4
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 4
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
• 210000003719 b-lymphocyte Anatomy 0.000 description 4
• 239000002585 base Substances 0.000 description 4
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
• 239000003054 catalyst Substances 0.000 description 4
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• 229940126214 compound 3 Drugs 0.000 description 4
• 238000005859 coupling reaction Methods 0.000 description 4
• 238000010511 deprotection reaction Methods 0.000 description 4
• 238000000132 electrospray ionisation Methods 0.000 description 4
• 239000003480 eluent Substances 0.000 description 4
• 229910052731 fluorine Inorganic materials 0.000 description 4
• 238000001727 in vivo Methods 0.000 description 4
• 239000003112 inhibitor Substances 0.000 description 4
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical class OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
• 239000011593 sulfur Chemical group 0.000 description 4
• YYVVOYJKQZWKFS-UHFFFAOYSA-N (3-chloropyrazin-2-yl)methanamine;hydrochloride Chemical compound Cl.NCC1=NC=CN=C1Cl YYVVOYJKQZWKFS-UHFFFAOYSA-N 0.000 description 3
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 3
• LEEWZFMVOTUQDG-NRFANRHFSA-N 1-[(2S)-2-[1-[4-[(2-fluorophenoxy)methyl]phenyl]imidazo[1,5-a]pyrazin-3-yl]pyrrolidin-1-yl]prop-2-en-1-one Chemical compound FC1=C(OCC2=CC=C(C=C2)C=2N=C(N3C=2C=NC=C3)[C@H]2N(CCC2)C(C=C)=O)C=CC=C1 LEEWZFMVOTUQDG-NRFANRHFSA-N 0.000 description 3
• 102000001714 Agammaglobulinaemia Tyrosine Kinase Human genes 0.000 description 3
• 108010029445 Agammaglobulinaemia Tyrosine Kinase Proteins 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 3
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• 239000002253 acid Substances 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• 230000008901 benefit Effects 0.000 description 3
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
• 230000015572 biosynthetic process Effects 0.000 description 3
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
• 229910052794 bromium Inorganic materials 0.000 description 3
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
• 229910000024 caesium carbonate Inorganic materials 0.000 description 3
• 229910052799 carbon Inorganic materials 0.000 description 3
• 210000004027 cell Anatomy 0.000 description 3
• 229910052801 chlorine Inorganic materials 0.000 description 3
• 235000015165 citric acid Nutrition 0.000 description 3
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• 229910052805 deuterium Inorganic materials 0.000 description 3
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• 238000002868 homogeneous time resolved fluorescence Methods 0.000 description 3
• 238000002347 injection Methods 0.000 description 3
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• 150000002500 ions Chemical class 0.000 description 3
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 3
• 238000004949 mass spectrometry Methods 0.000 description 3
• VQJJMPPJQLKXFJ-UHFFFAOYSA-N methyl 6-ethenylpyridine-3-carboxylate Chemical compound COC(=O)C1=CC=C(C=C)N=C1 VQJJMPPJQLKXFJ-UHFFFAOYSA-N 0.000 description 3
• 239000012299 nitrogen atmosphere Substances 0.000 description 3
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 3
• 238000002360 preparation method Methods 0.000 description 3
• 125000004076 pyridyl group Chemical group 0.000 description 3
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 3
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 3
• 230000002829 reductive effect Effects 0.000 description 3
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• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 3
• 229910052720 vanadium Inorganic materials 0.000 description 3
• NKZINEMIBDKICC-IBGZPJMESA-N (2S)-N,N-dimethyl-2-[8-(trifluoromethyl)-1-[4-[[4-(trifluoromethyl)pyridin-2-yl]carbamoyl]phenyl]imidazo[1,5-a]pyrazin-3-yl]piperidine-1-carboxamide Chemical compound CN(C(=O)N1[C@@H](CCCC1)C1=NC(=C2N1C=CN=C2C(F)(F)F)C1=CC=C(C=C1)C(NC1=NC=CC(=C1)C(F)(F)F)=O)C NKZINEMIBDKICC-IBGZPJMESA-N 0.000 description 2
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
• CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 2
• HIZVCIIORGCREW-UHFFFAOYSA-N 1,4-dioxene Chemical compound C1COC=CO1 HIZVCIIORGCREW-UHFFFAOYSA-N 0.000 description 2
• OGVBISBIDDHLMR-FQEVSTJZSA-N 1-[(2S)-2-[1-(6-phenoxypyridin-3-yl)imidazo[1,5-a]pyrazin-3-yl]pyrrolidin-1-yl]but-2-yn-1-one Chemical compound O(C1=CC=CC=C1)C1=CC=C(C=N1)C=1N=C(N2C=1C=NC=C2)[C@H]1N(CCC1)C(C#CC)=O OGVBISBIDDHLMR-FQEVSTJZSA-N 0.000 description 2
• RUOKSYHBICMNEH-IBGZPJMESA-N 1-[(2S)-2-[1-[4-(2-fluoro-3-methoxyphenoxy)phenyl]-5-methoxyimidazo[1,5-a]pyrazin-3-yl]pyrrolidin-1-yl]prop-2-en-1-one Chemical compound FC1=C(OC2=CC=C(C=C2)C=2N=C(N3C=2C=NC=C3OC)[C@H]2N(CCC2)C(C=C)=O)C=CC=C1OC RUOKSYHBICMNEH-IBGZPJMESA-N 0.000 description 2
• ATHBIZVLJDFNSG-FQEVSTJZSA-N 1-[(2S)-2-[1-[4-(2-fluoro-3-methoxyphenoxy)phenyl]-8-(trifluoromethyl)imidazo[1,5-a]pyrazin-3-yl]piperidin-1-yl]but-2-yn-1-one Chemical compound FC1=C(OC2=CC=C(C=C2)C=2N=C(N3C=2C(=NC=C3)C(F)(F)F)[C@H]2N(CCCC2)C(C#CC)=O)C=CC=C1OC ATHBIZVLJDFNSG-FQEVSTJZSA-N 0.000 description 2
• CBPBIDLOWQVSCA-IBGZPJMESA-N 1-[(2S)-2-[1-[4-(2-fluoro-3-methoxyphenoxy)phenyl]-8-(trifluoromethyl)imidazo[1,5-a]pyrazin-3-yl]piperidin-1-yl]prop-2-en-1-one Chemical compound FC1=C(OC2=CC=C(C=C2)C=2N=C(N3C=2C(=NC=C3)C(F)(F)F)[C@H]2N(CCCC2)C(C=C)=O)C=CC=C1OC CBPBIDLOWQVSCA-IBGZPJMESA-N 0.000 description 2
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