EA020479B1 - СОЕДИНЕНИЯ И КОМПОЗИЦИИ КАК ИНГИБИТОРЫ ПРОТЕИНКИНАЗЫ B-Raf - Google Patents

Info

Publication number

EA020479B1

EA020479B1 EA201200323A EA201200323A EA020479B1 EA 020479 B1 EA020479 B1 EA 020479B1 EA 201200323 A EA201200323 A EA 201200323A EA 201200323 A EA201200323 A EA 201200323A EA 020479 B1 EA020479 B1 EA 020479B1

Authority

EA

Eurasian Patent Office

Prior art keywords

alkyl

methyl

pyrimidin

cyclopropyl

propan

Prior art date

2009-08-28

Links

• Espacenet
• Global Dossier
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• 150000001875 compounds Chemical class 0.000 title claims abstract description 147
• 239000000203 mixture Substances 0.000 title description 166
• 102000004169 proteins and genes Human genes 0.000 title description 3
• 108090000623 proteins and genes Proteins 0.000 title description 3
• 239000002774 b raf kinase inhibitor Substances 0.000 title 1
• 238000011282 treatment Methods 0.000 claims abstract description 23
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 16
• -1 methoxy, methyl Chemical group 0.000 claims description 284
• KNTZCGBYFGEMFR-UHFFFAOYSA-N (propan-2-ylazaniumyl)formate Chemical compound CC(C)NC(O)=O KNTZCGBYFGEMFR-UHFFFAOYSA-N 0.000 claims description 81
• 238000000034 method Methods 0.000 claims description 68
• 150000003839 salts Chemical class 0.000 claims description 67
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 66
• 229910052736 halogen Inorganic materials 0.000 claims description 46
• 150000002367 halogens Chemical class 0.000 claims description 46
• 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 36
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 31
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
• 125000000217 alkyl group Chemical group 0.000 claims description 24
• 108091000080 Phosphotransferase Proteins 0.000 claims description 23
• 102000020233 phosphotransferase Human genes 0.000 claims description 23
• 125000001424 substituent group Chemical group 0.000 claims description 19
• 125000002947 alkylene group Chemical group 0.000 claims description 18
• 239000003814 drug Substances 0.000 claims description 18
• 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 claims description 17
• 206010028980 Neoplasm Diseases 0.000 claims description 17
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 14
• 125000006529 (C3-C6) alkyl group Chemical group 0.000 claims description 14
• 201000011510 cancer Diseases 0.000 claims description 12
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 12
• 229940124597 therapeutic agent Drugs 0.000 claims description 12
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
• 125000006536 (C1-C2)alkoxy group Chemical group 0.000 claims description 9
• 229910052739 hydrogen Inorganic materials 0.000 claims description 9
• 125000003545 alkoxy group Chemical group 0.000 claims description 8
• 239000003085 diluting agent Substances 0.000 claims description 8
• 229910052698 phosphorus Inorganic materials 0.000 claims description 8
• 125000006532 (C3-C5) alkyl group Chemical group 0.000 claims description 7
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 6
• 102000001253 Protein Kinase Human genes 0.000 claims description 6
• 208000035475 disorder Diseases 0.000 claims description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
• 108060006633 protein kinase Proteins 0.000 claims description 6
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
• 230000001575 pathological effect Effects 0.000 claims description 5
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 4
• 206010009944 Colon cancer Diseases 0.000 claims description 4
• 239000013256 coordination polymer Substances 0.000 claims description 4
• 229940079593 drug Drugs 0.000 claims description 4
• 201000001441 melanoma Diseases 0.000 claims description 4
• 230000001430 anti-depressive effect Effects 0.000 claims description 3
• 239000002260 anti-inflammatory agent Substances 0.000 claims description 3
• 229940121363 anti-inflammatory agent Drugs 0.000 claims description 3
• 239000000935 antidepressant agent Substances 0.000 claims description 3
• 229940005513 antidepressants Drugs 0.000 claims description 3
• 239000002111 antiemetic agent Substances 0.000 claims description 3
• XJNXDPBTZPNVPO-UHFFFAOYSA-N n-[2-chloro-3-(2-cyclopropyl-5-pyrimidin-4-yl-1h-imidazol-4-yl)-5-fluorophenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC(F)=CC(C2=C(NC(=N2)C2CC2)C=2N=CN=CC=2)=C1Cl XJNXDPBTZPNVPO-UHFFFAOYSA-N 0.000 claims description 3
• 230000000202 analgesic effect Effects 0.000 claims description 2
• 230000001093 anti-cancer Effects 0.000 claims description 2
• 230000001404 mediated effect Effects 0.000 claims description 2
• 229940124530 sulfonamide Drugs 0.000 claims description 2
• 208000003200 Adenoma Diseases 0.000 claims 2
• 208000021045 exocrine pancreatic carcinoma Diseases 0.000 claims 2
• 201000005296 lung carcinoma Diseases 0.000 claims 2
• 208000010570 urinary bladder carcinoma Diseases 0.000 claims 2
• 206010005003 Bladder cancer Diseases 0.000 claims 1
• 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
• 206010060862 Prostate cancer Diseases 0.000 claims 1
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
• 208000024770 Thyroid neoplasm Diseases 0.000 claims 1
• 229940125683 antiemetic agent Drugs 0.000 claims 1
• HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 claims 1
• 201000001531 bladder carcinoma Diseases 0.000 claims 1
• 239000000945 filler Substances 0.000 claims 1
• 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
• 150000003456 sulfonamides Chemical class 0.000 claims 1
• 201000002510 thyroid cancer Diseases 0.000 claims 1
• 201000010099 disease Diseases 0.000 abstract description 10
• KKVYYGGCHJGEFJ-UHFFFAOYSA-N 1-n-(4-chlorophenyl)-6-methyl-5-n-[3-(7h-purin-6-yl)pyridin-2-yl]isoquinoline-1,5-diamine Chemical compound N=1C=CC2=C(NC=3C(=CC=CN=3)C=3C=4N=CNC=4N=CN=3)C(C)=CC=C2C=1NC1=CC=C(Cl)C=C1 KKVYYGGCHJGEFJ-UHFFFAOYSA-N 0.000 abstract 1
• 101100381978 Mus musculus Braf gene Proteins 0.000 abstract 1
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 225
• 239000011541 reaction mixture Substances 0.000 description 181
• 239000000243 solution Substances 0.000 description 146
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 109
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 100
• 230000014759 maintenance of location Effects 0.000 description 98
• 238000006243 chemical reaction Methods 0.000 description 86
• 238000002360 preparation method Methods 0.000 description 86
• 239000007787 solid Substances 0.000 description 84
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 80
• 239000012267 brine Substances 0.000 description 63
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 63
• 239000010410 layer Substances 0.000 description 60
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 58
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 54
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
• 239000007864 aqueous solution Substances 0.000 description 48
• 238000003818 flash chromatography Methods 0.000 description 43
• 238000000746 purification Methods 0.000 description 42
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical class CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 36
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 35
• 239000003921 oil Substances 0.000 description 35
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 34
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 32
• 239000000126 substance Substances 0.000 description 30
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 27
• 239000000047 product Substances 0.000 description 27
• 239000000706 filtrate Substances 0.000 description 26
• 239000007858 starting material Substances 0.000 description 26
• 239000012044 organic layer Substances 0.000 description 25
• 239000000543 intermediate Substances 0.000 description 24
• 239000012074 organic phase Substances 0.000 description 23
• 229920006395 saturated elastomer Polymers 0.000 description 22
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
• 238000004458 analytical method Methods 0.000 description 20
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 19
• 239000000725 suspension Substances 0.000 description 19
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 18
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
• 229910052740 iodine Inorganic materials 0.000 description 18
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 17
• 239000011734 sodium Substances 0.000 description 17
• 239000002904 solvent Substances 0.000 description 17
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
• 229910052757 nitrogen Inorganic materials 0.000 description 16
• 238000003756 stirring Methods 0.000 description 15
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
• 238000004128 high performance liquid chromatography Methods 0.000 description 12
• HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 12
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
• 239000008346 aqueous phase Substances 0.000 description 11
• HCSHUEPPBIJJCB-UHFFFAOYSA-N carbamic acid;2,2,2-trifluoroacetic acid Chemical compound NC(O)=O.OC(=O)C(F)(F)F HCSHUEPPBIJJCB-UHFFFAOYSA-N 0.000 description 11
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 11
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 10
• 102100029721 DnaJ homolog subfamily B member 1 Human genes 0.000 description 10
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
• 101000866018 Homo sapiens DnaJ homolog subfamily B member 1 Proteins 0.000 description 10
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
• 238000001816 cooling Methods 0.000 description 10
• LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 10
• XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 10
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
• BHRDAUOXWKBEKC-UHFFFAOYSA-N 2-[[4-bromo-5-(2-chloropyrimidin-4-yl)-2-cyclopropylimidazol-1-yl]methoxy]ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCN1C(C2CC2)=NC(Br)=C1C1=CC=NC(Cl)=N1 BHRDAUOXWKBEKC-UHFFFAOYSA-N 0.000 description 9
• 230000015572 biosynthetic process Effects 0.000 description 9
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• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 9
• 230000000694 effects Effects 0.000 description 9
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• BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 9
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• 125000006239 protecting group Chemical group 0.000 description 9
• 239000000741 silica gel Substances 0.000 description 9
• 229910002027 silica gel Inorganic materials 0.000 description 9
• 238000003786 synthesis reaction Methods 0.000 description 9
• WFFDTMNHOINATE-UHFFFAOYSA-N 5-chloro-2-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC(Cl)=CC(N)=C1F WFFDTMNHOINATE-UHFFFAOYSA-N 0.000 description 8
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 8
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
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• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
• 239000004480 active ingredient Substances 0.000 description 8
• 229910052786 argon Inorganic materials 0.000 description 8
• 239000002585 base Substances 0.000 description 8
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 8
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• 239000013058 crude material Substances 0.000 description 7
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• UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 6
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• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
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• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
• 239000000908 ammonium hydroxide Substances 0.000 description 6
• 125000003118 aryl group Chemical group 0.000 description 6
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 6
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• 229910000104 sodium hydride Inorganic materials 0.000 description 6
• LXMXPKGROLGLJT-UHFFFAOYSA-N 2-chloro-5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC(F)=CC(N)=C1Cl LXMXPKGROLGLJT-UHFFFAOYSA-N 0.000 description 5
• HIZADWSSPWORHH-UHFFFAOYSA-N 3-bromo-2,6-difluoroaniline Chemical compound NC1=C(F)C=CC(Br)=C1F HIZADWSSPWORHH-UHFFFAOYSA-N 0.000 description 5
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• 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 5
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• 125000000753 cycloalkyl group Chemical group 0.000 description 5
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• 239000011777 magnesium Substances 0.000 description 5
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• 239000012453 solvate Substances 0.000 description 5
• 238000006467 substitution reaction Methods 0.000 description 5
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• QKWVGDAAZHJCLH-UHFFFAOYSA-N 2,5-difluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC(F)=CC(N)=C1F QKWVGDAAZHJCLH-UHFFFAOYSA-N 0.000 description 4
• JWWBQCGHXVOJNW-UHFFFAOYSA-N 2-chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=CC(N)=C1Cl JWWBQCGHXVOJNW-UHFFFAOYSA-N 0.000 description 4
• UTHYAAGLSHVKBB-UHFFFAOYSA-N 2-chloro-4-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline Chemical compound O1C(C)(C)C(C)(C)OB1C1=C(F)C=CC(N)=C1Cl UTHYAAGLSHVKBB-UHFFFAOYSA-N 0.000 description 4
• JQYPICYMRVGSCU-UHFFFAOYSA-N 2-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=CC(N)=C1F JQYPICYMRVGSCU-UHFFFAOYSA-N 0.000 description 4
• YZGMWJRUAGKYER-UHFFFAOYSA-N 3-bromo-2-chloro-5-fluoroaniline Chemical compound NC1=CC(F)=CC(Br)=C1Cl YZGMWJRUAGKYER-UHFFFAOYSA-N 0.000 description 4
• HKNLHCGTRMCOLV-UHFFFAOYSA-N 3-bromo-2-chloroaniline Chemical compound NC1=CC=CC(Br)=C1Cl HKNLHCGTRMCOLV-UHFFFAOYSA-N 0.000 description 4
• CSHMFIIPOVGVDN-UHFFFAOYSA-N 3-bromo-5-chloro-2-fluoroaniline Chemical compound NC1=CC(Cl)=CC(Br)=C1F CSHMFIIPOVGVDN-UHFFFAOYSA-N 0.000 description 4
• 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 4
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