SK2292003A3 - Tricyclic antitumor compounds being farnesyl protein transferase inhibitors - Google Patents

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Publication number

SK2292003A3

SK2292003A3 SK229-2003A SK2292003A SK2292003A3 SK 2292003 A3 SK2292003 A3 SK 2292003A3 SK 2292003 A SK2292003 A SK 2292003A SK 2292003 A3 SK2292003 A3 SK 2292003A3

Authority

SK

Slovakia

Prior art keywords

compound

mmol

solution

preparation

compounds

Prior art date

2000-08-30

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 814
• 230000000259 anti-tumor effect Effects 0.000 title description 2
• 239000003528 protein farnesyltransferase inhibitor Substances 0.000 title 1
• 150000003839 salts Chemical class 0.000 claims abstract description 21
• 239000012453 solvate Substances 0.000 claims abstract description 3
• 229910052799 carbon Inorganic materials 0.000 claims description 33
• 229910052757 nitrogen Inorganic materials 0.000 claims description 29
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 24
• 238000002360 preparation method Methods 0.000 abstract description 303
• 238000000034 method Methods 0.000 abstract description 60
• 206010028980 Neoplasm Diseases 0.000 abstract description 28
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 18
• 201000010099 disease Diseases 0.000 abstract description 16
• 230000002062 proliferating effect Effects 0.000 abstract description 16
• 230000002401 inhibitory effect Effects 0.000 abstract description 15
• 201000011510 cancer Diseases 0.000 abstract description 11
• 125000004030 farnesyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 abstract description 9
• 102000004357 Transferases Human genes 0.000 abstract description 8
• 108090000992 Transferases Proteins 0.000 abstract description 8
• 239000008194 pharmaceutical composition Substances 0.000 abstract description 3
• 239000000651 prodrug Substances 0.000 abstract 2
• 229940002612 prodrug Drugs 0.000 abstract 2
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 693
• 239000000243 solution Substances 0.000 description 415
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 321
• 238000001819 mass spectrum Methods 0.000 description 234
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 213
• 238000006243 chemical reaction Methods 0.000 description 202
• 239000000203 mixture Substances 0.000 description 173
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 165
• 239000012044 organic layer Substances 0.000 description 103
• 239000011541 reaction mixture Substances 0.000 description 99
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 92
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 91
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 90
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 90
• 239000003480 eluent Substances 0.000 description 84
• 239000007787 solid Substances 0.000 description 84
• 239000000047 product Substances 0.000 description 79
• 125000000217 alkyl group Chemical group 0.000 description 77
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 76
• 235000019439 ethyl acetate Nutrition 0.000 description 76
• -1 R 31 Chemical compound 0.000 description 75
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 72
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 66
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 66
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 64
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 64
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 59
• 239000012043 crude product Substances 0.000 description 59
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 52
• 125000001424 substituent group Chemical group 0.000 description 52
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
• 238000003756 stirring Methods 0.000 description 49
• 239000000460 chlorine Substances 0.000 description 48
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 42
• 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 42
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 36
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 36
• 239000012267 brine Substances 0.000 description 35
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 35
• 239000012948 isocyanate Substances 0.000 description 35
• 229920006395 saturated elastomer Polymers 0.000 description 35
• 238000010898 silica gel chromatography Methods 0.000 description 35
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 35
• 150000002513 isocyanates Chemical class 0.000 description 34
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 33
• 125000001072 heteroaryl group Chemical group 0.000 description 32
• 238000003818 flash chromatography Methods 0.000 description 31
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 30
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 30
• 239000000741 silica gel Substances 0.000 description 30
• 229910002027 silica gel Inorganic materials 0.000 description 30
• 239000012299 nitrogen atmosphere Substances 0.000 description 29
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 29
• 125000004446 heteroarylalkyl group Chemical group 0.000 description 28
• 238000010992 reflux Methods 0.000 description 28
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 27
• 239000002904 solvent Substances 0.000 description 27
• GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 26
• 125000004432 carbon atom Chemical group C* 0.000 description 25
• 229910052739 hydrogen Inorganic materials 0.000 description 24
• 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 23
• 150000001412 amines Chemical class 0.000 description 23
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 23
• 229910052736 halogen Inorganic materials 0.000 description 23
• XLSZMDLNRCVEIJ-UHFFFAOYSA-N 4-methylimidazole Chemical compound CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 description 22
• 125000003118 aryl group Chemical group 0.000 description 22
• 150000002367 halogens Chemical class 0.000 description 21
• 239000010410 layer Substances 0.000 description 21
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 20
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 20
• 239000002253 acid Substances 0.000 description 20
• 229910021529 ammonia Inorganic materials 0.000 description 20
• 125000005885 heterocycloalkylalkyl group Chemical group 0.000 description 19
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 18
• 229910052801 chlorine Inorganic materials 0.000 description 18
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 18
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 17
• 239000002246 antineoplastic agent Substances 0.000 description 17
• 125000003710 aryl alkyl group Chemical group 0.000 description 17
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 17
• 210000004027 cell Anatomy 0.000 description 17
• 238000004128 high performance liquid chromatography Methods 0.000 description 17
• 239000000543 intermediate Substances 0.000 description 17
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 17
• 102000016914 ras Proteins Human genes 0.000 description 17
• 108010014186 ras Proteins Proteins 0.000 description 17
• 229910000104 sodium hydride Inorganic materials 0.000 description 17
• 238000004440 column chromatography Methods 0.000 description 16
• 235000017557 sodium bicarbonate Nutrition 0.000 description 16
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 16
• 229910052794 bromium Inorganic materials 0.000 description 14
• 230000008018 melting Effects 0.000 description 14
• 238000002844 melting Methods 0.000 description 14
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 14
• 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 14
• 108091022875 Microtubule Proteins 0.000 description 13
• 102000029749 Microtubule Human genes 0.000 description 13
• 239000003795 chemical substances by application Substances 0.000 description 13
• GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 13
• 238000000354 decomposition reaction Methods 0.000 description 13
• 125000004447 heteroarylalkenyl group Chemical group 0.000 description 13
• 210000004688 microtubule Anatomy 0.000 description 13
• LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 12
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 12
• 229930012538 Paclitaxel Natural products 0.000 description 12
• 125000004429 atom Chemical group 0.000 description 12
• 125000000753 cycloalkyl group Chemical group 0.000 description 12
• 229960001592 paclitaxel Drugs 0.000 description 12
• 238000000926 separation method Methods 0.000 description 12
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 12
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
• INLLPKCGLOXCIV-UHFFFAOYSA-N bromoethene Chemical compound BrC=C INLLPKCGLOXCIV-UHFFFAOYSA-N 0.000 description 11
• FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 11
• 150000002148 esters Chemical class 0.000 description 11
• 239000000706 filtrate Substances 0.000 description 11
• 229910052731 fluorine Inorganic materials 0.000 description 11
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 11
• 238000000746 purification Methods 0.000 description 11
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 11
• 239000002585 base Substances 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 10
• 241000124008 Mammalia Species 0.000 description 9
• 230000002159 abnormal effect Effects 0.000 description 9
• 239000003054 catalyst Substances 0.000 description 9
• 230000010261 cell growth Effects 0.000 description 9
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 9
• 229940127089 cytotoxic agent Drugs 0.000 description 9
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 9
• 238000002953 preparative HPLC Methods 0.000 description 9
• 238000012746 preparative thin layer chromatography Methods 0.000 description 9
• YNCPXBIZAPNQIJ-UHFFFAOYSA-N 1h-imidazole;sodium Chemical compound [Na].C1=CNC=N1 YNCPXBIZAPNQIJ-UHFFFAOYSA-N 0.000 description 8
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
• 125000003342 alkenyl group Chemical group 0.000 description 8
• 125000002102 aryl alkyloxo group Chemical group 0.000 description 8
• 230000015572 biosynthetic process Effects 0.000 description 8
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 8
• 230000035772 mutation Effects 0.000 description 8
• 239000003921 oil Substances 0.000 description 8
• 239000011734 sodium Substances 0.000 description 8
• 125000005346 substituted cycloalkyl group Chemical group 0.000 description 8
• 239000000725 suspension Substances 0.000 description 8
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
• 239000005977 Ethylene Substances 0.000 description 7
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 7
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 7
• KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 7
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 7
• 238000000262 chemical ionisation mass spectrometry Methods 0.000 description 7
• 229940125833 compound 23 Drugs 0.000 description 7
• 238000010265 fast atom bombardment Methods 0.000 description 7
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 7
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 7
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 7
• 201000002528 pancreatic cancer Diseases 0.000 description 7
• 208000008443 pancreatic carcinoma Diseases 0.000 description 7
• 239000002244 precipitate Substances 0.000 description 7
• 230000009467 reduction Effects 0.000 description 7
• 239000000377 silicon dioxide Substances 0.000 description 7
• 239000000126 substance Substances 0.000 description 7
• 125000003107 substituted aryl group Chemical group 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 6
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
• 150000007513 acids Chemical class 0.000 description 6
• 150000001336 alkenes Chemical class 0.000 description 6
• 125000003545 alkoxy group Chemical group 0.000 description 6
• 150000008064 anhydrides Chemical class 0.000 description 6
• 229940034982 antineoplastic agent Drugs 0.000 description 6
• 125000002837 carbocyclic group Chemical group 0.000 description 6
• 238000004587 chromatography analysis Methods 0.000 description 6
• 125000004093 cyano group Chemical group *C#N 0.000 description 6
• NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 6
• 125000005842 heteroatom Chemical group 0.000 description 6
• 239000001257 hydrogen Substances 0.000 description 6
• 150000002460 imidazoles Chemical class 0.000 description 6
• 125000002883 imidazolyl group Chemical group 0.000 description 6
• 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 6
• 229910052740 iodine Inorganic materials 0.000 description 6
• 150000002576 ketones Chemical class 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 6
• 231100000590 oncogenic Toxicity 0.000 description 6
• 230000002246 oncogenic effect Effects 0.000 description 6
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 6
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
• 125000003386 piperidinyl group Chemical group 0.000 description 6
• 238000004237 preparative chromatography Methods 0.000 description 6
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
• WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 5
• IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 5
• TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 5
• YSWBFLWKAIRHEI-UHFFFAOYSA-N 4,5-dimethyl-1h-imidazole Chemical compound CC=1N=CNC=1C YSWBFLWKAIRHEI-UHFFFAOYSA-N 0.000 description 5
• XWQVQSXLXAXOPJ-QNGMFEMESA-N 4-[[[6-[5-chloro-2-[[4-[[(2r)-1-methoxypropan-2-yl]amino]cyclohexyl]amino]pyridin-4-yl]pyridin-2-yl]amino]methyl]oxane-4-carbonitrile Chemical compound C1CC(N[C@H](C)COC)CCC1NC1=CC(C=2N=C(NCC3(CCOCC3)C#N)C=CC=2)=C(Cl)C=N1 XWQVQSXLXAXOPJ-QNGMFEMESA-N 0.000 description 5
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
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