TWI282336B - A61p 29/00 200601 a i vhtw - Google Patents

Info

Publication number

TWI282336B

TWI282336B TWNONSTEROIA TW90118465A TWI282336B TW I282336 B TWI282336 B TW I282336B TW NONSTEROI A TWNONSTEROI A TW NONSTEROIA TW 90118465 A TW90118465 A TW 90118465A TW I282336 B TWI282336 B TW I282336B

Authority

TW

Taiwan

Prior art keywords

methyl

hydroxy

benzoindole

amino

fluorophenyl

Prior art date

2000-07-28

Links

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• Global Dossier
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• 150000001875 compounds Chemical class 0.000 claims abstract description 104
• 238000000034 method Methods 0.000 claims abstract description 53
• 229910052740 iodine Inorganic materials 0.000 claims abstract description 3
• -1 5-[4-(5-fluoro-2-nitrophenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentanoylamino]benzene Chemical compound 0.000 claims description 122
• 125000000217 alkyl group Chemical group 0.000 claims description 56
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 52
• UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 45
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 40
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 34
• 150000002576 ketones Chemical class 0.000 claims description 24
• 206010061218 Inflammation Diseases 0.000 claims description 23
• 239000002585 base Substances 0.000 claims description 23
• 230000004054 inflammatory process Effects 0.000 claims description 23
• 239000007789 gas Substances 0.000 claims description 22
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
• 206010020751 Hypersensitivity Diseases 0.000 claims description 17
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
• 201000010099 disease Diseases 0.000 claims description 16
• 230000007815 allergy Effects 0.000 claims description 15
• HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 claims description 15
• 229940067157 phenylhydrazine Drugs 0.000 claims description 15
• 239000002253 acid Substances 0.000 claims description 14
• AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims description 12
• 125000003118 aryl group Chemical group 0.000 claims description 12
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 12
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 11
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
• 230000002062 proliferating effect Effects 0.000 claims description 11
• 229920006395 saturated elastomer Polymers 0.000 claims description 11
• 208000026935 allergic disease Diseases 0.000 claims description 10
• 150000001412 amines Chemical class 0.000 claims description 10
• 229910052731 fluorine Inorganic materials 0.000 claims description 9
• 125000005843 halogen group Chemical group 0.000 claims description 9
• 150000002148 esters Chemical class 0.000 claims description 8
• 125000001072 heteroaryl group Chemical group 0.000 claims description 8
• 206010028980 Neoplasm Diseases 0.000 claims description 7
• 125000004432 carbon atom Chemical group C* 0.000 claims description 7
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
• 150000003839 salts Chemical class 0.000 claims description 7
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
• 125000004429 atom Chemical group 0.000 claims description 6
• 238000006243 chemical reaction Methods 0.000 claims description 6
• 125000001153 fluoro group Chemical group F* 0.000 claims description 6
• 229910052736 halogen Inorganic materials 0.000 claims description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
• 239000003054 catalyst Substances 0.000 claims description 5
• 125000004122 cyclic group Chemical group 0.000 claims description 5
• 239000011737 fluorine Substances 0.000 claims description 5
• 239000008194 pharmaceutical composition Substances 0.000 claims description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
• 101100240517 Caenorhabditis elegans nhr-11 gene Proteins 0.000 claims description 4
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
• 125000003342 alkenyl group Chemical group 0.000 claims description 4
• 125000003545 alkoxy group Chemical group 0.000 claims description 4
• 125000003277 amino group Chemical group 0.000 claims description 4
• 230000015556 catabolic process Effects 0.000 claims description 4
• 239000003795 chemical substances by application Substances 0.000 claims description 4
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 4
• 239000001307 helium Substances 0.000 claims description 4
• 229910052734 helium Inorganic materials 0.000 claims description 4
• SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 claims description 4
• 229910052739 hydrogen Inorganic materials 0.000 claims description 4
• 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 3
• 239000007818 Grignard reagent Substances 0.000 claims description 3
• 208000019693 Lung disease Diseases 0.000 claims description 3
• 208000025747 Rheumatic disease Diseases 0.000 claims description 3
• KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical group [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 3
• 150000001335 aliphatic alkanes Chemical class 0.000 claims description 3
• 229910000288 alkali metal carbonate Inorganic materials 0.000 claims description 3
• 150000008041 alkali metal carbonates Chemical class 0.000 claims description 3
• 229960002130 benzoin Drugs 0.000 claims description 3
• 125000002837 carbocyclic group Chemical group 0.000 claims description 3
• 230000002950 deficient Effects 0.000 claims description 3
• 238000006731 degradation reaction Methods 0.000 claims description 3
• 208000030533 eye disease Diseases 0.000 claims description 3
• 150000004673 fluoride salts Chemical class 0.000 claims description 3
• 150000004795 grignard reagents Chemical class 0.000 claims description 3
• 239000001257 hydrogen Substances 0.000 claims description 3
• 230000036961 partial effect Effects 0.000 claims description 3
• 230000035939 shock Effects 0.000 claims description 3
• PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 3
• RSPCKAHMRANGJZ-UHFFFAOYSA-N thiohydroxylamine Chemical compound SN RSPCKAHMRANGJZ-UHFFFAOYSA-N 0.000 claims description 3
• 208000023275 Autoimmune disease Diseases 0.000 claims description 2
• 208000008035 Back Pain Diseases 0.000 claims description 2
• 208000018522 Gastrointestinal disease Diseases 0.000 claims description 2
• 206010065390 Inflammatory pain Diseases 0.000 claims description 2
• 208000012902 Nervous system disease Diseases 0.000 claims description 2
• 208000025966 Neurological disease Diseases 0.000 claims description 2
• 208000015815 Rectal disease Diseases 0.000 claims description 2
• 206010047115 Vasculitis Diseases 0.000 claims description 2
• 150000007514 bases Chemical class 0.000 claims description 2
• 239000012965 benzophenone Substances 0.000 claims description 2
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
• 208000030172 endocrine system disease Diseases 0.000 claims description 2
• 208000014951 hematologic disease Diseases 0.000 claims description 2
• 208000017169 kidney disease Diseases 0.000 claims description 2
• 208000019423 liver disease Diseases 0.000 claims description 2
• 229960004448 pentamidine Drugs 0.000 claims description 2
• 229910052707 ruthenium Inorganic materials 0.000 claims description 2
• 208000017520 skin disease Diseases 0.000 claims description 2
• 239000002689 soil Substances 0.000 claims description 2
• 238000002560 therapeutic procedure Methods 0.000 claims description 2
• 208000019553 vascular disease Diseases 0.000 claims description 2
• 125000000304 alkynyl group Chemical group 0.000 claims 3
• PQLRKLNTODQYQC-UHFFFAOYSA-N 1h-benzo[e]indole Chemical compound C1=CC=CC2=C3CC=NC3=CC=C21 PQLRKLNTODQYQC-UHFFFAOYSA-N 0.000 claims 2
• HIYWOHBEPVGIQN-UHFFFAOYSA-N 1h-benzo[g]indole Chemical compound C1=CC=CC2=C(NC=C3)C3=CC=C21 HIYWOHBEPVGIQN-UHFFFAOYSA-N 0.000 claims 2
• MBGPFOBFPSVEKI-UHFFFAOYSA-N C1=CC=CC2=C3C(=O)C=NC3=CC=C21 Chemical compound C1=CC=CC2=C3C(=O)C=NC3=CC=C21 MBGPFOBFPSVEKI-UHFFFAOYSA-N 0.000 claims 2
• 125000005055 alkyl alkoxy group Chemical group 0.000 claims 2
• 229910052744 lithium Inorganic materials 0.000 claims 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 2
• 125000004894 pentylamino group Chemical group C(CCCC)N* 0.000 claims 2
• PCTMTFRHKVHKIS-BMFZQQSSSA-N (1s,3r,4e,6e,8e,10e,12e,14e,16e,18s,19r,20r,21s,25r,27r,30r,31r,33s,35r,37s,38r)-3-[(2r,3s,4s,5s,6r)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-19,25,27,30,31,33,35,37-octahydroxy-18,20,21-trimethyl-23-oxo-22,39-dioxabicyclo[33.3.1]nonatriaconta-4,6,8,10 Chemical compound C1C=C2C[C@@H](OS(O)(=O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2.O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 PCTMTFRHKVHKIS-BMFZQQSSSA-N 0.000 claims 1
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 1
• 206010001367 Adrenal insufficiency Diseases 0.000 claims 1
• 102100021809 Chorionic somatomammotropin hormone 1 Human genes 0.000 claims 1
• 102000016736 Cyclin Human genes 0.000 claims 1
• 108050006400 Cyclin Proteins 0.000 claims 1
• PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical compound C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 claims 1
• 101000895818 Homo sapiens Chorionic somatomammotropin hormone 1 Proteins 0.000 claims 1
• 101000956228 Homo sapiens Chorionic somatomammotropin hormone 2 Proteins 0.000 claims 1
• 208000012659 Joint disease Diseases 0.000 claims 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims 1
• 208000008930 Low Back Pain Diseases 0.000 claims 1
• 208000017515 adrenocortical insufficiency Diseases 0.000 claims 1
• 125000005605 benzo group Chemical group 0.000 claims 1
• AQNQQHJNRPDOQV-UHFFFAOYSA-N bromocyclohexane Chemical compound BrC1CCCCC1 AQNQQHJNRPDOQV-UHFFFAOYSA-N 0.000 claims 1
• AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical group [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 claims 1
• 125000000753 cycloalkyl group Chemical group 0.000 claims 1
• 208000010643 digestive system disease Diseases 0.000 claims 1
• 208000018685 gastrointestinal system disease Diseases 0.000 claims 1
• HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims 1
• GDOPTJXRTPNYNR-UHFFFAOYSA-N methylcyclopentane Chemical group CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 claims 1
• YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 claims 1
• 230000001568 sexual effect Effects 0.000 claims 1
• RABVRYVIGNKDSA-UHFFFAOYSA-N trifluoromethyl pentanoate Chemical compound FC(F)(F)OC(CCCC)=O RABVRYVIGNKDSA-UHFFFAOYSA-N 0.000 claims 1
• 230000008569 process Effects 0.000 abstract description 17
• 238000004519 manufacturing process Methods 0.000 abstract description 4
• 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 abstract description 2
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 abstract description 2
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 171
• 235000019439 ethyl acetate Nutrition 0.000 description 62
• 239000000243 solution Substances 0.000 description 54
• 229940093499 ethyl acetate Drugs 0.000 description 49
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 41
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
• 238000001704 evaporation Methods 0.000 description 35
• 230000008020 evaporation Effects 0.000 description 35
• 238000005481 NMR spectroscopy Methods 0.000 description 32
• VLKZOEOYAKHREP-UHFFFAOYSA-N methyl pentane Natural products CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
• 239000000203 mixture Substances 0.000 description 30
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 28
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
• 206010057190 Respiratory tract infections Diseases 0.000 description 22
• 230000000694 effects Effects 0.000 description 22
• 239000000047 product Substances 0.000 description 20
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
• 230000003110 anti-inflammatory effect Effects 0.000 description 19
• 238000004587 chromatography analysis Methods 0.000 description 19
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 17
• 238000002360 preparation method Methods 0.000 description 16
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
• 238000004440 column chromatography Methods 0.000 description 15
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
• 239000000460 chlorine Substances 0.000 description 14
• 238000012360 testing method Methods 0.000 description 14
• 108010042606 Tyrosine transaminase Proteins 0.000 description 13
• 239000004305 biphenyl Substances 0.000 description 13
• 239000003862 glucocorticoid Substances 0.000 description 13
• 238000000926 separation method Methods 0.000 description 13
• 239000011734 sodium Substances 0.000 description 13
• 239000000126 substance Substances 0.000 description 13
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
• 206010015150 Erythema Diseases 0.000 description 12
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
• 241001465754 Metazoa Species 0.000 description 12
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 12
• 239000012074 organic phase Substances 0.000 description 12
• 102000003676 Glucocorticoid Receptors Human genes 0.000 description 11
• 108090000079 Glucocorticoid Receptors Proteins 0.000 description 11
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
• 102000016540 Tyrosine aminotransferases Human genes 0.000 description 11
• 239000000284 extract Substances 0.000 description 11
• 238000005160 1H NMR spectroscopy Methods 0.000 description 10
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 10
• 239000007832 Na2SO4 Substances 0.000 description 10
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
• 239000002243 precursor Substances 0.000 description 10
• 229910052938 sodium sulfate Inorganic materials 0.000 description 10
• 235000011152 sodium sulphate Nutrition 0.000 description 10
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
• 239000003814 drug Substances 0.000 description 9
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
• 230000002411 adverse Effects 0.000 description 8
• 238000009835 boiling Methods 0.000 description 8
• 230000002503 metabolic effect Effects 0.000 description 8
• 239000003921 oil Substances 0.000 description 8
• AIHBPTWEQLZXKN-UHFFFAOYSA-N 2-(5-fluoro-2-methylphenyl)-2-methylpropanal Chemical compound CC1=CC=C(F)C=C1C(C)(C)C=O AIHBPTWEQLZXKN-UHFFFAOYSA-N 0.000 description 7
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 7
• 230000015572 biosynthetic process Effects 0.000 description 7
• 239000010949 copper Substances 0.000 description 7
• 229940117173 croton oil Drugs 0.000 description 7
• 230000005764 inhibitory process Effects 0.000 description 7
• 239000000741 silica gel Substances 0.000 description 7
• 229910002027 silica gel Inorganic materials 0.000 description 7
• 150000003431 steroids Chemical class 0.000 description 7
• 238000003756 stirring Methods 0.000 description 7
• 229940037128 systemic glucocorticoids Drugs 0.000 description 7
• 239000001142 4-methyl-2-oxopentanoic acid Substances 0.000 description 6
• 241000270281 Coluber constrictor Species 0.000 description 6
• 229910052799 carbon Inorganic materials 0.000 description 6
• OQZCSNDVOWYALR-UHFFFAOYSA-N flurochloridone Chemical compound FC(F)(F)C1=CC=CC(N2C(C(Cl)C(CCl)C2)=O)=C1 OQZCSNDVOWYALR-UHFFFAOYSA-N 0.000 description 6
• 210000004185 liver Anatomy 0.000 description 6
• 230000003637 steroidlike Effects 0.000 description 6
• 238000003786 synthesis reaction Methods 0.000 description 6
• 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 5
• 206010010356 Congenital anomaly Diseases 0.000 description 5
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• 108090001007 Interleukin-8 Proteins 0.000 description 5
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
• 229910000024 caesium carbonate Inorganic materials 0.000 description 5
• 210000004027 cell Anatomy 0.000 description 5
• 150000002367 halogens Chemical class 0.000 description 5
• IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 5
• 230000035755 proliferation Effects 0.000 description 5
• 238000000746 purification Methods 0.000 description 5
• 230000028327 secretion Effects 0.000 description 5
• 239000012312 sodium hydride Substances 0.000 description 5
• 229910000104 sodium hydride Inorganic materials 0.000 description 5
• 125000001424 substituent group Chemical group 0.000 description 5
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 5
• ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 4
• IEFAQDLMDRYGDV-UHFFFAOYSA-N 2-(5-fluoro-2-methylphenyl)-2-methylpropanenitrile Chemical compound CC1=CC=C(F)C=C1C(C)(C)C#N IEFAQDLMDRYGDV-UHFFFAOYSA-N 0.000 description 4
• YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 4
• 201000004624 Dermatitis Diseases 0.000 description 4
• 108090000790 Enzymes Proteins 0.000 description 4
• 102000004190 Enzymes Human genes 0.000 description 4
• NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 4
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