TWI673283B - ２’－氯胺基嘧啶酮及嘧啶二酮核苷類 - Google Patents

Info

Publication number

TWI673283B

TWI673283B TW104125796A TW104125796A TWI673283B TW I673283 B TWI673283 B TW I673283B TW 104125796 A TW104125796 A TW 104125796A TW 104125796 A TW104125796 A TW 104125796A TW I673283 B TWI673283 B TW I673283B

Authority

TW

Taiwan

Prior art keywords

alkyl

compound

pharmaceutically acceptable

reaction

acceptable salt

Prior art date

2014-08-21

Links

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• 239000002777 nucleoside Substances 0.000 title description 28
• 239000000203 mixture Substances 0.000 claims abstract description 163
• 230000009385 viral infection Effects 0.000 claims abstract description 57
• 230000000241 respiratory effect Effects 0.000 claims abstract description 35
• 230000004927 fusion Effects 0.000 claims abstract description 34
• 241000711904 Pneumoviridae Species 0.000 claims abstract description 21
• 238000011282 treatment Methods 0.000 claims abstract description 18
• 150000001875 compounds Chemical class 0.000 claims description 232
• 150000003839 salts Chemical class 0.000 claims description 128
• 229910052739 hydrogen Inorganic materials 0.000 claims description 65
• 125000004432 carbon atom Chemical group C* 0.000 claims description 60
• 125000000217 alkyl group Chemical group 0.000 claims description 59
• 239000003814 drug Substances 0.000 claims description 51
• 229910052799 carbon Inorganic materials 0.000 claims description 49
• 125000001424 substituent group Chemical group 0.000 claims description 44
• 229910052760 oxygen Inorganic materials 0.000 claims description 33
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 31
• 229910052757 nitrogen Inorganic materials 0.000 claims description 28
• 125000003118 aryl group Chemical group 0.000 claims description 27
• 239000001257 hydrogen Substances 0.000 claims description 27
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 26
• 125000000623 heterocyclic group Chemical group 0.000 claims description 25
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 23
• 229910052731 fluorine Inorganic materials 0.000 claims description 23
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 22
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
• 239000008194 pharmaceutical composition Substances 0.000 claims description 21
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 16
• 239000001301 oxygen Substances 0.000 claims description 15
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
• 229910052736 halogen Inorganic materials 0.000 claims description 14
• 150000002367 halogens Chemical class 0.000 claims description 14
• 208000015181 infectious disease Diseases 0.000 claims description 13
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 12
• 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 11
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 11
• 229920002554 vinyl polymer Polymers 0.000 claims description 11
• 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 10
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 10
• 229910052801 chlorine Inorganic materials 0.000 claims description 10
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 10
• 241000282412 Homo Species 0.000 claims description 9
• 241000700605 Viruses Species 0.000 claims description 9
• 125000005842 heteroatom Chemical group 0.000 claims description 9
• 125000005843 halogen group Chemical group 0.000 claims description 8
• 238000004519 manufacturing process Methods 0.000 claims description 8
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
• 239000003937 drug carrier Substances 0.000 claims description 7
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 7
• 238000006467 substitution reaction Methods 0.000 claims description 7
• 208000024891 symptom Diseases 0.000 claims description 7
• 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 6
• 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 6
• 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 6
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 5
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 5
• 206010006448 Bronchiolitis Diseases 0.000 claims description 5
• 206010035664 Pneumonia Diseases 0.000 claims description 5
• 125000002887 hydroxy group Chemical group [H]O* 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
• 238000002360 preparation method Methods 0.000 claims description 5
• 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 4
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
• 125000005884 carbocyclylalkyl group Chemical group 0.000 claims description 4
• 230000001225 therapeutic effect Effects 0.000 claims description 4
• 125000001963 4 membered heterocyclic group Chemical group 0.000 claims description 3
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 3
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 3
• 238000000034 method Methods 0.000 abstract description 58
• 238000009472 formulation Methods 0.000 abstract description 43
• VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 abstract description 4
• 150000008512 pyrimidinediones Chemical class 0.000 abstract description 3
• YCIPQJTZJGUXND-UHFFFAOYSA-N Aglaia odorata Alkaloid Natural products C1=CC(OC)=CC=C1C1(C(C=2C(=O)N3CCCC3=NC=22)C=3C=CC=CC=3)C2(O)C2=C(OC)C=C(OC)C=C2O1 YCIPQJTZJGUXND-UHFFFAOYSA-N 0.000 abstract 1
• 230000002194 synthesizing effect Effects 0.000 abstract 1
• 238000006243 chemical reaction Methods 0.000 description 349
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 234
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 174
• -1 alkyl R 10 Chemical compound 0.000 description 165
• 239000000243 solution Substances 0.000 description 148
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 144
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 144
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 110
• 238000010898 silica gel chromatography Methods 0.000 description 84
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 66
• 239000000047 product Substances 0.000 description 57
• 239000003480 eluent Substances 0.000 description 56
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 54
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
• 239000000706 filtrate Substances 0.000 description 51
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 46
• 150000002148 esters Chemical class 0.000 description 45
• 239000004480 active ingredient Substances 0.000 description 44
• 239000012074 organic phase Substances 0.000 description 43
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 41
• 229910052938 sodium sulfate Inorganic materials 0.000 description 40
• 235000011152 sodium sulphate Nutrition 0.000 description 40
• 239000012267 brine Substances 0.000 description 39
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 38
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 37
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 37
• 239000002274 desiccant Substances 0.000 description 36
• 238000001914 filtration Methods 0.000 description 36
• 239000012453 solvate Substances 0.000 description 34
• 229940124597 therapeutic agent Drugs 0.000 description 29
• 239000000543 intermediate Substances 0.000 description 27
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 25
• 229920006395 saturated elastomer Polymers 0.000 description 25
• 239000010410 layer Substances 0.000 description 24
• 125000006413 ring segment Chemical group 0.000 description 24
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 22
• 239000000843 powder Substances 0.000 description 22
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 21
• 239000002245 particle Substances 0.000 description 21
• 125000001072 heteroaryl group Chemical group 0.000 description 20
• 125000003003 spiro group Chemical group 0.000 description 20
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 18
• 150000003833 nucleoside derivatives Chemical class 0.000 description 18
• 238000003756 stirring Methods 0.000 description 18
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
• 239000007921 spray Substances 0.000 description 17
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 17
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 15
• 125000002619 bicyclic group Chemical group 0.000 description 15
• 150000001721 carbon Chemical group 0.000 description 15
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 15
• 235000017557 sodium bicarbonate Nutrition 0.000 description 15
• 229910052717 sulfur Inorganic materials 0.000 description 15
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 15
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
• 239000011259 mixed solution Substances 0.000 description 14
• 239000000651 prodrug Substances 0.000 description 14
• 229940002612 prodrug Drugs 0.000 description 14
• 230000002829 reductive effect Effects 0.000 description 14
• ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 13
• 239000000443 aerosol Substances 0.000 description 13
• 125000002837 carbocyclic group Chemical group 0.000 description 13
• 239000000463 material Substances 0.000 description 13
• JAPYIBBSTJFDAK-UHFFFAOYSA-N 2,4,6-tri(propan-2-yl)benzenesulfonyl chloride Chemical compound CC(C)C1=CC(C(C)C)=C(S(Cl)(=O)=O)C(C(C)C)=C1 JAPYIBBSTJFDAK-UHFFFAOYSA-N 0.000 description 12
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 12
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 12
• 235000008504 concentrate Nutrition 0.000 description 12
• 239000012141 concentrate Substances 0.000 description 12
• 230000000694 effects Effects 0.000 description 11
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 10
• 239000003795 chemical substances by application Substances 0.000 description 10
• 229940079593 drug Drugs 0.000 description 10
• 125000004446 heteroarylalkyl group Chemical group 0.000 description 10
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 10
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
• 239000000725 suspension Substances 0.000 description 10
• 239000003826 tablet Substances 0.000 description 10
• 238000005481 NMR spectroscopy Methods 0.000 description 9
• 235000019270 ammonium chloride Nutrition 0.000 description 9
• 238000004440 column chromatography Methods 0.000 description 9
• 241000712464 Orthomyxoviridae Species 0.000 description 8
• 125000002015 acyclic group Chemical group 0.000 description 8
• 125000003710 aryl alkyl group Chemical group 0.000 description 8
• 230000015572 biosynthetic process Effects 0.000 description 8
• 210000004027 cell Anatomy 0.000 description 8
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 8
• 239000007788 liquid Substances 0.000 description 8
• 239000012044 organic layer Substances 0.000 description 8
• SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 8
• 229910000104 sodium hydride Inorganic materials 0.000 description 8
• 229910004298 SiO 2 Inorganic materials 0.000 description 7
• NVQOFWZLYDVFMU-UHFFFAOYSA-N azane;oxolane Chemical class N.C1CCOC1 NVQOFWZLYDVFMU-UHFFFAOYSA-N 0.000 description 7
• 229940125898 compound 5 Drugs 0.000 description 7
• 239000012043 crude product Substances 0.000 description 7
• 239000000796 flavoring agent Substances 0.000 description 7
• 239000004615 ingredient Substances 0.000 description 7
• 238000002347 injection Methods 0.000 description 7
• 239000007924 injection Substances 0.000 description 7
• 239000012071 phase Substances 0.000 description 7
• 125000003367 polycyclic group Chemical group 0.000 description 7
• 125000004076 pyridyl group Chemical group 0.000 description 7
• 239000002904 solvent Substances 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• 238000012360 testing method Methods 0.000 description 7
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
• IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 6
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
• 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 6
• 125000003342 alkenyl group Chemical group 0.000 description 6
• 125000000304 alkynyl group Chemical group 0.000 description 6
• 238000004458 analytical method Methods 0.000 description 6
• 229910052794 bromium Inorganic materials 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• 239000006071 cream Substances 0.000 description 6
• 125000004122 cyclic group Chemical group 0.000 description 6
• 229940112141 dry powder inhaler Drugs 0.000 description 6
• 239000003995 emulsifying agent Substances 0.000 description 6
• 235000013355 food flavoring agent Nutrition 0.000 description 6
• 235000003599 food sweetener Nutrition 0.000 description 6
• 238000004128 high performance liquid chromatography Methods 0.000 description 6
• 150000002431 hydrogen Chemical class 0.000 description 6
• 229910052740 iodine Inorganic materials 0.000 description 6
• 239000002207 metabolite Substances 0.000 description 6
• 125000001624 naphthyl group Chemical group 0.000 description 6
• 239000003921 oil Substances 0.000 description 6
• 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 6
• 125000003107 substituted aryl group Chemical group 0.000 description 6
• 239000003765 sweetening agent Substances 0.000 description 6
• 238000002560 therapeutic procedure Methods 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
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical class N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical group CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 5
• 206010062106 Respiratory tract infection viral Diseases 0.000 description 5
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
• 230000000840 anti-viral effect Effects 0.000 description 5
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• 239000007900 aqueous suspension Substances 0.000 description 5
• 238000003556 assay Methods 0.000 description 5
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 5
• 230000037396 body weight Effects 0.000 description 5
• 238000004113 cell culture Methods 0.000 description 5
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• 125000000753 cycloalkyl group Chemical group 0.000 description 5
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• 239000003862 glucocorticoid Substances 0.000 description 5
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• 125000005017 substituted alkenyl group Chemical group 0.000 description 5
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• 125000004426 substituted alkynyl group Chemical group 0.000 description 5
• 239000000375 suspending agent Substances 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
• UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 4
• OBOHMJWDFPBPKD-UHFFFAOYSA-N 1-[chloro(diphenyl)methyl]-4-methoxybenzene Chemical compound C1=CC(OC)=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 OBOHMJWDFPBPKD-UHFFFAOYSA-N 0.000 description 4
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 4
• QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 4
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