WO2021104470A1 - Anti-hbv 1,7-naphthyridine compound - Google Patents
Anti-hbv 1,7-naphthyridine compound Download PDFInfo
- Publication number
- WO2021104470A1 WO2021104470A1 PCT/CN2020/132344 CN2020132344W WO2021104470A1 WO 2021104470 A1 WO2021104470 A1 WO 2021104470A1 CN 2020132344 W CN2020132344 W CN 2020132344W WO 2021104470 A1 WO2021104470 A1 WO 2021104470A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- compound
- pharmaceutically acceptable
- acceptable salt
- group
- alkyl
- Prior art date
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- -1 1,7-naphthyridine compound Chemical class 0.000 title abstract description 34
- 150000001875 compounds Chemical class 0.000 claims abstract description 97
- 150000003839 salts Chemical class 0.000 claims abstract description 43
- 229910052731 fluorine Inorganic materials 0.000 claims description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims description 29
- 125000000217 alkyl group Chemical group 0.000 claims description 27
- 238000002360 preparation method Methods 0.000 claims description 26
- 229910052794 bromium Inorganic materials 0.000 claims description 25
- 229910052801 chlorine Inorganic materials 0.000 claims description 25
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 24
- 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 claims description 22
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 21
- 239000003814 drug Substances 0.000 claims description 20
- 229910052740 iodine Inorganic materials 0.000 claims description 19
- 241000700721 Hepatitis B virus Species 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- 125000004429 atom Chemical group 0.000 claims description 15
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 14
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 230000000694 effects Effects 0.000 claims description 9
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 108091036055 CccDNA Proteins 0.000 claims 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 32
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- 239000012071 phase Substances 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 239000000460 chlorine Substances 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
- 125000001424 substituent group Chemical group 0.000 description 17
- 238000005481 NMR spectroscopy Methods 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 15
- 229940079593 drug Drugs 0.000 description 15
- 238000000034 method Methods 0.000 description 15
- 239000002253 acid Substances 0.000 description 14
- 239000000203 mixture Substances 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 235000019439 ethyl acetate Nutrition 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- 208000002672 hepatitis B Diseases 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 229940125904 compound 1 Drugs 0.000 description 8
- 238000000605 extraction Methods 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 238000010828 elution Methods 0.000 description 7
- 125000000524 functional group Chemical group 0.000 description 7
- 0 C*C1C=*CC1 Chemical compound C*C1C=*CC1 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 125000004404 heteroalkyl group Chemical group 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 5
- 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
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 5
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- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
- 235000019253 formic acid Nutrition 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 125000005647 linker group Chemical group 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 238000004020 luminiscence type Methods 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000011002 quantification Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- CFJJZVMYMPQIRD-UHFFFAOYSA-N 3-bromoquinolin-7-ol Chemical group C1=C(Br)C=NC2=CC(O)=CC=C21 CFJJZVMYMPQIRD-UHFFFAOYSA-N 0.000 description 3
- YLDFTMJPQJXGSS-UHFFFAOYSA-N 6-bromo-2-naphthol Chemical compound C1=C(Br)C=CC2=CC(O)=CC=C21 YLDFTMJPQJXGSS-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 102000014150 Interferons Human genes 0.000 description 3
- 108010050904 Interferons Proteins 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
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- 125000003277 amino group Chemical group 0.000 description 3
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
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- 238000012552 review Methods 0.000 description 1
- 210000003752 saphenous vein Anatomy 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229960004556 tenofovir Drugs 0.000 description 1
- VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229960004989 tetracycline hydrochloride Drugs 0.000 description 1
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000002053 thietanyl group Chemical group 0.000 description 1
- 125000005309 thioalkoxy group Chemical group 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 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 1
- 238000005406 washing Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Abstract
Description
化合物Compound | HBeAg EC 50(μM) HBeAg EC 50 (μM) | CC 50(μM) CC 50 (μM) |
化合物1Compound 1 | 0.0120.012 | >10>10 |
化合物2Compound 2 | 0.0620.062 | >10>10 |
化合物3Compound 3 | 0.0020.002 | >10>10 |
化合物5Compound 5 | 0.0120.012 | >10>10 |
化合物7Compound 7 | 1.1591.159 | >10>10 |
Claims (22)
- 式(I’)所示化合物或其药学上可接受的盐,The compound represented by formula (I') or a pharmaceutically acceptable salt thereof,其中,among them,R 1选自H、F和C 1~3烷基,所述任选被1、2或3个R a取代; R 1 is selected H, F, and C 1 ~ 3 alkyl group, the optionally substituted with 1, 2 or 3 R a;R 2选自H、F、Cl、Br和CF 3; R 2 is selected from H, F, Cl, Br and CF 3 ;R 3、R 4、R 5和R 6分别独立地选自H、F、Cl、Br、CN、C 1~6烷基、C 3~6环烷基、C 1~6杂烷基和3~6元杂环烷基,所述C 1~6烷基、C 3~6环烷基、C 1~6杂烷基和3~6元杂环烷基任选被1、2或3个R b取代; R 3 , R 4 , R 5 and R 6 are each independently selected from H, F, Cl, Br, CN, C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 heteroalkyl and 3 ~ 6-membered heterocycloalkyl, the C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 heteroalkyl and 3-6 membered heterocycloalkyl are optionally selected by 1, 2, or 3 R b replaces;L选自-O-、-S-、-SO 2-、-N(R 7)-和-C(R 7) 2-; L is selected from -O-, -S-, -SO 2 -, -N(R 7 )- and -C(R 7 ) 2 -;L 1选自-C(R 7) 2-; L 1 is selected from -C(R 7 ) 2 -;L 2选自-C(R 7) 2-; L 2 is selected from -C(R 7 ) 2 -;R 7分别独立地选自H、F、Cl、Br、I、C 1~6烷基、C 3~6环烷基、C 1~6杂烷基和3~6元杂环烷基,所述C 1~6烷基、C 3~6环烷基、C 1~6杂烷基和3~6元杂环烷基任选被1、2或3个R c取代; R 7 is each independently selected from H, F, Cl, Br, I, C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 heteroalkyl and 3-6 membered heterocycloalkyl, so The C 1-6 alkyl group, C 3-6 cycloalkyl group, C 1-6 heteroalkyl group and 3-6 membered heterocycloalkyl group are optionally substituted with 1, 2 or 3 R c ;T、T 1、T 2、T 3分别独立地选自CR 8和N; T, T 1 , T 2 , and T 3 are independently selected from CR 8 and N;R 8选自H、F、Cl、Br、I、CN、C 1~6烷基、C 3~6环烷基、C 1~6杂烷基和3~6元杂环烷基,所述C 1~6烷基、C 3~6环烷基、C 1~6杂烷基和3~6元杂环烷基任选被1、2或3个R d取代; R 8 is selected from H, F, Cl, Br, I, CN, C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 heteroalkyl and 3-6 membered heterocycloalkyl, said C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 heteroalkyl and 3-6 membered heterocycloalkyl are optionally substituted with 1, 2 or 3 R d ;m选自1、2、3和4;m is selected from 1, 2, 3 and 4;R 9分别独立地选自H、F、Cl、Br、I和C 1~3烷基,所述C 1~3烷基任选被1、2或3个R e取代; R 9 is each independently selected from H, F, Cl, Br, I, and C 1-3 alkyl groups, the C 1-3 alkyl groups are optionally substituted with 1, 2 or 3 R e ;R a、R b、R c、R d和R e分别独立地选自F、Cl、Br、I、OH、CN、NH 2、COOH、CF 3、-CHF 2、-CH 2F、-OCH 3、CH 3、-CH 2CH 3、-CH(CH 3) 2、-NHCH 3、-N(CH 3) 2和环丙基; R a, R b, R c , R d and R e are each independently selected from F, Cl, Br, I, OH, CN, NH 2, COOH, CF 3, -CHF 2, -CH 2 F, -OCH 3 , CH 3 , -CH 2 CH 3 , -CH(CH 3 ) 2 , -NHCH 3 , -N(CH 3 ) 2 and cyclopropyl;所述C 1~6杂烷基和3~6元杂环烷分别独立地包含1、2、3或4个独立地选自O、N、S和NH的原子或杂原子团。 The C 1-6 heteroalkyl group and 3-6 membered heterocycloalkane each independently include 1, 2, 3, or 4 atoms or heteroatom groups independently selected from O, N, S, and NH.
- 根据权利要求1所述的化合物或其药学上可接受的盐,其中,R 1选自H、F和CH 3,所述任选被1、2或3个R a取代。 The compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein, R & lt one selected from H, F and CH 3, said optionally substituted with 1, 2 or 3 R a.
- 根据权利要求2所述的化合物或其药学上可接受的盐,其中,R 1选自H和CH 3。 The compound according to claim 2 or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from H and CH 3 .
- 根据权利要求1所述的化合物或其药学上可接受的盐,其中,R 2选自Cl。 The compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R 2 is selected from Cl.
- 根据权利要求1所述的化合物或其药学上可接受的盐,其中,R 3、R 4、R 5和R 6分别独立地选自H。 The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 3 , R 4 , R 5 and R 6 are each independently selected from H.
- 根据权利要求1所述的化合物或其药学上可接受的盐,其中,R 7选自H、F、Cl、Br、I、-OCH 3、CH 3、-CH 2CH 3、-NHCH 3和环丙基,所述-OCH 3、CH 3、-CH 2CH 3、-NHCH 3和环丙基任选被1、2或3个R c取代。 The compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R 7 is selected from H, F, Cl, Br, I, -OCH 3 , CH 3 , -CH 2 CH 3 , -NHCH 3 and Cyclopropyl, the -OCH 3 , CH 3 , -CH 2 CH 3 , -NHCH 3 and cyclopropyl are optionally substituted with 1, 2 or 3 R c .
- 根据权利要求6所述的化合物或其药学上可接受的盐,其中,R 7选自H、F、Cl、Br、I、CF 3、-CHF 2、-CH 2F、-OCH 3、CH 3、-CH 2CH 3、-CH(CH 3) 2、-NHCH 3、-N(CH 3) 2和环丙基。 The compound or a pharmaceutically acceptable salt thereof according to claim 6, wherein R 7 is selected from H, F, Cl, Br, I, CF 3 , -CHF 2 , -CH 2 F, -OCH 3 , CH 3 , -CH 2 CH 3 , -CH(CH 3 ) 2 , -NHCH 3 , -N(CH 3 ) 2 and cyclopropyl.
- 根据权利要求1或7所述的化合物或其药学上可接受的盐,其中,L选自-O-、-S-、-SO 2-、-NH·-和-CH 2-。 The compound or a pharmaceutically acceptable salt thereof according to claim 1 or 7, wherein L is selected from -O-, -S-, -SO 2 -, -NH·- and -CH 2 -.
- 根据权利要求8所述的化合物或其药学上可接受的盐,其中,L选自-O-。The compound or a pharmaceutically acceptable salt thereof according to claim 8, wherein L is selected from -O-.
- 根据权利要求1或7所述的化合物或其药学上可接受的盐,其中,L 1选自-CH 2-、-CHF-和-CF 2-。 The compound or a pharmaceutically acceptable salt thereof according to claim 1 or 7, wherein L 1 is selected from -CH 2 -, -CHF- and -CF 2 -.
- 根据权利要求1或7所述的化合物或其药学上可接受的盐,其中,L 2选自-CH 2-、-CHF-和-CF 2-。 The compound or a pharmaceutically acceptable salt thereof according to claim 1 or 7, wherein L 2 is selected from -CH 2 -, -CHF- and -CF 2 -.
- 根据权利要求1所述的化合物或其药学上可接受的盐,其中,R 8选自H、F、Cl、Br、I、-OCH 3、CH 3、-CH 2CH 3、-NHCH 3和环丙基,所述-OCH 3、CH 3、-CH 2CH 3、-NHCH 3和环丙基任选被1、2或3个R d取代。 The compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R 8 is selected from H, F, Cl, Br, I, -OCH 3 , CH 3 , -CH 2 CH 3 , -NHCH 3 and Cyclopropyl, the -OCH 3 , CH 3 , -CH 2 CH 3 , -NHCH 3 and cyclopropyl are optionally substituted with 1, 2 or 3 Rd .
- 根据权利要求12所述的化合物或其药学上可接受的盐,其中,R 8选自H。 The compound according to claim 12 or a pharmaceutically acceptable salt thereof, wherein R 8 is selected from H.
- 根据权利要求1所述的化合物或其药学上可接受的盐,其中,R 9分别独立地选自H。 The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 9 is independently selected from H.
- 根据权利要求1~16任意一项所述的化合物或其药学上可接受的盐,其中,化合物选自The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-16, wherein the compound is selected from其中,among them,R 1、R 2、R 3、R 4、R 5、R 6、R 9、T、T 1、T 2、T 3、L 1、L 2和m如权利要求1~16所定义。 R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 9 , T, T 1 , T 2 , T 3 , L 1 , L 2 and m are as defined in claims 1-16.
- 根据根据权利要求1~20任意一项所述的化合物或其药学上可接受的盐在制备治疗乙型肝炎病毒药物中的应用。The use of the compound according to any one of claims 1-20 or a pharmaceutically acceptable salt thereof in the preparation of a medicine for the treatment of hepatitis B virus.
- 根据根据权利要求1~20任意一项所述的化合物或其药学上可接受的盐在制备抑制cccDNA的活性的药物中的应用。The use of the compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 20 in the preparation of a medicine for inhibiting the activity of cccDNA.
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1829709A (en) * | 2003-08-01 | 2006-09-06 | 健亚生物科技公司 | Bicyclic imidazol derivatives against flaviviridae |
US20090264426A1 (en) * | 2005-09-07 | 2009-10-22 | Shunji Sakuraba | Bicyclic aromatic substituted pyridone derivative |
CN103140474A (en) * | 2010-07-02 | 2013-06-05 | 吉里德科学公司 | Napht- 2 -ylacetic acid derivatives to treat aids |
WO2019204614A1 (en) * | 2018-04-19 | 2019-10-24 | Tvardi, Inc. | Stat3 inhibitors |
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GB0326963D0 (en) * | 2003-11-19 | 2003-12-24 | Glaxo Group Ltd | Compounds |
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- 2020-11-27 CN CN202080082572.2A patent/CN114761405A/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1829709A (en) * | 2003-08-01 | 2006-09-06 | 健亚生物科技公司 | Bicyclic imidazol derivatives against flaviviridae |
US20090264426A1 (en) * | 2005-09-07 | 2009-10-22 | Shunji Sakuraba | Bicyclic aromatic substituted pyridone derivative |
CN103140474A (en) * | 2010-07-02 | 2013-06-05 | 吉里德科学公司 | Napht- 2 -ylacetic acid derivatives to treat aids |
WO2019204614A1 (en) * | 2018-04-19 | 2019-10-24 | Tvardi, Inc. | Stat3 inhibitors |
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