KR20140027295A - 벤조티아졸 화합물 및 이들의 약학적 용도 - Google Patents
벤조티아졸 화합물 및 이들의 약학적 용도 Download PDFInfo
- Publication number
- KR20140027295A KR20140027295A KR1020137030857A KR20137030857A KR20140027295A KR 20140027295 A KR20140027295 A KR 20140027295A KR 1020137030857 A KR1020137030857 A KR 1020137030857A KR 20137030857 A KR20137030857 A KR 20137030857A KR 20140027295 A KR20140027295 A KR 20140027295A
- Authority
- KR
- South Korea
- Prior art keywords
- alkyl
- heterocycle
- heteroaryl
- aryl
- carbocycle
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
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- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical class C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 386
- 238000000034 method Methods 0.000 claims abstract description 83
- 150000003839 salts Chemical class 0.000 claims abstract description 73
- 241000124008 Mammalia Species 0.000 claims abstract description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
- 238000004519 manufacturing process Methods 0.000 claims abstract description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 528
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 499
- 125000001072 heteroaryl group Chemical group 0.000 claims description 487
- 125000003118 aryl group Chemical group 0.000 claims description 447
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 233
- -1 (C3-C7Cycloalkyl Chemical group 0.000 claims description 218
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 212
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 137
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 107
- 125000000217 alkyl group Chemical group 0.000 claims description 103
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 84
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 77
- 125000005843 halogen group Chemical group 0.000 claims description 67
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 56
- 239000003112 inhibitor Substances 0.000 claims description 55
- 125000004429 atom Chemical group 0.000 claims description 51
- 239000003814 drug Substances 0.000 claims description 49
- 125000004043 oxo group Chemical group O=* 0.000 claims description 45
- 125000001188 haloalkyl group Chemical group 0.000 claims description 36
- 229910052799 carbon Inorganic materials 0.000 claims description 33
- 229910052736 halogen Inorganic materials 0.000 claims description 32
- 229940124597 therapeutic agent Drugs 0.000 claims description 31
- 150000002367 halogens Chemical class 0.000 claims description 28
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 27
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 21
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 20
- 102100034343 Integrase Human genes 0.000 claims description 18
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 claims description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 17
- 125000000464 thioxo group Chemical group S=* 0.000 claims description 17
- 208000031886 HIV Infections Diseases 0.000 claims description 16
- 208000037357 HIV infectious disease Diseases 0.000 claims description 15
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 15
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 15
- 239000002777 nucleoside Substances 0.000 claims description 15
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 13
- 239000001301 oxygen Substances 0.000 claims description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 125000001054 5 membered carbocyclic group Chemical group 0.000 claims description 10
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 10
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 claims description 10
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 claims description 10
- 125000005217 alkenylheteroaryl group Chemical group 0.000 claims description 9
- 125000005025 alkynylaryl group Chemical group 0.000 claims description 9
- 229940099797 HIV integrase inhibitor Drugs 0.000 claims description 8
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 8
- 229940124784 gp41 inhibitor Drugs 0.000 claims description 8
- 239000003084 hiv integrase inhibitor Substances 0.000 claims description 8
- 239000002773 nucleotide Substances 0.000 claims description 8
- 125000003729 nucleotide group Chemical group 0.000 claims description 8
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 claims description 7
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 claims description 7
- 230000001225 therapeutic effect Effects 0.000 claims description 7
- 229940122440 HIV protease inhibitor Drugs 0.000 claims description 6
- 125000005024 alkenyl aryl group Chemical group 0.000 claims description 6
- 210000000234 capsid Anatomy 0.000 claims description 6
- 239000004030 hiv protease inhibitor Substances 0.000 claims description 6
- 238000006116 polymerization reaction Methods 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 238000002651 drug therapy Methods 0.000 claims description 3
- 235000012054 meals Nutrition 0.000 claims description 3
- 230000000069 prophylactic effect Effects 0.000 claims description 3
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims 8
- 229910052709 silver Inorganic materials 0.000 claims 8
- 239000004332 silver Substances 0.000 claims 8
- 229910003827 NRaRb Inorganic materials 0.000 claims 7
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 2
- AFCIMSXHQSIHQW-UHFFFAOYSA-N [O].[P] Chemical compound [O].[P] AFCIMSXHQSIHQW-UHFFFAOYSA-N 0.000 claims 1
- 241000725303 Human immunodeficiency virus Species 0.000 abstract description 36
- 208000030507 AIDS Diseases 0.000 abstract description 12
- 208000024891 symptom Diseases 0.000 abstract description 6
- 230000005727 virus proliferation Effects 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 216
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 149
- 238000002360 preparation method Methods 0.000 description 117
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 109
- 239000000243 solution Substances 0.000 description 101
- 235000019439 ethyl acetate Nutrition 0.000 description 97
- 239000000203 mixture Substances 0.000 description 85
- 238000005160 1H NMR spectroscopy Methods 0.000 description 77
- 239000011541 reaction mixture Substances 0.000 description 76
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 50
- 235000011054 acetic acid Nutrition 0.000 description 49
- 238000006243 chemical reaction Methods 0.000 description 49
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- 239000004480 active ingredient Substances 0.000 description 42
- 239000000741 silica gel Substances 0.000 description 38
- 229910002027 silica gel Inorganic materials 0.000 description 38
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 35
- 238000009472 formulation Methods 0.000 description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- 239000012044 organic layer Substances 0.000 description 30
- 229920006395 saturated elastomer Polymers 0.000 description 29
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 239000010410 layer Substances 0.000 description 25
- 239000000651 prodrug Substances 0.000 description 23
- 229940002612 prodrug Drugs 0.000 description 23
- 125000004432 carbon atom Chemical group C* 0.000 description 21
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 20
- ZYZCALPXKGUGJI-DDVDASKDSA-M (e,3r,5s)-7-[3-(4-fluorophenyl)-2-phenyl-5-propan-2-ylimidazol-4-yl]-3,5-dihydroxyhept-6-enoate Chemical compound C=1C=C(F)C=CC=1N1C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C(C(C)C)N=C1C1=CC=CC=C1 ZYZCALPXKGUGJI-DDVDASKDSA-M 0.000 description 18
- NPRYCHLHHVWLQZ-TURQNECASA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynylpurin-8-one Chemical compound NC1=NC=C2N(C(N(C2=N1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C NPRYCHLHHVWLQZ-TURQNECASA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 239000012074 organic phase Substances 0.000 description 17
- 125000006239 protecting group Chemical group 0.000 description 17
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 16
- 230000008569 process Effects 0.000 description 16
- 230000015572 biosynthetic process Effects 0.000 description 15
- HHEIMYAXCOIQCJ-UHFFFAOYSA-N ethyl 2,2-dimethylpropanoate Chemical class CCOC(=O)C(C)(C)C HHEIMYAXCOIQCJ-UHFFFAOYSA-N 0.000 description 15
- 239000011734 sodium Substances 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- 125000001424 substituent group Chemical group 0.000 description 15
- 238000003786 synthesis reaction Methods 0.000 description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 14
- 238000005481 NMR spectroscopy Methods 0.000 description 13
- 239000002253 acid Substances 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 11
- 125000002619 bicyclic group Chemical group 0.000 description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 11
- 239000000543 intermediate Substances 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 239000000546 pharmaceutical excipient Substances 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- OGZMTYGAYGHOEL-UHFFFAOYSA-N 2-bromo-7-(4-chlorophenyl)-6-methoxy-5-methyl-1,3-benzothiazole Chemical compound COC1=C(C)C=C2N=C(Br)SC2=C1C1=CC=C(Cl)C=C1 OGZMTYGAYGHOEL-UHFFFAOYSA-N 0.000 description 10
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- XTEOJPUYZWEXFI-UHFFFAOYSA-N butyl n-[3-[4-(imidazol-1-ylmethyl)phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate Chemical compound S1C(CC(C)C)=CC(C=2C=CC(CN3C=NC=C3)=CC=2)=C1S(=O)(=O)NC(=O)OCCCC XTEOJPUYZWEXFI-UHFFFAOYSA-N 0.000 description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 239000003826 tablet Substances 0.000 description 10
- 125000004452 carbocyclyl group Chemical group 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- LVCDPPSDHDLHRT-UHFFFAOYSA-N 6-methoxy-5-methyl-1,3-benzothiazol-2-amine Chemical compound C1=C(C)C(OC)=CC2=C1N=C(N)S2 LVCDPPSDHDLHRT-UHFFFAOYSA-N 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
- 239000013058 crude material Substances 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 125000000524 functional group Chemical group 0.000 description 8
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- 238000000746 purification Methods 0.000 description 8
- 229910052717 sulfur Chemical group 0.000 description 8
- 239000011593 sulfur Chemical group 0.000 description 8
- KJQUCTYWDHDJTQ-NRFANRHFSA-N (2s)-2-[7-(4-chlorophenyl)-5-methyl-2-(2-methylpropyl)-1,3-benzothiazol-6-yl]-2-[(2-methylpropan-2-yl)oxy]acetic acid Chemical compound C=12SC(CC(C)C)=NC2=CC(C)=C([C@H](OC(C)(C)C)C(O)=O)C=1C1=CC=C(Cl)C=C1 KJQUCTYWDHDJTQ-NRFANRHFSA-N 0.000 description 7
- WGFNXGPBPIJYLI-UHFFFAOYSA-N 2,6-difluoro-3-[(3-fluorophenyl)sulfonylamino]-n-(3-methoxy-1h-pyrazolo[3,4-b]pyridin-5-yl)benzamide Chemical compound C1=C2C(OC)=NNC2=NC=C1NC(=O)C(C=1F)=C(F)C=CC=1NS(=O)(=O)C1=CC=CC(F)=C1 WGFNXGPBPIJYLI-UHFFFAOYSA-N 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 7
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- 108010078851 HIV Reverse Transcriptase Proteins 0.000 description 7
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 description 7
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- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 7
- FNHHVPPSBFQMEL-KQHDFZBMSA-N (3S)-5-N-[(1S,5R)-3-hydroxy-6-bicyclo[3.1.0]hexanyl]-7-N,3-dimethyl-3-phenyl-2H-1-benzofuran-5,7-dicarboxamide Chemical compound CNC(=O)c1cc(cc2c1OC[C@@]2(C)c1ccccc1)C(=O)NC1[C@H]2CC(O)C[C@@H]12 FNHHVPPSBFQMEL-KQHDFZBMSA-N 0.000 description 6
- OOMDSUKMWJEZCE-UHFFFAOYSA-N 2-bromo-6-methoxy-5-methyl-1,3-benzothiazole Chemical compound C1=C(C)C(OC)=CC2=C1N=C(Br)S2 OOMDSUKMWJEZCE-UHFFFAOYSA-N 0.000 description 6
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 6
- 101150003085 Pdcl gene Proteins 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- HXVHCXAXDHRKFN-GFCCVEGCSA-N [(2s)-2-(7-bromo-2-chloro-5-methyl-1,3-benzothiazol-6-yl)-2-[(2-methylpropan-2-yl)oxy]ethyl] 2,2-dimethylpropanoate Chemical compound BrC1=C([C@@H](COC(=O)C(C)(C)C)OC(C)(C)C)C(C)=CC2=C1SC(Cl)=N2 HXVHCXAXDHRKFN-GFCCVEGCSA-N 0.000 description 6
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- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 description 6
- 239000003995 emulsifying agent Substances 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 125000001475 halogen functional group Chemical group 0.000 description 6
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 6
- 239000003765 sweetening agent Substances 0.000 description 6
- QUXZVSWSEYFARM-MRXNPFEDSA-N (2s)-2-[7-(4-chlorophenyl)-5-methyl-1,3-benzothiazol-6-yl]-2-[(2-methylpropan-2-yl)oxy]ethanol Chemical compound CC(C)(C)O[C@H](CO)C=1C(C)=CC=2N=CSC=2C=1C1=CC=C(Cl)C=C1 QUXZVSWSEYFARM-MRXNPFEDSA-N 0.000 description 5
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 5
- WONQAVVTOHKECK-UHFFFAOYSA-N 5-methyl-1,3-benzothiazol-6-ol Chemical compound C1=C(O)C(C)=CC2=C1SC=N2 WONQAVVTOHKECK-UHFFFAOYSA-N 0.000 description 5
- FJILDPNBUQDPHB-UHFFFAOYSA-N 7-(4-chlorophenyl)-5-methyl-2-(2-methylprop-1-enyl)-1,3-benzothiazol-6-ol Chemical compound C=12SC(C=C(C)C)=NC2=CC(C)=C(O)C=1C1=CC=C(Cl)C=C1 FJILDPNBUQDPHB-UHFFFAOYSA-N 0.000 description 5
- VVQDIDRPTZTAAM-UHFFFAOYSA-N 7-(4-chlorophenyl)-6-ethenyl-5-methyl-1,3-benzothiazole Chemical compound C=CC=1C(C)=CC=2N=CSC=2C=1C1=CC=C(Cl)C=C1 VVQDIDRPTZTAAM-UHFFFAOYSA-N 0.000 description 5
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- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 5
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- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
- CUFQBQOBLVLKRF-RZDMPUFOSA-N (4r)-3-[(2s,3s)-2-hydroxy-3-[(3-hydroxy-2-methylbenzoyl)amino]-4-phenylbutanoyl]-5,5-dimethyl-n-[(2-methylphenyl)methyl]-1,3-thiazolidine-4-carboxamide Chemical compound CC1=CC=CC=C1CNC(=O)[C@@H]1C(C)(C)SCN1C(=O)[C@@H](O)[C@@H](NC(=O)C=1C(=C(O)C=CC=1)C)CC1=CC=CC=C1 CUFQBQOBLVLKRF-RZDMPUFOSA-N 0.000 description 4
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/06—Peri-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4741—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having oxygen as a ring hetero atom, e.g. tubocuraran derivatives, noscapine, bicuculline
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
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- C07D277/62—Benzothiazoles
- C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
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- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D277/82—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/08—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing alicyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/052—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
Landscapes
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- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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| PCT/US2012/034593 WO2012145728A1 (en) | 2011-04-21 | 2012-04-20 | Benzothiazole compounds and their pharmaceutical use |
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| MA34397B1 (fr) | 2010-07-02 | 2013-07-03 | Gilead Sciences Inc | Dérivés d'acide napht-2-ylacétique dans le traitement du sida |
| WO2012003498A1 (en) | 2010-07-02 | 2012-01-05 | Gilead Sciences, Inc. | 2 -quinolinyl- acetic acid derivatives as hiv antiviral compounds |
| WO2012145728A1 (en) | 2011-04-21 | 2012-10-26 | Gilead Sciences, Inc. | Benzothiazole compounds and their pharmaceutical use |
| PT2729448E (pt) | 2011-07-06 | 2015-12-02 | Gilead Sciences Inc | Compostos para o tratamento de vih |
| WO2013103724A1 (en) | 2012-01-04 | 2013-07-11 | Gilead Sciences, Inc. | 2- (tert - butoxy) -2- (7 -methylquinolin- 6 - yl) acetic acid derivatives for treating aids |
| WO2013103738A1 (en) | 2012-01-04 | 2013-07-11 | Gilead Sciences, Inc. | Napthalene acetic acid derivatives against hiv infection |
| CN103204827B (zh) | 2012-01-17 | 2014-12-03 | 上海科州药物研发有限公司 | 作为蛋白激酶抑制剂的苯并噻二唑化合物及其制备方法和用途 |
| EP3070081B1 (en) | 2012-04-20 | 2018-02-28 | Gilead Sciences, Inc. | Benzothiazol-6-yl acetic acid derivatives and their use for treating an hiv infection |
| DK3067358T3 (da) | 2012-12-21 | 2019-11-04 | Gilead Sciences Inc | Polycykliske carbamoylpyridon-forbindelser og deres farmaceutiske anvendelse |
| TW201443037A (zh) | 2013-01-09 | 2014-11-16 | Gilead Sciences Inc | 治療用化合物 |
| JP5941598B2 (ja) | 2013-01-09 | 2016-06-29 | ギリアード サイエンシーズ, インコーポレイテッド | 5員ヘテロアリールおよびそれらの抗ウイルス剤としての使用 |
| NZ727792A (en) | 2013-01-09 | 2018-04-27 | Gilead Sciences Inc | Therapeutic compounds |
| TW201441197A (zh) * | 2013-01-31 | 2014-11-01 | Shionogi & Co | Hiv複製抑制劑 |
| TWI694071B (zh) | 2013-03-01 | 2020-05-21 | 美商基利科學股份有限公司 | 治療反轉錄病毒科(Retroviridae)病毒感染之治療性化合物 |
| EP2821082A1 (en) | 2013-07-05 | 2015-01-07 | Laboratoire Biodim | Method of producing an inactivated lentivirus, especially HIV, vaccine, kit and method of use |
| EP2821104A1 (en) | 2013-07-05 | 2015-01-07 | Laboratoire Biodim | Inhibitors of viral replication, their process of preparation and their therapeutical uses |
| PL3019503T3 (pl) | 2013-07-12 | 2018-01-31 | Gilead Sciences Inc | Policykliczne związki karbamoilopirydonowe i ich zastosowanie do leczenia infekcji hiv |
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| US9944656B2 (en) | 2014-02-12 | 2018-04-17 | VIIV Healthcare UK (No.5) Limited | Benzothiazole macrocycles as inhibitors of human immunodeficiency virus replication |
| US10202353B2 (en) | 2014-02-28 | 2019-02-12 | Gilead Sciences, Inc. | Therapeutic compounds |
| JP6579549B2 (ja) | 2014-05-16 | 2019-09-25 | 塩野義製薬株式会社 | Hiv複製阻害作用を有する3環性複素環誘導体 |
| TW201613936A (en) | 2014-06-20 | 2016-04-16 | Gilead Sciences Inc | Crystalline forms of(2R,5S,13aR)-8-hydroxy-7,9-dioxo-n-(2,4,6-trifluorobenzyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazepine-10-carboxamide |
| NO2717902T3 (enExample) | 2014-06-20 | 2018-06-23 | ||
| EA201790024A1 (ru) | 2014-07-11 | 2017-07-31 | Джилид Сайэнс, Инк. | Модуляторы toll-подобных рецепторов для лечения вич |
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