CA2862823C - Piperidino-pyrimidine derivatives for the treatment of viral infections. - Google Patents
Piperidino-pyrimidine derivatives for the treatment of viral infections. Download PDFInfo
- Publication number
- CA2862823C CA2862823C CA2862823A CA2862823A CA2862823C CA 2862823 C CA2862823 C CA 2862823C CA 2862823 A CA2862823 A CA 2862823A CA 2862823 A CA2862823 A CA 2862823A CA 2862823 C CA2862823 C CA 2862823C
- Authority
- CA
- Canada
- Prior art keywords
- compound
- formula
- nmr
- pharmaceutically acceptable
- tlr8
- 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.)
- Active
Links
- 208000036142 Viral infection Diseases 0.000 title abstract description 5
- 230000009385 viral infection Effects 0.000 title abstract description 4
- IAGROJPXACRRDT-UHFFFAOYSA-N 2-piperidin-1-ylpyrimidine Chemical class C1CCCCN1C1=NC=CC=N1 IAGROJPXACRRDT-UHFFFAOYSA-N 0.000 title description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
- 150000001875 compounds Chemical class 0.000 claims description 67
- 125000003118 aryl group Chemical group 0.000 claims description 26
- 239000000203 mixture Substances 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 22
- 102100033110 Toll-like receptor 8 Human genes 0.000 claims description 15
- 102100039390 Toll-like receptor 7 Human genes 0.000 claims description 14
- 125000001072 heteroaryl group Chemical group 0.000 claims description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 150000002825 nitriles Chemical class 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 8
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 8
- 101000582254 Homo sapiens Nuclear receptor corepressor 2 Proteins 0.000 claims description 7
- 102100030569 Nuclear receptor corepressor 2 Human genes 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 239000000969 carrier Substances 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000001424 substituent 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 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 125000006413 ring segment Chemical group 0.000 claims description 3
- 108010060825 Toll-Like Receptor 7 Proteins 0.000 claims 10
- 108010060752 Toll-Like Receptor 8 Proteins 0.000 claims 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 21
- 238000000034 method Methods 0.000 abstract description 7
- 230000008569 process Effects 0.000 abstract description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 58
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 54
- 238000005160 1H NMR spectroscopy Methods 0.000 description 38
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- 238000005481 NMR spectroscopy Methods 0.000 description 29
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 239000002904 solvent Substances 0.000 description 21
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 102000002689 Toll-like receptor Human genes 0.000 description 17
- 108020000411 Toll-like receptor Proteins 0.000 description 17
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 101000800483 Homo sapiens Toll-like receptor 8 Proteins 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 13
- 101000669402 Homo sapiens Toll-like receptor 7 Proteins 0.000 description 13
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 10
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- 102000045715 human TLR7 Human genes 0.000 description 9
- 102000045720 human TLR8 Human genes 0.000 description 9
- 125000000217 alkyl group Chemical group 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 239000012453 solvate Substances 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
- STIAPHVBRDNOAJ-UHFFFAOYSA-N carbamimidoylazanium;carbonate Chemical compound NC(N)=N.NC(N)=N.OC(O)=O STIAPHVBRDNOAJ-UHFFFAOYSA-N 0.000 description 7
- 239000002552 dosage form Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 238000010898 silica gel chromatography Methods 0.000 description 7
- 125000003545 alkoxy group Chemical group 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 241000282412 Homo Species 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- 125000003710 aryl alkyl group Chemical group 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 150000001733 carboxylic acid esters Chemical class 0.000 description 5
- GDTRAYDPXKZJGD-UHFFFAOYSA-N dichlorophosphoryl hypochlorite Chemical compound ClOP(Cl)(Cl)=O GDTRAYDPXKZJGD-UHFFFAOYSA-N 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
- -1 al koxy-(C1_4)al kyl Chemical group 0.000 description 4
- 125000003342 alkenyl group Chemical group 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- 101100097467 Arabidopsis thaliana SYD gene Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 101100495925 Schizosaccharomyces pombe (strain 972 / ATCC 24843) chr3 gene Proteins 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 125000000304 alkynyl group Chemical group 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 239000007822 coupling agent Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 238000004811 liquid chromatography Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 241000894007 species Species 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 2
- 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 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 150000002431 hydrogen Chemical group 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- ILAOVOOZLVGAJF-UHFFFAOYSA-N 1-methylpyrrole-2-carboxylic acid Chemical compound CN1C=CC=C1C(O)=O ILAOVOOZLVGAJF-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical class NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 101100439662 Arabidopsis thaliana CHR5 gene Chemical group 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 101000763579 Homo sapiens Toll-like receptor 1 Proteins 0.000 description 1
- 101000763537 Homo sapiens Toll-like receptor 10 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 108010006444 Leucine-Rich Repeat Proteins Proteins 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 101100481581 Mus musculus Tlr13 gene Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 241001441723 Takifugu Species 0.000 description 1
- 102100027010 Toll-like receptor 1 Human genes 0.000 description 1
- 102100027009 Toll-like receptor 10 Human genes 0.000 description 1
- ABRVLXLNVJHDRQ-UHFFFAOYSA-N [2-pyridin-3-yl-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound FC(C1=CC(=CC(=N1)C=1C=NC=CC=1)CN)(F)F ABRVLXLNVJHDRQ-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000008484 agonism Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- JFWMYCVMQSLLOO-UHFFFAOYSA-N cyclobutanecarbonyl chloride Chemical compound ClC(=O)C1CCC1 JFWMYCVMQSLLOO-UHFFFAOYSA-N 0.000 description 1
- ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 210000004901 leucine-rich repeat Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- DAZSWUUAFHBCGE-KRWDZBQOSA-N n-[(2s)-3-methyl-1-oxo-1-pyrrolidin-1-ylbutan-2-yl]-3-phenylpropanamide Chemical compound N([C@@H](C(C)C)C(=O)N1CCCC1)C(=O)CCC1=CC=CC=C1 DAZSWUUAFHBCGE-KRWDZBQOSA-N 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 229940083251 peripheral vasodilators purine derivative Drugs 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 125000000561 purinyl group Chemical class N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000005494 pyridonyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical group OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000004544 spot-on Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000012899 standard injection Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12154474 | 2012-02-08 | ||
| EP12154474.6 | 2012-02-08 | ||
| PCT/EP2013/052372 WO2013117615A1 (en) | 2012-02-08 | 2013-02-07 | Piperidino-pyrimidine derivatives for the treatment of viral infections |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2862823A1 CA2862823A1 (en) | 2013-08-15 |
| CA2862823C true CA2862823C (en) | 2020-09-22 |
Family
ID=47678822
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2862823A Active CA2862823C (en) | 2012-02-08 | 2013-02-07 | Piperidino-pyrimidine derivatives for the treatment of viral infections. |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US9133192B2 (enExample) |
| EP (1) | EP2812331B1 (enExample) |
| JP (1) | JP6283320B2 (enExample) |
| KR (1) | KR102064807B1 (enExample) |
| CN (1) | CN104245695B (enExample) |
| AU (1) | AU2013218072B2 (enExample) |
| BR (1) | BR112014019699B1 (enExample) |
| CA (1) | CA2862823C (enExample) |
| CL (1) | CL2014002093A1 (enExample) |
| DK (1) | DK2812331T3 (enExample) |
| EA (2) | EA039373B1 (enExample) |
| ES (1) | ES2716811T3 (enExample) |
| IL (1) | IL233499B (enExample) |
| IN (1) | IN2014MN01736A (enExample) |
| MX (1) | MX357296B (enExample) |
| MY (1) | MY169159A (enExample) |
| NZ (1) | NZ627036A (enExample) |
| PH (1) | PH12014501738B1 (enExample) |
| SG (1) | SG11201404743TA (enExample) |
| UA (1) | UA112668C2 (enExample) |
| WO (1) | WO2013117615A1 (enExample) |
| ZA (1) | ZA201405820B (enExample) |
Families Citing this family (165)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RS62254B1 (sr) | 2011-04-08 | 2021-09-30 | Janssen Sciences Ireland Unlimited Co | Derivati pirimidina za tretman virusnih infekcija |
| SG11201401244TA (en) | 2011-11-09 | 2014-09-26 | Janssen R & D Ireland | Purine derivatives for the treatment of viral infections |
| SG11201404743TA (en) | 2012-02-08 | 2014-09-26 | Janssen R & D Ireland | Piperidino-pyrimidine derivatives for the treatment of viral infections |
| HUE030685T2 (en) | 2012-07-13 | 2017-05-29 | Janssen Sciences Ireland Uc | Macrocyclic purines for treating viral infections |
| WO2014056953A1 (en) | 2012-10-10 | 2014-04-17 | Janssen R&D Ireland | Pyrrolo[3,2-d]pyrimidine derivatives for the treatment of viral infections and other diseases |
| MY171115A (en) | 2012-11-16 | 2019-09-26 | Janssen Sciences Ireland Uc | Heterocyclic substituted 2-amino-quinazoline derivatives for the treatment of viral infections |
| UA118751C2 (uk) | 2013-02-21 | 2019-03-11 | ЯНССЕН САЙЄНСІЗ АЙРЛЕНД ЮСі | Похідні 2-амінопіримідину для лікування вірусних інфекцій |
| AU2014242954B2 (en) | 2013-03-29 | 2018-03-15 | Janssen Sciences Ireland Uc | Macrocyclic deaza-purinones for the treatment of viral infections |
| MX365848B (es) | 2013-05-24 | 2019-06-17 | Janssen Sciences Ireland Uc | Derivados de piridona para el tratamiento de infecciones virales y enfermedades adicionales. |
| AU2014301089B2 (en) | 2013-06-27 | 2018-10-04 | Janssen Sciences Ireland Uc | Pyrrolo[3,2-d]pyrimidine derivatives for the treatment of viral infections and other diseases |
| AU2014298540B2 (en) | 2013-07-30 | 2018-08-09 | Janssen Sciences Ireland Uc | Thieno[3,2-d]pyrimidines derivatives for the treatment of viral infections |
| AU2016216673B2 (en) | 2015-03-04 | 2017-02-02 | Gilead Sciences, Inc. | Toll like receptor modulator compounds |
| JP2018525412A (ja) | 2015-08-26 | 2018-09-06 | ギリアード サイエンシーズ, インコーポレイテッド | 重水素化トール様受容体調節因子 |
| EP3349757A1 (en) | 2015-09-15 | 2018-07-25 | Gilead Sciences, Inc. | Modulators of toll-like recptors for the treatment of hiv |
| TWI814056B (zh) | 2015-12-15 | 2023-09-01 | 美商基利科學股份有限公司 | 人類免疫不全病毒中和抗體 |
| BR102017010009A2 (pt) | 2016-05-27 | 2017-12-12 | Gilead Sciences, Inc. | Compounds for the treatment of hepatitis b virus infection |
| SG11201809893WA (en) | 2016-05-27 | 2018-12-28 | Gilead Sciences Inc | Methods for treating hepatitis b virus infections using ns5a, ns5b or ns3 inhibitors |
| MA45539A (fr) | 2016-07-01 | 2019-05-08 | Janssen Sciences Ireland Unlimited Co | Dihydropyranopyrimidines pour le traitement d'infections virales |
| JOP20190024A1 (ar) | 2016-08-26 | 2019-02-19 | Gilead Sciences Inc | مركبات بيروليزين بها استبدال واستخداماتها |
| EP3507288B1 (en) | 2016-09-02 | 2020-08-26 | Gilead Sciences, Inc. | 4,6-diamino-pyrido[3,2-d]pyrimidine derivaties as toll like receptor modulators |
| AU2017318601B2 (en) | 2016-09-02 | 2020-09-03 | Gilead Sciences, Inc. | Toll like receptor modulator compounds |
| ES2905981T3 (es) * | 2016-09-09 | 2022-04-12 | Novartis Ag | Compuestos y composiciones como inhibidores de los receptores de tipo Toll endosomales |
| WO2018060317A1 (en) | 2016-09-29 | 2018-04-05 | Janssen Sciences Ireland Uc | Pyrimidine prodrugs for the treatment of viral infections and further diseases |
| US10662416B2 (en) | 2016-10-14 | 2020-05-26 | Precision Biosciences, Inc. | Engineered meganucleases specific for recognition sequences in the hepatitis B virus genome |
| TWI820984B (zh) | 2017-01-31 | 2023-11-01 | 美商基利科學股份有限公司 | 替諾福韋埃拉酚胺(tenofovir alafenamide)之晶型 |
| JOP20180008A1 (ar) | 2017-02-02 | 2019-01-30 | Gilead Sciences Inc | مركبات لعلاج إصابة بعدوى فيروس الالتهاب الكبدي b |
| JOP20180040A1 (ar) | 2017-04-20 | 2019-01-30 | Gilead Sciences Inc | مثبطات pd-1/pd-l1 |
| AR112412A1 (es) | 2017-08-17 | 2019-10-23 | Gilead Sciences Inc | Formas de sal de colina de un inhibidor de la cápside del vih |
| AR112413A1 (es) | 2017-08-17 | 2019-10-23 | Gilead Sciences Inc | Formas sólidas de un inhibidor de la cápside del vih |
| JP6934562B2 (ja) | 2017-08-22 | 2021-09-15 | ギリアード サイエンシーズ, インコーポレイテッド | 治療用複素環式化合物 |
| TW201915000A (zh) * | 2017-09-22 | 2019-04-16 | 大陸商江蘇恆瑞醫藥股份有限公司 | 稠合雜芳基衍生物、其製備方法及其在醫藥上的應用 |
| WO2019084060A1 (en) | 2017-10-24 | 2019-05-02 | Silverback Therapeutics, Inc. | CONJUGATES AND METHODS OF USE FOR THE SELECTIVE DELIVERY OF IMMUNOMODULATORY AGENTS |
| WO2019118884A1 (en) | 2017-12-15 | 2019-06-20 | Silverback Therapeutics, Inc. | Antibody construct-drug conjugate for the treatment of hepatitis |
| CN111511754B (zh) | 2017-12-20 | 2023-09-12 | 捷克共和国有机化学与生物化学研究所 | 活化sting转接蛋白的具有膦酸酯键的2’3’环状二核苷酸 |
| KR102492187B1 (ko) | 2017-12-20 | 2023-01-27 | 인스티튜트 오브 오가닉 케미스트리 앤드 바이오케미스트리 에이에스 씨알 브이.브이.아이. | Sting 어댑터 단백질을 활성화하는 포스포네이트 결합을 가진 3'3' 사이클릭 다이뉴클레오티드 |
| TWI796596B (zh) | 2018-02-13 | 2023-03-21 | 美商基利科學股份有限公司 | Pd‐1/pd‐l1抑制劑 |
| PL3752495T3 (pl) | 2018-02-15 | 2024-01-15 | Gilead Sciences, Inc. | Pochodne pirydynowe i ich zastosowanie do leczenia infekcji hiv |
| KR102587504B1 (ko) | 2018-02-16 | 2023-10-11 | 길리애드 사이언시즈, 인코포레이티드 | 레트로비리다에 바이러스 감염의 치료에 유용한 치료 화합물을 제조하기 위한 방법 및 중간체 |
| KR102526964B1 (ko) | 2018-02-26 | 2023-04-28 | 길리애드 사이언시즈, 인코포레이티드 | Hbv 복제 억제제로서의 치환된 피롤리진 화합물 |
| TWI772370B (zh) * | 2018-02-26 | 2022-08-01 | 瑞士商諾華公司 | 作為胞內體類鐸(toll-like)受體抑制劑之化合物及組合物 |
| TW202415645A (zh) | 2018-03-01 | 2024-04-16 | 愛爾蘭商健生科學愛爾蘭無限公司 | 2,4-二胺基喹唑啉衍生物及其醫學用途 |
| EP3774883A1 (en) | 2018-04-05 | 2021-02-17 | Gilead Sciences, Inc. | Antibodies and fragments thereof that bind hepatitis b virus protein x |
| TWI833744B (zh) | 2018-04-06 | 2024-03-01 | 捷克科學院有機化學與生物化學研究所 | 3'3'-環二核苷酸 |
| TW202005654A (zh) | 2018-04-06 | 2020-02-01 | 捷克科學院有機化學與生物化學研究所 | 2,2,─環二核苷酸 |
| TWI818007B (zh) | 2018-04-06 | 2023-10-11 | 捷克科學院有機化學與生物化學研究所 | 2'3'-環二核苷酸 |
| TW201945388A (zh) | 2018-04-12 | 2019-12-01 | 美商精密生物科學公司 | 對b型肝炎病毒基因體中之識別序列具有特異性之最佳化之經工程化巨核酸酶 |
| KR102591947B1 (ko) | 2018-04-19 | 2023-10-25 | 길리애드 사이언시즈, 인코포레이티드 | Pd-1/pd-l1 억제제 |
| US20190359645A1 (en) | 2018-05-03 | 2019-11-28 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 2'3'-cyclic dinucleotides comprising carbocyclic nucleotide |
| US12084460B2 (en) | 2018-05-18 | 2024-09-10 | Novartis Ag | Crystalline forms of a TLR7/TLR8 inhibitor |
| WO2020010107A1 (en) | 2018-07-03 | 2020-01-09 | Gilead Sciences, Inc. | Antibodies that target hiv gp120 and methods of use |
| CN112384283B (zh) | 2018-07-06 | 2023-08-15 | 吉利德科学公司 | 治疗性的杂环化合物 |
| CA3103987C (en) | 2018-07-06 | 2023-08-01 | Gilead Sciences, Inc. | Therapeutic heterocyclic compounds |
| MX2021000100A (es) | 2018-07-13 | 2021-03-25 | Gilead Sciences Inc | Inhibidores de muerte programada-1 (pd-1)/ ligando de muerte programada 1 (pd-l1). |
| KR20230141905A (ko) | 2018-07-16 | 2023-10-10 | 길리애드 사이언시즈, 인코포레이티드 | Hiv의 치료를 위한 캡시드 억제제 |
| WO2020028097A1 (en) | 2018-08-01 | 2020-02-06 | Gilead Sciences, Inc. | Solid forms of (r)-11-(methoxymethyl)-12-(3-methoxypropoxy)-3,3-dimethyl-8-0x0-2,3,8,13b-tetrahydro-1h-pyrido[2,1-a]pyrrolo[1,2-c] phthalazine-7-c arboxylic acid |
| KR20210081332A (ko) | 2018-09-12 | 2021-07-01 | 실버백 테라퓨틱스, 인크. | 면역 자극성 접합체를 사용한 질환의 치료를 위한 조성물 |
| EP3860717A1 (en) | 2018-10-03 | 2021-08-11 | Gilead Sciences, Inc. | Imidozopyrimidine derivatives |
| JP7158577B2 (ja) | 2018-10-24 | 2022-10-21 | ギリアード サイエンシーズ, インコーポレイテッド | Pd-1/pd-l1阻害剤 |
| HRP20240541T1 (hr) | 2018-10-31 | 2024-07-05 | Gilead Sciences, Inc. | Supstituirani spojevi 6-azabenzimidazola kao inhibitori hpk1 |
| KR102658602B1 (ko) | 2018-10-31 | 2024-04-19 | 길리애드 사이언시즈, 인코포레이티드 | Hpk1 억제 활성을 갖는 치환된 6-아자벤즈이미다졸 화합물 |
| MX2021009496A (es) | 2019-02-08 | 2021-09-08 | Progeneer Inc | Complejo de colesterol-agonista del receptor 7 u 8 tipo larga distancia, y uso del mismo. |
| WO2020176505A1 (en) | 2019-02-25 | 2020-09-03 | Gilead Sciences, Inc. | Protein kinase c agonists |
| WO2020176510A1 (en) | 2019-02-25 | 2020-09-03 | Gilead Sciences, Inc. | Protein kinase c agonists |
| WO2020178768A1 (en) | 2019-03-07 | 2020-09-10 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3'3'-cyclic dinucleotide analogue comprising a cyclopentanyl modified nucleotide as sting modulator |
| AU2020231115B2 (en) | 2019-03-07 | 2025-02-20 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3'3'-cyclic dinucleotides and prodrugs thereof |
| DK3934757T3 (da) | 2019-03-07 | 2023-04-17 | Inst Of Organic Chemistry And Biochemistry Ascr V V I | 2'3'-cykliske dinukleotider og prodrugs deraf |
| LT3938047T (lt) | 2019-03-22 | 2022-10-10 | Gilead Sciences, Inc. | Tilteliniai tricikliniai karbamoilpiridono junginiai ir jų naudojimas farmacijoje |
| TW202212339A (zh) | 2019-04-17 | 2022-04-01 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
| TWI751516B (zh) | 2019-04-17 | 2022-01-01 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
| TWI762925B (zh) | 2019-05-21 | 2022-05-01 | 美商基利科學股份有限公司 | 鑑別對使用gp120 v3聚醣導向之抗體的治療敏感之hiv病患的方法 |
| US11453681B2 (en) | 2019-05-23 | 2022-09-27 | Gilead Sciences, Inc. | Substituted eneoxindoles and uses thereof |
| WO2020255038A1 (en) | 2019-06-18 | 2020-12-24 | Janssen Sciences Ireland Unlimited Company | Combination of hepatitis b virus (hbv) vaccines and pyridopyrimidine derivatives |
| US20220249685A1 (en) | 2019-06-19 | 2022-08-11 | Silverback Therapeutics, Inc. | Anti-mesothelin antibodies and immunoconjugates thereof |
| KR102776925B1 (ko) | 2019-06-25 | 2025-03-11 | 길리애드 사이언시즈, 인코포레이티드 | Flt3l-fc 융합 단백질 및 사용 방법 |
| TWI879779B (zh) | 2019-06-28 | 2025-04-11 | 美商基利科學股份有限公司 | 類鐸受體調節劑化合物的製備方法 |
| WO2021011544A1 (en) | 2019-07-16 | 2021-01-21 | Gilead Sciences, Inc. | Hiv vaccines and methods of making and using |
| WO2021011891A1 (en) | 2019-07-18 | 2021-01-21 | Gilead Sciences, Inc. | Long-acting formulations of tenofovir alafenamide |
| WO2021034804A1 (en) | 2019-08-19 | 2021-02-25 | Gilead Sciences, Inc. | Pharmaceutical formulations of tenofovir alafenamide |
| FI4037708T3 (fi) | 2019-09-30 | 2024-10-31 | Gilead Sciences Inc | Hbv-rokotteita ja menetelmiä, hbv:n hoitamiseksi |
| WO2021067644A1 (en) | 2019-10-01 | 2021-04-08 | Silverback Therapeutics, Inc. | Combination therapy with immune stimulatory conjugates |
| EP4045083B1 (en) | 2019-10-18 | 2024-01-10 | Forty Seven, Inc. | Combination therapies for treating myelodysplastic syndromes and acute myeloid leukemia |
| CA3153636A1 (en) | 2019-10-31 | 2021-05-06 | Forty Seven, Inc. | Anti-cd47 and anti-cd20 based treatment of blood cancer |
| TWI778443B (zh) | 2019-11-12 | 2022-09-21 | 美商基利科學股份有限公司 | Mcl1抑制劑 |
| AU2020391466B2 (en) | 2019-11-26 | 2024-05-23 | Gilead Sciences, Inc. | Capsid inhibitors for the prevention of HIV |
| EP4567109A3 (en) | 2019-12-06 | 2025-09-17 | Precision Biosciences, Inc. | Optimized engineered meganucleases having specificity for a recognition sequence in the hepatitis b virus genome |
| PH12022551441A1 (en) | 2019-12-24 | 2023-11-20 | Carna Biosciences Inc | Diacylglycerol kinase modulating compounds |
| MX2022009947A (es) | 2020-02-14 | 2022-11-07 | Jounce Therapeutics Inc | Anticuerpos y proteinas de fusion que se unen a ccr8 y usos de estos. |
| JP7735291B2 (ja) | 2020-02-21 | 2025-09-08 | エーアールエス ファーマシューティカルズ、インコーポレイテッド | ネクチン-4抗体コンジュゲートおよびその使用 |
| WO2021177679A1 (ko) | 2020-03-02 | 2021-09-10 | 성균관대학교산학협력단 | 병원균 외벽 성분 기반 생병원체 모방 나노 입자 및 그 제조 방법 |
| US11718637B2 (en) | 2020-03-20 | 2023-08-08 | Gilead Sciences, Inc. | Prodrugs of 4′-C-substituted-2-halo-2′- deoxyadenosine nucleosides and methods of making and using the same |
| EP4143194A1 (en) | 2020-05-01 | 2023-03-08 | Gilead Sciences, Inc. | Cd73 inhibiting 2,4-dioxopyrimidine compounds |
| EP4146220A4 (en) | 2020-05-04 | 2024-05-29 | Amgen Inc. | HETEROCYCLIC COMPOUNDS AS TRIGGERING RECEPTORS EXPRESSED ON MYELOID CELL 2 AGONISTS AND METHODS OF USE |
| TW202208355A (zh) | 2020-05-04 | 2022-03-01 | 美商安進公司 | 作為骨髓細胞觸發受體2促效劑之雜環化合物及使用方法 |
| EP4153181A1 (en) | 2020-05-21 | 2023-03-29 | Gilead Sciences, Inc. | Pharmaceutical compositions comprising bictegravir |
| AU2021296607B2 (en) | 2020-06-25 | 2024-07-25 | Gilead Sciences, Inc. | Capsid inhibitors for the treatment of HIV |
| KR20230047361A (ko) | 2020-07-01 | 2023-04-07 | 아르스 파마슈티컬스 인크. | 항-asgr1 항체 접합체 및 이의 용도 |
| US20230355750A1 (en) | 2020-08-04 | 2023-11-09 | Progeneer Inc. | Kinetically acting adjuvant ensemble |
| CN116322751A (zh) | 2020-08-04 | 2023-06-23 | 蛋白科技先锋 | 包含能够动力学控制的佐剂的mRNA疫苗 |
| CN116056725A (zh) | 2020-08-04 | 2023-05-02 | 蛋白科技先鋒 | 活性位点暂时灭活的功能性药物与Toll样受体7或8激动剂的缀合物及其用途 |
| EP4192474B1 (en) | 2020-08-07 | 2025-09-10 | Gilead Sciences, Inc. | Prodrugs of phosphonamide nucleotide analogues and their pharmaceutical use |
| TW202406932A (zh) | 2020-10-22 | 2024-02-16 | 美商基利科學股份有限公司 | 介白素2-Fc融合蛋白及使用方法 |
| ES3045091T3 (en) | 2020-11-11 | 2025-11-27 | Gilead Sciences Inc | Methods of identifying hiv patients sensitive to therapy with gp120 cd4 binding site-directed antibodies |
| TW202304524A (zh) | 2021-04-10 | 2023-02-01 | 美商普方生物製藥美國公司 | Folr1結合劑、其結合物及使用方法 |
| TW202302145A (zh) | 2021-04-14 | 2023-01-16 | 美商基利科學股份有限公司 | CD47/SIRPα結合及NEDD8活化酶E1調節次單元之共抑制以用於治療癌症 |
| TW202308699A (zh) | 2021-04-23 | 2023-03-01 | 美商普方生物製藥美國公司 | Cd70結合劑、其結合物及其使用方法 |
| TW202310852A (zh) | 2021-05-13 | 2023-03-16 | 美商基利科學股份有限公司 | TLR8調節化合物及抗HBV siRNA療法之組合 |
| TW202313094A (zh) | 2021-05-18 | 2023-04-01 | 美商基利科學股份有限公司 | 使用FLT3L—Fc融合蛋白之方法 |
| CN117480155A (zh) | 2021-06-23 | 2024-01-30 | 吉利德科学公司 | 二酰基甘油激酶调节化合物 |
| US11999733B2 (en) | 2021-06-23 | 2024-06-04 | Gilead Sciences, Inc. | Diacylglycerol kinase modulating compounds |
| KR20240005901A (ko) | 2021-06-23 | 2024-01-12 | 길리애드 사이언시즈, 인코포레이티드 | 디아실글리세롤 키나제 조절 화합물 |
| CN117355531A (zh) | 2021-06-23 | 2024-01-05 | 吉利德科学公司 | 二酰基甘油激酶调节化合物 |
| TW202320857A (zh) | 2021-07-06 | 2023-06-01 | 美商普方生物製藥美國公司 | 連接子、藥物連接子及其結合物及其使用方法 |
| US20230183216A1 (en) | 2021-10-28 | 2023-06-15 | Gilead Sciences, Inc. | Pyridizin-3(2h)-one derivatives |
| CA3235986A1 (en) | 2021-10-29 | 2023-05-04 | Gilead Science, Inc. | Cd73 compounds |
| EP4440700A1 (en) | 2021-12-03 | 2024-10-09 | Gilead Sciences, Inc. | Therapeutic compounds for hiv virus infection |
| HRP20250928T1 (hr) | 2021-12-03 | 2025-09-26 | Gilead Sciences, Inc. | TERAPIJSKI SPOJEVI ZA INFEKCIJU VIRUSOM HIV-a |
| WO2023102523A1 (en) | 2021-12-03 | 2023-06-08 | Gilead Sciences, Inc. | Therapeutic compounds for hiv virus infection |
| US20230220106A1 (en) | 2021-12-08 | 2023-07-13 | Dragonfly Therapeutics, Inc. | Antibodies targeting 5t4 and uses thereof |
| JP2024545185A (ja) * | 2021-12-08 | 2024-12-05 | シャンハイ ヴィソンファーマ カンパニー,リミテッド | TLR7/8作動剤としてのピリド[4,3-d]ピリミジン系化合物 |
| US20230203202A1 (en) | 2021-12-08 | 2023-06-29 | Dragonfly Therapeutics, Inc. | Proteins binding nkg2d, cd16 and 5t4 |
| AU2022417491A1 (en) | 2021-12-22 | 2024-05-23 | Gilead Sciences, Inc. | Ikaros zinc finger family degraders and uses thereof |
| JP2024546851A (ja) | 2021-12-22 | 2024-12-26 | ギリアード サイエンシーズ, インコーポレイテッド | Ikarosジンクフィンガーファミリー分解剤及びその使用 |
| TW202340168A (zh) | 2022-01-28 | 2023-10-16 | 美商基利科學股份有限公司 | Parp7抑制劑 |
| CR20240386A (es) | 2022-03-17 | 2024-10-24 | Gilead Sciences Inc | Degradadores de dedos de zinc de la familia ikaros y usos de estos |
| AU2023240346A1 (en) | 2022-03-24 | 2024-09-19 | Gilead Sciences, Inc. | Combination therapy for treating trop-2 expressing cancers |
| TWI876305B (zh) | 2022-04-05 | 2025-03-11 | 美商基利科學股份有限公司 | 用於治療結腸直腸癌之組合療法 |
| TWI856796B (zh) | 2022-04-06 | 2024-09-21 | 美商基利科學股份有限公司 | 橋聯三環胺甲醯基吡啶酮化合物及其用途 |
| AU2023256670A1 (en) | 2022-04-21 | 2024-10-17 | Gilead Sciences, Inc. | Kras g12d modulating compounds |
| CA3260083A1 (en) | 2022-07-01 | 2024-01-04 | Gilead Sciences, Inc. | CD73 COMPOUNDS |
| TW202434566A (zh) | 2022-07-01 | 2024-09-01 | 美商基利科學股份有限公司 | 可用於hiv病毒感染之疾病預防性或治療性治療的治療性化合物 |
| WO2024015741A1 (en) | 2022-07-12 | 2024-01-18 | Gilead Sciences, Inc. | Hiv immunogenic polypeptides and vaccines and uses thereof |
| EP4577242A1 (en) | 2022-08-26 | 2025-07-02 | Gilead Sciences, Inc. | Dosing and scheduling regimen for broadly neutralizing antibodies |
| US20240091351A1 (en) | 2022-09-21 | 2024-03-21 | Gilead Sciences, Inc. | FOCAL IONIZING RADIATION AND CD47/SIRPa DISRUPTION ANTICANCER COMBINATION THERAPY |
| WO2024076915A1 (en) | 2022-10-04 | 2024-04-11 | Gilead Sciences, Inc. | 4'-thionucleoside analogues and their pharmaceutical use |
| AU2023409398A1 (en) | 2022-12-22 | 2025-06-05 | Gilead Sciences, Inc. | Prmt5 inhibitors and uses thereof |
| AU2024252725A1 (en) | 2023-04-11 | 2025-11-06 | Gilead Sciences, Inc. | Kras modulating compounds |
| TW202444363A (zh) | 2023-04-19 | 2024-11-16 | 美商基利科學股份有限公司 | 殼體抑制劑之給藥方案 |
| AU2024259556A1 (en) | 2023-04-21 | 2025-10-23 | Gilead Sciences, Inc. | Prmt5 inhibitors and uses thereof |
| WO2024249592A1 (en) | 2023-05-31 | 2024-12-05 | Gilead Sciences, Inc. | Quinazolinyl-indazole derivatives as therapeutic compounds for hiv |
| TW202504592A (zh) | 2023-05-31 | 2025-02-01 | 美商基利科學股份有限公司 | 固體形式 |
| WO2025006720A1 (en) | 2023-06-30 | 2025-01-02 | Gilead Sciences, Inc. | Kras modulating compounds |
| TW202519517A (zh) | 2023-07-26 | 2025-05-16 | 美商基利科學股份有限公司 | Parp7抑制劑 |
| WO2025024663A1 (en) | 2023-07-26 | 2025-01-30 | Gilead Sciences, Inc. | Parp7 inhibitors |
| WO2025029247A1 (en) | 2023-07-28 | 2025-02-06 | Gilead Sciences, Inc. | Weekly regimen of lenacapavir for the treatment and prevention of hiv |
| WO2025042394A1 (en) | 2023-08-23 | 2025-02-27 | Gilead Sciences, Inc. | Dosing regimen of hiv capsid inhibitor |
| US20250101042A1 (en) | 2023-09-08 | 2025-03-27 | Gilead Sciences, Inc. | Kras g12d modulating compounds |
| WO2025054530A1 (en) | 2023-09-08 | 2025-03-13 | Gilead Sciences, Inc. | Pyrimidine-containing polycyclic derivatives as kras g12d modulating compounds |
| AR133955A1 (es) | 2023-09-26 | 2025-11-19 | Profoundbio Us Co | Agentes de unión a ptk7, conjugados de éstos y métodos de uso de los mismos |
| US20250122219A1 (en) | 2023-10-11 | 2025-04-17 | Gilead Sciences, Inc. | Bridged tricyclic carbamoylpyridone compounds and uses thereof |
| US20250120989A1 (en) | 2023-10-11 | 2025-04-17 | Gilead Sciences, Inc. | Bridged tricyclic carbamoylpyridone compounds and uses thereof |
| WO2025080850A1 (en) | 2023-10-11 | 2025-04-17 | Gilead Sciences, Inc. | Bridged tricyclic carbamoylpyridone compounds and uses thereof |
| US20250154172A1 (en) | 2023-11-03 | 2025-05-15 | Gilead Sciences, Inc. | Prmt5 inhibitors and uses thereof |
| US20250230163A1 (en) | 2023-12-22 | 2025-07-17 | Gilead Sciences, Inc. | Solid forms of hiv integrase inhibitors |
| WO2025137640A1 (en) | 2023-12-22 | 2025-06-26 | Gilead Sciences, Inc. | Azaspiro wrn inhibitors |
| US20250296992A1 (en) | 2024-01-10 | 2025-09-25 | Genmab A/S | Slitrk6 binding agents, conjugates thereof and methods of using the same |
| WO2025181219A1 (en) | 2024-02-29 | 2025-09-04 | Genmab A/S | Egfr and c-met bispecific binding agents, conjugates thereof and methods of using the same |
| US20250333424A1 (en) | 2024-03-01 | 2025-10-30 | Gilead Sciences, Inc. | Antiviral compounds |
| WO2025184452A1 (en) | 2024-03-01 | 2025-09-04 | Gilead Sciences, Inc. | Solid forms of hiv integrase inhibitors |
| WO2025184447A1 (en) | 2024-03-01 | 2025-09-04 | Gilead Sciences, Inc. | Pharmaceutical compositions comprising hiv integrase inhibitors |
| WO2025240242A1 (en) | 2024-05-13 | 2025-11-20 | Gilead Sciences, Inc. | Combination therapies with ribavirin |
| WO2025240244A1 (en) | 2024-05-13 | 2025-11-20 | Gilead Sciences, Inc. | Combination therapies comprising bulevirtide and lonafarnib for use in the treatment of hepatitis d virus infection |
| WO2025240243A1 (en) | 2024-05-13 | 2025-11-20 | Gilead Sciences, Inc. | Combination therapies with bulevirtide and an inhibitory nucleic acid targeting hepatitis b virus |
| WO2025240246A1 (en) | 2024-05-13 | 2025-11-20 | Gilead Sciences, Inc. | Combination therapies with ribavirin |
| WO2025245003A1 (en) | 2024-05-21 | 2025-11-27 | Gilead Sciences, Inc. | Prmt5 inhibitors and uses thereof |
| US20260007683A1 (en) | 2024-06-14 | 2026-01-08 | Gilead Sciences, Inc. | Pharmaceutical compositions comprising hiv integrase inhibitors |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6028076A (en) | 1996-07-03 | 2000-02-22 | Japan Energy Corporation | Purine derivative |
| ES2205573T3 (es) | 1997-11-28 | 2004-05-01 | Sumitomo Pharmaceuticals Company, Limited | Nuevo compuestos heterociclicos. |
| WO2000012487A1 (en) * | 1998-08-27 | 2000-03-09 | Sumitomo Pharmaceuticals Co., Ltd. | Pyrimidine derivatives |
| WO2002088079A2 (en) * | 2001-05-01 | 2002-11-07 | Bristol-Myers Squibb Company | Dual inhibitors of pde 7 and pde 4 |
| EP1552842A1 (en) * | 2002-06-07 | 2005-07-13 | Kyowa Hakko Kogyo Co., Ltd. | Bicyclic pyrimidine derivatives |
| US7498409B2 (en) | 2005-03-24 | 2009-03-03 | Schering Corporation | Screening assay for TLR7, TLR8 and TLR9 agonists and antagonists |
| EA200702235A1 (ru) | 2005-05-04 | 2008-04-28 | Пфайзер Лимитед | Производные 2-амидо-6-амино-8-оксопурина в качестве модуляторов toll-подобных рецепторов для лечения рака и вирусных инфекций, таких как гепатит с |
| PE20091236A1 (es) * | 2007-11-22 | 2009-09-16 | Astrazeneca Ab | Derivados de pirimidina como immunomoduladores de tlr7 |
| CN102088974A (zh) * | 2008-02-07 | 2011-06-08 | 加利福尼亚大学校务委员会 | 用tlr7活化剂对膀胱疾病的治疗 |
| US20120122867A1 (en) * | 2009-05-21 | 2012-05-17 | Nicholas James Bennet | Novel pyrimidine derivatives and their use in the treatment of cancer and further diseases |
| TWI468402B (zh) * | 2009-07-31 | 2015-01-11 | 必治妥美雅史谷比公司 | 降低β-類澱粉生成之化合物 |
| US8637525B2 (en) * | 2009-07-31 | 2014-01-28 | Bristol-Myers Squibb Company | Compounds for the reduction of beta-amyloid production |
| JP2013032290A (ja) * | 2009-11-20 | 2013-02-14 | Dainippon Sumitomo Pharma Co Ltd | 新規縮合ピリミジン誘導体 |
| SG11201404743TA (en) | 2012-02-08 | 2014-09-26 | Janssen R & D Ireland | Piperidino-pyrimidine derivatives for the treatment of viral infections |
-
2013
- 2013-02-07 SG SG11201404743TA patent/SG11201404743TA/en unknown
- 2013-02-07 KR KR1020147022432A patent/KR102064807B1/ko not_active Expired - Fee Related
- 2013-02-07 EP EP13703055.7A patent/EP2812331B1/en active Active
- 2013-02-07 ES ES13703055T patent/ES2716811T3/es active Active
- 2013-02-07 BR BR112014019699-0A patent/BR112014019699B1/pt not_active IP Right Cessation
- 2013-02-07 WO PCT/EP2013/052372 patent/WO2013117615A1/en not_active Ceased
- 2013-02-07 NZ NZ627036A patent/NZ627036A/en not_active IP Right Cessation
- 2013-02-07 US US14/377,064 patent/US9133192B2/en active Active
- 2013-02-07 IN IN1736MUN2014 patent/IN2014MN01736A/en unknown
- 2013-02-07 AU AU2013218072A patent/AU2013218072B2/en not_active Ceased
- 2013-02-07 JP JP2014556041A patent/JP6283320B2/ja not_active Expired - Fee Related
- 2013-02-07 MY MYPI2014002281A patent/MY169159A/en unknown
- 2013-02-07 EA EA201992133A patent/EA039373B1/ru unknown
- 2013-02-07 CN CN201380008467.4A patent/CN104245695B/zh not_active Expired - Fee Related
- 2013-02-07 EA EA201491486A patent/EA033907B1/ru unknown
- 2013-02-07 CA CA2862823A patent/CA2862823C/en active Active
- 2013-02-07 MX MX2014009556A patent/MX357296B/es active IP Right Grant
- 2013-02-07 DK DK13703055.7T patent/DK2812331T3/en active
- 2013-07-02 UA UAA201407816A patent/UA112668C2/uk unknown
-
2014
- 2014-07-03 IL IL233499A patent/IL233499B/en active IP Right Grant
- 2014-08-01 PH PH12014501738A patent/PH12014501738B1/en unknown
- 2014-08-07 ZA ZA2014/05820A patent/ZA201405820B/en unknown
- 2014-08-07 CL CL2014002093A patent/CL2014002093A1/es unknown
-
2015
- 2015-08-04 US US14/818,094 patent/US9365571B2/en active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2862823C (en) | Piperidino-pyrimidine derivatives for the treatment of viral infections. | |
| AU2018236703B2 (en) | Pyrimidine derivatives for the treatment of viral infections | |
| EP2882721B1 (en) | Alkylpyrimidine derivatives for the treatment of viral infections and further diseases | |
| CA2886630C (en) | 1,2,4-triazine derivatives for the treatment of viral infections | |
| EP2925729B1 (en) | Heterocyclic substituted 2-amino-quinazoline derivatives for the treatment of viral infections | |
| AU2014220717A1 (en) | 2-aminopyrimidine derivatives for the treatment of viral infections | |
| CA2912338A1 (en) | Pyridone derivatives for the treatment of viral infections and further diseases | |
| HK1201254B (en) | Piperidino-pyrimidine derivatives for the treatment of viral infections | |
| NZ709769B2 (en) | 2-aminopyrimidine derivatives for the treatment of viral infections | |
| NZ714519A (en) | Thieno[3,2-d]pyrimidines derivatives for the treatment of viral infections | |
| NZ754320A (en) | Pyrrolo[3,2-d]pyrimidine derivatives for the treatment of viral infections and other diseases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20171127 |