KR102371500B1 - 피롤로[3,2-d]피리미딘 화합물의 제조 방법, 및 이의 중간체 - Google Patents
피롤로[3,2-d]피리미딘 화합물의 제조 방법, 및 이의 중간체 Download PDFInfo
- Publication number
- KR102371500B1 KR102371500B1 KR1020187024628A KR20187024628A KR102371500B1 KR 102371500 B1 KR102371500 B1 KR 102371500B1 KR 1020187024628 A KR1020187024628 A KR 1020187024628A KR 20187024628 A KR20187024628 A KR 20187024628A KR 102371500 B1 KR102371500 B1 KR 102371500B1
- Authority
- KR
- South Korea
- Prior art keywords
- compound
- formula
- acid
- sodium
- hydroxide
- 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
- 238000000034 method Methods 0.000 title claims abstract description 39
- -1 pyrrolo[3,2-D]pyrimidine compound Chemical class 0.000 title abstract description 6
- 239000000543 intermediate Substances 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 108
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 34
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 28
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 24
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 claims description 18
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 14
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 14
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 14
- 235000011181 potassium carbonates Nutrition 0.000 claims description 14
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 12
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 claims description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 8
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 239000003638 chemical reducing agent Substances 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 235000011054 acetic acid Nutrition 0.000 claims description 4
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 claims description 4
- 229910001863 barium hydroxide Inorganic materials 0.000 claims description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 4
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 4
- 239000000920 calcium hydroxide Substances 0.000 claims description 4
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 4
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims description 4
- 239000000347 magnesium hydroxide Substances 0.000 claims description 4
- 229910001862 magnesium hydroxide Inorganic materials 0.000 claims description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 4
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 claims description 4
- 239000011736 potassium bicarbonate Substances 0.000 claims description 4
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 4
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 4
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 4
- 229940086066 potassium hydrogencarbonate Drugs 0.000 claims description 4
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 4
- 235000011009 potassium phosphates Nutrition 0.000 claims description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims description 4
- 235000017550 sodium carbonate Nutrition 0.000 claims description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 4
- 238000005906 dihydroxylation reaction Methods 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims 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 claims description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims description 2
- 235000015165 citric acid Nutrition 0.000 claims description 2
- 235000019253 formic acid Nutrition 0.000 claims description 2
- 239000001530 fumaric acid Substances 0.000 claims description 2
- 235000011087 fumaric acid Nutrition 0.000 claims description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
- 239000011976 maleic acid Substances 0.000 claims description 2
- 239000001630 malic acid Substances 0.000 claims description 2
- 235000011090 malic acid Nutrition 0.000 claims description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 2
- 235000019260 propionic acid Nutrition 0.000 claims description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 2
- 229960004889 salicylic acid Drugs 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 abstract description 18
- 230000008569 process Effects 0.000 abstract description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 239000007787 solid Substances 0.000 description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 108010060825 Toll-Like Receptor 7 Proteins 0.000 description 10
- 102100039390 Toll-like receptor 7 Human genes 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 9
- 125000005842 heteroatom Chemical group 0.000 description 9
- 102100033110 Toll-like receptor 8 Human genes 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 229950003036 vesatolimod Drugs 0.000 description 8
- 108010060752 Toll-Like Receptor 8 Proteins 0.000 description 7
- 230000014509 gene expression Effects 0.000 description 7
- 102000002689 Toll-like receptor Human genes 0.000 description 6
- 108020000411 Toll-like receptor Proteins 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 229940044616 toll-like receptor 7 agonist Drugs 0.000 description 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 description 5
- 239000012295 chemical reaction liquid Substances 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 5
- BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 4
- 108090000695 Cytokines Proteins 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 229950010550 resiquimod Drugs 0.000 description 4
- BXNMTOQRYBFHNZ-UHFFFAOYSA-N resiquimod Chemical compound C1=CC=CC2=C(N(C(COCC)=N3)CC(C)(C)O)C3=C(N)N=C21 BXNMTOQRYBFHNZ-UHFFFAOYSA-N 0.000 description 4
- 125000006413 ring segment Chemical group 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 125000003821 2-(trimethylsilyl)ethoxymethyl group Chemical group [H]C([H])([H])[Si](C([H])([H])[H])(C([H])([H])[H])C([H])([H])C(OC([H])([H])[*])([H])[H] 0.000 description 3
- OOPNBYLNZQFYEC-UHFFFAOYSA-N 2-butoxy-5H-pyrrolo[3,2-d]pyrimidin-4-amine Chemical compound C(CCC)OC=1N=C(C2=C(N=1)C=CN2)N OOPNBYLNZQFYEC-UHFFFAOYSA-N 0.000 description 3
- VMDGIQUJSYPMLF-UHFFFAOYSA-N C(CCC)OC=1N=C(C2=C(N=1)C(=CN2)CC1=CC=C(C=C1)CN1CCCC1)N Chemical compound C(CCC)OC=1N=C(C2=C(N=1)C(=CN2)CC1=CC=C(C=C1)CN1CCCC1)N VMDGIQUJSYPMLF-UHFFFAOYSA-N 0.000 description 3
- 102000006992 Interferon-alpha Human genes 0.000 description 3
- 108010047761 Interferon-alpha Proteins 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- 229940125904 compound 1 Drugs 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- AURIURYPRQKJEL-UHFFFAOYSA-N C(CCC)OC=1N=C(C2=C(N=1)C=CN2COCC[Si](C)(C)C)N Chemical compound C(CCC)OC=1N=C(C2=C(N=1)C=CN2COCC[Si](C)(C)C)N AURIURYPRQKJEL-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- ULPZLZRREVRBAS-UHFFFAOYSA-N ClC=1N=C(C2=C(N=1)C=CN2COCC[Si](C)(C)C)Cl Chemical compound ClC=1N=C(C2=C(N=1)C=CN2COCC[Si](C)(C)C)Cl ULPZLZRREVRBAS-UHFFFAOYSA-N 0.000 description 2
- VWWVETGBIIMDQI-UHFFFAOYSA-N ClC=1N=C(C2=C(N=1)C=CN2COCC[Si](C)(C)C)N Chemical compound ClC=1N=C(C2=C(N=1)C=CN2COCC[Si](C)(C)C)N VWWVETGBIIMDQI-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 102000014150 Interferons Human genes 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- UJZDELOVOPPFQM-UHFFFAOYSA-N NC=1C2=C(N=C(N=1)OCCCC)C(=CN2)C(O)C1=CC=C(C=C1)CN1CCCC1 Chemical compound NC=1C2=C(N=C(N=1)OCCCC)C(=CN2)C(O)C1=CC=C(C=C1)CN1CCCC1 UJZDELOVOPPFQM-UHFFFAOYSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
- MVTLFDKTYGKJEX-UHFFFAOYSA-N 2,4-dichloro-5h-pyrrolo[3,2-d]pyrimidine Chemical compound ClC1=NC(Cl)=C2NC=CC2=N1 MVTLFDKTYGKJEX-UHFFFAOYSA-N 0.000 description 1
- MTBYCACQSYAYCC-UHFFFAOYSA-N 4-(pyrrolidin-1-ylmethyl)benzaldehyde Chemical compound C1=CC(C=O)=CC=C1CN1CCCC1 MTBYCACQSYAYCC-UHFFFAOYSA-N 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000000419 Chronic Hepatitis B Diseases 0.000 description 1
- 208000006154 Chronic hepatitis C Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 101000800483 Homo sapiens Toll-like receptor 8 Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- KCTZOTUQSGYWLV-UHFFFAOYSA-N N1C=NC=C2N=CC=C21 Chemical class N1C=NC=C2N=CC=C21 KCTZOTUQSGYWLV-UHFFFAOYSA-N 0.000 description 1
- ACDSTJKTNVCXHR-UHFFFAOYSA-N NC=1C2=C(N=C(N=1)OCCCC)C(=CN2)C(C1=CC=C(C=O)C=C1)O Chemical compound NC=1C2=C(N=C(N=1)OCCCC)C(=CN2)C(C1=CC=C(C=O)C=C1)O ACDSTJKTNVCXHR-UHFFFAOYSA-N 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 108010057466 NF-kappa B Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000002725 anti-mycoplasma Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229930189065 blasticidin Natural products 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 239000002975 chemoattractant Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 208000010710 hepatitis C virus infection Diseases 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 229960002751 imiquimod Drugs 0.000 description 1
- DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
- 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 150000004944 pyrrolopyrimidines Chemical class 0.000 description 1
- 238000005316 response function Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- SYXYWTXQFUUWLP-UHFFFAOYSA-N sodium;butan-1-olate Chemical compound [Na+].CCCC[O-] SYXYWTXQFUUWLP-UHFFFAOYSA-N 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- KUCOHFSKRZZVRO-UHFFFAOYSA-N terephthalaldehyde Chemical compound O=CC1=CC=C(C=O)C=C1 KUCOHFSKRZZVRO-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610082028.3A CN107043378A (zh) | 2016-02-05 | 2016-02-05 | 一种吡咯并[3,2-d]嘧啶类化合物的制备方法及其中间体 |
| CN201610082028.3 | 2016-02-05 | ||
| PCT/CN2017/072893 WO2017133686A1 (zh) | 2016-02-05 | 2017-02-04 | 一种吡咯并[3,2-d]嘧啶类化合物的制备方法及其中间体 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20180104724A KR20180104724A (ko) | 2018-09-21 |
| KR102371500B1 true KR102371500B1 (ko) | 2022-03-07 |
Family
ID=59500148
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020187024628A Active KR102371500B1 (ko) | 2016-02-05 | 2017-02-04 | 피롤로[3,2-d]피리미딘 화합물의 제조 방법, 및 이의 중간체 |
Country Status (28)
| Country | Link |
|---|---|
| US (2) | US10654856B2 (enExample) |
| EP (1) | EP3412673B1 (enExample) |
| JP (1) | JP6877449B2 (enExample) |
| KR (1) | KR102371500B1 (enExample) |
| CN (2) | CN107043378A (enExample) |
| AR (1) | AR107549A1 (enExample) |
| AU (1) | AU2017214134B2 (enExample) |
| BR (1) | BR112018015879B1 (enExample) |
| CA (1) | CA3013520C (enExample) |
| CL (1) | CL2018002094A1 (enExample) |
| DK (1) | DK3412673T3 (enExample) |
| EA (1) | EA034581B1 (enExample) |
| ES (1) | ES2852323T3 (enExample) |
| HR (1) | HRP20210103T1 (enExample) |
| HU (1) | HUE053455T2 (enExample) |
| IL (1) | IL260999B (enExample) |
| LT (1) | LT3412673T (enExample) |
| MX (1) | MX374298B (enExample) |
| MY (1) | MY190551A (enExample) |
| NZ (1) | NZ744885A (enExample) |
| PH (1) | PH12018501642A1 (enExample) |
| PL (1) | PL3412673T3 (enExample) |
| PT (1) | PT3412673T (enExample) |
| SG (1) | SG11201806685VA (enExample) |
| SI (1) | SI3412673T1 (enExample) |
| TW (1) | TW201728590A (enExample) |
| UA (1) | UA124100C2 (enExample) |
| WO (1) | WO2017133686A1 (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA201891620A1 (ru) | 2016-02-05 | 2019-02-28 | Денали Терапьютикс Инк. | Ингибиторы взаимодействующей с рецептором протеинкиназы 1 |
| CN107043380A (zh) * | 2016-02-05 | 2017-08-15 | 正大天晴药业集团股份有限公司 | 一种tlr7激动剂的马来酸盐、其晶型c、晶型d、晶型e、制备方法和用途 |
| 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. |
| WO2021177679A1 (ko) | 2020-03-02 | 2021-09-10 | 성균관대학교산학협력단 | 병원균 외벽 성분 기반 생병원체 모방 나노 입자 및 그 제조 방법 |
| EP4194006A4 (en) | 2020-08-04 | 2024-12-04 | Progeneer Inc. | mRNA VACCINE WITH AN ADJUVANT CAPABLE OF KINETIC CONTROL |
| JP2023536954A (ja) | 2020-08-04 | 2023-08-30 | プロジェニア インコーポレイテッド | 活性化部位が一時的に不活性化したトール様受容体７または８作用薬と機能性薬物の結合体およびその用途 |
| US20230355750A1 (en) | 2020-08-04 | 2023-11-09 | Progeneer Inc. | Kinetically acting adjuvant ensemble |
| MX2024008648A (es) | 2022-01-12 | 2024-09-23 | Denali Therapeutics Inc | Formas cristalinas de (s)-5-bencil-n-(5-metil-4-oxo-2,3,4,5-tetrah idropirido [3,2- b][1,4]oxacepin-3-il)-4h-1,2,4-triazol-3-carboxam ida. |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014081644A1 (en) | 2012-11-20 | 2014-05-30 | Glaxosmithkline Llc | Novel compounds |
| WO2014081645A1 (en) | 2012-11-20 | 2014-05-30 | Glaxosmithkline Llc | Novel compounds |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009082247A1 (en) | 2007-12-21 | 2009-07-02 | Industrial Research Limited | Process for preparing immucillins having a methylene link |
| NZ593110A (en) | 2008-12-09 | 2013-06-28 | Gilead Sciences Inc | pteridinone derivatives as MODULATORS OF TOLL-LIKE RECEPTORS |
| MX365114B (es) * | 2012-10-10 | 2019-05-23 | Janssen Sciences Ireland Uc | Derivados pirrolo[3,2-d]pirimidinicos para el tratamiento de infecciones viricas y otras enfermedades. |
| PL3137470T3 (pl) * | 2014-05-01 | 2021-10-11 | Novartis Ag | Związki i kompozycje jako agonisty receptora toll-like 7 |
| PL3190113T3 (pl) * | 2014-08-15 | 2021-10-25 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Związki pirolopirymidynowe stosowane jako agonista TLR7 |
| CN105367576A (zh) | 2014-08-15 | 2016-03-02 | 正大天晴药业集团股份有限公司 | 作为tlr7激动剂的吡咯并嘧啶化合物 |
| BR112018008880B1 (pt) | 2015-11-05 | 2023-01-17 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | 7-(tiazol-5-il) pirrolopirimidina, seu uso, e composição farmacêutica |
| CN107043379A (zh) * | 2016-02-05 | 2017-08-15 | 正大天晴药业集团股份有限公司 | 一种tlr7激动剂的晶型a、其制备方法和医药用途 |
| CN107043377A (zh) * | 2016-02-05 | 2017-08-15 | 正大天晴药业集团股份有限公司 | 一种tlr7激动剂的三氟乙酸盐、晶型b及其制备方法、药物组合物和用途 |
| CN107043380A (zh) * | 2016-02-05 | 2017-08-15 | 正大天晴药业集团股份有限公司 | 一种tlr7激动剂的马来酸盐、其晶型c、晶型d、晶型e、制备方法和用途 |
-
2016
- 2016-02-05 CN CN201610082028.3A patent/CN107043378A/zh active Pending
-
2017
- 2017-02-03 TW TW106103696A patent/TW201728590A/zh unknown
- 2017-02-04 HR HRP20210103TT patent/HRP20210103T1/hr unknown
- 2017-02-04 ES ES17747006T patent/ES2852323T3/es active Active
- 2017-02-04 CA CA3013520A patent/CA3013520C/en active Active
- 2017-02-04 US US16/075,300 patent/US10654856B2/en active Active
- 2017-02-04 JP JP2018540720A patent/JP6877449B2/ja active Active
- 2017-02-04 PT PT177470069T patent/PT3412673T/pt unknown
- 2017-02-04 KR KR1020187024628A patent/KR102371500B1/ko active Active
- 2017-02-04 EA EA201891769A patent/EA034581B1/ru not_active IP Right Cessation
- 2017-02-04 MX MX2018009502A patent/MX374298B/es active IP Right Grant
- 2017-02-04 MY MYPI2018702701A patent/MY190551A/en unknown
- 2017-02-04 SG SG11201806685VA patent/SG11201806685VA/en unknown
- 2017-02-04 NZ NZ744885A patent/NZ744885A/en unknown
- 2017-02-04 AU AU2017214134A patent/AU2017214134B2/en active Active
- 2017-02-04 WO PCT/CN2017/072893 patent/WO2017133686A1/zh not_active Ceased
- 2017-02-04 BR BR112018015879-8A patent/BR112018015879B1/pt active IP Right Grant
- 2017-02-04 SI SI201730605T patent/SI3412673T1/sl unknown
- 2017-02-04 UA UAA201809087A patent/UA124100C2/uk unknown
- 2017-02-04 CN CN201780009748.XA patent/CN108602832B/zh active Active
- 2017-02-04 HU HUE17747006A patent/HUE053455T2/hu unknown
- 2017-02-04 DK DK17747006.9T patent/DK3412673T3/da active
- 2017-02-04 LT LTEP17747006.9T patent/LT3412673T/lt unknown
- 2017-02-04 EP EP17747006.9A patent/EP3412673B1/en active Active
- 2017-02-04 PL PL17747006T patent/PL3412673T3/pl unknown
- 2017-02-06 AR ARP170100298A patent/AR107549A1/es active IP Right Grant
-
2018
- 2018-08-02 PH PH12018501642A patent/PH12018501642A1/en unknown
- 2018-08-03 CL CL2018002094A patent/CL2018002094A1/es unknown
- 2018-08-05 IL IL260999A patent/IL260999B/en active IP Right Grant
-
2020
- 2020-04-13 US US16/847,394 patent/US20200239484A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014081644A1 (en) | 2012-11-20 | 2014-05-30 | Glaxosmithkline Llc | Novel compounds |
| WO2014081645A1 (en) | 2012-11-20 | 2014-05-30 | Glaxosmithkline Llc | Novel compounds |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR102371500B1 (ko) | 피롤로[3,2-d]피리미딘 화합물의 제조 방법, 및 이의 중간체 | |
| KR102393280B1 (ko) | Tlr7 작용제 결정형 a, 이의 제조 방법 및 용도 | |
| KR102138393B1 (ko) | 바이러스 감염의 치료를 위한 1,2,4-트라이아진 유도체 | |
| KR102112192B1 (ko) | Tlr7 효능제로서의 7-(티아졸-5-일)피롤로피리미딘 화합물 | |
| KR102393281B1 (ko) | Tlr7 작용제 트리플루오로아세테이트 염 및 이의 결정형 b, 제조방법 및 용도 | |
| EP2896617B1 (de) | Verfahren zur herstellung von substituierten (z)-alpha-fluoro-beta-amino-acrylaldehyden | |
| KR102393279B1 (ko) | Tlr7 작용제 말레에이트 염, 이의 결정형 c, d 및 e, 말레에이트 염 및 결정형의 제조 방법 및 용도 | |
| EP3272746B1 (en) | Salts of quinazoline derivative and method for preparing same | |
| EP3257855B1 (en) | Method for preparing ibrutinib | |
| CIGNARELLA et al. | Bicyclic Homologs of Piperazine. Synthesis of 8-Methyl-3, 8-diazabicyclooctanes. I | |
| CH668424A5 (de) | 4-benzyloxy-3-pyrrolin-2-on-l-yl-acetamid, dessen herstellung und verwendung. | |
| HK1259183B (zh) | 一种吡咯并[3，2-d]嘧啶类化合物的制备方法及其中间体 | |
| Pasternack et al. | Degradation of terramycin | |
| Sun et al. | A Solution‐Phase Parallel Synthesis of 5‐Substituted 3, 6‐Dihydro‐7H‐1, 2, 3‐triazolo [4, 5‐d] pyrimidin‐7‐ones | |
| Morisawa et al. | The Preparation of Some α 4-Norpyridoxol Analogs | |
| HK1250983B (zh) | 作为tlr7激动剂的7-(噻唑-5-基)吡咯并嘧啶化合物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20180827 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20200228 Comment text: Request for Examination of Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20210804 Patent event code: PE09021S01D |
|
| E701 | Decision to grant or registration of patent right | ||
| PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 20211220 |
|
| GRNT | Written decision to grant | ||
| PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 20220302 Patent event code: PR07011E01D |
|
| PR1002 | Payment of registration fee |
Payment date: 20220303 End annual number: 3 Start annual number: 1 |
|
| PG1601 | Publication of registration | ||
| PR1001 | Payment of annual fee |
Payment date: 20250108 Start annual number: 4 End annual number: 4 |