BR112018015879B1 - Processo para preparação de pirrol[3,2-d]pirimidina, e seus intermediários composto, composição farmacêutica e usos de compostos - Google Patents
Processo para preparação de pirrol[3,2-d]pirimidina, e seus intermediários composto, composição farmacêutica e usos de compostos Download PDFInfo
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- BR112018015879B1 BR112018015879B1 BR112018015879-8A BR112018015879A BR112018015879B1 BR 112018015879 B1 BR112018015879 B1 BR 112018015879B1 BR 112018015879 A BR112018015879 A BR 112018015879A BR 112018015879 B1 BR112018015879 B1 BR 112018015879B1
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- Prior art keywords
- compound
- formula
- acid
- sodium
- hydroxide
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 91
- 238000000034 method Methods 0.000 title claims abstract description 18
- 230000008569 process Effects 0.000 title claims description 17
- 239000000543 intermediate Substances 0.000 title abstract 2
- 238000002360 preparation method Methods 0.000 title description 14
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 title description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 title description 4
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- -1 pyrrolo[3,2-d]pyrimidine compound Chemical class 0.000 claims abstract description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 30
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 28
- 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 23
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 18
- 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
- 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
- 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 claims description 12
- 238000005906 dihydroxylation reaction Methods 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 10
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 8
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 claims description 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-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
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical group 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 229910000029 sodium carbonate Inorganic materials 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
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid 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
- 239000003638 chemical reducing agent Substances 0.000 claims description 5
- 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
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 4
- 235000011009 potassium phosphates Nutrition 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
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000011736 potassium bicarbonate Substances 0.000 claims description 3
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 3
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-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
- 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
- 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
- 239000012279 sodium borohydride Substances 0.000 claims description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 claims 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 claims 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 1
- 239000011976 maleic acid Substances 0.000 claims 1
- 229910052700 potassium Inorganic materials 0.000 claims 1
- 239000011591 potassium Substances 0.000 claims 1
- AKEKKCGPLHMFCI-UHFFFAOYSA-L potassium sodium hydrogen carbonate Chemical compound [Na+].[K+].OC([O-])=O.OC([O-])=O AKEKKCGPLHMFCI-UHFFFAOYSA-L 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 19
- 239000007787 solid Substances 0.000 description 19
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
- 238000003756 stirring Methods 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-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
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 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
- 125000000217 alkyl group Chemical group 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 230000014509 gene expression Effects 0.000 description 9
- 125000005842 heteroatom Chemical group 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
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- 238000001914 filtration Methods 0.000 description 8
- 108010060825 Toll-Like Receptor 7 Proteins 0.000 description 7
- 102100039390 Toll-like receptor 7 Human genes 0.000 description 7
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
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- 125000004429 atom Chemical group 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 239000012295 chemical reaction liquid Substances 0.000 description 6
- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 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
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- 102000004127 Cytokines Human genes 0.000 description 4
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- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
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- 125000005843 halogen group Chemical group 0.000 description 1
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- 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
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Classifications
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- 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)
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| 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 |
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| CN118994191A (zh) | 2016-02-05 | 2024-11-22 | 戴纳立制药公司 | 受体相互作用蛋白激酶1的抑制剂 |
| 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 |
| JP7287708B2 (ja) | 2019-02-08 | 2023-06-06 | プロジェニア インコーポレイテッド | Ｔｏｌｌ－ｌｉｋｅ受容体７または８アゴニストとコレステロールの結合体およびその用途 |
| JP2023516372A (ja) | 2020-03-02 | 2023-04-19 | プロジェニア インコーポレイテッド | 病原菌外壁成分基盤の生病原体模倣ナノ粒子及びその製造方法 |
| WO2022031057A1 (ko) | 2020-08-04 | 2022-02-10 | 성균관대학교산학협력단 | 활성화 부위가 일시적으로 비활성화된 톨-유사 수용체 7 또는 8 작용자와 기능성 약물의 결합체 및 그 용도 |
| US20230355750A1 (en) | 2020-08-04 | 2023-11-09 | Progeneer Inc. | Kinetically acting adjuvant ensemble |
| EP4194006A4 (en) | 2020-08-04 | 2024-12-04 | Progeneer Inc. | mRNA VACCINE WITH AN ADJUVANT CAPABLE OF KINETIC CONTROL |
| AU2023206890A1 (en) | 2022-01-12 | 2024-08-22 | Denali Therapeutics Inc. | Crystalline forms of (s)-5-benzyl-n-(5-methyl-4-oxo-2, 3,4,5- tetrahydropyrido [3,2-b] [l,4]oxazepin-3-yl)-4h-l,2,4-triazole-3-carboxamide |
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| TW201639852A (zh) | 2008-12-09 | 2016-11-16 | 吉李德科學股份有限公司 | 用於製備可用作類鐸受體調節劑之化合物的中間體化合物 |
| SI2906563T1 (en) * | 2012-10-10 | 2018-06-29 | Janssen Sciences Ireland Uc | Derivatives of pyrrolo (3,2-d) pyrimidine for the treatment of viral infections and other diseases |
| RU2643371C2 (ru) * | 2012-11-20 | 2018-02-01 | ГЛАКСОСМИТКЛАЙН ЭлЭлСи | Новые соединения |
| NZ707319A (en) * | 2012-11-20 | 2019-09-27 | Glaxosmithkline Llc | 5h-pyrrolo[3,2-d]pyrimidin-4-amine compounds and their use in the treatment of allergic diseases and other inflammatory conditions |
| MX362341B (es) * | 2014-05-01 | 2019-01-11 | Novartis Ag | Compuestos y composiciones como agonistas del receptor tipo toll 7. |
| 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 |
| SI3190113T1 (sl) * | 2014-08-15 | 2021-09-30 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Pirolopirimidinske spojine, ki se uporabljajo kot agonist TLR7 |
| UA121345C2 (uk) | 2015-11-05 | 2020-05-12 | Чіа Тай Тяньцин Фармасьютікал Груп Ко., Лтд. | 7-(тіазол-5-іл)піролопіримідин як агоніст рецептора tlr7 |
| 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 |
| 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 |
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| B06W | Patent application suspended after preliminary examination (for patents with searches from other patent authorities) chapter 6.23 patent gazette] | ||
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