CN115119508A - 大环tlr7激动剂、其制备方法、药物组合物及其用途 - Google Patents
大环tlr7激动剂、其制备方法、药物组合物及其用途 Download PDFInfo
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- CN115119508A CN115119508A CN202280002672.9A CN202280002672A CN115119508A CN 115119508 A CN115119508 A CN 115119508A CN 202280002672 A CN202280002672 A CN 202280002672A CN 115119508 A CN115119508 A CN 115119508A
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- Prior art keywords
- substituted
- alkyl
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- alkylene
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- 230000004071 biological effect Effects 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 150000001621 bismuth Chemical class 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- UNXISIRQWPTTSN-UHFFFAOYSA-N boron;2,3-dimethylbutane-2,3-diol Chemical compound [B].[B].CC(C)(O)C(C)(C)O UNXISIRQWPTTSN-UHFFFAOYSA-N 0.000 description 1
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- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 1
- 210000005220 cytoplasmic tail Anatomy 0.000 description 1
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- 125000005959 diazepanyl group Chemical group 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
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- KMFJVYMFCAIRAN-UHFFFAOYSA-N methyl 3-bromobenzoate Chemical compound COC(=O)C1=CC=CC(Br)=C1 KMFJVYMFCAIRAN-UHFFFAOYSA-N 0.000 description 1
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- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
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- 125000002971 oxazolyl group Chemical group 0.000 description 1
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- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
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- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
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- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
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- 102000004169 proteins and genes Human genes 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 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 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 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
- 239000011986 second-generation catalyst Substances 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
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- 235000015523 tannic acid Nutrition 0.000 description 1
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- 229920002258 tannic acid Polymers 0.000 description 1
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- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 description 1
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- 125000003554 tetrahydropyrrolyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
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- 125000001425 triazolyl group Chemical group 0.000 description 1
- 229940086542 triethylamine Drugs 0.000 description 1
- WVLBCYQITXONBZ-UHFFFAOYSA-N trimethyl phosphate Chemical compound COP(=O)(OC)OC WVLBCYQITXONBZ-UHFFFAOYSA-N 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
-
- 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
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- 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
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
- A61P31/20—Antivirals for DNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
Abstract
一种大环TLR7激动剂、其制备方法、药物组合物及其用途。所述的大环TLR7激动剂如式I所示化合物。该化合物结构新颖，活性较好，具有良好的应用前景。
Description
PCT国内申请，说明书已公开。
Claims (12)
- PCT国内申请，权利要求书已公开。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110075854 | 2021-01-20 | ||
| CN2021100758546 | 2021-01-20 | ||
| PCT/CN2022/072556 WO2022156678A1 (zh) | 2021-01-20 | 2022-01-18 | 大环tlr7激动剂、其制备方法、药物组合物及其用途 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115119508A true CN115119508A (zh) | 2022-09-27 |
Family
ID=82527414
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210054984.6A Pending CN114805392A (zh) | 2021-01-20 | 2022-01-18 | 大环tlr7激动剂、其制备方法、药物组合物及其用途 |
| CN202280002672.9A Pending CN115119508A (zh) | 2021-01-20 | 2022-01-18 | 大环tlr7激动剂、其制备方法、药物组合物及其用途 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210054984.6A Pending CN114805392A (zh) | 2021-01-20 | 2022-01-18 | 大环tlr7激动剂、其制备方法、药物组合物及其用途 |
Country Status (2)
| Country | Link |
|---|---|
| CN (2) | CN114805392A (zh) |
| WO (1) | WO2022156678A1 (zh) |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016023511A1 (zh) * | 2014-08-15 | 2016-02-18 | 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 |
| 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 |
| WO2017188287A1 (ja) * | 2016-04-26 | 2017-11-02 | 大日本住友製薬株式会社 | 置換プリン誘導体 |
| CN110372703A (zh) * | 2018-04-13 | 2019-10-25 | 罗欣生物科技（上海）有限公司 | 五元杂环并嘧啶类化合物及其用途 |
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| WO2020188448A1 (en) * | 2019-03-15 | 2020-09-24 | Janssen Sciences Ireland Unlimited Company | Toll-like receptor agonists for use in the treatment of hepatitis b |
| CN112105620A (zh) * | 2018-05-25 | 2020-12-18 | 正大天晴药业集团股份有限公司 | 用于治疗肺癌的tlr7激动剂及其药物组合 |
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2022
- 2022-01-18 CN CN202210054984.6A patent/CN114805392A/zh active Pending
- 2022-01-18 CN CN202280002672.9A patent/CN115119508A/zh active Pending
- 2022-01-18 WO PCT/CN2022/072556 patent/WO2022156678A1/zh active Application Filing
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| WO2016023511A1 (zh) * | 2014-08-15 | 2016-02-18 | 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 |
| 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 |
| WO2017188287A1 (ja) * | 2016-04-26 | 2017-11-02 | 大日本住友製薬株式会社 | 置換プリン誘導体 |
| CN110372703A (zh) * | 2018-04-13 | 2019-10-25 | 罗欣生物科技（上海）有限公司 | 五元杂环并嘧啶类化合物及其用途 |
| CN112105620A (zh) * | 2018-05-25 | 2020-12-18 | 正大天晴药业集团股份有限公司 | 用于治疗肺癌的tlr7激动剂及其药物组合 |
| WO2020028608A1 (en) * | 2018-08-03 | 2020-02-06 | Bristol-Myers Squibb Company | 1H-PYRAZOLO[4,3-d]PYRIMIDINE COMPOUNDS AS TOLL-LIKE RECEPTOR 7 (TLR7) AGONISTS AND METHODS AND USES THEREFOR |
| WO2020073942A1 (zh) * | 2018-10-11 | 2020-04-16 | 江苏恒瑞医药股份有限公司 | 一种tlr7激动剂前药、其制备方法及其在医药上的应用 |
| WO2020074006A1 (zh) * | 2018-10-12 | 2020-04-16 | 正大天晴药业集团股份有限公司 | 用于治疗结直肠癌的tlr7激动剂及其药物组合 |
| WO2020160710A1 (en) * | 2019-02-07 | 2020-08-13 | Beigene, Ltd. | Imidazo [2, 1-f] [1, 2, 4] triazin-4-amine derivatives as tlr7 agonist |
| WO2020160711A1 (en) * | 2019-02-07 | 2020-08-13 | Beigene, Ltd. | Imidazo [2, 1-f] [1, 2, 4] triazin-4-amine derivatives as tlr7 agonist |
| WO2020188448A1 (en) * | 2019-03-15 | 2020-09-24 | Janssen Sciences Ireland Unlimited Company | Toll-like receptor agonists for use in the treatment of hepatitis b |
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| CN114805392A (zh) | 2022-07-29 |
| WO2022156678A1 (zh) | 2022-07-28 |
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Application publication date: 20220927 Assignee: Suzhou Shentuo Pharmaceutical Technology Co.,Ltd. Assignor: Shanghai Weishen Pharmaceutical Co.,Ltd. Contract record no.: X2023990000874 Denomination of invention: Macrocyclic TLR7 agonist, its preparation method, drug composition, and its use License type: Common License Record date: 20231016 |