CN108456194A - 三氮唑抗菌衍生物、其药物组合物和用途 - Google Patents
三氮唑抗菌衍生物、其药物组合物和用途 Download PDFInfo
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- CN108456194A CN108456194A CN201810130090.4A CN201810130090A CN108456194A CN 108456194 A CN108456194 A CN 108456194A CN 201810130090 A CN201810130090 A CN 201810130090A CN 108456194 A CN108456194 A CN 108456194A
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- MWUXSHHQAYIFBG-UHFFFAOYSA-N nitrogen oxide Inorganic materials O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims abstract description 51
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- 238000002360 preparation method Methods 0.000 claims description 235
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- 238000006243 chemical reaction Methods 0.000 claims description 106
- -1 pentamethylene propionic acid Chemical compound 0.000 claims description 83
- 239000002253 acid Substances 0.000 claims description 65
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- 125000000623 heterocyclic group Chemical group 0.000 claims description 42
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- 239000007858 starting material Substances 0.000 claims description 40
- 239000002994 raw material Substances 0.000 claims description 37
- 125000001072 heteroaryl group Chemical group 0.000 claims description 34
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 25
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- 241000222122 Candida albicans Species 0.000 claims description 10
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- ZGCHLAJIRWDGFE-UHFFFAOYSA-N 1-aminopropane-1,1-diol Chemical compound CCC(N)(O)O ZGCHLAJIRWDGFE-UHFFFAOYSA-N 0.000 claims description 9
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- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 9
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- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 9
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- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 125000005546 pivalic acid group Chemical group 0.000 description 1
- 239000010773 plant oil Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- QVLTXCYWHPZMCA-UHFFFAOYSA-N po4-po4 Chemical compound OP(O)(O)=O.OP(O)(O)=O QVLTXCYWHPZMCA-UHFFFAOYSA-N 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- IVRIRQXJSNCSPQ-UHFFFAOYSA-N propan-2-yl carbonochloridate Chemical class CC(C)OC(Cl)=O IVRIRQXJSNCSPQ-UHFFFAOYSA-N 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 150000005837 radical ions Chemical class 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 229910001958 silver carbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229960001922 sodium perborate Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- GRONZTPUWOOUFQ-UHFFFAOYSA-M sodium;methanol;hydroxide Chemical compound [OH-].[Na+].OC GRONZTPUWOOUFQ-UHFFFAOYSA-M 0.000 description 1
- YKLJGMBLPUQQOI-UHFFFAOYSA-M sodium;oxidooxy(oxo)borane Chemical compound [Na+].[O-]OB=O YKLJGMBLPUQQOI-UHFFFAOYSA-M 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229940042055 systemic antimycotics triazole derivative Drugs 0.000 description 1
- 229960000580 terconazole Drugs 0.000 description 1
- 125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 1
- PIFRQYRFCQGLRI-FVGYRXGTSA-N tert-butyl (2s)-4-amino-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)N[C@@H](CCN)C(=O)OC(C)(C)C PIFRQYRFCQGLRI-FVGYRXGTSA-N 0.000 description 1
- KUYMVWXKHQSIAS-UHFFFAOYSA-N tert-butyl 2-chloroacetate Chemical compound CC(C)(C)OC(=O)CCl KUYMVWXKHQSIAS-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
- XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical compound CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229960002898 threonine Drugs 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- NNBZCPXTIHJBJL-UHFFFAOYSA-N trans-decahydronaphthalene Natural products C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 229940005605 valeric acid Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 239000012224 working solution Substances 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further 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
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
-
- 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
- A61P31/10—Antimycotics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
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- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
- C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
- C07H13/04—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals attached to acyclic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
- C07H13/12—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by acids having the group -X-C(=X)-X-, or halides thereof, in which each X means nitrogen, oxygen, sulfur, selenium or tellurium, e.g. carbonic acid, carbamic acid
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- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
化合物编号 | 溶解度(mg/mL) | 化合物编号 | 溶解度(mg/mL) |
伏立康唑 | <1 | QR16019 | >50 |
QR16001 | >50 | QR16020 | >50 |
QR16002 | >50 | QR16021 | >50 |
QR16003 | >50 | QR16022 | >50 |
QR16004 | >50 | QR16023 | >50 |
QR16005 | >50 | QR16024 | >50 |
QR16006 | >50 | QR16025 | >50 |
QR16007 | >50 | QR16028 | >50 |
QR16008 | >50 | QR16029 | 14.2 |
QR16009 | >50 | QR16030 | >50 |
SF16002 | >50 | QR16032 | >50 |
QR16011 | >50 | QR16033 | >50 |
QR16012 | >50 | QR16034 | 12.5 |
QR16013 | >50 | QR16040 | 16.8 |
QR16014 | >50 | QR16042 | >50 |
QR16015 | >50 | SF16001 | >50 |
QR16016 | >50 | QR16045 | >50 |
QR16017 | >50 | QR16046 | >50 |
QR16018 | >50 |
化合物编号 | 25℃30天总杂增加量 | 化合物编号 | 25℃30天总杂增加量 |
QR16001 | 0.53% | SF16013 | 0.48% |
QR16002 | 1.02% | SF16014 | 0.36% |
QR16003 | 1.37% | SF16015 | 0.32% |
QR16006 | 1.14% | QR16024 | 2.84% |
QR16007 | 0.73% | QR16025 | 1.57% |
QR16008 | 1.05% | QR16028 | 1.52% |
QR16009 | 0.71% | QR16029 | 1.17% |
SF16002 | 0.67% | QR16030 | 0.94% |
QR16011 | 0.96% | 16031 | 0.97% |
QR16012 | 0.92% | QR16035 | 1.21% |
QR16013 | 0.42% | QR16036 | 1.35% |
QR16014 | 0.53% | 16037 | 2.15% |
QR16015 | 0.39% | QR16039 | 1.22% |
QR16016 | 0.62% | QR16040 | 2.84% |
QR16017 | 0.55% | SF16001 | 0.37% |
QR16018 | 1.15% | QR16045 | 2.23% |
QR16019 | 0.88% | QR16046 | 0.79% |
QR16020 | 0.56% | SF16020 | 0.62% |
QR16021 | 1.14% | SF16016 | 0.49% |
QR16023 | 2.63% | SF16017 | 0.46% |
Claims (10)
Applications Claiming Priority (2)
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CN201710087041 | 2017-02-17 | ||
CN2017100870412 | 2017-02-17 |
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Publication Number | Publication Date |
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CN108456194A true CN108456194A (zh) | 2018-08-28 |
CN108456194B CN108456194B (zh) | 2021-06-22 |
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CN201810130090.4A Active CN108456194B (zh) | 2017-02-17 | 2018-02-08 | 三氮唑抗菌衍生物、其药物组合物和用途 |
Country Status (4)
Country | Link |
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US (1) | US11040958B2 (zh) |
EP (1) | EP3584245A4 (zh) |
CN (1) | CN108456194B (zh) |
WO (1) | WO2018149359A1 (zh) |
Cited By (3)
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CN110204548A (zh) * | 2019-06-04 | 2019-09-06 | 河南科技大学第一附属医院 | 一种具有杀菌消毒作用的哒嗪并三氮唑类药物分子及其制备方法和应用 |
CN114907319A (zh) * | 2021-02-06 | 2022-08-16 | 华创合成制药股份有限公司 | 一种氘代三唑类化合物及其制备方法和用途 |
CN115248266A (zh) * | 2022-02-22 | 2022-10-28 | 植恩生物技术股份有限公司 | 伏立康唑中间产品中可挥发杂质六甲基二硅氧烷和三甲基硅醇的检测方法 |
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US10683387B2 (en) | 2016-10-04 | 2020-06-16 | Massachusetts Institute Of Technology | Bottlebrush copolymers and uses thereof |
CA3068318A1 (en) | 2017-06-30 | 2019-01-03 | Massachusetts Institute Of Technology | Branched multi-functional macromonomers and related polymers and uses thereof |
US11752221B2 (en) | 2017-06-30 | 2023-09-12 | Massachusetts Institute Of Technology | Brush-arm star polymer imaging agents and uses thereof |
US10988491B2 (en) | 2018-08-17 | 2021-04-27 | Massachusetts Institute Of Technology | Degradable polymers of a cyclic silyl ether and uses thereof |
CA3154334A1 (en) * | 2019-10-16 | 2021-04-22 | Jeremiah A. Johnson | Brush prodrugs and uses thereof |
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CN114907319A (zh) * | 2021-02-06 | 2022-08-16 | 华创合成制药股份有限公司 | 一种氘代三唑类化合物及其制备方法和用途 |
CN115248266A (zh) * | 2022-02-22 | 2022-10-28 | 植恩生物技术股份有限公司 | 伏立康唑中间产品中可挥发杂质六甲基二硅氧烷和三甲基硅醇的检测方法 |
CN115248266B (zh) * | 2022-02-22 | 2024-04-16 | 植恩生物技术股份有限公司 | 伏立康唑中间产品中可挥发杂质六甲基二硅氧烷和三甲基硅醇的检测方法 |
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WO2018149359A1 (zh) | 2018-08-23 |
US11040958B2 (en) | 2021-06-22 |
EP3584245A1 (en) | 2019-12-25 |
EP3584245A4 (en) | 2020-08-26 |
US20190382375A1 (en) | 2019-12-19 |
CN108456194B (zh) | 2021-06-22 |
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