CN114437098A - Design and synthesis of near-infrared fluorescence labeled GSH response type podophyllotoxin prodrug - Google Patents
Design and synthesis of near-infrared fluorescence labeled GSH response type podophyllotoxin prodrug Download PDFInfo
- Publication number
- CN114437098A CN114437098A CN202011199710.3A CN202011199710A CN114437098A CN 114437098 A CN114437098 A CN 114437098A CN 202011199710 A CN202011199710 A CN 202011199710A CN 114437098 A CN114437098 A CN 114437098A
- Authority
- CN
- China
- Prior art keywords
- dichloromethane
- prodrug
- stopped
- reaction
- give
- 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.)
- Pending
Links
- YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 title claims abstract description 8
- YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-XVVDYKMHSA-N 0.000 title claims abstract description 8
- 229960001237 podophyllotoxin Drugs 0.000 title claims abstract description 8
- YVCVYCSAAZQOJI-UHFFFAOYSA-N podophyllotoxin Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YVCVYCSAAZQOJI-UHFFFAOYSA-N 0.000 title claims abstract description 8
- 229940002612 prodrug Drugs 0.000 title claims abstract description 7
- 239000000651 prodrug Substances 0.000 title claims abstract description 7
- 230000004044 response Effects 0.000 title claims abstract description 5
- 230000015572 biosynthetic process Effects 0.000 title abstract description 3
- 238000013461 design Methods 0.000 title abstract description 3
- 238000003786 synthesis reaction Methods 0.000 title abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 34
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 12
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- 229960000549 4-dimethylaminophenol Drugs 0.000 claims description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 6
- 239000003480 eluent Substances 0.000 claims description 6
- 239000012044 organic layer Substances 0.000 claims description 6
- 239000012074 organic phase Substances 0.000 claims description 6
- 239000000741 silica gel Substances 0.000 claims description 6
- 229910002027 silica gel Inorganic materials 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 238000005303 weighing Methods 0.000 claims description 4
- 230000003213 activating effect Effects 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 2
- JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 claims description 2
- 239000012065 filter cake Substances 0.000 claims description 2
- 239000005457 ice water Substances 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 description 10
- 238000011282 treatment Methods 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 239000007850 fluorescent dye Substances 0.000 description 3
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 229940044683 chemotherapy drug Drugs 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 210000002570 interstitial cell Anatomy 0.000 description 2
- VATYWCRQDJIRAI-UHFFFAOYSA-N p-aminobenzaldehyde Chemical compound NC1=CC=C(C=O)C=C1 VATYWCRQDJIRAI-UHFFFAOYSA-N 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- JXPDNDHCMMOJPC-UHFFFAOYSA-N 2-hydroxybutanedinitrile Chemical compound N#CC(O)CC#N JXPDNDHCMMOJPC-UHFFFAOYSA-N 0.000 description 1
- YYSCJLLOWOUSHH-UHFFFAOYSA-N 4,4'-disulfanyldibutanoic acid Chemical compound OC(=O)CCCSSCCCC(O)=O YYSCJLLOWOUSHH-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011503 in vivo imaging Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012502 risk assessment Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
-
- 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
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1003—Carbocyclic compounds
- C09K2211/1007—Non-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1088—Heterocyclic compounds characterised by ligands containing oxygen as the only heteroatom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses design and synthesis of a near-infrared fluorescence labeled GSH response type podophyllotoxin prodrug, which has a structure shown in a formula,
Description
Technical Field
The invention belongs to the field of diagnosis and treatment
Background
Chemotherapeutic drugs remain the first line of cancer treatment, but treatment regimens cannot exclude individual differences; the side effect of the chemotherapy drugs is obvious; the efficacy assessment is delayed.
The microenvironment of a tumor is a component of its physiology, structure and function. The relationship between tumor and interstitial cell is essentially the growth and development of tumor or cell, and the non-malignant cells and secreted proteins of tumor and interstitial cell are involved in the generation and development of tumor. Research shows that the tumor microenvironment has low pH, hypoxia and metabolic disorder of various enzymes. The clinical relevance of the tumor microenvironment to tumor treatment should therefore be emphasized. Increased awareness of this interaction may provide valuable references for cancer management, risk assessment, and diagnostic treatment.
The small molecular fluorescent probe has the advantages of high sensitivity, good selectivity and the like, and can be used for detecting related substances. If the small molecular fluorescent probe is used for marking the antitumor drugs, the adverse reaction of the related drugs can be reduced, and the in-vivo positioning condition and the treatment effect of the drugs can be traced and reported. And the near-infrared fluorescent probe has the advantages of longer emission wavelength (650-900nm), strong tissue penetration capacity, small cell damage, small organism autofluorescence interference and the like, and is suitable for in vivo imaging of organisms.
Disclosure of Invention
The invention provides a synthesis method of a near-infrared fluorescence labeled GSH response type podophyllotoxin prodrug, which aims to solve the existing problems and provide application of the compound in antitumor drugs.
A process for synthesizing a near-infrared fluorescence labeled GSH-responsive podophyllotoxin prodrug comprises the following steps:
Reagents and conditions：(i)malonitrile，piperidine，EtOH，65℃，4h；
(ii)p-aminobenzaldehyde，piperidine，MeCN，90℃，overnight；
(iii)4，4′-disulfanediyldibutyric acid，DMAP/EDC，0℃，DCM；r.t.，overnight；
(vi)podophyllotoxin，DMAP/EDC，0℃，DCM；r.t.，overnight；
the preparation method comprises the following steps of,
the preparation method comprises the following steps of,
step 1. weigh A (2.76g, 20mmol), B (1.32g, 2)0mmol), dissolving with 10mL of absolute ethyl alcohol, adding an appropriate amount of piperidine, and reacting for 4 hours at 65 ℃. The reaction was stopped, cooled to room temperature and poured into 100mL of ice water, a brown solid precipitated, filtered and the filter cake dried to give a brown solid C, yield 90%, m.p.120-121 ℃.1H NMR(600MHz，Chloroform-d)δ7.19(s，1H)，2.44(s，3H)，2.14(s，2H)，1.96(d，J＝1.1Hz，2H)，0.94(s，6H).MS EI+：196.26(C12H14N2，[M]+).
Step 2. weigh C (1.96g, 10mmol) and D (1.21g, 10mmol), add 10mL acetonitrile as solvent, appropriate piperidine as catalyst, and react at 90 ℃ overnight. The reaction was stopped, extracted with dichloromethane and water, the organic phases combined, the organic layer dried over anhydrous sodium sulfate and chromatographed on silica gel (eluent VPE: VAcOEt ═ 4: 1) to give E as a reddish brown solid in 80% yield. m.p.160 ℃.1H NMR(600MHz，Chloroform-d)δ7.66(d，J＝7.2Hz 2H)，6.85(m，J＝7.1Hz 2H)，7.31(d，J＝7.0Hz 2H)，6.3(s，1H)，5.48(s，2H).1.82(d，J＝1.3Hz 4H)，1.00(s，6H)，MS EI+：289.38(C19H19N3，[M]+).
Step 3. weighing compound F (95.4mg, 0.4mmol), EDC (143mg, 0.75mmol), DMAP (5.5mg, 0.045mmol) in anhydrous dichloromethane (10mL), activating in ice bath for 1h, then adding compound E (116mg, 0.4mmol), stirring at room temperature overnight. The reaction was stopped, extracted with dichloromethane and water, the organic phases combined and the organic layer dried over anhydrous sodium sulfate and chromatographed on silica gel (eluent VPE: VAcOEt ═ 1: 1) to give G as a yellow solid in 20% yield. m.p.180 ℃.1H NMR(600MHz，Chloroform-d)δ12.01(s，1H)，10.01(s，1H)，7.91(d，J＝7.2Hz 2H)，7.55(m，J＝7.1Hz，2H)，6.85(d，J＝7.0Hz，2H)，6.3(s，1H)，2.54(m，J＝1.5Hz，4H).2.39(d，J＝1.3HZ，2H)，2.3(d，J＝1.3HZ，2H)，1.97(d，J＝1.3HZ，2H)，1.86(d，J＝1.3HZ，2H)，1.82(d，J＝1.3Hz 4H)，1.00(s，6H)，MS EI+：509.7(C27H31N3O3S2[M]+).
Step 4. weighing Compound G (50.9mg, 0.1 mmo)l), EDC (19mg, 0.1mmol), DMAP (12mg, 0.1mmol) were dissolved in anhydrous dichloromethane (10mL), activated in ice bath for 1H, then Compound H (40mg, 0.1mmol) was added and stirred at room temperature overnight. The reaction was stopped, extracted with dichloromethane and water, the organic phases combined, the organic layer dried over anhydrous sodium sulfate and chromatographed on silica gel (eluent VPE: VAcOEt ═ 2: 1) to give the final compound of formula I. The yield was 10%. m.p.230-231 ℃.1H NMR(600MHz，Chloroform-d)δ10.2(s，1H)，7.91(d，J＝7.2Hz 2H)，7.75(m，J＝7.1Hz 2H)，6.85(d，J＝7.0Hz 2H)，6.62(d，J＝7.2HZ，2H)，6.2(s，1H)，6.0(s，2H)，5.9(m，J＝2.85Hz，1H)，3.83(dd，J＝0.85Hz，6H)，3.7(s，3H)，3.58(m，J＝1.37Hz，4H)，2.9(m，J＝1.3Hz，2H)，2.54(m，J＝1.5Hz，4H).2.39(d，J＝1.3HZ，2H)，2.2(m，J＝0.87Hz，1H)，2.3(d，J＝1.3HZ，2H)，1.97(d，J＝1.3HZ，2H)，1.86(d，J＝1.3HZ，2H)，1.82(d，J＝1.3Hz 4H)，1.7(m，J＝1.1Hz，1H)，1.00(s，J＝0.37Hz 6H)，MS EI+：892.1(C49H53N3O9S2[M]+).
Although the preferred embodiments of the present invention have been described in detail, the present invention is not limited to the details of the embodiments, and various equivalent modifications can be made within the technical spirit of the present invention, and the scope of the present invention is also within the scope of the present invention. It should be noted that the various features described in the above embodiments may be combined in any suitable manner without departing from the scope of the invention. The invention is not described in detail in order to avoid unnecessary repetition. In addition, any combination of the various embodiments of the present invention can be made, and the same should be considered as the disclosure of the present invention as long as the idea of the present invention is not violated.
Claims (2)
1. Structure of near-infrared fluorescence labeled GSH response type podophyllotoxin prodrug
2. A method for synthesizing a GSH-responsive podophyllotoxin prodrug labeled by near infrared fluorescence has a structure shown in the formula
The preparation method comprises the following steps of,
step 1. weigh A (2.76g, 20mmol), B (1.32g, 20mmol), dissolve with 10mL absolute ethanol, add appropriate amount of piperidine, react for 4 hours at 65 ℃. The reaction was stopped, cooled to room temperature and poured into 100mL of ice water, a brown solid precipitated, filtered and the filter cake dried to give C.
Step 2. weigh C (1.96g, 10mmol) and D (1.21g, 10mmol), add 10mL acetonitrile as solvent, appropriate piperidine as catalyst, and react at 90 ℃ overnight. The reaction was stopped, extracted with dichloromethane and water, the organic phases combined and the organic layer dried over anhydrous sodium sulfate and chromatographed on silica gel (eluent VPE: VAcOEt ═ 4: 1) to give E as a reddish brown solid.
Step 3. weighing Compound F (95.4mg, 0.4mmol), EDC (143mg, 0.75mmol), DMAP (5.5m g, 0.045mmol) in anhydrous dichloromethane (10mL), activating in ice bath for 1h, then adding Compound E (116mg, 0.4mmol), stirring at room temperature overnight. The reaction was stopped, extracted with dichloromethane and water, the organic phases combined and the organic layer dried over anhydrous sodium sulfate and chromatographed on silica gel (eluent VPE: VAcOEt ═ 1: 1) to give G as a yellow solid.
Step 4. weighing Compound G (50.9mg, 0.1mmol), EDC (19mg, 0.1mmol), DMAP (12m G, 0.1mmol) in anhydrous dichloromethane (10mL), activating in ice bath for 1H, then adding Compound H (40mg, 0.1mmol), stirring at room temperature overnight. The reaction was stopped, extracted with dichloromethane and water, the organic phases combined, the organic layer dried over anhydrous sodium sulfate and chromatographed on silica gel (eluent VPE: VAcOEt ═ 2: 1) to give the final compound of formula I.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011199710.3A CN114437098A (en) | 2020-10-30 | 2020-10-30 | Design and synthesis of near-infrared fluorescence labeled GSH response type podophyllotoxin prodrug |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011199710.3A CN114437098A (en) | 2020-10-30 | 2020-10-30 | Design and synthesis of near-infrared fluorescence labeled GSH response type podophyllotoxin prodrug |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114437098A true CN114437098A (en) | 2022-05-06 |
Family
ID=81358161
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011199710.3A Pending CN114437098A (en) | 2020-10-30 | 2020-10-30 | Design and synthesis of near-infrared fluorescence labeled GSH response type podophyllotoxin prodrug |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114437098A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114539275A (en) * | 2020-11-26 | 2022-05-27 | 南京碳硅人工智能生物医药技术研究院有限公司 | Based on camptothecin on H2O2Design and synthesis of responsive fluorescently labeled prodrugs |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103804388A (en) * | 2014-01-29 | 2014-05-21 | 邹忠梅 | 4beta-nitrogen-substituted furan tertiary amine podophyllotoxin derivative as well as preparation method and application thereof |
| CN104945409A (en) * | 2015-05-15 | 2015-09-30 | 东华大学 | Prodrug of compound podophyllotoxin PPT with anti-tumour activity and preparation method thereof |
-
2020
- 2020-10-30 CN CN202011199710.3A patent/CN114437098A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103804388A (en) * | 2014-01-29 | 2014-05-21 | 邹忠梅 | 4beta-nitrogen-substituted furan tertiary amine podophyllotoxin derivative as well as preparation method and application thereof |
| CN104945409A (en) * | 2015-05-15 | 2015-09-30 | 东华大学 | Prodrug of compound podophyllotoxin PPT with anti-tumour activity and preparation method thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114539275A (en) * | 2020-11-26 | 2022-05-27 | 南京碳硅人工智能生物医药技术研究院有限公司 | Based on camptothecin on H2O2Design and synthesis of responsive fluorescently labeled prodrugs |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110283583B (en) | Gamma-glutamyl transpeptidase responsive molecular probe and application thereof | |
| CN109320536B (en) | Aza-BODIPY based near-infrared two-window fluorescent probe and preparation and application thereof | |
| CN110511245B (en) | Near-infrared fluorescent probe SHCy-P based on thiohemicyanine dye and preparation method and application thereof | |
| CN109369719B (en) | Molecular probe for alkaline phosphatase detection and preparation method and application thereof | |
| CN111196819B (en) | D-A-D type benzopyrazines compound, preparation method and application thereof | |
| CN110551056B (en) | Cyanine compound, preparation method and application in detection of Golgi pH | |
| CN112341474B (en) | Fluorescent imaging probe and preparation method and application thereof | |
| CN110041723A (en) | The fluorescent dye and preparation method thereof of near-infrared the second window excitation/emission | |
| CN113200940B (en) | Aβ plaque response type fluorescent probe and preparation and application thereof | |
| CN104945322A (en) | Compound for detecting tumor hypoxia and preparation method thereof | |
| CN110423487B (en) | Rhodol derivative dye and application thereof | |
| CN105367566B (en) | Substituted cumarin-thiazole orange derivative and its preparation method and application | |
| CN114437098A (en) | Design and synthesis of near-infrared fluorescence labeled GSH response type podophyllotoxin prodrug | |
| CN114437013A (en) | Coumarin-benzopyrylium salt derivative MI-BP-CC and synthetic method and application thereof | |
| CN111334066B (en) | 640nm excited near-infrared fluorescent dye and preparation method thereof | |
| CN113072574B (en) | Fluoroborazine 29897 | |
| CN112707916A (en) | Design and synthesis of fluorescence labeled prodrug based on response of camptothecin to GSH | |
| CN111793371B (en) | 3, 5-asymmetrically modified BODIPY near-infrared fluorescent dye and preparation method thereof | |
| CN109369569B (en) | Fluorescent probe for detecting methylglyoxal and preparation method and application thereof | |
| CN109796444B (en) | Near-infrared dual-fluorescence probe compound, preparation method and application | |
| CN112079823A (en) | Near-infrared frequency up-conversion fluorescence molecular probe, preparation method and application | |
| CN111606839A (en) | Diagnosis and treatment combined molecular lead compound synthesis method and application in mitochondrial imaging | |
| CN111196821B (en) | Compounds, preparation method thereof and application thereof as near-infrared two-region fluorescent probe for detecting methylglyoxal | |
| CN114437053B (en) | Nanometer probe and application thereof in detecting superoxide anions in golgi | |
| CN112538089B (en) | Near-infrared silicon-based rhodamine fluorescent dye, preparation method and application thereof in-situ wash-free imaging of mitochondrial ridge membrane |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20220506 |