33419-42-0 Usage
Pharmacological effects
The chemical name of etoposide is 9-(4, 6-O-ethylidene-β-D-glucopyranoside)-4'-demethyl-epipodophyllotoxin. It is an off-white crystalline powder and is odorless. Upon being exposed to light, heat, its color is easy to change. It is also hydroscopic. It is almost insoluble in water, slight soluble in methanol, dimethyl sulfoxide and also ethanol.
Etoposide is the newly semi-synthetic derivative of epipodophyllotoxin and belongs to mitotic inhibitors which can make the cells be stalled in the mid-mitosis stage. It is a cell cycle specific anticancer drug. This product can act on the DNA topoisomerase II (Topo II), to form a "Drug-enzyme-DNA" complex, preventing Topo II from participating in DNA repair, resulting in the stallation of DNA replication, thereby inhibiting the proliferation of tumor cell(IC 50 = 59.2 μ M). It mainly takes effects on S phase, G2 phase cells, and caused cell arrest in the G2 phase. The experimental study has found that the complex can be reversed with the elimination of drug. In that case, Top II will become free again so the damaged DNA get repair again, reducing its anti-tumor effect. Therefore, extending the treatment time can enhance the anti-tumor activity. It is mainly used for the treatment of small cell lung cancer, malignant lymphoma, malignant germ cell tumors, and leukemia and also has certain efficacy on treating neuroblastoma, rhabdomyosarcoma, ovarian cancer, non-small cell lung cancer, stomach cancer and esophageal cancer.
This product has a bioavailability of 48% (25% to 74%) after oral administration. The plasma concentration can reach peak at 0.5 to 4 hours after taking this drug. After intravenous injection of this product, the plasma concentration of this drug exhibits biphasic elimination with the half-life of α phase being (1.4 ± 0.4) h and half-life of β phase being (5.7 ± 1.8) hours. The plasma protein binding rate is 74% to 90% with the highest concentration being found in intestine, liver, and kidney while the drug concentration in the cerebrospinal liquid is only 2% to 10% of that in the blood. It is primarily subject to renal excretion with 45% being excreted in the urine at 72 hours after the administration wherein prototype accounts for two-thirds and metabolites account for 15%. 1.5% to 16% of the drug is excreted through from faeces via the bile.
Side effects
1. Over-rapid intravenous infusion rate (less than 30 minutes for the first time of administration) may cause rash, chills, fever, bronchospasm, dyspnea and other allergic reactions.
2. The drug can cause obvious myelosuppression reaction including anemia, leukopenia and thrombocytopenia. This frequently occurs in 7 to 14 days after treatment and can recover after 20 days of stopping administration. Severe neutropenia is the dose-limiting toxicity of the drug.
3. There may be loss of appetite, nausea, vomiting, stomatitis, diarrhea, abdominal pain and constipation. Liver toxicity is rare and may be accompanied with increased level of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase and bilirubin.
4. There may be occasional elevated level of blood urea nitrogen.
5. There may be dizziness, fatigue and tiredness with occasional numbness, headaches and so on; there may be heart palpitations, ECG changes, hypotension; interstitial pneumonia may also occur; hair loss is also common.
Figure 1 the structural formula of etoposide
Contraindications
1. Patients of significantly lower amount of white blood cells and platelets should be disabled.
2. Patients of heart, liver and kidney dysfunction should be disabled.
3. Pregnant women and lactating women should be disabled.
4. Patients allergic to this drug should be disabled.
Uses
Different sources of media describe the Uses of 33419-42-0 differently. You can refer to the following data:
1. It is used as anti-cancer drug mainly used for the treatment of small cell lung cancer, testicular cancer, malignant lymphoma and acute leukemia. It also has certain efficacy in treating neuroblastoma, rhabdomyosarcoma, ovarian cancer, non-small cell lung cancer, stomach cancer and breast cancer.
2. Etoposide is used for germinogenic tumors, ovarian, stomach, and lung cancer, Hodgkin’s
disease, and non-Hodgkin’s lymphoma for both monotherapy and in combination therapy.
3. An antitumur agent that complexes with topoisomerase II and DNA to enhance double-strand and single strand cleavage of DNA and reversible inhitit religation. Blocks the cell cycle in S-phase and G2-phase of the cell cycle. Induces apoptosis in nor
4. A DNA topoisomerase II inhibitor. Semi-synthetic derivative of podophyllotoxin, related structurally to Teniposide. Antineoplastic.
5. anticonvulsant
Usage and Dosage
1. Oral: single-administration; daily: 60~100mg /m2; continuously apply for 10 days and repeat every 3 to 4 weeks. For combination chemotherapy, apply 50 mg/m2 per day and continue to take 3 or 5 days.
2. Intravenous infusion: Use sodium chloride injection for dilute this product of required amount (this drug is instable in 5% glucose injection and can form a fine precipitate). The concentration should not be more than 0.25 mg/ml with the intravenous infusion time being not less than 30 minutes.
Solid tumors: 60~100mg/m2 per day; continue for 3 to 5 days with repeating the medication every 3 to 4 weeks.
Leukemia: 60~100mg/m2 per day; apply for 5 consecutive days; repeat the medication at certain interval according to the blood condition.
Common pediatric dose: for intravenous infusion, administer based on volume/surface area 100~150mg/m2 for continuous 3 to 4 days.
Precautions
1. This product is not suitable for intravenous injection and the intravenous infusion rate should not be too fast and should at least last for half an hour, otherwise it can easily lead to hypotension, laryngeal spasm and other allergic reactions.
2. Don’t choose chest, abdomen and intrathecal injection for administration.
3. During the medication period, the patients should be subject be regular investigation on the peripheral blood condition as well as liver and kidney function.
4. This product should be administrated immediately after dilution. If precipitate occurs, it should be strictly prohibited.
5. This product can cause reproductive toxicity and teratogenicity to animals and can be excreted through breast milk. FDA provided the pregnancy safety of this drug being classified as D class.
This information is edited by Xiongfeng Dai from lookchem.
Drug Interactions
1. Because this product has significant bone marrow suppression effect and should be taken care of when be used in combination with other anticancer drugs.
2. This product can inhibit the body's immune defense mechanism, so that vaccination is not able to stimulate the body to produce antibodies.
3. Within 3 months after the end of chemotherapy, it is not recommended for applying the vaccine virus.
4. This product has a high binding rate to the plasma protein and therefore, the drug bound to plasma protein can affect the excretion of this product.
Chemical Properties
White or almost white, crystalline powder, slightly hygroscopic
Originator
Etopos,Lemery,Mexico
Indications
Etoposide (VePesid) is a semisynthetic derivative of
podophyllotoxin that is produced in the roots of the
American mandrake, or May apple. Unlike podophyllotoxin
and vinca alkaloids, etoposide does not bind to microtubules.
It forms a complex with the enzyme topoisomerase
II, which results in a single-strand breakage of
DNA. It is most lethal to cells in the S- and G2-phases of
the cell cycle. Drug resistance to etoposide is thought to
be caused by decreased cellular drug accumulation.
Etoposide is most useful against testicular and ovarian
germ cell cancers, lymphomas, small cell lung cancers,
and acute myelogenous and lymphoblastic
leukemia.Toxicities include mild nausea, alopecia, allergic
reaction, phlebitis at the injection site, and bone
marrow toxicity.
Manufacturing Process
Preparation of 2,3-Di-O-dichloroacetyl-(4,6-O-ethylidene)-β-D-glucopyranose
(hydrogenolysis)An over-dried 100 mL three-necked round bottom flask fitted with a stir bar,
low temperature thermometer, and H2 inlet was charged with 2,3-di-Oetoposide dichloroacetyl-1-O-benzyloxycarbonyl-(4,6-O-ethylidene)-β-D-glucopyranose
(1.8 mmol), in acetone (15-30% concentration) and 10% palladium on
activated carbon powder (0.2 mmol). The solution was stirred until uniform
and then cooled to -10°C to 0°C. After the reaction was over the catalyst was
filtered over sintered glass containing a plug of celite under reduced pressure.
The sintered glass is washed trice with one times the total reaction volume of
anhydrous acetone and the filtrates are pooled and then concentrated to
dryness under reduced pressure at a temperature close to 30°C. The crude
residue was dried under vacuum at ambient temperature and above
compound was thus obtained as white foam in 98% yield with a melting point
of 130°-132°C (from acetone).Preparation of 4'-Demethyl-epi-podophyllotoxin-4-(2,3-di-O-dichloroacetyl-
4,6-O-ethylidene)-β-D-glucopyranosideAn oven-dried, three-neck 250 mL round bottom flask was fitted with a stir
bar, low temperature thermometer, septa and argon inlet, was introduced with
4'-demethyl-epi-podophyllotoxin (1 mmol), dry molecular sieve (1/16 δ
pellets) and anhydrous dichloromethane (20-50% concentration). 2-3-Di-Odichloroacetyl-(
4,6-O-ethylidene)-β-D-glucopyranose (1.7 mmol) in
dichloromethane (10-20% concentration) was added via double-ended needle.
The suspension was stirred until homogenous and then cooled to -40°C to -
60°C in an atmosphere of argon and in the absence of moisture. To the stirred
suspension was added via a syringe, trimethylsilyl trifluoromethane sulfonate
(2 mmol) over 30 minutes. The reaction was held at between -50°C and -
40°C for 30 minutes. The course of the coupling reaction was monitored by
thin layer chromatography. The suspension was allowed to warm to about -
30°C and filtered through a short celite/basic alumina column, eluting twice
with one times the total reaction volume of dichloromethane. The pooled
filtrate was evaporated under reduced pressure to yield the crude
intermediate product 4'-demethyl-epi-podophyllotoxin-4-(2,3-di-Odichloroacetyl-
4,6-O-ethylidene)-β-D-glucopyranose (yield 80%). This crude
product is used directly in the next step without any purification. A sample
was purified by the chromatraton for spectroscopic identification. The results
are as follows: m.p.: 242°-243°C (from methanol).Preparation of 4-Demethyl-epi-podophyllotoxin-4-(4,6-O-ethylidene)-β-Dglucopyranose
(etoposide)To 0.8 mmol of 4'-demethyl-epi-podophyllotoxin-4-(2,3-di-O-dichloroacetyl-
4,6-O-ethylidene)-β-D-glucopyranose in 10-25% concentration in methanol is
added 1.5 mmol of zinc acetate dihydrate. The reaction mixture is refluxed
with stirring under heating for 90 minutes. After completion of the reaction,
the mixture is cooled and the volume reduced to one third by rotary
evaporation under reduced pressure. Working up is effected by diluting the
reaction solution with 100 mL dichloromethane and 100 mL of water. The
aqueous phase was washed with 50 mL of dichloromethane. The combined
dichloromethane phases was washed twice with 50 mL water, 15 mL of
methanol was added to the first wash to prevent precipitation of etoposide.
The organic phase was dried over anhydrous sodium sulphate, filtered and
concentrated by evaporation under vacuum to an amorphous solid. This solid
was re-crystallized from methanol/n-pentane at -4°C to 0°C, thus obtaining
colorless amorphous powder of Etoposide (yield 68%), if the mother liquors
are treated the yield will be higher). Melting point: 256°-258°C.Preparation of Etoposide employing 2,3-di-O-dichloroacetyl-(4,6-Oethylidene)-
β-D-glucopyranose and boron trifluoride etherate as catalyst4'-Demethyl-epi-podophyllotoxin (1 mmol) and 2,3-di-O-dichloroacetyl-(4,6-
O-ethylidene)-β-D-glucopyranose (2 mmol) were introduced into dry
dichloromethane under anhydrous condition. When the temperature was
stabilized to -20°C to -30°C, boron trifluoride etherate (1.5 mmol) was added
slowly with stirring. Reaction was continued at this temperature and
monitored by thin layer chromatography. After the completion of the reaction
as evidenced by TLC, the solution was washed with water, dried over
anhydrous sodium sulfate and concentrated under reduced pressure to afford
the crude intermediate product 4'-demethyl-epi-podophyllotoxin-4-(2,3-di-Odichloroacetyl-
4,6-O-ethylidene)-β-D-glucopyranose. This crude product was
then converted to etoposide by following the procedure as above described.
The yield of final product etoposide was about 60%.
Brand name
Toposar(Sicor); Vepesid (Bristol-Myers Squibb).
Therapeutic Function
Antitumor, Antineoplastic
General Description
Etoposide is available in 50- and 100-mg capsules for oral useand in 100-mg vials for IV use. The agent is approved for usein testicular cancer and small cell lung cancer. It has alsobeen used in a wide variety of cancers including NSCLC,Hodgkin’s and non-Hodgkin’s disease, Kaposi sarcoma,acute lymphocytic leukemia, neuroblastoma, choriocarcinoma,and epithelial, ovarian, testicular, gastric, endometrial,and breast cancers. Etoposide is one of the few natural productderivatives that can be administered orally. When givenby this route, bioavailability is 50%. Administration by the IVroute is also utilized, and the drug is widely distributed whengiven by either route. The agent is highly protein bound(90%) primarily to albumin. Low albumin levels may lead toan increase in free drug and require a lowering of the dose.The drug does not penetrate the blood-brain barrier at normaldoses but does during high-dose therapy. Elimination occursprimarily in the urine with 30% to 40% of an IV dose appearingas unchanged drug. The elimination half-life is 5 to 10hours. Metabolism involves opening of the lactone ring togive the hydroxy acid as the major metabolite. Epimerizationoccurs at C-3 to give the cis-lactone, which may also undergohydrolysis to give the hydroxy acid. Glucuronidation and sulfationof the 4'-OH give products that are inactive. Activemetabolites are formed as a result of CYP3A4 mediated oxidative-O-demethylation of the 3'-methoxy group to give thecatechol followed by oxidation to give the quinone. The toxicitiesof etoposide include dose-limiting myelosuppression,produces nausea and vomiting in 30% to 40% of patients,which is more commonly seen when the drug is administeredorally. The agent also produces anorexia, alopecia, mucositis,and hypersensitivity reactions that may be caused by etoposideor Cremophor EL (polyoxyethylated castor oil), which isused as a vehicle for IV administration of the drug. Leukemia,especially acute myelogenous leukemia, has been associatedwith the drugs’ ability to produce strand breaks with resultanttranslocation of genetic material. The leukemias are generallyseen 5 to 8 years posttreatment and have been associated withtranslocation of several different genes resulting in breakpointsaround the mixed lineage leukemia (MLL) gene.Transcription and translation of this altered DNA giveschimeric proteins, which form partly from the translocatedgene and partly from the MLL gene. Exactly how thesechimeric proteins lead to leukemia is not known, but similaralterations are seen with other topoisomerase inhibitors.
Biochem/physiol Actions
Etoposide is an antitumor agent that complexes with topoisomerase II and DNA to enhance double-strand and single-strand cleavage of DNA and reversibly inhibit religation. Blocks the cell cycle in in S-phase and G2-phase of the cell cycle; induces apoptosis in normal and tumor cell lines; inhibits synthesis of the oncoprotein Mdm2 and induces apoptosis in tumor lines that overexpress Mdm2.
Clinical Use
Etoposide is utilized in the treatment of small cell lung cancer and in combination with other agents in refractory testicular cancer.
Safety Profile
Poison by ingestion,
intraperitoneal, intravenous, and
subcutaneous routes. An experimental
teratogen. Human systemic effects by
ingestion and inhalation: agranulocytosis,
aplastic anemia, and other changes in bone
marrow. Experimental reproductive effects.
Human mutation data reported. When
heated to decomposition it emits acrid
smoke and fumes.
Synthesis
Etoposide, [[5R-(5α,5aβ,8aα,9β)]-9-[4,6-O-ethylidene-β-D-glucopyranosyl)
oxy]-] 5,8,8a,9-tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)furo[3,4: 6,7]-naphtho[2,3-
d]-1,3-dioxol-6(5aH)-one (30.4.5), is made from 4-desmethylepipodophyllotoxin (30.4.3),
the phenolic group of which being previously protected by benzyl chloroformate, which
makes 4-carbobenzyloxy-4-desmethylepipodophyllotoxin (30.4.3). Next, the hydroxyl
group at position C9 is esterified with 4,6-O-ethylyden-2,3-di-O-acetyl-β-D-glucopyranose in
the presence of boron trifluoride to make the corresponding glucopyranoside 30.4.4.
Removing the acetyl group in the glucopyranosyl part of the molecule using zinc acetate in
sodium methoxide, and also removing the benzyloxycarbonyl protection by hydrogenation
using a palladium on carbon catalyst gives the desired etoposide (30.4.5).
Drug interactions
Potentially hazardous interactions with other drugs Anticoagulants: possibly enhanced anticoagulant
effect with coumarins.
Antipsychotics: avoid concomitant use with
clozapine, increased risk of agranulocytosis.
Ciclosporin: 50% reduction in etoposide clearance.
Metabolism
The drug is more than 96% protein bound, undergoes biphasic elimination, and has a terminal half-life of 4 to 11 hours. Approximately 35 to 45% of a dose is eliminated via the kidneys, with less than 6% excreted in feces. The drug should be used with caution in patients with renal or liver disease.
References
Hande, K. R. "Etoposide: four decades of development of a topoisomerase II inhibitor." European Journal of Cancer34.10(1998):1514.
Noda, K, et al. "Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer." New England Journal of Medicine 346.2(2002):85-91.
Check Digit Verification of cas no
The CAS Registry Mumber 33419-42-0 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 3,3,4,1 and 9 respectively; the second part has 2 digits, 4 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 33419-42:
(7*3)+(6*3)+(5*4)+(4*1)+(3*9)+(2*4)+(1*2)=100
100 % 10 = 0
So 33419-42-0 is a valid CAS Registry Number.
33419-42-0Relevant articles and documents
Dually Enzyme- And Acid-Triggered Self-Immolative Ketal Glycoside Nanoparticles for Effective Cancer Prodrug Monotherapy
Yu, Na,Liu, Tao,Zhang, Xi,Gong, Ningqiang,Ji, Tianjiao,Chen, Jing,Liang, Xing-Jie,Kohane, Daniel S.,Guo, Shutao
, p. 5465 - 5472 (2020)
The use of glycoside prodrugs is a promising strategy for developing new targeted medicines for chemotherapy. However, the in vivo utility of such prodrugs is hindered by insufficient activation and the lack of convenient synthetic methods. We have developed an innovative strategy for synthesizing ketal glycoside prodrugs that are unique in being activated by a dual enzyme- and acid-triggered self-immolative mechanism. Amphiphilic glucosyl acetone-based ketal-linked etoposide glycoside prodrug isomers were synthesized and fabricated into excipient-free nanoparticles for effective cancer prodrug monotherapy. Hydrolysis of the glycosidic linkage or the ketal linkage triggered hydrolysis of the other linkage, which resulted in spontaneous self-immolative hydrolysis of the prodrugs. Nanoparticles of the prodrug isomer that was the most labile in a lysosome-mimicking environment displayed high intratumoral accumulation and strong antitumor activity in an A549 xenograft mouse model. Our strategy may be useful for the development of stimulus-responsive self-immolative prodrugs and their nanomedicines.
Real-time monitoring of etoposide prodrug activated by hydrogen peroxide with improved safety
Zhu, Jiawen,Chen, Jingting,Song, Dongmei,Zhang, Wenda,Guo, Jianpeng,Cai, Guiping,Ren, Yuhao,Wan, Chengying,Kong, Lingyi,Yu, Wenying
, p. 7548 - 7557 (2019)
Etoposide is one of the most used first-line chemotherapeutic drugs. However, its application is still limited by its side effects. Herein, we designed a novel H2O2 sensitive prodrug 6YT for selectively releasing the anti-cancer drug etoposide in cancer cells. In this paper, etoposide and a hydrogen peroxide (H2O2) sensitive aryl borate ester group were linked by a fluorescent coumarin and finally the prodrug 6YT was generated. The fluorescence of coumarin was quenched before the connected aryl borate ester group was cleaved by H2O2. However, in the high level H2O2 environment of the tumor, the fluorescence could be activated simultaneously with the release of etoposide, and the drug release state of the prodrug was monitored real-time. With the support of 6YT, we obtained direct and visual evidence of etoposide release in a high H2O2 environment both in cells and zebrafish. The prodrug 6YT was also verified with comparable activity and improved safety with etoposide both in cells and in a mouse model. As a safe and effective prodrug, 6YT is expected to be one of the promising candidates in chemotherapy against cancer.
Preparation method of etoposide, teniposide and analogs of etoposide and teniposide
-
Paragraph 0106; 0107; 0108, (2017/01/02)
The invention discloses a preparation method of etoposide, teniposide and analogs of etoposide and teniposide. The preparation method includes the following steps of 1, selective protection of 4'domethylpodophyllotoxin4'hydroxy; 2, introduction of 4 hydroxy hydroxyl; 3, removal of a protecting group. The method is mild in reaction condition and environmentally friendly, and the yield and purity of the products are high.
Analogues of Etoposide for the Treatment of Tumours
-
Paragraph 0062; 0063, (2013/06/04)
Compounds for treatment of a patient having a tumour that is metastatic and/or that reduces an organ function, wherein the compounds are of the general formula: wherein X is O, NH and S, wherein n is 0, 1 or 2, wherein R1 and R2 are H, methyl or ethyl, or together form a group CR3R4, and wherein R3 and R4 are H, methyl or ethyl.
ANALOGUES OF ETOPOSIDE FOR THE TREATMENT OF TUMOURS
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Page/Page column 11; 13, (2011/11/01)
Analogues of etoposide for the treatment of patients having a tumour, more particularly a tumour that is metastatic and/or that reduces an organ function, are provided. The invention also relates to an in vitro method of selecting a respective patient for treatment with an analogue of etoposide.
ANALOGUES OF ETOPOSIDE FOR THE TREATMENT OF TUMOURS
-
Page/Page column 13; 15, (2011/11/01)
Analogues of etoposide for the treatment of patients having a tumour, more particularly a tumour that is metastatic and/or that reduces an organ function, are provided. The invention also relates to an in vitro method of selecting a respective patient for treatment with an analogue of etoposide.
THERAPEUTIC FOR HEPATIC CANCER
-
, (2011/02/18)
A novel pharmaceutical composition for treating or preventing hepatocellular carcinoma and a method of treatment are provided. A pharmaceutical composition for treating or preventing liver cancer is obtained by combining a chemotherapeutic agent with an anti-glypican 3 antibody. Also disclosed is a pharmaceutical composition for treating or preventing liver cancer which comprises as an active ingredient an anti-glypican 3 antibody for use in combination with a chemotherapeutic agent, or which comprises as an active ingredient a chemotherapeutic agent for use in combination with an anti-glypican 3 antibody. Using the chemotherapeutic agent and the anti-glypican 3 antibody in combination yields better therapeutic effects than using the chemotherapeutic agent alone, and mitigates side effects that arise from liver cancer treatment with the chemotherapeutic agent.
Therapeutic use of at least one botulinum neurotoxin in the treatment of pain induced by at least one anti-neoplastic agent
-
, (2010/04/23)
The present invention relates to a method of treating or preventing pain or pains induced by an anti-neoplastic agent, comprising the step of administering an effective amount of at least one botulinum neurotoxin to a patient in need thereof.
Anti-Claudin 3 Monoclonal Antibody and Treatment and Diagnosis of Cancer Using the Same
-
, (2010/05/13)
Monoclonal antibodies that bind specifically to Claudin 3 expressed on cell surface are provided. The antibodies of the present invention are useful for diagnosis of cancers that have enhanced expression of Claudin 3, such as ovarian cancer, prostate cancer, breast cancer, uterine cancer, liver cancer, lung cancer, pancreatic cancer, stomach cancer, bladder cancer, and colon cancer. The present invention provides monoclonal antibodies showing cytotoxic effects against cells of these cancers. Methods for inducing cell injury in Claudin 3-expressing cells and methods for suppressing proliferation of Claudin 3-expressing cells by contacting Claudin 3-expressing cells with a Claudin 3-binding antibody are disclosed. The present application also discloses methods for diagnosis or treatment of cancers.
BIOREDUCTIVELY-ACTIVATED PRODRUGS
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Page/Page column 20-21, (2008/06/13)
A compound of formula (1), or a pharmaceutically acceptable salt thereof, wherein: - Ar is a substituted heteroaryl group bearing at least one nitro or azido group or is a benzoquinone, naphthoquinone or fused heterocyloquinone; - R1 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl or optionally substituted heteroaryl; - R2 is a glycoside, OH, optionally substituted alkyl, optionally substituted alkoxy, C2-C8 alkenyl, C1-C8 hydroxyalkyl, optionally substituted arylamino, optionally substituted aryl C1-C4 alkylamino or hydroxyalkylamino; and - R3 and R4 are each independently H or halo.
T:Toxic;
