Contact us: +91 9550333722 040 - 40102781
Structured search
India
Choose your country
Different countries will display different contents
Try our best to find the right business for you.
My chemicalbook

Welcome back!

HomeProduct name listTopotecan hydrochloride

Topotecan hydrochloride

  • CAS NO.:119413-54-6
  • Empirical Formula: C23H24ClN3O5
  • Molecular Weight: 457.91
  • MDL number: MFCD00866235
  • EINECS: 601-607-9
  • SAFETY DATA SHEET (SDS)
  • Update Date: 2024-11-19 23:02:33
Topotecan hydrochloride Structural

What is Topotecan hydrochloride?

Description

Topotecan is a chemotherapeutic agent medication and acts as a topoisomerase inhibitor. Topotecan is asynthetic, water-soluble analog of camptothecin. It is used in the form of its hydrochloride salt to treat ovarian cancer, lung cancer and other cancer types.

Chemical properties

White Crystalline Solid

Originator

Hycamtin,SmithKline Beecham Pharmaceuticals,UK

The Uses of Topotecan hydrochloride

Naturally occurring amino acid; precursor of tetrapyrroles in the biosynthesis of chlorophyll and heme. Antineoplastic (photosensitizer)

The Uses of Topotecan hydrochloride

antineoplastic; topoisomerase I inhibitor

The Uses of Topotecan hydrochloride

A DNA topoisomerase I inhibitor; semisynthetic analog of Camptothecin. Antineoplastic. Topotecan hydrochloride is a chemotherapy agent that is a topoisomerase 1 inhibitor.

What are the applications of Application

Topotecan Hydrochloride Labeled d6 is an isotope labeled Topo I inhibitor

What are the applications of Application

Topotecan Hydrochloride is a water-soluble inhibitor of DNA Topo I

Manufacturing Process

Camptothecin (CPT) - a compound isolated from the bark, leaves and fruit of Camptotheca acuminate (Wall M. E. et al., J. Am. Chem. Soc. 88, 3888, 1966).
10-Hydroxycamptothecin (10-HCPT) was prepared by subjecting CPT (3.2 g 0.0092 mol), 0.8 g of Pt0 (prepared by pre-reduction of 8 g of amorphous PtO2 in 80 ml of acetic acid for 1.5 h under 1 atm hydrogen pressure) and acetic acid to 1 atm of H2 for 8.5 h after which theoretical amount of H2 absorbed (slightly more than 0.4 L) and uptake of H2 gets slowed down. The reaction mixture was degassed under steam of helium and filtered through celite and washed with acetic acid (20 ml). The resulting solution was treated immediately with Pb(OAc)4 (6.4 g 0.014 mol) in portions and reaction mixture, stirred vigorously under helium for 30 min. Gumy residue was obtained on evaporation of solvent which was triturated with cold water (100 ml) to produce light brown solid. The solid was collected, washed with cold water and air dried overnight when a mixture of 10-HCPT (44%), acetyl 10- hydroxycamptothecin (10-AcHCPT, 26%) and unreacted CPT (32%) on HPLC basis was obtained. This crude mixture was combined with 150 ml of 50% acetic acid and heated under reflux conditions overnight. The reaction mixture was cooled, concentrated to 20 ml and treated with cold water (100 ml) to produce precipitate, which is filtered, washed with more cold water and dried to afford 2.1 g of solid containing 10-HCPT (70%), 10-AcCPT (1.2%) and CPT (21.3%) on the basis HPLC. Mixture was triturating with 0.5% aq HCl to dissolve the water-soluble. When insoluble CPT was removed by filtration. Water-soluble was extracted with chloroform and crystallized from boiling solution of 20% of MeOH in CHCl3 by adding EtOAC dropwise until turbidity appeared to obtain pure yellow 10-(HCPT), melting point 268°-270°C. 10-HCPT (0.364 g 0.01 mmol) and 40% aqueous dimethylamine (12 ml) was added in dichloromethane (50 ml) in which anhydrous potassium carbonate (2.17 g, 15 mmol) has been suspended. The reaction mixture was stirred at room temperature for 5 h, then filtered and solid extracted with ethylacetate (20 ml). The solvent is evaporated in vacuo giving a residue. The residue was triturated with 0.5% aq HCl (50 ml) to dissolve the water-soluble adduct. Water-soluble were partitioned with petroleum ether (3 times 50 ml) and followed by ethylacetate (3 times 50 ml). The aqueous layer was lyophilized as an off white hydrochloride salt of 9-[(dimethylamino)methyl]10- hydroxy(20S)-camptothecin (topotecan hydrochloride) yield 0.236 g (65%).

brand name

Topotecan is INN and BAN.

Therapeutic Function

Antineoplastic

General Description

Topotecan is supplied in 4-mg vials and administered IV forthe treatment of ovarian cancer, cervical cancer, and smallcell lung cancer in those patients who did not respond tofirst-line therapy. Following IV administration, the drug iswidely distributed with 10% to 35% of the agent bound toplasma proteins. There is evidence that the agent may crossthe blood-brain barrier to some extent. In plasma, an equilibriumis established between the lactone and the less activehydroxy acid with 20% of the drug present as the lactone 1hour after the infusion is complete. In contrast to irinotecan,both the lactone and the hydroxy acid bind equally well tohuman serum albumin. N-Demethylation of the tertiaryamine to give the secondary amine is mediated by CYP3A4and represents a minor route of metabolism. Glucuronidationof the parent and the phase I metabolites also occurs to a limited(10%) extent.Elimination occurs primarily in theurine, with 30% of the dose being recovered as unchangeddrug. The terminal elimination half-life is 2 to 3 hours. Themajor toxicity seen for topotecan is dose-limiting myelosuppression.Nausea and vomiting are seen in most (70%–80%)patients, along with diarrhea and abdominal pain. Other toxicitiesinclude headache myalgias, alopecia and elevation ofserum transaminases, alkaline phosphatases, and bilirubin.Microscopic hematuria (blood in the urine) may also be seen.

Biological Activity

topotecan hcl(skf104864)is an inhibitor of topoisomerase 1 and semisynthetic analogue of camptothecin [1].topotecan hcl(skf104864)has been reported to have a potent antitumor activity against tumors in murine models. in addition, topotecan hcl has also shown the potent effect against intravenously implanted p388 leukemia and both intravenously and subcutaneously implanted lewis lung carcinoma. topotecan hcl has noted the activity against subcutaneously implanted solid tumors including chemorefractory tumors and human colon carcinoma xenograft ht-29. topotecan hcl has been found to induce regressions in the lung tumor model (lewis lung carcinoma and b16 melanoma), compared to camptothecin and 9-amino-camptothecin. in the preclinical toxicology studies, topotecan hcl has been revealed to have a concentration-dependent, reversible and limited toxoicity to rapidly proliferation tissues such as bone marrow and gastro-intestinal epithelium [1].

Pharmacokinetics

Topotecan elimination is biphasic, with a terminal half-life of 2.0 to 3.5 hours. Lactone hydrolysis is rapid, and binding to serum proteins is limited to between 25 and 40%. CYP3A4-mediated N-dealkylation to mono?and didealkylated metabolites occurs to a limited extent, and the O-glucuronides that form at multiple points along the metabolic path are excreted via the kidney.

Clinical Use

This active camptothecin analogue is used by the IV route in the treatment of ovarian and small cell lung cancer that has not responded to first-line therapy.

storage

Store at -20°C

References

[1] creemers gj1, lund b, verweij j. topoisomerase i inhibitors: topotecan and irenotecan. cancer treat rev. 1994 jan;20(1):73-96.

Properties of Topotecan hydrochloride

Melting point: 213-218°C
storage temp.  Sealed in dry,Room Temperature
solubility  DMSO (Slightly), Methanol (Slightly), Water (Slightly)
form  Light yellow to greenish powder.
color  White to Off-White
Stability: Hygroscopic
CAS DataBase Reference 119413-54-6(CAS DataBase Reference)

Safety information for Topotecan hydrochloride

Computed Descriptors for Topotecan hydrochloride

Related products of tetrahydrofuran

You may like

Statement: All products displayed on this website are only used for non medical purposes such as industrial applications or scientific research, and cannot be used for clinical diagnosis or treatment of humans or animals. They are not medicinal or edible.