Topotecan

Base Information

• Chemical Name: Topotecan
• CAS No.: 123948-87-8
• Deprecated CAS: 133242-28-1,138121-88-7
• Molecular Formula: C23H23N3O5
• Molecular Weight: 421.453
• Hs Code.: 2942000000
• European Community (EC) Number: 687-471-1
• NSC Number: 641007
• UNII: 7M7YKX2N15
• DSSTox Substance ID: DTXSID3042685
• Nikkaji Number: J2.256.755A,J2.256.757H,J362.027A
• Wikipedia: Topotecan
• Wikidata: Q419953
• NCI Thesaurus Code: C1413
• RXCUI: 57308
• Pharos Ligand ID: ND1VZLURMY8N
• Metabolomics Workbench ID: 43272
• ChEMBL ID: CHEMBL84
• Mol file: 123948-87-8.mol

Synonyms:9 Dimethylaminomethyl 10 hydroxycamptothecin;9-Dimethylaminomethyl-10-hydroxycamptothecin;Hycamtamine;Hycamtin;Hydrochloride, Nogitecan;Hydrochloride, Topotecan;Nogitecan Hydrochloride;NSC 609699;NSC-609699;NSC609699;SK and F 104864 A;SK and F-104864-A;SK and F104864A;SKF 104864 A;SKF-104864-A;SKF104864A;Topotecan;Topotecan Hydrochloride;Topotecan Monohydrochloride, (S)-Isomer

Chemical Property of Topotecan

Chemical Property:

• Appearance/Colour: light yellow needle crystal or crystalline powder
• Vapor Pressure: 613 psi ( 21.1 °C)
• Melting Point: ?114 °C
• Refractive Index: 1.733
• Boiling Point: 782.9 °C at 760 mmHg
• PKA: 8.92±0.40(Predicted)
• Flash Point: 427.3 °C
• PSA: 104.89000
• Density: 1.49 g/cm³
• LogP: 1.84680
• Storage Temp.: 2-8°C
• Solubility.: H2O: soluble
• XLogP3: 0.5
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 3
• Exact Mass: 421.16377084
• Heavy Atom Count: 31
• Complexity: 867

Purity/Quality:

99% ^*data from raw suppliers

(S)-Topotecan ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T,C,F,Xi
• Hazard Codes: T,C,F,Xi
• Statements: 36/37/38-67-35-20-11-34-48-46-36
• Safety Statements: 26-45-36/37/39-37/39-36-22-24/25-16-7

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCC1(C2=C(COC1=O)C(=O)N3CC4=CC5=C(C=CC(=C5CN(C)C)O)N=C4C3=C2)O
• Isomeric SMILES: CC[C@@]1(C2=C(COC1=O)C(=O)N3CC4=CC5=C(C=CC(=C5CN(C)C)O)N=C4C3=C2)O
• Recent ClinicalTrials: A Study of MORAb-202 Versus Investigator's Choice Chemotherapy in Female Participants With Platinum-resistant High-grade Serous (HGS) Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
• Recent EU Clinical Trials: A Phase 3, Multicenter, Open-Label, Randomized Study of Nemvaleukin Alfa in Combination With Pembrolizumab Versus Investigator’s Choice Chemotherapy in Patients With Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARTISTRY-7)
• Recent NIPH Clinical Trials: Berzosertib+topotecan in relapsed platinum resistant SCLC
• Uses: Anti-cancer drugs.It can be used alone for the treatment of initially or continuously ineffective chemotherapy metastatic ovarian cancer. antineoplastic;DNA topoisomerase type 1 inhibitor (S)-Topotecan is a DNA topoisomerase I inhibitor; semisynthetic analog of Camptothecin. Antineoplastic. Topotecan hydrochloride is a chemotherapy agent that is a topoisomerase 1 inhibitor. Topotecan has been used as a positive control for the identification and analysis of HIF-1α and VEGF inhibitors in human glioma cells under hypoxic conditions1. It has also been used for in vitro apoptosis assays in PA317 cells2.
• Description: Topotecan was launched in the US for the second-line treatment of ovarian cancer. It can be prepared in four steps from camptothecin and is a water soluble derivative of the natural product with decreased toxicity. Unlike its chemical relative irinotecan, topotecacan in not a prodrug and does not require bioactivation. It is an inhibitor of topoisomerase I. Specifically, it inhibits the release of topoisomerase I from DNA, where it relaxes supercoiled DNA, giving rise to single-strand breaks. When the replication fork reaches this complex, double-stand breaks can occur. This signals apoptosis and eventually gives rise to cell death. Evidence indicates hycamtin is safe for people with impaired hepatic function.
• Therapeutic Function: Antineoplastic
• Clinical Use: Antineoplastic agent: Treatment of metastatic ovarian, cervical and small cell lung cancer
• Drug interactions: Potentially hazardous interactions with other drugs None knownccccc

Technology Process of Topotecan

There total 5 articles about Topotecan which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 65.0%

formaldehyd (50-00-0,30525-89-4,61233-19-0) + (S)-10-hydroxycamptothecin (19685-09-7,64439-81-2) + dimethyl amine (124-40-3) → topotecan (123948-87-8)

Guidance literature:

With acetic acid;

DOI:10.1016/j.bmcl.2005.05.108

Reference yield: 65.0%

dichloromethane (75-09-2) + (S)-10-hydroxycamptothecin (19685-09-7,64439-81-2) + dimethyl amine (124-40-3) → topotecan (123948-87-8)

Guidance literature:

With potassium carbonate; at 20 ℃; for 5h;

DOI:10.1081/SCC-200026247

Reference yield:

(S)-10-hydroxycamptothecin (19685-09-7,64439-81-2) + N,N-dimethyl(methylene)ammonium chloride (30354-18-8) → topotecan (123948-87-8)

Guidance literature:

With triethylamine; In dichloromethane; isopropyl alcohol; at 20 - 35 ℃; for 12h;

upstream raw materials:

formaldehyd

(S)-10-hydroxycamptothecin

dimethyl amine

dichloromethane

Downstream raw materials:

C₂₁H₁₈N₂O₆

10-hydroxy-9-<(trimethylammonio)methyl>-(20S)-camptothecin methanosulfonate

10-acetoxy-9-acetoxymethyl-(20S)-camptothecin

10,20(S)-diacetoxy-9-acetoxymethyl-(20S)-camptothecin

Refernces

• 1、 Zhang, Shixuan,Geng, Tao,Jiang, Bo,Song, Ge,Ha, Lisha,Sun, Chenguang,Qian, Yuan,Fan, Qingyu,Guo, Hongmin. "Cyclane-aminol 10-hydroxycamptothecin analogs as novel DNA topoisomerase I inhibitors induce apoptosis selectively in tumor cells". . p. 614 - 623. Retrieved 2014.
• 2、 -. "Therapeutic use of at least one botulinum neurotoxin in the treatment of pain induced by at least one anti-neoplastic agent". . . Retrieved 2010/04/23.