Rubitecan

Base Information

• Chemical Name: Rubitecan
• CAS No.: 91421-42-0
• Molecular Formula: C20H15N3O6
• Molecular Weight: 393.356
• Hs Code.: 29399990
• UNII: H19C446XXB
• DSSTox Substance ID: DTXSID7046752
• Nikkaji Number: J448.357J
• Wikipedia: Rubitecan
• Wikidata: Q510113
• NCI Thesaurus Code: C1485
• Metabolomics Workbench ID: 149649
• ChEMBL ID: CHEMBL77305
• Mol file: 91421-42-0.mol

Synonyms:9-nitro-20(S)-camptothecin;9-nitrocamptothecin;9-nitrocamptothecin, (S)-isomer;RFS 2000;RFS-2000;RFS2000;rubitecan

Chemical Property of Rubitecan

Chemical Property:

• Appearance/Colour: Yellow amorphous powder
• Vapor Pressure: 3.53E-28mmHg at 25°C
• Melting Point: 182-186 °C
• Refractive Index: 1.761
• Boiling Point: 816.3 °C at 760 mmHg
• PKA: 11.16±0.20(Predicted)
• Flash Point: 447.5 °C
• PSA: 127.24000
• Density: 1.63 g/cm³
• LogP: 2.51100
• Storage Temp.: Room temp
• Solubility.: DMSO, Chloroform, Methanol
• XLogP3: 0.8
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 1
• Exact Mass: 393.09608521
• Heavy Atom Count: 29
• Complexity: 861

Purity/Quality:

99% ^*data from raw suppliers

Rubitecan ^*data from reagent suppliers

Safty Information:

• Safety Statements: 24/25

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCC1(C2=C(COC1=O)C(=O)N3CC4=CC5=C(C=CC=C5[N+](=O)[O-])N=C4C3=C2)O
• Isomeric SMILES: CC[C@@]1(C2=C(COC1=O)C(=O)N3CC4=CC5=C(C=CC=C5[N+](=O)[O-])N=C4C3=C2)O
• Recent ClinicalTrials: Nitrocamptothecin in Treating Patients With Stage IV Prostate Cancer That Has Not Responded to Hormone Therapy
• Description: Rubitecan, marketed by Supergen as Orathecin, is a promising oral treatment for solid melanoma, prostate, breast, ovarian, and other cancers, as well as leukemia. It is a derivative of camptothecin, a topoisomerase inhibitor known from Chinese Traditional Medicine. It selectively targets the critical S-stage of cellular reproduction – particularly in acidic environments, as in many cancer cells – relaxing DNA supercoiling and generating lethal breaks in the DNA. Due to insolubility, its biological delivery mechanism is not yet effective, and it has not been approved for clinical use. Rubitecan is a DNA topoisomerase I inhibitor. It inhibits DNA topoisomerase I and increases the fraction of supercoiled DNA in a cell-free assay in a concentration-dependent manner. Rubitecan inhibits the growth of A121 ovarian and H460 lung cancer cells (IC50s = 4 and 2 nM, respectively). It also inhibits the growth of doxorubicin-susceptible and -resistant MCF-7 breast cancer cells (IC50s = 2 and 3 nM, respectively). Rubitecan (4 mg/kg twice per week) reduces tumor growth in a U937 leukemia mouse xenograft model.
• Uses: Semisynthetic camptothecin which inhibits DNA topoisomerase I. Prodrug of 9-aminocamptothecin. Antineoplastic Semisynthetic camptothecin which inhibits DNA topoisomerase I. Prodrug of 9-aminocamptothecin. Antineoplastic.

Technology Process of Rubitecan

There total 20 articles about Rubitecan 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: 85.0%

(4S)-4-ethyl-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione (110351-94-5) + 2-amino-6-nitrobenzaldehyde (130133-53-8) → rubitecan (91421-42-0)

Guidance literature:

With hydrogenchloride; acetic acid; for 4h; Heating;

DOI:10.1021/jm00070a013

Reference yield: 84.0%

4-nitro-benzenesulfonic acid 4-ethyl-4-hydroxy-10-nitro-3,13-dioxo-3,4,12,13-tetrahydro-1H-2-oxa-6,12a-diaza-dibenzo[b,h]fluoren-9-yl ester (172917-96-3) → rubitecan (91421-42-0)

Guidance literature:

With 1,1'-bis-(diphenylphosphino)ferrocene; formic acid; triethylamine; palladium diacetate; In 1,4-dioxane; at 70 ℃;

DOI:10.1055/s-2006-942359

Reference yield: 84.0%

Benzenesulfonic acid (S)-4-ethyl-4-hydroxy-10-nitro-3,13-dioxo-3,4,12,13-tetrahydro-1H-2-oxa-6,12a-diaza-dibenzo[b,h]fluoren-9-yl ester (172917-94-1) → rubitecan (91421-42-0)

Guidance literature:

With 1,1'-bis-(diphenylphosphino)ferrocene; formic acid; triethylamine; palladium diacetate; In 1,4-dioxane; at 70 ℃;

DOI:10.1055/s-2006-942359

upstream raw materials:

(4S)-4-ethyl-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione

2-amino-6-nitrobenzaldehyde

camptothecin

4-methoxy-benzenesulfonic acid 4-ethyl-4-hydroxy-10-nitro-3,13-dioxo-3,4,12,13-tetrahydro-1H-2-oxa-6,12a-diaza-dibenzo[b,h]fluoren-9-yl ester

Downstream raw materials:

camptothecin

9-methoxycamptothecin

10-hydroxycamptothecin

9-amino-20(S)-camptothecin

Refernces

• 1、 Gao, Mingzhang,Miller, Kathy D.,Sledge, George W.,Zheng, Qi-Huang. "Radiosynthesis of carbon-11-labeled camptothecin derivatives as potential positron emission tomography tracers for imaging of topoisomerase I in cancers". . p. 3865 - 3869. Retrieved 2007/10/03.
• 2、 -. "Antiangiogenic combination therapy for the treatment of cancer". . . Retrieved 2008/06/13.