91421-42-0

Basic information

• Product Name: Rubitecan
• Synonyms: 9-NITRO-CPT;9-NITRO-20(S)-CAMPTOTHECIN;(4s)-4-ethyl-4-hydroxy-10-nitro-1h-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4h,12h)-dione;CAMPTOTHECIN, 9-NITRO-20(S)-;RUBETICAN;RUBITECAN;orathecin;Rubitecane
• CAS NO: 91421-42-0
• Molecular Formula: C₂₀H₁₅N₃O₆
• Molecular Weight: 393.35
• Product Categories: API;Intermediates & Fine Chemicals;Pharmaceuticals;Anti-cancer & immunity
• Mol File: 91421-42-0.mol

Chemical Properties

• Melting Point: 182-186°C
• Boiling Point: 816.3 °C at 760 mmHg
• Flash Point: 106℃
• Appearance: Yellow amorphous powder
• Density: 1.63
• Vapor Pressure: 3.53E-28mmHg at 25°C
• Refractive Index: 1.761
• Storage Temp.: Room temp
• Solubility: DMSO, Chloroform, Methanol
• PKA: 11.16±0.20(Predicted)
• Merck: 14,8288
• CAS DataBase Reference: Rubitecan(CAS DataBase Reference)
• NIST Chemistry Reference: Rubitecan(91421-42-0)
• EPA Substance Registry System: Rubitecan(91421-42-0)

Safety Data

• Safety Statements: 24/25
• WGK Germany: 3
• RTECS: UQ0493300
• Hazardous Substances Data: 91421-42-0(Hazardous Substances Data)

Usage

Uses

Used in Oncology:
Rubitecan is used as an antineoplastic agent for inhibiting the growth of various cancer cells, such as A121 ovarian, H460 lung, and doxorubicin-susceptible and -resistant MCF-7 breast cancer cells. It demonstrates potent inhibitory effects on tumor growth, with IC50s of 4 nM, 2 nM, 2 nM, and 3 nM, respectively.
Used in Preclinical Cancer Research:
Rubitecan is used as a prodrug of 9-aminocamptothecin in preclinical cancer research, where it has shown to reduce tumor growth in a U937 leukemia mouse xenograft model when administered at a dosage of 4 mg/kg twice per week. This highlights its potential as a promising candidate for further development and investigation in cancer treatment.

Reference

https://www.sciencedirect.com/topics/medicine-and-dentistry/rubitecan https://en.wikipedia.org/wiki/Rubitecan https://en.wikipedia.org/wiki/Topoisomerase_inhibitor https://en.wikipedia.org/wiki/Camptothecin#cite_note-Y.Pommier_2003-14 https://www.ncbi.nlm.nih.gov/pubmed/1995300

InChI:InChI=1/C20H15N3O6/c1-2-20(26)13-7-16-17-10(8-22(16)18(24)12(13)9-29-19(20)25)6-11-14(21-17)4-3-5-15(11)23(27)28/h3-7,26H,2,8-9H2,1H3/t20-/m0/s1

Upstream product

• 110351-94-5 (4S)-4-ethyl-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione 
• 130133-53-8 2-amino-6-nitrobenzaldehyde 
• 7689-03-4 camptothecin 
• 172917-97-4 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 
• 909094-10-6 4-bromo-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 
• 164159-91-5 4-fluoro-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 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 
• 164159-93-7 Methanesulfonic 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 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 
• 164159-99-3 9-nitro-10-(p-toluenesulfonyl)camptothecin 
• 172917-95-2 Naphthalene-1-sulfonic 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 
• 19685-09-7 (S)-10-hydroxycamptothecin 
• 104267-73-4 9-nitro-10-hydroxy-20(S)-camptothecin 
• 870527-52-9 1,2,6,7-tetrahydro-(20S)-camphthotecine 

Downstream Products

• 91421-43-1 9-amino-20(S)-camptothecin 
• 67656-30-8 10-hydroxycamptothecin 
• 39026-92-1 9-methoxycamptothecin 
• 7689-03-4 camptothecin 

Relevant articles and documents

A practical regiospecific synthesis of 9-nitrocamptothecin

9-Nitrocamptothecin has shown potent antitumor activity against many types of human cancers. A practical scale-up procedure for this compound is reported by selective reduction of corresponding sulfonate. Georg Thieme Verlag Stuttgart.

Radiosynthesis of carbon-11-labeled camptothecin derivatives as potential positron emission tomography tracers for imaging of topoisomerase I in cancers

Four carbon-11-labeled camptothecin derivatives, 9-[11C]methoxy- 20(S)-camptothecin ([11C]5), 10-[11C]methoxy-20(S)- camptothecin ([11C]7), 9-nitro-10-[11C]methoxy-20(S)- camptothecin ([11C]9), and 9-[([11C]trimethylamino)methyl] -10-hydroxy-20(S)-camptothecin ([11C]11), have been synthesized as potential positron emission tomography tracers for imaging of topoisomerase I in cancers.

Urea-mediated regioselective nitration of (20s)-camptothecin

A facile and efficient procedure for the regioselective nitration of (20S) camptothecin, using urea mediated reagent system under relatively mild experimental conditions, yielding promising anticancer drug 9-nitro-(20S)- camptothecin in 40% yield with purity of 94.5% (on HPLC) is being reported.

Antiangiogenic combination therapy for the treatment of cancer

The present invention provides combinations of a DNA topoisomerase I inhibiting agent and a selective COX-2 inhibiting agent for preventing, treating, and/or reducing the risk of developing a neoplasia disorder in a mammal.

Aromatic esters of camptothecins and methods to treat cancers

Aromatic camptothecin ester compounds having the formula: are described as well as formulations containing the compounds. Methods of treating cancer and/or tumors are also disclosed.

Polymeric derivatives of camptothecins

The invention relates to polymeric conjugates of 20-O-[glycyl-aminoacyl-glycyl]-camptothecins and a process for producing the same.

Highly lipophilic camptothecin derivatives

This invention relates to novel derivatives of camptothecin, and will, particularly to derivatives having a substitution at the C-7 position, or at one of the C-9, C-10, C-11 or C-12 positions, or to disubstituted derivatives having a first substitution at C-7 and a second at one of C-9, C-10, C-11 or C-12. The invention also includes methods of using the compounds as Topoisomerase I inhibitors to treat patients with cancer. The invention also includes pharmaceutical formulations which consist of the novel compounds in solution or suspension with one or more pharmaceutical excipients or dilutes.

PROCESS FOR THE PREPARATION OF 9-AMINO CAMPTOTHECIN

A process for preparing the 9-amino camptothecin of formula (I) said process comprising: (1) reacting a compound of formula (III) wherein the hydroxy group on ring A is in the 10- or 12-position, with a nitrating agent, so obtaining a corresponding compound of formula (IV) (2) converting the compound of formula (IV) into a corresponding compound of formula (V) wherein XO is a group that can be removed reductively; and (3) reductively removing the said XO group and reducing the nitro group of the compound of formula (V), so obtaining the 9-amino camptothecin of formula (I), a known antitumor compound. The present invention includes also in its scope compounds having the above reported formula (V) and compound of formula (VII) which are endowed with antitumor activity.p

Methods of preparing and purifying 9-nitro-20-camptothecin

A method is disclosed for the preparation of 9-nitrocamptothecin which involves reacting 20-camptothecin with at least one inorganic nitrate salt and at least one acid effective in catalyzing the formation of a nitronium ion, where the reaction occurs at a temperature and for a time sufficient to form the 9-nitrocamptothecin. Also, methods of further purifying the 9-nitrocamptothecin by column chromatography or by reprecipatation is also disclosed.

Nitration of camptothecin with various inorganic nitrate salts in concentrated sulfuric acid: A new preparation of anticancer drug 9- nitrocamptothecin

The nitration reactions of camptothecin (1) with 19 commonly used inorganic nitrate salts and a combination of two or more different nitrate salts in concentrated sulfuric acid are discussed. A new preparation of a promising anticancer drug 9-nitro-camptothecin (4) with a combination of potassium nitrate and thallium(I) nitrate as the nitrating reagents in concentrated sulfuric acid is described.