194468-36-5

Basic information

• Product Name: F 12158
• Synonyms: 20',20'-Difluoro-3',4'-dihydrovinorelbine Ditartrate;4'-Deoxy-20',20'-difluoro-5'-norvincaleukoblastine Ditartrate;BMS 710485;F 12158;Javlor;Vinflunine Ditartrate;(2β,3β,4β,5α,12β,19α)-4-(Acetyloxy)-6,7-didehydro-15-[(2R,4R,6S,8S)-4-(1,1-difluoroethyl)-1,3,4,5,6,7,8,9-octahydro-8-(Methoxycarbonyl)-2,6-Methano-2H-azecino[4,3-b]indol-8-yl]-3-hydroxy-16-Methoxy-1-MethylaspidosperMidine-3-carboxylic Acid Methyl Ester (2R,3R)-2,3-Dihydroxybutanedioate;Ditartrate
• CAS NO: 194468-36-5
• Molecular Formula: C49H59F2N4O14
• Molecular Weight: 966.0079664
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 194468-36-5.mol
• Article Data: 1

Chemical Properties

• Melting Point: 244-246°C (dec)
• Appearance: /
• Storage Temp.: -20°C Freezer
• Solubility: DMSO (Slightly), Methanol (Slightly)
• CAS DataBase Reference: F 12158(CAS DataBase Reference)
• NIST Chemistry Reference: F 12158(194468-36-5)
• EPA Substance Registry System: F 12158(194468-36-5)

Safety Data

• Hazardous Substances Data: 194468-36-5(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Uses

Different sources of media describe the Uses of 194468-36-5 differently. You can refer to the following data:
1. Vinflunine Ditartrate can be used as Semisynthetic Vinca alkaloid with microtubule destabilizing and antiangiogenic activity; derivative of Vinorelbine.
2. Vinflunine is a semisynthetic Vinca alkaloid with microtubule destabilizing and antiangiogenic activity. Vinflunine is a derivative of Vinorelbine. Vinflunine is used as an antineoplastic.

Clinical Use

Vinflunine ditartrate is a second generation difluorinated analog of the naturally-occuring substance vinorelbine and it is approved for the treatment of non-small cell lung cancer, metastatic breast cancer and ovarian cancer. Vinflunine, a tubulin polymerization inhibitor, belongs to the vinca alkaloid class of anti-cancer agents. Introduction of the difluoro group of vinflunine dramatically improved antitumor activity of the parent vinorelbine structure. Vinflunine was discovered by Pierre Fabre Laboratories and in 2004 was licensed to Bristol-Myers Squibb for development and commercialization. In 2007, the rights to venflunine were returned to Pierre Fabre which completed its development.

Synthesis

Vinflunine can be prepared directly from vinorelbine (155) through the use of superacid chemistry. Reaction of 155 with antimony pentaflouride in hydrofluoric acid and Nbromosuccinimide followed by treatment with two equivalents of tartaric acid produced vinflunine ditartrate (XV) in 25% yield. An alternative synthesis of vinflunine was realized through reaction of vinblastine or 3’,4’-dihydrovinblastine (156) with antimony pentaflouride and hydrofluoric acid in chloroform to give the difluoro alkaloid 157 in 40% yield Ring contraction was effected by reaction with trifluoroacetic acid and N-bromosuccinimide followed by aqueous sodium bicarbonate and silver tetrafluoroborate to give vinflunine in 88% yield. Vinflunine ditartrate (XV) was prepared by treating a solution of vinflunine in toluene with two equivalents of tartaric acid.

Relevant articles and documents

CRYSTALLINE FORM OF VINFLUNINE DITARTRATE

The present invention relates to a novel crystalline form of vinflunine, to a process for preparing it, and to its uses in the therapeutic field, in particular for treating cancer.