Epothilone derivatives and their synthesis and use

US6531497B1 · kind B1 · utility

Assignee

• THE SCRIPPS RESEARCH INSTITUTE · US

Inventors

• Kyriacos C. Nicolaou · Philadelphia, US
• Nigel Paul King · Harlow, GB
• Maruice Raymond Verschoyle Finlay · Macclesfield, GB
• Yun He · San Diego, US
• Frank Roschangar · Glen Allen, US
• Dionisios Vourloumis · San Diego, US
• Hans Vallberg · Huddinge, SE
• Antony Bigot · Massy, FR

Key dates

• Filing date: Apr 19, 2001
• Grant date: Mar 11, 2003
• Expiry date: Apr 19, 2021

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y02P20/55
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The invention relates to epothilone analog represented by formula (I) wherein (i) R2 is absent or oxygen; “a” can be either a single or double bond; “b” can be either absent or a single bond; and “c” can be either absent or a single bond, with the proviso that if R2 is oxygen then “b” and “c” are both a single bond and “a” is a single bond; if R2 is absent then “b” and “c” are absent and “a” is a double bond; and if “a” is a double bond, then R2, “b” and “c” are absent; R3 is a radical selected from the group consisting of hydrogen; lower alkyl; —CH═CH2; —C≡CH; —CH2F; —CH2Cl; —CH2—OH; —CH2—O—(C1-C6-alkyl); and —CH2—S—(C1-C6-alkyl); R4 and R5 are independently selected from hydrogen, methyl or a protecting group; and R1 is as defined in the specification, or a salt of a compound of formula (I) where a salt-forming group is present. A further aspect of the invention is related to the synthesis of epothilone E. These compounds have inter alia microtubuli depolym…