Water soluble camptothecin derivatives

US5559235A · kind A · utility

Assignee

• Glaxo Wellcome Inc. · US

Inventors

• Michael Joseph Luzzio · Noank, US
• Jeffrey Besterman · Durham, US
• Michael G. Evans · Pittsboro, US
• Peter L. Myers · Aylesbury, GB

Key dates

• Filing date: Jun 10, 1994
• Grant date: Sep 24, 1996
• Expiry date: Jun 10, 2014

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D317/66
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

The present invention relates to water soluble, camptothecin derivatives of formula (I), ##STR1## wherein: 1) R.sup.1 and R.sup.2 represent independently, hydrogen, lower alkyl, C.sub.3-7)cycloalkyl, C.sub.3-7)cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, lower alkoxy lower alkyl; PA1 ii) R.sup.1 represents hydrogen, lower alkyl, C.sub.3-7)cycloalkyl, C.sub.3-7)cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl or lower alkoxy lower alkyl, and R.sup.2 represents --COR.sup.3, PA2 wherein: PA3 R.sup.3 represents hydrogen, lower alkyl, perhalo-lower alkyl, C.sub.3-7)cycloalkyl, C.sub.3-7)cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, lower alkoxy or lower alkoxy lower alkyl; or PA1 iii) R.sup.1 and R.sup.2 taken together with the linking nitrogen form a saturated 3 to 7 atom heterocyclic group of formula (IA) ##STR2## wherein: Y represents O, S, SO, SO.sub.2, CH.sub.2 or NR.sup.4 PA1 wherein: PA2 R.sup.4 represents hydrogen, lower alkyl, perhalo lower alkyl, aryl, aryl substituted with one or more lower alkyl, lower alkoxy, halogen, nitro, amino, lower alkyl amino, perhalo-lower alkyl, hydroxy lower alkyl, lower alkoxy lower alkyl groups or; PA2 --CO…