Unsymmetrical pyrrolobenzodiazepine-dimers for treatment of proliferative diseases

US8592576B2 · kind B2 · utility

Assignee

• SPIROGEN SARL · CH

Inventors

• Philip Wilson Howard · London, GB
• Stephen John Gregson · London, GB
• Luke Masterson · Cambridge, GB

Key dates

• Filing date: Oct 16, 2009
• Grant date: Nov 26, 2013
• Expiry date: Apr 18, 2030

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61P43/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Claimed are unsymmetrical Pyrrolobenzodiazepine-dimers (PBD-dimers) of formula (I), that are unsymmetrical due at least to the values that the variables R12 and R2 represent. Formula (I), wherein: R2 is of formula (II), where A is a C5-7 aryl group, X is selected from the group comprising: OH, SH, CO2H, COH, N═C═O, NHRN, wherein RN is selected from the group comprising H and C1-4 alkyl, and (OC2H4)mOCH3, where m is 1 to 3, and either: (i) Q1 is a single bond, and Q2 is selected from a single bond and —Z—(CH2)n—, where Z is selected from a single bond, O, S and NH and n is from 1 to 3; or (ii) Q1 is —CH═CH—, and Q2 is a single bond; R12 is a C5-10 aryl group, optionally substituted by one or more substituents selected from the group comprising: halo, nitro, cyano, ether, C1-7 alkyl, C3-7 heterocyclyl and bis-oxy-C1-3 alkylene. The other variables are as defined in the claims. The compounds are useful for the treatment of proliferative diseases.