Unsymmetrical pyrrolobenzodiazepine-dimers for treatment of proliferative diseases
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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.
111 Citations
42 Claims
- 1. A compound with the formula I:
- 20. A compound of formula II:
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41. A compound of the formula:
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42. A compound of the formula:
Specification
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- Resources
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Current AssigneeMedImmune Ltd. (Astrazeneca PLC)
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Original AssigneeSpirogen SARL
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InventorsHoward, Philip Wilson, Gregson, Stephen John, Masterson, Luke
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Primary Examiner(s)Loewe, Sun Jae
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Application NumberUS13/123,327Publication NumberTime in Patent Office1,502 DaysField of SearchNoneUS Class Current540/496CPC Class CodesA61P 35/00 Antineoplastic agentsA61P 35/02 specific for leukemiaA61P 43/00 Drugs for specific purposes...C07D 487/04 Ortho-condensed systems
