US 2014/0271922 A1Published application

Pirenzepine as an agent in cancer treatment

AssigneeProteosys AG

InventorAndre SCHRATTENHOLZ

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Abstract

The present invention generally relates to the neuroprotective activity of condensed diazepinones, e.g. condensed benzodiazepinones such as pirenzepine or compounds which are metabolized to condensed benzodiazepinones such as olanzapine. These compounds are suitable as co-medicaments for the prevention and/or treatment of drug-induced neurotoxic effects in general and neurotoxic side effects during cancer treatments with cytostatic drugs such as platinum-derivatives, e.g. cis-, carbo- and oxaliplatin, taxanes, bleomycin, cyclophosphamide and vincristine etc. Further, these compounds have an intrinisic anti-cancer activity on their own due to PARP-1 inhibition, which prevents NADH depletion in oxidative metabolism of healthy cells thus preventing the shift to anoxygenic, glycolytic metabolism present in many types of tumour cells thus eliminating this crucial metabolic advantage favouring tumour growth. These results exploit the fact of differential PARP-1 expression between many cancer cells and healthy tissues.

Claims16

Dependent claims

Use of a compound of formula I

wherein A and B are a five- or six-membered ring optionally containing at least one heteroatom selected from N, S and O, wherein the ring is optionally mono- or polysubstituted with halo, C1-C4-(halo)-alkyl, C1-C4-(halo)-alkoxy, amino, C1-C4-alkyl-amino, or di(C1-C4-alkyl)amino,
W is S, O, NR, or CHR,
R1 is hydrogen, Y or COY,
R2 is hydrogen or C1-C4-(halo)-alkyl, and
Y is C1-C6 (halo)alkyl, or C3-C8 cyclo-(halo)-alkyl, wherein the alkyl or cycloalkyl group is optionally substituted with a five- or six-membered ring optionally containing at least one heteroatom selected from N, S and O, wherein the ring is optionally mono- or poly-substituted with halo, C1-C4-(halo)alkyl, C1-C4(halo)alkoxy, amino, C1-C4-alkyl amino, di(C1-C4-alkyl)amino or Z,
wherein Z is a C1-C6 (halo)alkyl group an w-substituted with a group N(R4)2, wherein each R4 is independently hydrogen, C1-C8 alkyl, or CO—C1-C8-alkyl or wherein both R4 together form a five- or six-membered ring optionally containing at least one further heteroatom selected from N, S and O, wherein the ring is optionally mono- or polysubstituted with halo, C1-C4(halo)-alkyl and C1-C4(halo)alkoxy,
or of a salt or derivative thereof for the manufacture of a cytostatic medicament.

4 more elements

Dependencies are inferred from the claim text.

Facts

Application: 14/056,028Filed 17 Oct 2013
Priority: 13 Jan 2009
Published: 18 Sep 2014
Term ends: Not estimatedThe source records don’t support an estimate.

Classification14 codes

C07D 487/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61K 31/55
Having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins: having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61K 31/551
Having seven-membered rings, e.g. azelastine, pentylenetetrazole: having two nitrogen atoms, e.g. dilazep
A61K 31/5513
Having two nitrogen atoms, e.g. dilazep: 1,4-Benzodiazepines, e.g. diazepam or clozapine

Family

Application61/144,204Us provisional application · filed 13 Jan 2009
Application61/166,839Us provisional application · filed 6 Apr 2009
Application13/144,349Continuation · filed 13 Jul 2011
Application14/056,028Continuation
US 2011/0294791 A1Published application
US 2014/0271922 A1This patent

From the US filing history. Foreign family members aren’t listed.