N-(substituted-phenyl)-sulfonamide derivatives as kinase inhibitors

Patent metadata

Field	Value
Publication number	US-11833153-B2
Application number	US-202217936576-A
Country	US
Kind code	B2
Filing date	Sep 29, 2022
Priority date	Jun 21, 2016
Publication date	Dec 5, 2023
Grant date	Dec 5, 2023

Abstract

The invention relates to N-(substituted-phenyl)-sulfonamide compounds, which are extremely useful as inhibitors of protein kinases (e.g. PERK kinase) and accordingly can be used for the treatment of cell proliferative disorders, such as cancer, or diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing pharmaceutical compositions comprising these compounds.

First claim

The invention claimed is:

1. A combined preparation for simultaneous, separate or sequential use in anticancer therapy, said combined preparation comprising a compound of formula (I)

wherein
n is 0, 1 or 2;
R1 is an optionally substituted group selected from straight or branched (C1-C8) alkyl, (C2-C8) alkenyl, (C2-C8) alkynyl, (C3-C8) cycloalkyl, (C3-C8) cycloalkenyl, heterocyclyl, aryl and heteroaryl;
R2 and R3 are independently halogen, cyano, OR4 or an optionally substituted group selected from straight or branched (C1-C8) alkyl, (C2-C8) alkenyl, (C2-C8) alkynyl and (C3-C8) cycloalkyl, wherein
R4 is an optionally substituted group selected from straight or branched (C1-C8) alkyl, (C2-C8) alkenyl, (C2-C8) alkynyl and (C3-C8) cycloalkyl;
E1 and E2 are independently CH or N;
A is O, S or NRS, wherein
R5 is hydrogen or an optionally substituted group selected from straight or branched (C1-C8) alkyl, (C2-C8) alkenyl, (C2-C8) alkynyl, (C3-C8) cycloalkyl, (C3-C8) cycloalkenyl, heterocyclyl, aryl and heteroaryl;
or a pharmaceutically acceptable salt thereof, and
one or more chemotherapeutic agents.

2. The combined preparation according to claim 1 , wherein the chemotherapeutic agent is selected from the group consisting of: antihormonal agents, topoisomerase I inhibitors, topoisomerase II inhibitors, agents that target microtubules, platin-based agents, alkylating agents, DNA damaging or intercalating agents, antineoplastic antimetabolites, other kinase inhibitors, other anti-angiogenic agents, inhibitors of kinesins, therapeutic monoclonal antibodies, inhibitors of mTOR, histone deacetylase inhibitors, farnesyl transferase inhibitors, and inhibitors of hypoxic response.

3. The combined preparation according to claim 2 , wherein the antihormonal agents are selected from the group consisting of antiestrogens, antiandrogens and aromatase inhibitors.

Assignees

• Nerviano Medical Sciences Srl

Inventors

• Bindi Simona
• Carenzi Davide
• Motto Ilaria
• Pulici Maurizio

Classifications

• A61K31/519 Primary

  ortho- or peri-condensed with heterocyclic rings · CPC title

• A61K31/4355 Primary

  the heterocyclic ring system containing a five-membered ring having oxygen as a ring hetero atom · CPC title

• A61K31/4365

  the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title