Aryl hydrocarbon receptor (AhR) modifiers as novel cancer therapeutics

Patent metadata

Field	Value
Publication number	US-10314810-B2
Application number	US-201113812375-A
Country	US
Kind code	B2
Filing date	Jul 27, 2011
Priority date	Jul 27, 2010
Publication date	Jun 11, 2019
Grant date	Jun 11, 2019

Abstract

Provided herein are novel agents that modulate AhR activity for use in therapeutic compositions and methods thereof for inhibiting cancer cell proliferation and tumor cell invasion and metastasis. The agents comprise AhR inhibitors or non-constitutive AhR agonists of Formula (I) and (II) for the inhibition of cancer cell growth and parameters that characterize tumor metastasis, such as tumor cell invasiveness.

First claim

We claim:

1. A pharmaceutical composition comprising an aryl hydrocarbon receptor (AhR) modulator according to Formula (Ia) and a pharmaceutically acceptable excipient, carrier or stabilizer:

wherein:
X′ is H, unsubstituted alkyl, aminosulfonyl, acyl, aryl, or heteroaryl, where each of aminosulfonyl, acyl, aryl, or heteroaryl may be optionally substituted;
n is 0-6;
R 2 is H, alkyl, acyl, heteroaryl, arylalkyl, cycloalkyl, heteroarylalkyl, heterocyclyl, or haloalkyl, each of which may be optionally substituted;
R 3 , R 4 , R 5 and R 6 are independently H, alkyl, acyl, halo, aryl, or heteroaryl, each of which may be optionally substituted; or
a steroisomer or
pharmaceutically acceptable salt thereof; and
wherein the pharmaceutical composition is formulated as a capsule, pill, caplet or tablet.

2. A pharmaceutical composition comprising an aryl hydrocarbon receptor (AhR) modulator CB7993113 of the chemical structure

or a stereoisomer or pharmaceutically acceptable salt thereof;
and a pharmaceutically acceptable excipient, carrier or stabilizer,
wherein the pharmaceutical composition is formulated as a capsule, pill, caplet or tablet.

3. A pharmaceutical composition comprising an aryl hydrocarbon receptor (AhR) modulator according to Formula (Ia), which has the chemical structure

wherein:
X′ is optionally substituted amino,
n is 0-6,
R 2 is optionally substituted heteroaryl, and
R 3 , R 4 , R 5 and R 6 are independently H,
or a stereoisomer or pharmaceutically acceptable salt thereof;
and a pharmaceutically acceptable excipient, carrier or stabilizer,
wherein the pharmaceutical composition is formulated as a capsule, pill, caplet or tablet.

4. The pharmaceutical composition of claim 1 or claim 2 or claim 3 , wherein the pharmaceutical composition is free of lactose.

Assignees

• Sherr David H
• Pollastri Michael
• Schlezinger Jennifer
• Haigh Molina Sarah
• Schaus Scott
• Giguere Joshua Robert
• Univ Boston
• Univ Northeastern
• Boston Medical Ct Corp

Inventors

• Sherr David H
• Pollastri Michael
• Schlezinger Jennifer
• Haigh Molina Sarah
• Schaus Scott
• Giguere Joshua Robert

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D407/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title