US 10,765,673 B2 · Methods and compositions useful for treating diseases involving Bcl-2 family proteins with quinoline derivatives

Abstract

The present invention relates to compositions and methods for cancer treatment comprising compounds of Formulae I, II, and III. In some aspects, the invention relates to the treatment of B-cell Lymphoma or other hematopoietic cancers. In other aspects, the invention provides methods for treating particular types of hematopoietic cancers, such as, for example, B-cell lymphoma, using a combination of one or more compounds of Formulae I, II, and III. Combination therapy with, for example, 26S proteasome inhibitors, such as, for example, Bortezomib, are also included. In another aspect the present invention relates to autoimmune treatment with compounds of Formulae I, II, and III. In another aspect, this invention relates to methods for identifying compounds, for example, compounds of the BH3 mimic class, that have in vitro properties that predict in vivo efficacy against B-cell lymphoma tumors and other cancers as well as autoimmune disease.

Claims10

Dependent claims

A method of inhibiting MCL-1 in a cell, comprising contacting the cell with an effective amount of a compound selected from:

7-((4-methoxyphenyl)(morpholino)methyl)quinolin-8-ol (1);
7-((2,6-dimethylmorpholino)(pyridin-2-yl)methyl)quinolin-8-ol (2);
7-(morpholino(pyridin-2-yl)methyl)quinolin-8-ol (3);
7-(morpholino(4-(trifluoromethyl)phenyl)methyl)quinolin-8-ol (5);
7-((4-chlorophenyl)(piperidin-1-yl)methyl)quinolin-8-ol (6);
7-((4-fluorophenyl)(morpholino)methyl)quinolin-8-ol (7);
ethyl 4-((8-hydroxyquinolin-7-yl)(pyridin-2-yl)methyl)piperazine-1-carboxylate (10),
7-((4-(2-hydroxyethyl)piperazin-1-yl)(phenyl)methyl)quinolin-8-ol (13);
and
tert-butyl 4-((4-fluorophenyl)(8-hydroxyquinolin-7-yl)methyl)piperazine-1-carboxylate (14).

7 more elements

Dependencies are inferred from the claim text.

Facts

Application

15/943,112Filed 2 Apr 2018 · continuation

Priority

20 Jun 2012

Published

US 2018/0221366 A19 Aug 2018

Granted

8 Sep 2020

Term ends

Not estimatedThe source records don’t support an estimate.

Classification17 codes

A61K 31/496
Having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines: non-condensed piperazines…
A61K 31/454
Containing further heterocyclic ring systems: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/4709
Quinolines; Isoquinolines: non-condensed quinolines and containing further heterocyclic rings
A61K 31/5377
1,4-Oxazines, e.g. morpholine: not condensed and containing further heterocyclic rings, e.g. timolol

Family

Application61/662,084Us provisional application · filed 20 Jun 2012

PCT/US2013/046826Parent of this continuation · filed 20 Jun 2013

US 2018/0221366 A1Pre-grant publication · published 9 Aug 2018

Application14/409,789Parent of this continuation

US 2015/0150869 A1Published application

US 10,765,673 B2This patent

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

Methods and compositions useful for treating diseases involving Bcl-2 family proteins with quinoline derivatives

Life of this patent

Methods and compositions useful for treating diseases involving Bcl-2 family proteins with quinoline derivatives

Life of this patent

Abstract

Claims10