US 2017/0000784 A1 · Autophagy Inhibitors

Abstract

The present invention relates to compounds of Formula III, Formula 111(a), Formula V, Formula V(a), Formula A, Formula A 1, Formula A2, Formula A 3, or a pharmaceutically acceptable salt thereof that are useful as pharmaceutical agents, individually and/or in a combination with a chemotherapeutic agent: PLX-4032 (vemurafenib), or the catalytic mTOR inhibitor AZD8055, to treat a cancer and/or a cancer metastasis, for example a cancer harboring a BRAF protein kinase mutation and/or a HRAS protein mutation. Also, a method of treating and/or preventing malaria in a subject, the method comprising administering a therapeutically effective amount of a compound of Formula A, Formula A 1, Formula A2, Formula A 3, or a pharmaceutically acceptable salt thereof to the subject in need.

Claims132

Dependent claims

A method of treating a cancer, or a cancer metastasis in a subject in need thereof, the method comprising:

administering to the subject, a therapeutically effective amount of a compound of Formula A:
or a pharmaceutically acceptable salt thereof,
wherein:
A is an optionally substituted aryl or optionally substituted cycloalkyl;
Z is a 3 to 7 membered heterocycloalkyl;
X is H, halogen, or —CF3;
nD is 1 to 3;
RA is optionally substituted C1-6 alkyl;
and
RB is H, optionally substituted C1-6 alkyl, or optionally substituted C1-6 alkoxyl.

7 more elements

A method of sensitizing cancer cells in a subject undergoing a chemotherapeutic treatment for the treatment of cancer, the method comprising:

identifying cancer cells in the subject, and if the cancer cells are identified in said subject, administering to the subject simultaneously or sequentially, a combination comprising a therapeutically effective amount of a compound of Formula III, Formula III(a), Formula V, Formula V(a), Formula A, Formula A1, Formula A2, Formula A3, or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of an anti-cancer agent, wherein said anti-cancer agent is selected from the group consisting of N-[3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluorophenyl]propane-1-sulfonamide and AZD8055.

A method for the treatment of a cancer or a cancer metastasis in a subject, the method comprising:

administering to the subject simultaneously or sequentially, a therapeutically effective amount of a combination of an anti-cancer agent selected from the group consisting of N-[3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluorophenyl]propane-1-sulfonamide and AZD-8055;
and a compound of Formula A having a structure:
or a pharmaceutically acceptable salt thereof,
wherein:
A is an optionally substituted aryl or optionally substituted cycloalkyl;
Z is a 3 to 7 membered heterocycloalkyl;
X is H, halogen, or —CF3;
nD is 1 to 3;
RA is optionally substituted C1-6 alkyl;
and
RB is H, optionally substituted C1-6 alkyl, or optionally substituted C1-6 alkoxyl;
wherein the compound of Formula A or a pharmaceutically acceptable salt thereof sensitizes the cancer or cancer metastasis to the effects of the anti-cancer agent.

9 more elements

A method for treating a cancer or a cancer metastasis in a subject, the method comprising administering to said subject, simultaneously or sequentially, a synergistically effective therapeutic amount of a combination of a compound of Formula III, Formula III(a), Formula V, Formula V(a), Formula A, Formula A1, Formula A2, Formula A3, or a pharmaceutically acceptable salt thereof, and an anti-cancer agent selected from the group consisting of N-[3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluorophenyl]propane-1-sulfonamide and AZD-8055.

Dependencies are inferred from the claim text.

Autophagy Inhibitors

Life of this patent

Autophagy Inhibitors

Life of this patent

Abstract

Claims132