# US 12,180,189 B2 · Proteostasis regulators

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- Number: US 12,180,189 B2
- Document ID: US12180189B2
- Status: Granted
- Kind: B2
- Application number: 16/691,390
- Filed: 2019-11-21
- Published: 2020-09-24
- Granted: 2024-12-31
- Earliest claimed: 2011-05-12
- Assignees: Kineta, Inc.
- Applicants: Kineta, Inc.
- Inventors: Megan Foley; Bradley Tait; Matthew Cullen
- Web page: https://patentgrep.com/patent/US12180189B2

## CPC

- C07D 403/06: linked by a carbon chain containing only aliphatic carbon atoms
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 21/02: Muscle relaxants, e.g. for tetanus or cramps
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/28: 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
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 207/333: Radicals substituted by oxygen or sulfur atoms
- C07D 207/337: Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 231/12: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 249/06: with aryl radicals directly attached to ring atoms
- C07D 263/32: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 275/02: not condensed with other rings
- C07D 295/185: from aliphatic carboxylic acids
- C07D 333/20: by nitrogen atoms (nitro, nitroso radicals C07D333/12)
- C07D 333/22: Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
- C07D 401/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 405/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 471/04: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention is directed to compounds having the Formulae (Ia-Ie), (II), (IIIa-IIId), (IVa-IVc), (Va-Vb), (VIa-VIe), (VII), (VIIIa-VIIIc), and (IX), pharmaceutically acceptable salts, prodrugs and solvates thereof, compositions of any of thereof and methods for the treatment of a condition associated with a dysfunction in proteostasis comprising an effective amount of these compounds.

## Claims

### Claim 1

A compound having the Formula (VII):
or a pharmaceutically acceptable salt thereof; wherein:
Ring T is a ring selected from the group consisting of:
A6 is phenyl substituted with halogen;
each Rd is independently hydrogen or methyl;
R16 and R17 are hydrogen;
Z6 is selected from the group consisting of optionally substituted C3-C12 cycloalkyl, optionally substituted heterocyclic, optionally substituted aryl, optionally substituted heteroaryl and NRcRc;
each Rc is independently selected from the group consisting of optionally substituted C1-C10 alkyl, and optionally substituted C3-C12 cycloalkyl; alternatively, two Rc groups are taken together with the nitrogen atom which they are attached to form a optionally substituted 3- to 8-membered heterocycle; and
n is 0, 1 or 2.

### Claim 2 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Z6 is NRcRc, and the two Rc groups are taken together with the nitrogen atom to which they are attached to form a 5- to 6-membered heterocycle.

### Claim 3 (depends on 1)

The compound of claim 1, wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 1)

A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound of claim 1, or a pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 1)

The compound of claim 1, wherein Ring T is
or a pharmaceutically acceptable salt thereof.

### Claim 6

A compound, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from:

### Claim 7 (depends on 5)

The compound of claim 5, or a pharmaceutically acceptable salt thereof, wherein:
A6 is phenyl substituted with halogen;
each Rd is independently hydrogen or methyl;
R16 and R17 are each hydrogen;
Z6 is NRcRc; and
each Rc is independently selected from the group consisting of optionally substituted C1-C10 alkyl, and optionally substituted C3-C12 cycloalkyl; alternatively, two Rc groups are taken together with the nitrogen atom to which they are attached to form an optionally substituted 3- to 8-membered heterocycle.

### Claim 8 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:
Ring T is
A6 is phenyl substituted with halogen;
each Rd is independently hydrogen or methyl;
R16 and R17 are each hydrogen;
Z6 is NRcRc, and the two Rc groups are taken together with the nitrogen atom to which they are attached to form a 5- to 6-membered heterocycle.

### Claim 9 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring T is

### Claim 10 (depends on 9)

The compound of claim 9, or a pharmaceutically acceptable salt thereof, wherein:
A6 is phenyl substituted with halogen;
each Rd is independently hydrogen or methyl;
R16 and R17 are each hydrogen;
Z6 is NRcRc; and
each Rc is independently selected from the group consisting of optionally substituted C1-C10 alkyl and optionally substituted C3-C12 cycloalkyl; alternatively, two Rc groups are taken together with the nitrogen atom to which they are attached to form an optionally substituted 3- to 8-membered heterocycle.