# US 10,118,913 B2 · Heterocyclic modulators of lipid synthesis

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- Number: US 10,118,913 B2
- Document ID: US10118913B2
- Status: Granted
- Kind: B2
- Application number: 15/941,387
- Filed: 2018-03-30
- Published: 2018-08-09
- Granted: 2018-11-06
- Earliest claimed: 2012-07-03
- Assignees: 3-V Biosciences, Inc.
- Applicants: 3-V Biosciences, Inc.
- Inventors: Johan D. Oslob; Robert S. McDowell; Russell Johnson; Hanbiao Yang; Marc Evanchik; Cristiana A. Zaharia; Haiying Cai; Lily W. Hu; Allan S. Wagman
- Web page: https://patentgrep.com/patent/US10118913B2

## CPC

- C07D 403/14: containing three or more hetero rings
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes
- A61P 15/08: for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 205/04: having no double bonds between ring members or between ring members and non-ring members
- C07D 211/16: with acylated ring nitrogen atom
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 401/10: linked by a carbon chain containing aromatic rings
- C07D 401/14: containing three or more hetero rings
- C07D 403/10: linked by a carbon chain containing aromatic rings
- C07D 405/04: directly linked by a ring-member-to-ring-member bond
- C07D 405/14: containing three or more hetero rings
- C07D 413/14: containing three or more hetero rings
- C07D 471/04: Ortho-condensed systems
- C07D 487/04: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Heterocyclic modulators of lipid synthesis are provided as well as pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising such compounds; and methods of treating conditions characterized by disregulation of a fatty acid synthase pathway by the administration of such compounds.

## Claims

### Claim 1

A compound of Structure IIIb:
IIIb, or pharmaceutically acceptable salts thereof, wherein:
L-Ar is
or
Ar is
Het is a 5- to 6-membered heteroaryl;
R1 is H, —CN, halogen, C1-C4 alkyl, O(C3-C5 cycloalkyl), O-(4- to 6-membered heterocycle) or O(C1-C4 alkyl), wherein when R1 is not H, —CN or halogen, R1 is optionally substituted with one or more halogens;
each R2 is independently hydrogen, halogen or C1-C4 alkyl;
R3 is H or F;
R11 is H or CH3;
R21 is H, halogen, C1-C4 alkyl, C3-C5 cycloalkyl or 4- to 6-membered heterocycle;
R22 is H, halogen or C1-C2 alkyl; and
each R24 and R25 is independently H, halogen, —CN, (C1-C4 alkyl)-CN, C1-C4 alkyl, (C1-C4 alkyl)-OH, (C1-C4 alkyl)-N(R241)2, (C1-C4 alkyl)1-O(C3-C5 cycloalkyl), (C1-C4 alkyl)t-Ou-(4- to 6-membered heterocycle) or (C1-C4 alkyl)t-O(C1-C4 alkyl),
wherein:
each t is independently 1:
each u is independently 0 or 1; and
each R241 is independently H or C1-C2 alkyl,
wherein the compound is not:

### Claim 2 (depends on 1)

The compound of claim 1 wherein when L-Ar is
Ar is not

### Claim 3 (depends on 1)

The compound of claim 1 wherein L-Ar is
and Ar is

### Claim 4 (depends on 3)

The compound of claim 3 wherein L-Ar is
and Ar is

### Claim 5 (depends on 4)

The compound of claim 4 wherein Ar is R2

### Claim 6 (depends on 1)

The compound of claim 1 wherein R1 is halogen, —CN or C1-C2 haloalkyl.

### Claim 7 (depends on 1)

The compound of claim 1 wherein R2 is H.

### Claim 8 (depends on 1)

The compound of claim 1 wherein R21 is halogen, C1-C4 alkyl, C3-C5 cycloalkyl or 4- to 6-membered heterocycle.

### Claim 9 (depends on 1)

The compound of claim 1 wherein R22 is H or C1-C2 alkyl.

### Claim 10 (depends on 1)

The compound of claim 1 wherein R24 is H, —CN, —Cl, C1-C4 alkyl, (C1-C4 alkyl)-OH, (C1-C4 alkyl)-N(R241)2, (C1-C4 alkyl)t-Ou(C3-C5 cycloalkyl), (C1-C4 alkyl)t-Ou-(4- to 6-membered heterocycle) or (C1-C4 alkyl)-O(C1-C4 alkyl).

### Claim 11 (depends on 1)

The compound of claim 1 wherein R24 is substituted with one or more substituents selected from halogen, C3-C5 cycloalkyl and C1-C2 alkoxy.

### Claim 12 (depends on 11)

The compound of claim 11 wherein R24 is substituted with one or more substituents selected from F, cyclopropyl and OCH3.

### Claim 13 (depends on 1)

The compound of claim 1 wherein R25 is CN, halogen, (C1-C4 alkyl)t-O(C3-C5 cycloalkyl) or (C1-C4 alkyl)t-O(C1-C4 alkyl).

### Claim 14 (depends on 1)

A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier, excipient, or diluent.

### Claim 15 (depends on 1, 14)

A method of treating a hepatitis C infection in a subject comprising administering to the subject a therapeutically effective amount of a compound of claim 1 or a pharmaceutical composition of claim 14.

### Claim 16 (depends on 1, 14)

A method of inhibiting fatty acid synthase activity in a subject by administering to the subject a therapeutically effective amount of a compound of claim 1 or a pharmaceutical composition of claim 14.

### Claim 17 (depends on 1, 14)

A method of treating cancer in a subject comprising administering to the subject a therapeutically effective amount of a compound of claim 1 or a pharmaceutical composition of claim 14, wherein the cancer is selected from the group consisting of breast, lung, thyroid, lymph node, kidney, ureter, bladder, ovary, teste, prostate, bone, skeletal muscle, bone marrow, stomach, esophagus, small bowel, colon, rectum, pancreas, liver, smooth muscle, brain, spinal cord, nerves, ear, eye, nasopharynx, oropharynx, salivary gland, or heart tissue.

### Claim 18 (depends on 17)

The method of claim 17 wherein the cancer is breast cancer, pancreatic cancer, or colon cancer.

### Claim 19 (depends on 18)

The method of claim 18, wherein the cancer is pancreatic cancer.

### Claim 20 (depends on 1)

The compound of claim 1, wherein the compound is: