# US 2023/0265104 A1 · Novel heterocyclic compounds

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- Number: US 2023/0265104 A1
- Document ID: US20230265104A1
- Status: Published application
- Kind: A1
- Application number: 18/014,556
- Filed: 2021-07-16
- Published: 2023-08-24
- Earliest claimed: 2020-07-16
- Assignees: PRISM BioLab Co., Ltd.
- Applicants: Prism Biolab Co., Ltd.
- Inventors: Hajime TAKASHIMA; Eiji HONDA; Tomonori TAGURI; Jun OZAWA; Haruyuki NISHIDA; Yoichiro HIROSE; Keisuke KIMURA
- Web page: https://patentgrep.com/patent/US20230265104A1

## CPC

- C07D 498/04: Ortho-condensed systems
- A61P 35/00: Antineoplastic agents
- C07D 487/04: Ortho-condensed systems
- C07D 519/00: Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

A compound of the formula (I): wherein each symbol is as defined in the DESCRIPTION, or a pharmaceutically acceptable salt thereof has a superior inhibitory activity on cancer cell proliferation.

## Claims

### Claim 1

A compound represented by the following formula (I):
wherein
Q is a hydrogen atom or is represented by any of the following formulas (II-1) to (II-8):
R1 is a hydrogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkylalkyl, or —(CO)—R1a;
R1a is optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, or optionally substituted heteroaryl;
R1b is a hydrogen atom, or 1 to 3 same or different alkyls;
Q1a is a single bond, optionally substituted alkylene;
Q1b is a hydrogen atom, hydroxy, halogen, cyano,-Q1c, —COQ1c, —CONQ1cQ1d, CONQ1c—OQ1d, —NQ1cQ1d, or —OQ1c;
Q1c is a hydrogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl;
Q1d is a hydrogen atom or optionally substituted alkyl;
Q2a is optionally substituted cycloalkylene;
Q2b and Q2c are the same or different and each is a hydrogen atom or optionally substituted alkyl;
U is —CO— or —CH2—;
R2 is a hydrogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl, or —X—N(R2a)(R2b);
X is an alkylene group;
R2a and R2b are the same or different and each is a hydrogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, or optionally substituted cycloalkylalkyl;
V is an optionally substituted aryl ring, an optionally substituted heteroaryl ring, an optionally substituted partially saturated heteroaryl ring, or an optionally substituted heterocycloalkyl ring;
R3 is a hydrogen atom, hydroxy, halogen, cyano, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, —C≡C—R3a or —COOR3b;
R3a is a hydrogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl,
R3b is a hydrogen atom or optionally substituted alkyl,
is represented by any of the following formulas (III-1) to (III-4):
R4 is a hydrogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl, or optionally substituted heterocycloalkylalkyl, and
Ar2 is an optionally substituted aryl ring or an optionally substituted heteroaryl ring; and
R5 is a hydrogen atom, or optionally substituted alkyl; and
R6 and R7 are the same or different and each is a hydrogen atom or halogen,
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound according to claim 1, wherein the compound is represented by the following formula (I-a):
wherein
R1 is a hydrogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkylalkyl, or —(CO)—R1a;
R1a is optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, or optionally substituted heteroaryl;
is represented by any of the following formulas (II-1-a) to (11-6-a):
R1b is a hydrogen atom, or 1 to 3 same or different alkyls;
R2 is a hydrogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl, or —X—N(R2a)(R2b);
X is an alkylene group;
R2a and R2b are the same or different and each is a hydrogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, or optionally substituted cycloalkylalkyl;
Ar1 is an optionally substituted aryl ring or an optionally substituted heteroaryl ring;
R3 is a hydrogen atom, hydroxy, halogen, cyano, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, —C≡C—R3a or —COOR3b;
R3a is a hydrogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl,
R3b is a hydrogen atom or optionally substituted alkyl,
is represented by any of the following formulas (III-1) to (III-3):
R4 is a hydrogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl, or optionally substituted heterocycloalkylalkyl, and
Ar2 is an optionally substituted aryl ring or an optionally substituted heteroaryl ring; and
R5 is a hydrogen atom, or optionally substituted alkyl,
or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 1)

The compound according to claim 1, wherein the compound is represented by the following formula (IV):
wherein each symbol is as defined in claim 1,
or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 1, 2)

The compound according to claim 1, wherein the compound is represented by the following formula (IV-a):
wherein each symbol is as defined in claim 2,
or a pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 1)

The compound according to claim 1, wherein
Q is represented by any of the following formulas (VI-1) to (VI-3):
wherein each symbol is as defined in claim 1,
or a pharmaceutically acceptable salt thereof.

### Claim 6 (depends on 1)

The compound according to claim 1, wherein
Q is represented by the following formulas (II-7):
and
Q1a is an alkylene and Q1b is —CONH-Q1c, -Q1d, —CO-Q1d, —N(Q1c)-Q1d, wherein Q1c is a hydrogen atom or an alkyl and Q1a is a hydrogen atom or heterocycloalkyl optionally substituted by alkyl,
or a pharmaceutically acceptable salt thereof.

### Claim 7 (depends on 2)

The compound according to claim 2, wherein
is represented by any of the following formulas (VI-1-a) to (VI-3-a):
or a pharmaceutically acceptable salt thereof.

### Claim 8 (depends on 2)

The compound according to claim 2, wherein Ar1 is an optionally substituted pyridine ring, an optionally substituted thiazole ring, an optionally substituted benzothiazole ring, or an optionally substituted quinoxaline ring, or a pharmaceutically acceptable salt thereof.

### Claim 9 (depends on 8)

The compound according to claim 8, wherein
is represented by the following formula (VII-1-a), (VII-2-a), or (VII-3-a):
or a pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 1)

The compound according to claim 1, wherein
R1 is a hydrogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl, or —(CO)—R1a;
R1a is optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, or optionally substituted heteroaryl;
R1b is a hydrogen atom;
R2 is optionally substituted alkyl, or optionally substituted arylalkyl;
R3a is a hydrogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl,
R4 is optionally substituted alkyl,
Ar2 is an optionally substituted aryl ring, and
R5 is a hydrogen atom,
or a pharmaceutically acceptable salt thereof.

### Claim 11 (depends on 1)

The compound according to claim 1, wherein
is represented by the following formula (V):
and
R4′ is optionally substituted alkyl or optionally substituted cycloalkyl,
or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 11)

The compound according to claim 11, wherein
R4′ is an alkyl group,
or a pharmaceutically acceptable salt thereof.

### Claim 13 (depends on 11)

The compound according to claim 11, wherein R4′ is an isobutyl group, or a pharmaceutically acceptable salt thereof.

### Claim 14 (depends on 1)

The compound according to claim 1, wherein R2 is alkyl optionally substituted by alkylthio or alkylsulfonyl, or arylalkyl, or a pharmaceutically acceptable salt thereof.

### Claim 15 (depends on 14)

The compound according to claim 14, wherein R2 is isobutyl, neopentyl, sec-butyl, or benzyl, or a pharmaceutically acceptable salt thereof.

### Claim 16 (depends on 1)

The compound according to claim 1, wherein R1 is alkyl or alkyl substituted by 1 or 2 hydroxys, or a pharmaceutically acceptable salt thereof.

### Claim 17 (depends on 1)

The compound according to claim 1, wherein R3 is a hydrogen atom, hydroxy, or —C≡C—R3a; and R3a is alkyl substituted by hydroxy, or a pharmaceutically acceptable salt thereof.

### Claim 18 (depends on 1)

A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable carrier or diluent.

### Claim 19

(canceled)

### Claim 20 (depends on 1)

A method of treating or preventing a cancer, comprising administering to a subject in need thereof a compound according to claim 1 or a pharmaceutically acceptable salt thereof, in an amount effective to treat or prevent the cancer.

### Claim 21

(canceled)

### Claim 22

(canceled)