# US 2019/0169140 A1 · Ido1 inhibitor and preparation method and application thereof

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- Number: US 2019/0169140 A1
- Document ID: US20190169140A1
- Status: Published application
- Kind: A1
- Application number: 16/322,914
- Filed: 2017-08-02
- Published: 2019-06-06
- Earliest claimed: 2016-08-02
- Applicants: Shandong Luye Pharmaceutical Co., Ltd.
- Inventors: Yang ZHANG; Zhifei FU; Miaorong LUO; Jian LI; Shuhui CHEN
- Web page: https://patentgrep.com/patent/US20190169140A1

## CPC

- C07D 271/04: 1,2,3-Oxadiazoles; Hydrogenated 1,2,3-oxadiazoles
- A61K 31/4245: Oxadiazoles
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 27/12: for cataracts
- A61P 35/00: Antineoplastic agents
- A61P 37/00: Drugs for immunological or allergic disorders
- C07D 271/08: 1,2,5-Oxadiazoles; Hydrogenated 1,2,5-oxadiazoles
- C07D 413/12: linked by a chain containing hetero atoms as chain links
- C07D 413/14: containing three or more hetero rings
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

A compound as an indoleamine-2,3-dioxygenase 1 (IDO1) inhibitor, and an application thereof in the field of IDO1-related diseases, and in particular a compound as shown in formula (I) and a pharmaceutically acceptable salts thereof.

## Claims

### Claim 1

A compound represented by formula (I) or a pharmaceutically acceptable salt thereof,
wherein
D is O, S or —S(═O)—;
L is selected from a single bond, or selected from the group consisting of —C1-10 alkyl- group, —C3-6 cycloalkyl- group, —C3-6 cycloalkyl-C1-3 alkyl- group, -phenyl-group, 3- to 6-membered heterocycloalkyl- group, and 3- to 6-membered heterocycloalkyl-C1-3 alkyl- group, one or more of which are optionally substituted by 1, 2, or 3 R groups;
R1 is selected from the group consisting of H, F, Cl, Br, I, OH, and NH2, or selected from the group consisting of C1-6 alkyl group, C3-6 cycloalkyl group, C1-6 heteroalkyl group, N,N-bis(C1-6 alkyl)amino group, 3- to 6-membered heterocycloalkyl group, C2-6 alkenyl group, phenyl group, 5- to 9-membered heteroaryl group,
one or more of which are optionally substituted by 1, 2, or 3 R groups;
R2 is OH or CN;
R3, R4, and R5 are each independently selected from the group consisting of H, F, Cl, Br, I, OH, CN, and NH2, or selected from the group consisting of C1-6 alkyl group, C3-6 cycloalkyl group, C1-6 heteroalkyl group, N,N-bis(C1-6 alkyl)amino group, and 3- to 6-membered heterocycloalkyl group, one or more of which are optionally substituted by 1, 2, or 3 R groups;
R is selected from the group consisting of H, F, Cl, Br, I, OH, CN, and NH2, or selected from the group consisting of C1-6 alkyl group, C1-6 heteroalkyl group, N,N-bis(C1-6 alkyl)amino group, C3-6 cycloalkyl group, C2-6 alkenyl group, phenyl group, and thienyl group, one or more of which are optionally substituted by 1, 2, or 3 R′ groups;
R′ is selected from the group consisting of F, Cl, Br, I, OH, CN, and NH2;
“hetero” moieties in the -3- to 6-membered heterocycloalkyl, the -3- to 6-membered heterocycloalkyl-C1-3 alkyl-, the C1-6 heteroalkyl, the 3- to 6-membered heterocycloalkyl, or the 5- to 9-membered heteroaryl groups are each independently selected from the group consisting of —C(═O)NH—, —NH—, —S(═O)2NH—, —S(═O)NH—, N, —O—, —S—, ═O, ═S, —C(═O)O—, —C(═O)—, —C(═S)—, —S(═O)—, —S(═O)2—, —NHC(═O)NH—, —NHC(═S)NH—, and —H2P(═O)—NH— groups; and
in any of above cases, number of heteroatom or heteroatom group is each independently selected from 1, 2 or 3.

### Claim 2 (depends on 1)

The compound or the pharmaceutically acceptable salt thereof according to claim 1, wherein R is selected from the group consisting of H, F, Br, I, OH, CN, and NH2, or selected from the group consisting of C1-6 alkyl group, C1-6 alkoxy group, C1-6 alkylamino group, N,N-bis(C1-6 alkyl)amino group, C2-6 alkenyl group, C3-6 cycloalkyl group, phenyl group, and thienyl group, one or more of which are optionally substituted by 1, 2, or 3 R′ groups.

### Claim 3 (depends on 2)

The compound or the pharmaceutically acceptable salt thereof according to claim 2, wherein R is selected from the group consisting of H, F, Cl, Br, I, OH, CN, and NH2, or selected from the group consisting of Me, Et,
one or more of which are optionally substituted by 1, 2, or 3 R′ groups.

### Claim 4 (depends on 3)

The compound or the pharmaceutically acceptable salt thereof according to claim 3, wherein R is selected form the group consisting of H, F, Cl, Br, I, OH, CN, NH2, Me, Et, CF3, CHF2, CH2F,

### Claim 5 (depends on 1)

The compound or the pharmaceutically acceptable salt thereof according to any claim 1, wherein L is selected from a single bond, or selected from the group consisting of —C1-5 alkyl- group, —C3-6 cycloalkyl- group, —C3-6 cycloalkyl-C1-3 alkyl- group, and -3- to 6-membered azacycloalkyl-C1-3 alkyl- group, one or more of which are optionally substituted by 1, 2 or 3 R groups.

### Claim 6 (depends on 5)

The compound or the pharmaceutically acceptable salt thereof according to claim 5, wherein L is selected from a single bond, or selected from the group consisting of —CH2— group,
one or more of which are optionally substituted by 1, 2, or 3 R groups.

### Claim 7 (depends on 6)

The compound or the pharmaceutically acceptable salt thereof according to claim 6, wherein L is selected from the group consisting of a single bond, —CH2— group,

### Claim 8 (depends on 1)

The compound or the pharmaceutically acceptable salt thereof according to claim 1, wherein R1 is selected from the group consisting of H, F, Cl, Br, I, OH, and NH2, or selected from the group consisting of C1-6 alkyl group, C1-6 alkoxy group, C1-6 alkylthio group, C1-6 alkylamino group, N,N′-bis(C1-3 alkyl)amino group, C3-6 cycloalkyl group, tetrahydrofuryl group, oxetanyl group, C2-6 alkenyl group, phenyl group, thienyl group, pyridyl group, imidazolyl group, thiazolyl group, 2-oxo-imidazolidinyl group, NH2C(═S)—NH— group, C1-6 alkyl-S(═O)— group, C1-6 alkyl-S(═O)2— group, C1-6 alkoxy-C(═O)—NH— group, NH2—S(═O)—NH— group, —NH2—C(═O)— group, NH2—C(═O)—NH— group, H—C(═O)—NH— group, H—S(═O)2—NH— group,
one or more of which are optionally substituted by 1, 2 or 3 R groups.

### Claim 9 (depends on 8)

The compound or the pharmaceutically acceptable salt thereof according to claim 8, wherein R1 is selected from the group consisting of H, F, Cl, Br, I, OH, and NH2, or selected from the group consisting of Me, Et, BOC—NH—, CH2═CH—,
one or more of which are optionally substituted by 1, 2, or 3 R groups.

### Claim 10 (depends on 9)

The compound or the pharmaceutically acceptable salt thereof according to claim 9, wherein R1 is selected from the group consisting of H, F, Cl, Br, I, OH, NH2,
Me, CF3, BOC—NH—, CH2═CH—,

### Claim 11 (depends on 7)

The compound or the pharmaceutically acceptable salt thereof according to claim 7, wherein a structural unit R1-L- is selected from the group consisting of H, NH2,
Me, BOC—NH—,

### Claim 12 (depends on 1)

The compound or the pharmaceutically acceptable salt thereof according to claim 1, wherein R3, R4, and R5 are each independently selected from the group consisting of H, F, Cl, Br, I, OH, CN, and NH2, or selected from the group consisting of Me, Et, C3-6 cycloalkyl, and C1-3 alkoxy, one or more of which are optionally substituted by 1, 2, or 3 R groups.

### Claim 13 (depends on 12)

The compound or the pharmaceutically acceptable salt thereof according to claim 12, wherein R3, R4, and R5 are each independently selected from the group consisting of H, F, Cl, Br, I, OH, CN, and NH2, or selected from the group consisting of Me, Et,
one or more of which are optionally substituted by 1, 2, or 3 R groups.

### Claim 14 (depends on 13)

The compound or the pharmaceutically acceptable salt thereof according to claim 13, wherein R3, R4, and R5 are each independently selected from the group consisting of H, F, Cl, Br, I, CN, CH2F, CHF2, CF3,

### Claim 15 (depends on 1)

The compound or the pharmaceutically acceptable salt thereof according to claim 1, wherein a structural unit
is selected from

### Claim 16 (depends on 14)

The compound or the pharmaceutically acceptable salt thereof according to claim 14, wherein the structural unit
is selected from the group consisting of

### Claim 17 (depends on 1)

The compound or the pharmaceutically acceptable salt thereof according to claim 1, represented by:
wherein
R2, R3, R4, and R5 are as defined claim 1;
R6 is selected from H, or selected from the group consisting of C1-3 alkyl group and C3-6 cycloalkyl group, one or more of which are optionally substituted by 1, 2, or 3 R′ groups; and provided that
R6 is not Me.

### Claim 18 (depends on 17)

The compound or the pharmaceutically acceptable salt thereof according to claim 17, wherein R6 is selected from the group consisting of H, CF3, Et,

### Claim 19 (depends on 1)

The compound or the pharmaceutically acceptable salt thereof according to claim 1, selected from the group consisting of

### Claim 20 (depends on 1)

A pharmaceutical composition, comprising a therapeutically effective amount of the compound or the pharmaceutically acceptable salt thereof according claim 1 as an active ingredient and a pharmaceutical acceptable carrier.

### Claim 21 (depends on 1)

A method for treatment of IDO1-related diseases in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound of claim 1.