# US 2014/0155387 A1 · Anti-Inflammation Compounds

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- Number: US 2014/0155387 A1
- Document ID: US20140155387A1
- Status: Published application
- Kind: A1
- Application number: 14/112,933
- Filed: 2012-04-20
- Published: 2014-06-05
- Earliest claimed: 2011-04-21
- Assignees: Qurient Co., Ltd.; Institut Pasteur Korea
- Inventors: Zaesung No; Jaeseung Kim; Sung-Jun Han; Jung Hwan Kim; Young Sam Park; Sangchul Lee; Kiyean Nam; Jeongjun Kim; Jinhwa Lee; Sunhee Kang; Min Jung Seo; Saeyeon Lee; Gahee Choi
- Web page: https://patentgrep.com/patent/US20140155387A1

## CPC

- C07D 491/113: with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
- A61K 31/4353: ortho- or peri-condensed with heterocyclic ring systems
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/06: Antiasthmatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- C07D 471/04: Ortho-condensed systems
- 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)
- 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

The present invention refers to: a compound having the general formula (I), wherein n is 0, 1, 2 or; m is 0, 1, 2 or 3; o is 0, 1, 2 or 3; W, X, Y and Z are independently selected from CH, N or N-oxide; A is NR4, C═O, C═S, OP(O)(O), P═O, CH2, or a heteroarly selected from the group consisting of (a), (b), (c), (d), (e), (f), (g); V is C═O, O, S, CH2, or NR5; as well as its use in treating inflammatory diseases such as asthma, COPD, inflammation post infection, arthritis, atherosclerosis, pain and dermatitis.

## Claims

### Claim 1

A method for treating an inflammatory disease, comprising the application or administration, to a patient in need of such treatment, of an effective amount of a compound having the general formula I:
wherein
n is 0, 1, 2, or 3;
m is 0, 1, 2, or 3;
o is 0, 1, 2, or 3;
W, X, Y and Z are independently selected from CH, N or N-oxide;
A is NR4, C═O, C═S, OP(O), P═O, CH2, or a heteroaryl selected from the group consisting of
V is C═O, O, S, CH2 or NR5;
R1 is a moiety selected from the group consisting of
m and n being, independently at each occurrence, selected from 0, 1, 2 or 3;
R2 is, at each occurrence, independently, selected from the group consisting of hydrogen, halogen, C1-C10 alkyl, C3-C10cycloalkyl, C2-C10 alkenyl, C3-C10 cycloalkenyl, C2-C10alkynyl, C1-C10haloalkyl, —OH, —OR5, C1-C10 alkoxy, C3-C10cycloalkoxy, C3-C15cycloalkylalkoxy, C3-C15cycloalkylalkyl, —CN, —NO2, —NH2, —N(R5)2, —C(O)R5, —C(O)OR5, —C(O)N(R5)2, —P(O)OR5, —P(O)OR5N(R5)2, —SR5, —S(O)R5, —S(O)2R5, —S(O)2N(R5)2, aryl, and heterocyclyl, any of which is optionally substituted;
R3 is, at each occurrence, independently selected from the group consisting of hydrogen, halogen, C1-C10 alkyl, C3-C10cycloalkyl, C1-C3 haloalkyl, hydroxyl, —OR6, —CN, —NO2, —NH2, —N(R6)C(O)R6, —C(O)R6, —C(O)OR6, —C(O)N(R6)2, —S(O)R6, —S(O)2R6, —S(O)2N(R6)2, aryl, and heterocyclyl, any of which is optionally substituted, or two groups of R3 are connected to each other to make a five or six membered cyclic or heterocyclic ring, any of which is optionally substituted;
R4 and R5 are, at each occurrence, independently selected from the group consisting of hydrogen, C1-C10 alkyl, C3-C10cycloalkyl, C2-C10 alkenyl, C3-C10 cycloalkenyl, C2-C10alkynyl, C1-C10haloalkyl, —OH, —OR7, C1-C10 alkoxy, C3-C10cycloalkoxy, C3-C15cycloalkylalkoxy, C3-C15cycloalkylalkyl, —NH2, —N(R7)2, —C(O)R7, —C(O)OR7, —C(O)N(R7)2, —S(O)R7, —S(O)2R7, —S(O)2N(R7)2, aryl, and heterocyclyl, any of which is optionally substituted;
R6 is, at each occurrence, independently selected from the group consisting of hydrogen, C1-C10 alkyl, C3-C10cycloalkyl, C2-C10 alkenyl, C3-C10 cycloalkenyl, C2-C10alkynyl, C1-C10haloalkyl, hydroxyl, —OR8, —C(O)R8, —R(R8)C(O)R8, —C(O)OR8, —R8(R8)C(O)OR8, —CN, —NO2, —NH2, —N(R8)2, —C(O)N(R8)2, —R8(R8)C(O)N(R8)2, —S(O)R8, —S(O)2R8, —S(O)2N(R8)2, aryl, and heterocyclyl, any of which is optionally substituted;
R7 is, at each occurrence, independently selected from the group consisting of hydrogen, C1-C10 alkyl, C3-C10cycloalkyl, C2-C10 alkenyl, C3-C10 cycloalkenyl, C2-C10alkynyl, C1-C10haloalkyl, aryl, and heterocyclyl, any of which is optionally substituted; and
R8 is, at each occurrence, independently selected from the group consisting of hydrogen, C1-C8 alkyl optionally substituted with at least one hydroxyl or halogen; C3-C7cycloalkyl, C2-C10 alkenyl, C3-C10 cycloalkenyl, C2-C10alkynyl, C1-C10haloalkyl, aryl, and heterocyclyl, any of which is optionally substituted,
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The method use according to claim 1, wherein said compound has an inhibitory activity on an enzyme involved in an inflammatory pathway, at a concentration of said compound between 0.01-30 μM, having an IC50 on arachidonate 5-lipoxygenase of less than 1 μM and/or having an EC50 of less than 1 μM on the production of leukotriene B4 (LTB4) in peripheral blood mononuclear cells (PBMC).

### Claim 3 (depends on 1)

The method according to claim 1, wherein said compound has one of the formulae 1-403, as shown in Tables 1-3 and/or Example 4 or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 1)

The method according to claim 1, wherein said compound has one of the formulae 127, 128, 189, 219, 224, 225, 232, 243, 265, 266, 299, 311, 312, 313, 314, 380, 393-396 and 398-403 as shown in Tables 2 and/or 3, or a pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 1)

The method according to claim 1, wherein said compound is in a composition that also comprises a pharmaceutically acceptable carrier.

### Claim 6 (depends on 1)

The method according to claim 1, wherein said inflammatory disease is asthma, arthritis, dermatitis chronic obstructive pulmonary disease (COPD), inflammation post infection, atherosclerosis, or pain.

### Claim at position 7

7-9. (canceled)

### Claim 10 (depends on 1)

The method according to claim 1, wherein said effective amount is an amount in the range of 0.01 mg/kg body weight to 1 g/kg body weight of said patient.

### Claim 11 (depends on 1)

A compound that competitively inhibits the specific binding of a compound as defined in claim 1 to arachidonate 5-lipoxygenase (5-lipoxygenase, 5-LO, Alox5).

### Claim 12 (depends on 11)

A method for treating an inflammatory disease comprising administering or applying, to a patient in need of such treatment, an effective amount of a compound according to claim 11.

### Claim 13 (depends on 12)

The method of treatment according to claim 12, wherein said patient is a patient suffering from asthma, atherosclerosis, pain, chronic obstructive pulmonary disease (COPD), inflammation post infection, arthritis and/or dermatitis.

### Claim 14 (depends on 1)

The method, according to claim 1, used to treat asthma.

### Claim 15 (depends on 2)

The method, according to claim 2, wherein said enzyme is arachidonate 5 lipoxygenase.

### Claim 16 (depends on 3)

The method, according to claim 3, wherein said compound has one of the formulae 58, 70, 85, 86, 100, 103, 110, 123, 124, 126, 127, 128, 130, 143, 157, 161, 164, 174, 175, 181, 189, 190, 193, 194, 197, 207, 208, 209, 211, 217, 219, 223, 224, 225, 227, 228, 231, 232, 243, 260, 265, 266, 295, 296, 298, 299, 304, 311, 312, 313, 314, 324, 347, 375, 376, 380, 393-396, and 398-403 as shown in Tables 1 and/or 2, or a pharmaceutically acceptable salt thereof.