# US 2024/0197685 A1 · Selective angiotensin ii receptor ligands

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- Number: US 2024/0197685 A1
- Document ID: US20240197685A1
- Status: Published application
- Kind: A1
- Application number: 18/283,484
- Filed: 2022-03-23
- Published: 2024-06-20
- Earliest claimed: 2021-03-23
- Assignees: Vicore Pharma AB
- Applicants: Vicore Pharma AB
- Inventors: Tomas Fex; Bengt Ohlsson; Anders Hallberg; Mats Larhed
- Web page: https://patentgrep.com/patent/US20240197685A1

## CPC

- A61K 31/4178: not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
- A61P 37/00: Drugs for immunological or allergic disorders
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 13/02: of urine or of the urinary tract, e.g. urine acidifiers
- C07D 409/10: linked by a carbon chain containing aromatic rings
- C07D 409/14: containing three or more hetero rings
- 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
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

There is provided pharmaceutical compounds of formula (I), wherein R1, R2, R3, R4, R5, R6, Y1, Y2, Y3 and Y4 have meanings given in the description, which compounds are useful in the treatment of autoimmune and/or fibrotic diseases, including interstitial lung diseases, such as idiopathic pulmonary fibrosis and sarcoidosis.

## Claims

### Claim 1

A compound of formula I,
wherein:
R1 represents C1-2 alkyl (optionally substituted by one or more fluorine atoms), OR7 or a fluorine atom;
R2 and R3 each independently represent H or C1-6 alkyl, optionally substituted by one or more halogen atoms;
Y1, Y2, Y3 and Y4 independently represent —CH—, —CF— or —N—;
R4 represents C1-6 alkyl, C1-6 alkoxy, C1-6 alkoxy-CA-6 alkyl, the alkyl part of which are optionally substituted by one or more halogen atoms, or
R4 represents aryl, C1-6 alkylaryl, C1-3 alkenylaryl, heteroaryl, C1-6 alkylheteroaryl or C1-3 alkenylheteroaryl, each of which are optionally substituted by one or more substituents selected from halogen, —CF3, CF3O—, C1-6 alkyl, and C1-6 alkoxy;
R5 represents H or C1-6 alkyl, each of which is optionally substituted by one or more halogen atoms;
R6 represents C2-4 alkyl, optionally substituted by one or more halogens; and
R7 represents H or methyl, optionally substituted by one or more fluorine atoms,
or a pharmaceutically-acceptable salt thereof.

### Claim 2 (depends on 1)

A compound as claimed in claim 1, wherein R1 represents C1-2 alkyl, optionally substituted by up to three fluorine atoms, or OR7.

### Claim 3 (depends on 2)

A compound as claimed in claim 2, wherein R1 represents methyl.

### Claim 4

A compound as claimed in any one of the preceding claims, wherein R2 and R3 both represent H.

### Claim 5

A compound as claimed in any one of the preceding claims, wherein R4 represents C1-4 alkyl or C1-4 alkoxy-C1-4 alkyl group, phenyl; C1-3 alkylaryl; or C1-3 alkylheteroaryl, each of which is optionally substituted by one or more halogen atoms.

### Claim 6

A compound as claimed in any one of the preceding claims, wherein R5 represents H, methyl, ethyl, n-propyl, n-butyl or isobutyl.

### Claim 7

A compound as claimed in any one of the preceding claims, wherein R6 represents n-propyl, n-butyl or isobutyl.

### Claim 8

A compound as claimed in any one of the preceding claims, wherein R7 represents H or methyl.

### Claim 9

A compound as claimed in any one of the preceding claims, wherein Y1 represents —CF— or —CH and Y2, Y3 and Y4 all represent —CH—.

### Claim 10

A compound as claimed in any one of the preceding claims, which is:
furan-2-ylmethyl-3-[[5-isobutyl-3-[4-[(2-tert-butyl-imidazol-1-yl)methyl]phenyl]-2-thienyl]sulfonyl]urea,
thiophen-2-ylmethyl-3-[[5-isobutyl-3-[4-[(2-tert-butyl-imidazol-1-yl)methyl]phenyl]-2-thienyl]sulfonylurea,
2-methoxyethyl-3-[[5-isobutyl-3-[4-[(2-tert-butyl-imidazol-1-yl)methyl]phenyl]-2-thienyl]sulfonylurea,
pyridin-2-ylmethyl-3-[[5-isobutyl-3-[4-[(2-tert-butyl-imidazol-1-yl)methyl]phenyl]-2-thienyl]sulfonylurea,
1-[[3-[4-[(2-tert-butylimidazol-1-yl)methyl]-3-fluoro-phenyl]-5-isobutyl-2-thienyl]sulfonyl]-3-(2-pyridylmethyl)urea,
1-[[3-[4-[(2-tert-butylimidazol-1-yl)methyl]-3-fluoro-phenyl]-5-isobutyl-2-thienyl]sulfonyl]-3-ethyl-urea, or
1-[[3-[4-[(2-tert-butylimidazol-1-yl)methyl]-3-fluoro-phenyl]-5-isobutyl-2-thienyl]sulfonyl]-3-(2-thienylmethyl)urea.

### Claim 11

A compound as defined in any one of the preceding claims, for use as a pharmaceutical.

### Claim 12 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10)

A pharmaceutical formulation comprising a compound as defined in any one of claims 1 to 10 in admixture with a pharmaceutically-acceptable, adjuvant, diluent or carrier.

### Claim 13 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10)

A compound as defined in any one of claims 1 to 10, for use in the treatment of an autoimmune disease, a viral respiratory tract infection and/or pneumonia as a consequence thereof, a fibrotic disease, a chronic kidney disease, pulmonary hypertension, heart failure and/or myocardial infarction.

### Claim 14 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10)

The use of a compound as defined in any one of claims 1 to 10, for the manufacture of a medicament for the treatment of an autoimmune disease, a viral respiratory tract infection and/or pneumonia as a consequence thereof, a fibrotic disease, a chronic kidney disease, pulmonary hypertension, heart failure and/or myocardial infarction.

### Claim 15 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10)

A method of treatment of an autoimmune disease, a viral respiratory tract infection and/or pneumonia as a consequence thereof, a fibrotic disease, a chronic kidney disease, pulmonary hypertension, heart failure and/or myocardial infarction, which comprises administering a compound as defined in any one of claims 1 to 10 to a patient in need of such treatment.

### Claim 16 (depends on 13, 14)

A compound for use as claimed in claim 13, a use as claimed in claim 14, or a method of treatment as claimed in claim 14, wherein the disease is an interstitial lung disease.

### Claim 17 (depends on 16)

A compound for use, a use, or a method of treatment as claimed in claim 16, wherein the interstitial lung disease is idiopathic pulmonary fibrosis or sarcoidosis.

### Claim 18 (depends on 13, 14, 15)

A compound for use as claimed in claim 13, a use as claimed in claim 14, or a method of treatment as claimed in claim 15, wherein the autoimmune disease is rheumatoid arthritis or systemic sclerosis.

### Claim 19 (depends on 13, 14, 15)

A compound for use as claimed in claim 13, a use as claimed in claim 14, or a method of treatment as claimed in claim 15, wherein the chronic kidney disease is diabetic nephropathy.

### Claim 20 (depends on 13, 14, 15)

A compound for use as claimed in claim 13, a use as claimed in claim 14, or a method of treatment as claimed in claim 15, wherein the pulmonary hypertension is pulmonary arterial hypertension.

### Claim 21 (depends on 13, 14, 15)

A compound for use as claimed in claim 13, a use as claimed in claim 14, or a method of treatment as claimed in claim 15, wherein the heart failure is with preserved ejection fraction.

### Claim 22 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10)

A process for the preparation of a compound of formula I as defined in any one of the preceding claims, which process comprises:
(i) reaction of a compound of formula II,
wherein R1, R2, R3, R6, Y1, Y2, Y3 and Y4 are as defined in any one of claims 1 to 10 and L represents C1-6 alkyl or aryl with a compound of formula III,
NHR4R5 III
wherein R4 and R5 are as defined in any one of claims 1 to 10;
(ii) for compounds of formula I in which R5 represents H, reaction of a compound of formula IV,
wherein R1, R2, R3, R, Y1, Y2, Y3 and Y4 are as defined in any one of claims 1 to 10, with a compound of Formula V,
R4—C═O V
or a compound of formula VI,
wherein X1 is a suitable leaving group, and wherein, in each case, R4 is as defined in any one of claims 1 to 10.