Selective angiotensin II receptor ligands

1 . A compound of formula I,

wherein:

R 1 represents C 1-2 alkyl (optionally substituted by one or more fluorine atoms), OR 7 or a fluorine atom;

R 2 and R 3 each independently represent H or C 1-6 alkyl, optionally substituted by one or more halogen atoms;

Y 1 , Y 2 , Y 3 and Y 4 independently represent —CH—, —CF— or —N—;

R 4 represents;

(i) C 1-6 alkyl, C 1-6 alkoxy, or C 1-6 alkoxy-C 1-6 alkyl, the alkyl part of which are optionally substituted by one or more halogen atoms, or

(ii) aryl, C 1-6 alkylaryl, C 1-3 alkenylaryl, heteroaryl, C 1-6 alkylheteroaryl or C 1-3 alkenylheteroaryl, each of which are optionally substituted by one or more substituents selected from halogen, —CF 3 , CF 3 O—, C 1-6 alkyl, and C 1-6 alkoxy;

R 5 represents H or C 1-6 alkyl, each of which is optionally substituted by one or more halogen atoms;

R 6 represents C 2-4 alkyl, optionally substituted by one or more halogens; and

R 7 represents H or methyl, optionally substituted by one or more fluorine atoms,

or a pharmaceutically-acceptable salt thereof.

2 . A compound as claimed in claim 1 , wherein R 1 represents C 1-2 alkyl, optionally substituted by up to three fluorine atoms, or OR 7 .

3 . A compound as claimed in claim 1 , wherein R 1 represents methyl.

4 . A compound as claimed in claim 1 , wherein R 2 and R 3 both represent H.

5 . A compound as claimed in claim 1 , wherein R 4 represents C 1-4 alkyl or C 1-4 alkoxy-C 1-4 alkyl group, phenyl; C 1-3 alkylaryl; or C 1-3 alkylheteroaryl, each of which is optionally substituted by one or more halogen atoms.

6 . A compound as claimed in claim 1 , wherein R 5 represents H, methyl, ethyl, n-propyl, n-butyl or isobutyl.

7 . A compound as claimed in claim 1 , wherein R 6 represents n-propyl, n-butyl or isobutyl.

8 . A compound as claimed in claim 1 , wherein R 7 represents H or methyl.

9 . A compound as claimed in claim 1 , wherein Y 1 represents —CF— or —CH and Y 2 , Y 3 and Y 4 all represent —CH—.

10 . A compound as claimed in claim 1 , 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.

11 . A pharmaceutical formulation comprising a compound as defined in claim 1 , or a pharmaceutically acceptable salt thereof in admixture with a pharmaceutically-acceptable, adjuvant, diluent or carrier.

12 . A method of treatment of:

(i) an autoimmune disease selected from the group consisting of arthritis, rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, multiple sclerosis, psoriasis and inflammatory bowel disease;

(ii) a viral respiratory tract infection and/or pneumonia as a consequence thereof;

(iii) a fibrotic disease;

(iv) a chronic kidney disease;

(v) pulmonary hypertension;

(vi) heart failure; and/or

(vii) myocardial infarction;

which comprises administering an effective amount of a compound as defined in claim 1 , or a pharmaceutically acceptable salt thereof, to a patient in need of such treatment.

13 . A method of treatment as claimed in claim 12 , wherein the disease is an interstitial lung disease.

14 . A method of treatment as claimed in claim 13 , wherein the interstitial lung disease is idiopathic pulmonary fibrosis or sarcoidosis.

15 . A method of treatment as claimed in claim 12 , wherein the autoimmune disease is rheumatoid arthritis or systemic sclerosis.

16 . A method of treatment as claimed in claim 12 , wherein the chronic kidney disease is diabetic nephropathy.

17 . A method of treatment as claimed in claim 12 , wherein the pulmonary hypertension is pulmonary arterial hypertension.

18 . A method of treatment as claimed in claim 12 , wherein the heart failure is with preserved ejection fraction.

19 . A process for the preparation of a compound of formula I as defined in claim 1 , which process comprises:

(i) reaction of a compound of formula II,

wherein R 1 , R 2 , R 3 , R 6 , Y 1 , Y 2 , Y 3 and Y 4 are as defined in claim 1 and L represents C 1-6 alkyl or aryl with a compound of formula III,

wherein R 4 and R 5 are as defined in claim 1 ;

(ii) for compounds of formula I in which R 5 represents H, reaction of a compound of formula IV,

wherein R 1 , R 2 , R 3 , R 6 , Y 1 , Y 2 , Y 3 and Y 4 are as defined in claim 1 , with a compound of formula V,

or a compound of formula VI,

wherein X 1 is a suitable leaving group, and wherein, in each case, R 4 is as defined in claim 1 .

20 . A compound as claimed in claim 10 , which is:

pyridin-2-ylmethyl-3-[[5-isobutyl-3-[4-[(2-tert-butyl-imidazol-1-yl)methyl]phenyl]-2-thienyl]sulfonylurea.