Kinase inhibitors

1. A compound of formula I,

wherein:

T represents:

W represents O, S or NCH 3 ;

V represents N or CR 1 ;

R 1 represents C 1-3 alkoxy, C 1-3 alkyl, C 2-3 alkenyl, C 2-3 alkynyl, which latter four groups are optionally substituted by one or more substituents selected from the group consisting of halo, hydroxy and C 1-2 alkoxy, or R 1 represents H;

R 2 represents —NR A1 S(O) 2 R B1 , —S(O) 1-2 R B2 , —P(O)R B3 R B4 , C(O)NR A2 R A3 or —CH 2 NR A4 C(O)R A5 ;

R A1 to R A5 independently represent H or C 1-3 alkyl optionally substituted by one or more substituents selected from the group consisting of halo, hydroxy, NR C R D and C 1-2 alkoxy, or R A2 and R A3 together represent C 3-6 n-alkylene or C 4-5 n-alkylene interrupted between C2 and C3 by —O—, —S(O) q — or —N(R E )—;

R B1 to R B4 independently represent C 1-3 alkyl or C 3-6 cycloalkyl, which latter two groups are optionally substituted by one or more halo substituents;

R C and R D independently represent H or C 1-3 alkyl, which latter substituent is optionally substituted by hydroxyl or C 1-2 alkoxy, or R C and R D together combine to form C 4-6 alkylene optionally interrupted between C2 and C3 by —O—, —S(O) q — or —N(R E )—;

R E represents H or methyl;

q represents 0, 1 or 2;

R 3 represents C 2-7 alkyl, C 2-7 alkenyl, C 2-7 alkynyl or C 3-7 cycloalkyl, which latter four groups are optionally substituted by hydroxyl, C 1-2 alkoxy or halo, or R 3 represents morpholinyl or trimethylsilyl;

A represents CH or N;

R 4 represents C 1-3 alkoxy, C 3-5 cycloalkoxy, or C 1-3 alkyl, which latter three groups are optionally substituted by one or more halo substituents, or R 4 represents ethynyl, cyano, S(O) 2 CH 3 , halo or H;

Q represents O, S(O) p , SO 2 N(R 6 ) or C(O)N(R 6 );

n represents 1, 2 or 3;

p represents 0, 1 or 2;

R 5a and R 5b independently represent H, methyl or halo, or R 5a and R 5b together represent C 2-6 n-alkylene;

when n represents 1, Z represents O, S or NR 7 or,

when n represents 2 or 3, Z represents either

an O-atom on each occurrence, or

either an S-atom or NR 7 on one occurrence and an O-atom on each other occurence;

R 6 and R 7 independently represent H or methyl;

G represents —[(CH 2 ) r -Het 1 ] 0-1 -C(O) 2 H or a carboxylic acid isostere;

r represents 0 or, when Het 1 is attached to (CH 2 ) r via a ring heteroatom, r may alternatively represent 1; and

Het 1 represents

a 5- or 6-membered heterocyclic group that is fully aromatic, which group contains one or more heteroatoms selected from the group consisting of N, O and S or

a 4- to 7-membered heterocyclic group that is fully saturated or partially unsaturated, and is monocyclic or is fused or bridged bicyclic, which group contains one or more heteroatoms selected from the group consisting of N, O and S,

wherein Het 1 is optionally substituted by one or more substituents selected from the group consisting of C 1-3 alkyl, C 1-3 alkoxy, halo, hydroxyl and oxo,

or a pharmaceutically acceptable salt thereof.

2. A compound of formula Iy,

or a pharmaceutically acceptable salt thereof.

3. A compound according to claim 2 that is 2-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)acetic acid.

4. A compound as claimed in claim 1 that is a compound of formula Ix or Ia,

wherein R 1 to R 4 , R 5a , R 5b , A, Q and n are defined in claim 1 , or a pharmaceutically acceptable salt thereof.

5. A compound as claimed in claim 1 that is a compound of formula Ib,

wherein R 2 , A, Q and n are defined in claim 1 , or a pharmaceutically acceptable salt thereof.

6. A compound as claimed in claim 1 , wherein:

R 1 represents methoxy or deuterated methoxy;

R 3 represents trimethylsilyl or —C(CH 3 ) 2 -R, wherein R represents ethynyl or methyl; and/or

R 4 represents cyclopropoxy or methoxy, which latter group is optionally substituted by one or more halo substituents.

7. A compound as claimed in claim 1 , wherein R 2 represents —C(O)NH 2 , —C(O)NHCH 3 , —S(O) 1-2 CH 3 , —S(O) 1-2 CH 2 CH 3 , —P(O)(CH 3 ) 2 , —N(CH 3 )S(O) 2 CH 3 , —NHS(O) 2 CH 2 CH 3 or —NHS(O) 2 CH 3 .

8. A compound as claimed in claim 1 , wherein A represents CH.

9. A compound as claimed in claim 1 , wherein Q represents C(O)NH, S(O), S(O) 2 or O.

10. A compound as claimed in claim 1 , wherein:

n represents 2;

R 5a and R 5b independently represent H or methyl or R 5a and R 5b together represent —(CH 2 ) 2 —; and/or

G represents —CO 2 H or -Het 1 -CO 2 H, wherein the -Het 1 -CO 2 H moiety is a structural fragment selected from the group consisting of:

or G represents a carboxylic acid isostere selected from the group consisting of tetrazolyl, —C(O)N(H)—S(O) 2 CH 3 , —C(O)N(H)—S(O) 2 N(CH 3 ) 2 ,

or a tautomer of any of the latter three groups.

11. A compound as claimed in claim 1 , wherein:

R 2 represents —NHS(O) 2 CH 3 ;

Q represents C(O)NH or O; and

n represents 2.

12. A compound as claimed in claim 1 which is a compound selected from the group consisting of:

2-(2-(2-(3-((4-((4-(3-(5-(tert-butyI)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxybenzamido)ethoxy)ethoxy)acetic acid;

2-(2-(2-(3-((4-((4-(3-(5-(tert-butyI)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyrimidin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)acetic acid;

2-(2-(2-((3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenyl)sulfonyl)ethoxy)ethoxy)acetic acid;

2-(2-(2-((3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenyl)sulfinyl)ethoxy)ethoxy)acetic acid;

2-(2-(2-((3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonyl)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenyl)sulfonyl)ethoxy)ethoxy)acetic acid;

2-(2-(2-((3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfinyl)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenyl)sulfonyl)ethoxy)ethoxy)acetic acid;

2-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-(trifluoromethyl)phenoxy)ethoxy)ethoxy)acetic acid;

6-((2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)methyl)pyridazine-3-carboxylic acid;

5-((2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)methyl)-1,2,4-oxadiazole-3-carboxylic acid;

2-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-cyclopropoxyphenoxy)ethoxy)ethoxy)acetic acid;

1-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)cyclopropane-1-carboxylic acid;

4-((2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)methyl)thiophene-2-carboxylic acid;

1-((2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)methyl)-3-methyl-1H-pyrazole-4-carboxylic acid;

2-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-ethylphenoxy)ethoxy)ethoxy)acetic acid;

2-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-(methoxy-d 3 )-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)acetic acid;

2-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)-N-(methylsulfonyl)acetamide;

2-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylcarbamoyl)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)acetic acid;

2-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfinyl)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)acetic acid;

2-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonyl)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)acetic acid;

2-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-3-(dimethylphosphoryl)-2-methoxyphenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)acetic acid;

2-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(N-methylmethylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)acetic acid;

5-((2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)methyl)furan-3-carboxylic acid;

5-((2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)methyl)tetrahydrofuran-3-carboxylic acid;

2-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)propanoic acid;

2-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-3-(ethylsulfonyl)-2-methoxyphenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)acetic acid;

2-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-3-(ethylsulfonamido)-2-methoxyphenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)acetic acid;

2-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)isoxazol-3-yl)ureido)naphthalen- 1 -yl)oxy)pyridin-2-y 1 )amino)-5-methoxyphenoxy)ethoxy)ethoxy)acetic acid;

N-(5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-((5-oxo-2,5-dihydroisoxazol-3-yl)methoxy)ethoxy)ethoxy)phenyl)amino)pyridin-4-yl)oxy)naphthalen-1-yl)ureido)phenyl)-methanesulfonamide;

2-((2-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethyl)thio)acetic acid;

2-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)propanoic acid, (R)-isomer;

2-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)propanoic acid, (S)-isomer;

2-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)-2-methylpropanoic acid;

1-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethyl)-1H-pyrazole-4-carboxylic acid;

N-(3-(3-(4-((2-((3-(2-(2-((1H-tetrazol-5-yl)methoxy)ethoxy)ethoxy)-5-methoxyphenyl)amino)-pyridin-4-yl)oxy)naphthalen-1-yl)ureido)-5-(tert-butyl)-2-methoxyphenyl)methanesulfonamide;

2-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)acetic acid;

2-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)-N-(N,N-dimethylsulfamoyl)acetamide;

5-((2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)methyl)thiophene-2-carboxylic acid;

5-((2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)methyl)thiophene-3-carboxylic acid;

2-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-(difluoromethoxy)phenoxy)ethoxy)ethoxy)acetic acid;

2-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-ethynylphenoxy)ethoxy)ethoxy)acetic acid;

N-(5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-((5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)methoxy)ethoxy)ethoxy)phenyl)amino)pyridin-4-yl)oxy)naphthalen-1-yl)ureido)phenyl)methanesulfonamide;

2-(2-(2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-(trifluoromethoxy)phenoxy)ethoxy)ethoxy)acetic acid;

N-(5-(tert-butyl)-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-((3-oxo-2,3-dihydroisoxazol-5-yl)methoxy)ethoxy)ethoxy)phenyl)amino)pyridin-4-yl)oxy)naphthalen-1-yl)ureido)phenyl)-methanesulfonamide; and

5-((2-(3-((4-((4-(3-(5-(tert-butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)methyl)-1-methyl-1H-pyrrole-2-carboxylic acid,

and a pharmaceutically acceptable salt thereof.

13. 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.

14. A pharmaceutical formulation comprising a compound as defined in claim 2 , or a pharmaceutically acceptable salt thereof, in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier.

15. A combination product comprising

(A) a compound as defined in claim 1 , or a pharmaceutically acceptable salt thereof, and

(B) another therapeutic agent,

wherein each of components (A) and (B) is formulated in admixture with a pharmaceutically-acceptable adjuvant, diluent or carrier.

16. A combination product comprising

(A) a compound as defined in claim 2 , or a pharmaceutically acceptable salt thereof, and

(B) another therapeutic agent,

wherein each of components (A) and (B) is formulated in admixture with a pharmaceutically-acceptable adjuvant, diluent or carrier.

17. A method of treating an inflammatory disease, said method comprising administering to a subject an effective amount of a compound as defined in claim 1 , or pharmaceutically acceptable salt thereof, or 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, or a combination product comprising:

(A) a compound as defined in claim 1 , or a pharmaceutically acceptable salt thereof, and

(B) another therapeutic agent,

wherein each of components (A) and (B) is formulated in admixture with a pharmaceutically-acceptable adjuvant, diluent or carrier.

18. A method of treating an inflammatory disease, said method comprising administering to a subject an effective amount of a compound as defined in claim 2 , or pharmaceutically acceptable salt thereof, or a pharmaceutical formulation comprising a compound as defined in claim 2 , or a pharmaceutically acceptable salt thereof, in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier, or a combination product comprising:

(A) a compound as defined in claim 2 , or a pharmaceutically acceptable salt thereof, and

(B) another therapeutic agent,

wherein each of components (A) and (B) is formulated in admixture with a pharmaceutically-acceptable adjuvant, diluent or carrier.

19. A method according to claim 17 , wherein the inflammatory disease is selected from the group consisting of cystic fibrosis, pulmonary hypertension, lung sarcoidosis, idiopathic pulmonary fibrosis, COPD, chronic bronchitis, emphysema, asthma, paediatric asthma, atopic dermatitis, allergic dermatitis, contact dermatitis or psoriasis, allergic rhinitis, rhinitis, sinusitis, conjunctivitis, allergic conjunctivitis, keratoconjunctivitis sicca, dry eye, xerophthalmia, glaucoma, diabetic retinopathy, macular oedema, diabetic macular oedema, central retinal vein occlusion (CRVO), dry and/or wet age related macular degeneration (AMD), post-operative cataract inflammation, uveitis, posterior uveitis, anterior uveitis, pan uveitis, corneal graft and limbal cell transplant rejection, gluten sensitive enteropathy (coeliac disease), eosinophilic esophagitis, intestinal graft versus host disease, Crohn's disease and ulcerative colitis.

20. A method according to claim 18 , wherein the inflammatory disease is selected from the group consisting of cystic fibrosis, pulmonary hypertension, lung sarcoidosis, idiopathic pulmonary fibrosis, COPD, chronic bronchitis, emphysema, asthma, paediatric asthma, atopic dermatitis, allergic dermatitis, contact dermatitis or psoriasis, allergic rhinitis, rhinitis, sinusitis, conjunctivitis, allergic conjunctivitis, keratoconjunctivitis sicca, dry eye, xerophthalmia, glaucoma, diabetic retinopathy, macular oedema, diabetic macular oedema, central retinal vein occlusion (CRVO), dry and/or wet age related macular degeneration (AMD), post-operative cataract inflammation, uveitis, posterior uveitis, anterior uveitis, pan uveitis, corneal graft and limbal cell transplant rejection, gluten sensitive enteropathy (coeliac disease), eosinophilic esophagitis, intestinal graft versus host disease, Crohn's disease and ulcerative colitis.

21. A method according to claim 19 , wherein the inflammatory disease is uveitis, keratoconjunctivitis sicca, dry eye, xerophthalmia, Crohn's disease or ulcerative colitis.

22. A method according to claim 20 , wherein the inflammatory disease is uveitis, keratoconjunctivitis sicca, dry eye, xerophthalmia, Crohn's disease or ulcerative colitis.

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

(a) for compounds of formula I in which G represents —[(CH 2 ) r -Het 1 ] 0-1 -C(O) 2 H, hydrolysis or hydrogenolysis of an ester of formula I(P),

wherein R x represents C 1-6 alkyl or benzyl, respectively, and T, R 4 , R 5a , R 5b , A, Q, Z, n, r and Het 1 are as defined in claim 1 ;

(b) reaction of a compound of formula II,

with a compound of formula III,

wherein one of Z 1 and Z 2 is a structural fragment of formula IVa or IVb,

and the other of Z 1 and Z 2 is a structural fragment of formula V,

wherein W, V, R 1 to R 4 , R 5a , R 5b , A, Q, Z, G and n are as defined in claim 1 ;

(c) reaction of a compound of formula IIa,

 wherein Z 1 is as defined above, with a suitable azide-forming agent,

which reaction is followed, without isolation, by thermal rearrangement of the intermediate acyl azide (of formula Z 1 —C(O)—N 3 ) to provide, in situ, a compound of formula II, which compound is then reacted with a compound of formula III as defined above;

(d) reaction of a compound of formula IIb,

wherein LG 1 represents a leaving group and Z 1 is as defined above, with a compound of formula III, as defined above;

(e) reaction of a compound of formula VI,

wherein LG 2 represents a leaving group and R 1 to R 3 and A are as defined in claim 1 , with a compound of formula VII,

wherein R 4 , R 5a , R 5b , Q, Z, G and n are as defined in claim 1 ;

(f) for compounds of formula I in which Q represents S(O) 1-2 , oxidation of a corresponding compound of formula I in which Q represents S;

(g) for compounds of formula I in which Q represents C(O)NH, reaction of a compound of formula VIII,

wherein LG 3 represents OH, OR x or a leaving group, R x is as defined above and R 1 to R 3 , and A are as defined in claim 1 , with a compound of formula IX,

wherein R 5a , R 5b , Z, G and n are as defined in claim 1 ;

(h) for compounds of formula I in which G represents —[(CH 2 ) r -Het 1 ] 0-1 -C(O) 2 H, oxidation of an alcohol of formula Xa,

wherein T, R 4 , R 5a , R 5b , A, Q, Z, n, r and Het 1 are as defined in claim 1 ; or

(i) for compounds of formula I in which G represents —C(O)N(H)OH, —C(O)N(H)OCH 3 , —C(O)N(H)-S(O) 2 CH 3 or —C(O)N(H)—S(O) 2 N(CH 3 ) 2 , coupling of a corresponding compound of formula I in which G represents —CO 2 H with hydroxylamine, methoxyamine, methanesulfonamide or dimethylsulfamide, respectively;

(k) for compounds of formula I in which G represents a hydroxy-substituted isoxazole having the structure:

reaction of a compound of formula Xb,

wherein T, A, R 4 , R 5a , R 5b , Q, Z and n are as defined in claim 1 and R x is as defined above, with hydroxylamine;

(l) for compounds of formula I in which G represents tetrazol-5-yl, reaction of a compound of formula Xc,

wherein T, A, R 4 , R 5a , R 5b , Q, Z, and n are as defined in claim 1 , with a source of azide;

(m) for compounds of formula I in which G represents 5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl, reaction of a compound of formula Xc, as defined above, with hydroxylamine, followed by reaction of the resulting N-hydroxyamidine (amidoxime) compound with a —C(O)— source;

(n) deprotection of a protected derivative of a compound of formula I, wherein the protected derivative bears a protecting group on an O- or N-atom of the compound of formula I.