Antibacterial compounds
The present invention provides a compound of the following formula and salts thereof: Also provided is the use of these compounds as antibacterials, compositions comprising them and processes for their manufacture.
1. A compound of the following general formula or salt thereof:
wherein
R 1 is selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, S(O) 2 OH, S(O) 2 —C 1-6 alkyl, and M where M represents a monovalent or divalent cation;
R 2 is joined to the same ring B atom as the —C(═O)—X— R 1 moiety and is selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, (C 1-6 alkyl) t C 3-7 cycloalkyl, (C 1-6 alkyl) t aryl, (C 1-6 alkyl) t heterocyclyl, (C 1-6 alkyl) t heteroaryl, NH 2 , NH(C 1-6 alkyl), N(C 1-6 alkyl) 2 , CN, OH, C 1-6 alkoxy, SO 2 H, SO 2 C 1-6 alkyl, SH, SC 1-6 alkyl, halo, haloC 1-6 alkyl, —NH(C═O)OC 1-6 alkyl, —NH(C═O)OC(C 1-3 alkyl) 3 , and wherein C 1-3 alkyl, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl, aryl and heterocyclyl in each case may be further optionally substituted, in particular, with one or more substituents selected from NH 2 , NH(C 1-6 alkyl), N(C 1-6 alkyl) 2 , CN, OH, C 1-6 alkoxy, SO 2 H, SO 2 C 1-6 alkyl, SH, SC 1-6 alkyl and halo or R 2 is a chain of 3 or 4 carbon atoms or carbon and heteroatoms which joins with an adjacent B ring atom to form a fused carbocyclylic or heterocycylic ring which is optionally further substituted;
ring “A” is optionally substituted and is selected from saturated or unsaturated monocyclic C 3-7 cycloalkyl, saturated or unsaturated monocyclic 3-7 membered heterocycle, saturated or unsaturated fused bicyclic C 8-10 cycloalkyl, saturated or unsaturated fused bicyclic 8-10 membered-heterocyclyl, C 6-10 aryl and 5-10 membered heteroaryl;
ring “B” is optionally substituted and is selected from saturated or unsaturated monocyclic C 3-7 cycloalkyl, saturated or unsaturated monocyclic 3-7 membered heterocycle, saturated or unsaturated fused bicyclic C 8-10 cycloalkyl, saturated or unsaturated fused bicyclic 8-12 membered heterocyclyl, C 6-10 aryl, 5-10 membered heteroaryl, and a Spiro bicyclic 8-12 membered heterocyclic ring system;
or ring “A” and ring “B” may join together to form a saturated or unsaturated fused bicyclic C 8-10 cycloalkyl, a saturated or unsaturated fused bicyclic 8-10 membered heterocyclyl and a spiro bicyclic 8-12 membered heterocyclic ring system;
Each Z is independently selected from C—H, C—C 1-3 alkyl, C—OH, C—OC 1-3 alkyl, C-halo, C-haloC 1-3 alkyl, C—CN, or C—(X 2 ) n R 3 wherein R 3 is H, halo, OH, CN, C 1-6 alkyl, C 1-6 alkoxy, haloC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkenyl, saturated or unsaturated monocyclic C 3-7 cycloalkyl, saturated or unsaturated monocyclic 3-7 membered heterocycle, saturated or unsaturated fused bicyclic C 8-10 cycloalkyl, saturated or unsaturated fused bicyclic 8-10 membered heterocyclyl, C 6-10 aryl and 5-10 membered heteroaryl wherein each R 3 may be optionally substituted; provided that one Z is C substituted with ring “A”;
X is O, NH or N(C 1-6 alkyl);
m, n and t are each independently an integer 0 or 1;
X 1 is a covalent bond, a spiro ring centre, or a fused ring bond when m is 0 or when m is 1 is selected from optionally substituted C 1-3 alkylene, optionally substituted C 2-3 alkenylene and optionally substituted C 2-3 alkynylene and wherein each carbon atom in C 1-3 alkylene may be optionally replaced by an oxygen or nitrogen heteroatom or C(═O);
X 2 is a covalent bond when n is 0 or when n is 1 is selected from optionally substituted C 1-4 alkylene, optionally substituted C 2-3 alkenylene and optionally substituted C 2-3 alkynylene and wherein each carbon atom in C 1-3 alkylene and C 2-3 alkenylene may be optionally replaced by an oxygen or nitrogen heteroatom (wherein the nitrogen atom may be substituted with H or C 1-3 alkyl) or C(═O);
Y 1 and Y 2 are each independently selected from C, N, O or S;
Y 3 is selected from C;
------indicates a double or a single bond as the case may be; and
Alk is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl.
2. A compound according to claim 1 of Formula I or a salt thereof
wherein
Z 1 , Z 2 and Z 3 are each independently selected from C—H, C—C 1-3 alkyl, C—OH, C—OC 1-3 alkyl, C-halo, C-haloC 1-3 alkyl, C—CN, or C—(X 2 ) n —R 3 wherein R 3 is H, halo, OH, CN, C 1-6 alkyl, C 1-6 alkoxy, haloC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkenyl, saturated or unsaturated monocyclic C 3-7 cycloalkyl, saturated or unsaturated monocyclic 3-7 membered heterocycle, saturated or unsaturated fused bicyclic C 8-10 cycloalkyl, saturated or unsaturated fused bicyclic 8-10 membered heterocyclyl, C 6-10 aryl and 5-10 membered heteroaryl wherein each R 3 may be optionally substituted;
and wherein R 1 , R 2 , ring “A”, ring “B”, X, Y 1 , Y 2 , Y 3 , m, ------ and Alk are as previously defined in claim 1 .
3. A compound of claim 2 of Formula Ia or a salt thereof
wherein R 1 , R 2 , R 3 , X 1 , X 2 , Z 1 , Z 2 , Y 1 , Y 2 , ring A, ring B, Alk, m and n are as defined in claim 2 .
4. A compound according to claim 3 of Formula Ia-(i) or a salt thereof
wherein
D 1 , D 2 , D 3 and D 4 are each independently selected from C—H, C—C 1-3 alkyl, C—C 1-3 alkoxy, C-halo and N;
each —(CH 2 )— moiety is optionally substituted with one or more substituents independently selected from C 1-3 alkyl, C 1-3 alkoxy, halo, haloC 1-3 alkoxy, haloC 1-3 alkyl, OH and ═O;
q and r are each an integer independently selected from 0, 1, 2, 3, 4 and 5 provided that q and r together are at least 1 and no more than 6; and
R 1 , R 2 , R 3 , X 1 , X 2 , Z 1 , Z 2 , m and n are as defined in claim 2 .
5. A compound according to claim 4 of formula Ia-(iv) and salts thereof
wherein R 2 , R 3 , Z 1 , Z 2 , X 2 , n, D 1 and D 2 are as defined in claim 4 .
6. A compound according to claim 3 of Formula Ia-(ii) or a salt thereof
wherein
D 1 , D 2 , D 3 and D 4 are each independently selected from C—H, C—C 1-3 alkyl, C 1-3 alkoxy, C-halo and N;
each —(CH 2 )— moiety is optionally substituted with one or more substituents selected from C 1-3 alkyl, C 1-3 alkoxy, halo, haloC 1-3 alkoxy, haloC 1-3 alkyl, OH and ═O;
q and r are each an integer independently selected from 0, 1, 2, 3, 4 and 5 provided that q and r together are at least 1 and no more than 6; and
R 1 , R 2 , R 3 , X 1 , X 2 , Z 1 , Z 2 , m and n are as defined in claim 2 .
7. A compound according to claim 3 of Formula Ia-(iii) and salts thereof
wherein
D 1 , D 2 , D 3 and D 4 are each independently selected from C—H, C—C 1-3 alkyl, C 1-3 alkoxy, C-halo and N; and
R 1 , R 2 , R 3 , X 1 , X 2 , Z 1 , Z 2 , m and n are as defined in claim 2 .
8. A compound according to claim 2 of Formula Ib and salts thereof
wherein R 1 , R 2 , R 3 , X 1 , X 2 , Z 1 , Z 2 , Y 1 , Y 2 , ring A, ring B, Alk, m and n are as defined in claim 2 .
9. A compound according to claim 1 or salt thereof selected from the group consisting of:
1) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
2) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-2-methyl-piperidine-2-carboxylic acid;
3) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-hydroxy-3-methyl-piperidine-3-carboxylic acid;
4) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]-2-pyridyl]-4-methyl-piperidine-4-carboxylic acid;
5) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]-3-methyl-2-pyridyl]-4-methyl-piperidine-4-carboxylic acid;
6) 1-[5-[2-(ethylcarbamoylamino)-7-(4-methyl-2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
7) 1-[5-[7-(5,6-dimethoxy-2-pyridyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
8) 1-[5-[2-(ethylcarbamoylamino)-7-(4-methoxypyrimidin-2-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
9) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-3,4-dimethyl-piperidine-4-carboxylic acid;
10) 1-[5-[2-(ethylcarbamoylamino)-7-(4-fluoro-2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
11) 1-[5-[2-(ethylcarbamoylamino)-7-pyrazin-2-yl-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
12) 1-[5-[2-(ethylcarbamoylamino)-7-(4-methylpyrimidin-2-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
13) 1-[5-[7-(3-cyano-2-pyridyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
14) 1-[5-[7-(5-cyano-2-pyridyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
15) 1-[5-[2-(ethylcarbamoylamino)-7-(6-methoxypyrimidin-4-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
16) 1-[5-[7-(4-cyano-2-pyridyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
17) 1-[5-[2-(ethylcarbamoylamino)-7-(4-methoxy-2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
18) 1-[5-[2-(ethylcarbamoylamino)-7-(3-fluoro-2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
19) 1-[5-[2-(ethylcarbamoylamino)-7-oxazol-2-yl-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
20) 1-[5-[2-(ethylcarbamoylamino)-7-thiazol-5-yl-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
21) 1-[5-[2-(ethylcarbamoylamino)-7-thiazol-4-yl-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
22) 1-[5-[2-(ethylcarbamoylamino)-7-hex-1-ynyl-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
23) 1-[5-[2-(ethylcarbamoylamino)-7-(2-methoxythiazol-4-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
24) 1-[5-[2-(ethylcarbamoylamino)-7-(1-methylpyrazol-4-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
25) 1-[5-[2-(ethylcarbamoylamino)-7-(1H-pyrazol-4-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
26) 1-[5-[2-(ethylcarbamoylamino)-7-hydroxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
27) 1-[5-[2-(ethylcarbamoylamino)-7-[4-(hydroxymethyl)thiazol-2-yl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
28) 1-[5-[2-(ethylcarbamoylamino)-7-ethynyl-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
29) 1-[5-[2-(ethylcarbamoylamino)-7-pyrazol-1-yl-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
30) 1-[5-[2-(ethylcarbamoylamino)-7-(1-methylpyrrol-2-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
31) 1-[5-[2-(ethylcarbamoylamino)-7-(5-methyl-2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
32) 1-[5-[7-(6-cyano-2-pyridyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
33) 1-[5-[2-(ethylcarbamoylamino)-7-imidazol-1-yl-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
34) 1-[5-[2-(ethylcarbamoylamino)-7-(5-fluoropyrimidin-2-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
35) 1-[5-[2-(ethylcarbamoylamino)-7-[5-(trifluoromethyl)-2-pyridyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
36) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]-3-fluoro-2-pyridyl]-4-methyl-piperidine-4-carboxylic acid;
37) 1-[5-[7-ethyl-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
38) 1-[5-[2-(ethylcarbamoylamino)-7-methyl-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
39) 1-[5-[7-cyclohexyl-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
40) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrazin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
41) 1-[5-[2-(ethylcarbamoylamino)-7-(1-phenyltriazol-4-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
42) 1-[5-[2-(ethylcarbamoylamino)-7-(2-methoxypyrimidin-4-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
43) 1-[5-[2-(ethylcarbamoylamino)-7-(2-methylpyrimidin-4-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
44) 1-[5-[7-(2-cyanopyrimidin-4-yl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
45) 1-[5-[2-(ethylcarbamoylamino)-7-(6-methylpyrimidin-4-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
46) 1-[5-[2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
47) 1-[5-[2-(ethylcarbamoylamino)-7-tetrahydropyran-4-yl-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
48) 1-[5-[2-(ethylcarbamoylamino)-7-(6-isopropoxypyrimidin-4-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
49) 1-[5-[2-(ethylcarbamoylamino)-7-[6-(2-methoxyethoxy)-2-methyl-pyrimidin-4-yl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
50) 1-[5-[2-(ethylcarbamoylamino)-7-(1-methyltriazol-4-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
51) 1-[5-[2-(ethylcarbamoylamino)-7-(5-methoxypyrimidin-2-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
52) 1-[5-[2-(ethylcarbamoylamino)-7-(6-methoxy-2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
53) 1-[5-[2-(ethylcarbamoylamino)-7-(5-fluoro-6-methyl-2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
54) 1-[5-[7-(3,5-difluoro-2-pyridyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
55) 1-[5-[2-(ethylcarbamoylamino)-7-(3-fluoro-4-methoxy-2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
56) 1-[5-[2-(ethylcarbamoylamino)-7-(5-methoxypyrazin-2-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
57) 1-[5-[2-(ethylcarbamoylamino)-7-(1-isopropyl-6-oxo-pyrimidin-4-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
58) 1-[5-[7-(5-cyano-6-methyl-2-pyridyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
59) 1-[5-[2-(ethylcarbamoylamino)-7-(5-methylpyrimidin-2-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
60) 1-[5-[2-(ethylcarbamoylamino)-7-(5-ethylpyrimidin-2-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
61) 1-[5-[2-(ethylcarbamoylamino)-7-(3-methoxy-2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
62) 1-[5-[7-(3-amino-6-methoxy-2-pyridyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
63) 1-[5-[7-(5-cyano-3-fluoro-2-pyridyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
64) 1-[5-[2-(ethylcarbamoylamino)-7-(3-methoxy-6-methyl-2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
65) 1-[5-[7-(3-cyano-5-methyl-2-pyridyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
66) 1-[5-[2-(ethylcarbamoylamino)-7-(5-methylpyrazin-2-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
67) 1-[5-[2-(ethylcarbamoylamino)-7-pyrimidin-4-yl-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
68) 1-[5-[7-(4-ethoxy-2-pyridyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
69) 1-[5-[7-(5-cyano-3-methyl-2-pyridyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
70) 1-[5-[2-(ethylcarbamoylamino)-7-furo[3,2-c]pyridin-4-yl-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
71) 1-[5-[7-[3-cyano-4-(dimethylamino)-2-pyridyl]-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
72) 1-[5-[2-(ethylcarbamoylamino)-7-[(E)-methoxyiminomethyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
73) 1-[5-[7-(6-tert-butoxypyrazin-2-yl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
74) 1-[5-[7-(1-acetyl-4-piperidyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
75) 1-[5-[7-[2-(dimethylamino)thiazol-5-yl]-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
76) 1-[5-[2-(ethylcarbamoylamino)-7-(2-morpholinothiazol-5-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
77) 1-[5-[2-(ethylcarbamoylamino)-7-(2-ethylthiazol-5-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
78) 1-[5-[7-(2-ethoxythiazol-5-yl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
79) 1-[5-[2-(ethylcarbamoylamino)-7-(1-methyl-2-oxo-4-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
80) 1-[5-[2-(ethylcarbamoylamino)-7-[1-(2-methoxyethyl)-6-oxo-pyrimidin-4-yl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
81) 1-[5-[2-(ethylcarbamoylamino)-7-(6-methoxypyrazin-2-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
82) 1-[5-[7-[5-(cyanomethyl)-2-pyridyl]-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
83) 1-[5-[2-(ethylcarbamoylamino)-7-(5-ethylpyrazin-2-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid
84) 1-[5-[2-(ethylcarbamoylamino)-7-(3-methylpyrazin-2-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
85) 1-[5-[2-(ethylcarbamoylamino)-7-(5-fluoro-4-methyl-2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
86) 1-[5-[2-(ethylcarbamoylamino)-7-(3-methoxypyrazin-2-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
87) 1-[5-[7-cyclopropyl-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
88) 1-[5-[2-(ethylcarbamoylamino)-7-[(E)-N-methoxy-C-methyl-carbonimidoyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
89) 1-[5-[2-(ethylcarbamoylamino)-7-(4-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
90) 1-[5-[7-(3-cyano-4-methoxy-2-pyridyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
91) 1-[5-[2-(ethylcarbamoylamino)-7-[ethyl(methyl)carbamoyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
92) 1-[5-[7-(5-cyano-4-methyl-2-pyridyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
93) 1-[5-[2-(ethylcarbamoylamino)-7-(3-fluoro-5-methyl-2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
94) 1-[5-[2-(ethylcarbamoylamino)-7-[(E)-C-methyl-N-(2,2,2-trifluoroethoxyl)carbonimidoyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
95) 1-[5-[2-(ethylcarbamoylamino)-7-[(E)-N-hydroxy-C-methyl-carbonimidoyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
96) 1-[5-[7-[(E)-N-ethoxy-C-methyl-carbonimidoyl]-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
97) 1-[5-[7-(ethylcarbamoyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
98) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid;
99) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-pyrazin-2-yl-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid;
100) 1-[5-[7-(4-cyano-2-pyridyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-ethyl-piperidine-4-carboxylic acid;
101) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-(4-methylpyrimidin-2-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid;
102) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-(4-methoxy-2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid;
103) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]-2-pyridyl]piperidine-4-carboxylic acid;
104) 1-[5-[7-(3-cyano-2-pyridyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-ethyl-piperidine-4-carboxylic acid;
105) 1-[5-[7-(5-cyano-2-pyridyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-ethyl-piperidine-4-carboxylic acid;
106) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid;
107) 1-[5-[7-bromo-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-ethyl-piperidine-4-carboxylic acid;
108) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrazin-2-yl]piperidine-4-carboxylic acid;
109) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-(4-methoxypyrimidin-2-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid;
110) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-(6-methoxypyrimidin-4-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid;
111) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-(6-oxo-1H-pyrimidin-4-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid;
112) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-(4-methylpyrimidin-2-yl)-1,3-benzothiazol-5-yl]pyrazin-2-yl]piperidine-4-carboxylic acid;
113) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid;
114) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-morpholino-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid;
115) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-(4-fluorophenyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid;
116) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-[(E)-N-methoxy-C-methyl-carbonimidoyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid;
117) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-propyl-piperidine-4-carboxylic acid;
118) 1-[5-[2-(ethylcarbamoylamino)-7-pyrazin-2-yl-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-propyl-piperidine-4-carboxylic acid;
119) 1-[5-[7-bromo-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-propyl-piperidine-4-carboxylic acid;
120) 1-[5-[2-(ethylcarbamoylamino)-7-(4-methylpyrimidin-2-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-propyl-piperidine-4-carboxylic acid;
121) 1-[5-[2-(ethylcarbamoylamino)-7-(6-methoxypyrimidin-4-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-propyl-piperidine-4-carboxylic acid;
122) 1-[5-[2-(ethylcarbamoylamino)-7-(4-methoxy-2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-propyl-piperidine-4-carboxylic acid;
123) 1-[5-[7-(4-cyano-2-pyridyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-propyl-piperidine-4-carboxylic acid;
124) 1-[5-[7-(5-cyano-2-pyridyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-propyl-piperidine-4-carboxylic acid;
125) 1-[5-[2-(ethylcarbamoylamino)-7-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-propyl-piperidine-4-carboxylic acid;
126) 1-[5-[7-(3-cyano-2-pyridyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-propyl-piperidine-4-carboxylic acid;
127) 1-[5-[2-(ethylcarbamoylamino)-7-(4-methoxypyrimidin-2-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-propyl-piperidine-4-carboxylic acid;
128) 4-amino-1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid;
129) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-phenyl-piperidine-4-carboxylic acid;
130) 4-cyano-1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid;
131) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-hydroxy-piperidine-4-carboxylic acid;
132) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methoxy-piperidine-4-carboxylic acid;
133) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methylsulfonyl-piperidine-4-carboxylic acid;
134) 4-benzyl-1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid;
135) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-fluoro-piperidine-4-carboxylic acid;
136) 4-allyl-1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid;
137) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-isopropyl-piperidine-4-carboxylic acid;
138) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methylsulfanyl-piperidine-4-carboxylic acid;
139) 4-allyl-1-[5-[2-(ethylcarbamoylamino)-7-pyrazin-2-yl-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid;
140) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-(2,2,2-trifluoroethyl)piperidine-4-carboxylic acid;
141) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-(methoxymethyl)piperidine-4-carboxylic acid;
142) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-(trifluoromethyl)piperidine-4-carboxylic acid;
143) 4-cyclopropyl-1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid;
144) 1-[5-[2-(ethylcarbamoylamino)-7-[2-(3-methylimidazol-4-yl)ethynyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
145) 1-[5-[2-(ethylcarbamoylamino)-7-(thiazol-2-ylcarbamoyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
146) 1-[5-[2-(ethylcarbamoylamino)-7-(pyrimidine-2-carbonylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
147) 1-[5-[2-(ethylcarbamoylamino)-7-[[methyl(pyrimidin-2-yl)amino]methyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
148) 1-[5-[2-(ethylcarbamoylamino)-7-[2-(3-pyridyl)ethynyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
149) 1-[5-[2-(ethylcarbamoylamino)-7-(pyridine-2-carbonylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
150) 1-[5-[7-(2-cyclopentylethynyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
151) 1-[5-[2-(ethylcarbamoylamino)-7-[2-(4-pyridyl)ethynyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
152) 1-[5-[2-(ethylcarbamoylamino)-7-[2-(6-methoxy-2-pyridyl)ethynyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
153) 1-[5-[2-(ethylcarbamoylamino)-7-[2-(5-methyl-1,3,4-thiadiazol-2-yl)ethynyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
154) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyrimidin-2-ylethynyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
155) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyrimidin-4-ylethynyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
156) 1-[5-[2-(ethylcarbamoylamino)-7-(2-thiazol-2-ylethynyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
157) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyrazin-2-ylethynyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
158) 1-[5-[2-(ethylcarbamoylamino)-7-(morpholinomethyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
159) 1-[5-[2-(ethylcarbamoylamino)-7-(morpholine-4-carbonyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
160) 1-[[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]methyl]-4-methyl-piperidine-4-carboxylic acid;
161) 1-[5-[2-(ethylcarbamoylamino)-4-fluoro-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
163) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-2-methyl-pyrrolidine-2-carboxylic acid;
164) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-3-(trifluoromethyl)pyrrolidine-3-carboxylic acid;
165) 2-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-1,3,4,5,6,6a-hexahydrocyclopenta[c]pyrrole-3a-carboxylic acid;
166) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-azepane-4-carboxylic acid;
167) methyl 4-(tert-butoxycarbonylamino)-1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylate;
168) methyl 4-amino-1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylate;
169) methyl 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate;
170) methyl 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-3-methyl-4-oxo-piperidine-3-carboxylate;
171) ethyl 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate;
172) methyl 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-hydroxy-3-methyl-piperidine-3-carboxylate;
173) methyl 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-hydroxy-piperidine-4-carboxylate;
174) ethyl 4-cyano-1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylate;
175) methyl 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methoxy-piperidine-4-carboxylate;
176) ethyl 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methylsulfonyl-piperidine-4-carboxylate;
177) ethyl 4-benzyl-1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylate;
178) ethyl 1-[5-[2-(ethylcarbamoylamino)-7-tetrahydropyran-4-yl-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate;
179) ethyl 1-[5-[7-(1-acetyl-4-piperidyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate;
180) methyl 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-3-(trifluoromethyl)pyrrolidine-3-carboxylate;
181) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]-3-pyridyl]-4-methyl-piperidine-4-carboxylic acid;
182) 1-[4-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]-2-pyridyl]-4-methyl-piperidine-4-carboxylic acid;
183) 3-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]-2-pyridyl]-5-methyl-4H-isoxazole-5-carboxylic acid;
184) ethyl 3-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]-2-pyridyl]-5-methyl-4H-isoxazole-5-carboxylate;
185) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-phenyl-piperidine-4-carboxamide;
186) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-N-methylsulfonyl-piperidine-4-carboxamide;
187) 1-[5-[2-(ethylcarbamoylamino)-7-[(E)-N-(2-hydroxyethoxy)-C-methyl-carbonimidoyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
188) 1-[5-[2-(ethylcarbamoylamino)-7-[(E)-N-(2-methoxyethoxy)-C-methyl-carbonimidoyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid;
189) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-[(E)-methoxyiminomethyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid;
190) 7-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]-2-methyl-3-oxo-4H-pyrido[3,2-b][1,4]oxazine-2-carboxylic acid;
191) ethyl 1-[5-[2-(ethylcarbamoylamino)-6-methoxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate
192) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidine-2-carbonyl]-4-methyl-piperidine-4-carboxylic acid
193) 1-[5-[7-carbamoyl-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-ethyl-piperidine-4-carboxylic acid
194) 1-[5-[2-(ethylcarbamoylamino)-7-(2-methoxyethoxymethyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid
195) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyridazin-3-yl]-4-methyl-piperidine-4-carboxylic acid
196) 5-[[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]amino]-2-methyl-1,3-dioxane-2-carboxylic acid
197) 1-[5-[7-(4,5-dihydroisoxazol-3-yl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-ethyl-piperidine-4-carboxylic acid
198) 1-[5-[2-(ethylcarbamoylamino)-6-methoxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid
199) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-formyl-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid
200) 1-[5-[2-(ethylcarbamoylamino)-7-methoxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid
201) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-3-methyl-pyrrolidine-3-carboxylic acid
202) 1-[5-[2-(ethylcarbamoylamino)-7-(methoxymethyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid
203) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-(methoxymethyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid
204) 1-[5-[7-[(E)-ethoxyiminomethyl]-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid
205) 1-[5-[2-(ethylcarbamoylamino)-7-[5-(morpholinomethyl)-2-pyridyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid
206) 3-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]pyrrolidine-3-carboxylic acid
207) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-propanoyl-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid
208) 1-[5-[7-bromo-2-(ethylcarbamoylamino)-6-methoxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid
209) 4-ethyl-1-[4-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]thiazol-2-yl]piperidine-4-carboxylic acid
211) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-[(Z)—C-ethyl-N-methoxy-carbonimidoyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid
212) 4-ethoxy-1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid
213) 1-[5-[2-(ethylcarbamoylamino)-7-(5-methyl-1,2,4-oxadiazol-3-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid
214) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]-4-methyl-pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid
215) 1-[5-[7-bromo-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid
216) ethyl 5-[[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]amino]-2-methyl-1,3-dioxane-2-carboxylate
217) 1-[5-[7-[5-[(4,4-difluoro-1-piperidyl)methyl]-2-pyridyl]-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid
218) 4-[[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-methyl-amino]-1-methyl-cyclohexanecarboxylic acid
219) 2-ethyl-7-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-7-azaspiro[3.5]nonane-2-carboxylic acid
220) 1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]-4-methoxy-pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid
221) 4-Ethyl-1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]thiazol-2-yl]piperidine-4-carboxylic acid
222) 4-[[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]amino]-1-methyl-cyclohexanecarboxylic acid
223) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-(C-ethyl-N-methoxy-carbonimidoyl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid
224) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-[(E)-C-ethyl-N-methoxy-carbonimidoyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid
225) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-[(Z)-methoxyiminomethyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid
226) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-(5-methylpyrimidin-2-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid
228) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-pyrimidin-2-yl-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid
229) 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1H-benzimidazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylic acid
232) 4-ethyl-1-(3-{2-[(ethylcarbamoyl)amino]-7-(pyridin-2-yl)-1,3-benzothiazol-5-yl}-1,2,4-thiadiazol-5-yl)piperidine-4-carboxylic acid
233) 1-(5-{2-[(ethylcarbamoyl)amino]-7-(pyridin-2-yl)-1,3-benzothiazol-5-yl}-1,2,4-thiadiazol-3-yl)-4-methylpiperidine-4-carboxylic acid; and
234) Diethyl 1,1′-({2-[(ethylcarbamoyl)amino]-1,3-benzoxazole-5,7-diyl}dipyrimidine-5,2-diyl)bis(4-ethylpiperidine-4-carboxylate).
10. A compound according to claim 1 or a pharmaceutically acceptable salt thereof for use in the treatment of a bacterial infection.
11. A compound according to claim 1 or a pharmaceutically acceptable salt thereof for use as a gyrase inhibitor.
12. An antibacterial agent comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof.
13. A composition comprising a compound according to claim 1 or a salt thereof.
14. A process for the manufacture of a compound of Formula I according to claim 2 comprising the step of coupling an intermediate of Formula IIa with an L-(X 2 ) n —R 3 precursor moiety;
or alternatively comprising the step of coupling an intermediate of Formula IIb
with a precursor moiety of general formula
to form a compound of Formula I;
wherein R 1 , X, R 2 , (X 1 ) m , ring A, ring B, Z 1 , Z 2 , Y 1 , Y 2 , Alk, (X 2 ) n and R 3 are as defined in claim 2 and L is a suitable reactive group.
15. A process for the manufacture of a compound of Formula I according to claim 2 comprising the step of coupling a precursor of Formula Ma with a boronic acid intermediate of Formula IVa
or alternatively comprising the step of coupling a boronic acid intermediate of Formula IVb with a halo-(X 2 ) n —R 3 precursor moiety
to form a compound of Formula I;
wherein R 1 , X, R 2 , (X 1 ) m , ring A, ring B, Z 1 , Z 2 , Y 1 , Y 2 , Alk, (X 2 ) n and R 3 are as defined in claim 2 and B(OR) 2 is a boronic acid (B(OH) 2 ) or a pinacolborane.
16. A method for the treatment of a bacterial infection comprising administration of a compound according to claim 1 or a pharmaceutically acceptable salt thereof to a subject suffering from said infection, wherein the bacterial infection is caused by (i) a Gram positive bacteria selected from the group consisting of Staphylococci, Enterococci, and Streptococci, or (ii) a Gram negative bacteria selected from the group Haemophili.
17. A method of treating bacterial contamination of a substrate comprising applying to the site of such contamination an amount of a compound according claim 1 or pharmaceutically acceptable salt thereof sufficient to inhibit bacterial growth, wherein the bacterial infection is caused by (i) a Gram positive bacteria selected from the group consisting of Staphylococci, Enterococci, and Streptococci, or (ii) a Gram negative bacteria selected from the group Haemophili.