IP Library Granted Patent US 9,181,234
Granted Patent B2
US 9,181,234 · App. 13/268,154 · Granted Nov 10, 2015

Antibacterial compounds

Inventors: James T Palmer (Notting Hill, AU); Christopher James Lunnis (Notting Hill, AU); Daniel A Offermann (Notting Hill, AU); Lorraine Claire Axford (Notting Hill, AU); Michael Blair (Notting Hill, AU); Dale Mitchell (Essex, GB); Nicholas Palmer (Essex, GB); Christopher Steele (Essex, GB); John Atherall (Essex, GB); David Watson (Essex, GB); David Haydon (Yarnton, GB); Lloyd Czaplewski (Yarnton, GB); David Davies (Yarnton, GB); Ian Collins (Yarnton, GB); Edward Malcolm Tyndall (NottingHill, AU); Laura Andrau (Notting Hill, AU); Gary Robert William Pitt (Notting Hill, AU)
Assignee: Biota Europe Ltd.
C07D417/14A01N47/36C07D491/04C07D513/04
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Quick Facts
Patent No.
US 9,181,234
App. No.
13/268,154
Granted
Nov 10, 2015
Kind
B2
Abstract

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.

Claims (287)

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.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 12, 2016
From: BIOTA EUROPE LIMITED
To: SPERO GYRASE, INC.
Reel/Frame 038569/0773 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 22, 2012
From: TYNDALL, EDWARD MALCOLM; ANDRAU, LAURA; PITT, GARY ROBERT WILLIAM
To: BIOTA EUROPE LTD.
Reel/Frame 028247/0477 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 19, 2011
From: PALMER, JAMES T.; LUNNISS, CHRISTOPHER JAMES; OFFERMANN, DANIEL A.; AXFORD, LORRAINE CLAIRE; BLAIR, MICHAEL; MITCHELL, DALE; PALMER, NICHOLAS; STEELE, CHRISTOPHER; ATHERALL, JOHN; WATSON, DAVID; HAYDON, DAVID; CZAPLEWSKI, LLOYD; DAVIES, DAVID; COLLINS, IAN
To: BIOTA EUROPE LTD.
Reel/Frame 027406/0687 →
Continuity (2)
Provisional Application 61391163 · Oct 8, 2010
Related Publication 20120088750A1 · Apr 12, 2012