Viral Polymerase Inhibitors

• US 20090087409A1
• Filed: 11/26/2008
• Published: 04/02/2009
• Est. Priority Date: 07/25/2001
• Status: Active Grant

• Current Assignee: Boehringer Ingelheim Canada Ltd (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim Canada Ltd (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Fazal, Gulrez, Gillard, James, Rancourt, Jean, Jolicoeur, Eric, Poirier, Martin, Kukolj, George, Beaulieu, Pierre Louis, Goulet, Sylvie, Tsantrizos, Youla S., Poupart, Marc-Andre
• Granted Patent: US 7,893,084 B2
• Time in Patent Office: Days
• US Class Current: 424/85.500
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 209/08 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 209/30 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 209/42 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 333/62 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 403/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 409/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 413/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

An isomer, enantiomer, diastereoisomer or tautomer of a compound, represented by formula I:

wherein:
A is O, S, NR¹, or CR¹, wherein R¹ is defined herein;
represents either a single or a double bond;
R² is selected from: H, halogen, R²¹, OR²¹, SR²¹, COOR²¹, SO₂N(R²²)₂, N(R²²)₂, CON(R²²)₂, NR²²C(O)R²² or NR²²C(O)NR²² wherein R²¹ and each R²² is defined herein;
B is NR³ or CR³, with the proviso that one of A or B is either CR¹ or CR³,
wherein R³ is defined herein;
K is N or CR⁴, wherein R⁴ is defined herein;
L is N or CR⁵, wherein R⁵ has the same definition as R⁴;
M is N or CR⁷, wherein R⁷ has the same definition as R⁴;
Y¹ is O or S;
Z is N(R^6a)R⁶ or OR⁶, wherein R^6a is H or alkyl or NR⁶¹R⁶² wherein R⁶¹ and R⁶² are defined herein; and R⁶ is H, alkyl, cycloalkyl, alkenyl, Het, alkyl-aryl, alkyl-Het;
or R⁶ is

wherein R⁷ and R⁸ and Q are as defined herein;
Y² is O or S;
R⁹ is H, (C_1-6 alkyl), (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6)alkyl-aryl or (C_1-6)alkyl-Het, all of which optionally substituted with R⁹⁰; or R⁹ is covalently bonded to either of R⁷ or R⁸ to form a 5- or 6-membered heterocycle; a salt or a derivative thereof, as an inhibitor of HCV NS5B polymerase.

Claims

1. An isomer, enantiomer, diastereoisomer, or tautomer of a compound, represented by formula I:

2. A compound of formula (II):

3. The compound according to claim 2, wherein A is NR¹.

4. The compound according to claim 2, wherein M, K and L is CH or N.

5. The compound according to claim 4, wherein M, K and L is CH.

6. A compound of formula (III):

7. The compound according to claim 6, wherein M, K and L is CH or N.

8. The compound according to claim 7, wherein M, K and L is CH.

9. A compound of the formula:

10. The compound according to claim 1, wherein R¹ is selected from:

H or (C_1-6)alkyl.

11. The compound according to claim 10, wherein R¹ is H, CH₃, isopropyl, or isobutyl.

12. The compound according to claim 11, wherein R¹ is H or CH₃.

13. The compound according to claim 12, wherein R¹ is CH₃.

14. The compound according to claim 1, wherein R² is CON(R²²)₂, wherein each R²² is independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_5-7)cycloalkenyl, 6 or 10-membered aryl or Het, or both R²² are bonded together to form a 5, 6 or 7-membered saturated heterocycle with the nitrogen to which they are attached;

or R² is selected from;

H, halogen, (C_1-6)alkyl, haloalkyl, (C_2-6)alkenyl, (C_5-7)cycloalkenyl, 6 or 10-membered aryl or Het;

wherein each of said alkyl, haloalkyl, (C_2-6)alkenyl, (C_5-7)cycloalkenyl, aryl or Het is optionally substituted with R²⁰, wherein R²⁰ is defined as;

1 to 4 substituents selected from;

halogen, NO₂, cyano, azido, C(═

NH)NH₂, C(═

NH)NH(C_1-6)alkyl or C(═

NH)NHCO(C_1-6)alkyl;

or

1 to 4 substituents selected from;

a) (C_1-6) alkyl or haloalkyl, (C_3-7)cycloalkyl, (C_2-6)alkenyl, (C_2-8)alkynyl, (C_1-6) alkyl-(C_3-7)cycloalkyl, all of which optionally substituted with R¹⁵⁰;

b) OR¹⁰⁴ wherein R¹⁰⁴ is H, (C_1-6alkyl), (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

c) OCOR¹⁰⁵ wherein R¹⁰⁵ is (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

d) SR¹⁰⁸, SO₂N(R¹⁰⁸)₂ or SO₂N(R¹⁰⁸)C(O)R¹⁰⁸ wherein each R¹⁰⁸ is independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or both R¹⁰⁸ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or heterocycle being optionally substituted with R¹⁵⁰;

e) NR¹¹¹R¹¹² wherein R¹¹¹ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, and R¹¹² is H, CN, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl, (C_1-6alkyl)Het, COOR¹¹⁵ or SO₂R¹¹⁵ wherein R¹¹⁵ is (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or both R¹¹¹ and R¹¹² are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or heterocycle being optionally substituted with R¹⁵⁰;

f) NR¹¹⁶COR¹¹⁷ wherein R¹¹⁶ and R¹¹⁷ is each H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

g) NR¹¹⁸CONR¹¹⁹R¹²⁰, wherein R¹¹⁸, R¹¹⁹ and R¹²⁰ is each H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or R¹¹⁸ is covalently bonded to R¹¹⁹ and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle;

or R¹¹⁹ and R¹²⁰ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle;

said alkyl, cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or heterocycle being optionally substituted with R¹⁵⁰;

h) NR¹²¹COCOR¹²² wherein R¹²¹ and R¹²² is each H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, a 6- or 10-membered aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said alkyl, cycloalkyl, alkyl-cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

or R¹²² is OR¹²³ or N(R¹²⁴)₂ wherein R¹²³ and each R¹²⁴ is independently H (C_1-6alkyl), (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or R¹²⁴ is OH or O(C_1-6alkyl) or both R¹²⁴ are covalently bonded together to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, alkyl-cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het and heterocycle being optionally substituted with R¹⁵⁰;

i) COR¹²⁷ wherein R¹²⁷ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

j) COOR¹²⁸ wherein R¹²⁸ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl and (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

k) CONR¹²⁹R¹³⁰ wherein R¹²⁹ and R¹³⁰ are independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or both R¹²⁹ and R¹³⁰ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, alkyl-cycloalkyl, aryl, Het, (C_1-6alkyl)aryl, (C_1-6alkyl)Het and heterocycle being optionally substituted with R¹⁵⁰;

l) aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, all of which being optionally substituted with R¹⁵⁰;

wherein R¹⁵⁰ is;

1 to 3 substituents selected from;

halogen, NO₂, cyano or azido;

or

1 to 3 substituents selected from;

a) (C_1-6) alkyl or haloalkyl, (C_3-7)cycloalkyl, (C_2-6)alkenyl, (C_2-8)alkynyl, (C_1-6) alkyl-(C_3-7)cycloalkyl, all of which optionally substituted with R¹⁶⁰;

b) OR¹⁰⁴ wherein R¹⁰⁴ is H, (C_1-6alkyl) or (C_3-7)cycloalkyl, said alkyl or cycloalkyl optionally substituted with R¹⁶⁰;

d) SR¹⁰⁸, SO₃H, SO₂N(R¹⁰⁸)₂ or SO₂N(R¹⁰⁸)C(O)R¹⁰⁸ wherein each R¹⁰⁸ is independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, or both R¹⁰⁸ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, aryl, Het and heterocycle being optionally substituted with R¹⁶⁰;

e) NR¹¹¹R¹¹² wherein R¹¹¹ is H, (C_1-6)alkyl, or (C_3-7)cycloalkyl, and R¹¹² is H, (C_1-6)alkyl or (C_3-7)cycloalkyl, COOR¹¹⁵ or SO₂R¹¹⁵ wherein R¹¹⁵ is (C_1-6)alkyl or (C_3-7)cycloalkyl, or both R¹¹¹ and R¹¹² are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl and heterocycle being optionally substituted with R¹⁶⁰;

f) NR¹¹⁶COR¹¹⁷ wherein R¹¹⁶ and R¹¹⁷ is each H, (C_1-6)alkyl or (C_3-7)cycloalkyl said (C_1-6)alkyl and (C_3-7)cycloalkyl being optionally substituted with R¹⁶⁰;

g) NR¹¹⁸CONR¹¹⁹R¹²⁰, wherein R¹¹⁸, R¹¹⁹ and R¹²⁰ is each H, (C_1-6)alkyl or (C_3-7)cycloalkyl, or R¹¹⁸ is covalently bonded to R¹¹⁹ and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, or R¹¹⁹ and R¹²⁰ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, and heterocycle being optionally substituted with R¹⁶⁰;

h) NR¹²¹COCOR¹²² wherein R¹²¹ is H, (C_1-6)alkyl or (C_3-7)cycloalkyl, said alkyl and cycloalkyl being optionally substituted with R¹⁶⁰;

or R¹²² is OR¹²³ or N(R¹²⁴)₂ wherein R¹²³ and each R¹²⁴ is independently H, (C_1-6alkyl) or (C_3-7)cycloalkyl, or both R¹²⁴ are covalently bonded together to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl and heterocycle being optionally substituted with R¹⁶⁰;

i) COR¹²⁷ wherein R¹²⁷ is H, (C_1-6)alkyl or (C_3-7)cycloalkyl, said alkyl and cycloalkyl being optionally substituted with R¹⁶⁰;

j) COOR¹²⁸ wherein R¹²⁸ is H, (C_1-6)alkyl or (C_3-7)cycloalkyl, said (C_1-6)alkyl and (C_3-7)cycloalkyl being optionally substituted with R¹⁶⁰; and

k) CONR¹²⁹R¹³⁰ wherein R¹²⁹ and R¹³⁰ are independently H, (C_1-6)alkyl or (C_3-7)cycloalkyl, or both R¹²⁹ and R¹³⁰ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl and heterocycle being optionally substituted with R¹⁶⁰;

wherein R¹⁶⁰ is defined as 1 or 2 substituents selected from;

halogen, CN, C_1-6alkyl, haloalkyl, COOR¹⁶¹, OR¹⁶¹, N(R¹⁶²)₂, SO₂N(R¹⁶²)₂, NR¹⁶²COR¹⁶² or CON(R¹⁶²)₂, wherein R¹⁶¹ and each R¹⁶² is independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl;

or both R¹⁶² are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle.

15. The compound according to claim 14, wherein R² is selected from:

aryl or Het, each optionally monosubstituted or disubstituted with substituents selected from the group consisting of;

halogen, haloalkyl, N₃, or

a) (C_1-6)alkyl optionally substituted with OH, O(C_1-6)alkyl or SO₂(C_1-6 alkyl);

b) (C_1-6)alkoxy;

e) NR¹¹¹R¹¹² wherein both R¹¹¹ and R¹¹² are independently H, (C_1-6)alkyl (C_3-7)cycloalkyl, or R¹¹² is 6- or 10-membered aryl, Het, (C_1-6)alkyl-aryl or (C_1-6)alkyl-Het;

or both R¹¹¹ and R¹¹² are covalently bonded together and to the nitrogen to which they are attached to form a nitrogen-containing heterocycle, each of said alkyl, cycloalkyl, aryl, Het, alkyl-aryl or alkyl-Het;

being optionally substituted with halogen or;

OR^2h or N(R^2h)₂, wherein each R^2h is independently H, (C_1-6)alkyl, or both R^2h are covalently bonded together and to the nitrogen to which they are attached to form a nitrogen-containing heterocycle;

f) NHCOR¹¹⁷ wherein R¹¹⁷ is (C_1-6)alkyl, O(C_1-6)alkyl or O(C_3-7)cycloalkyl;

i) CO-aryl; and

k) CONH₂, CONH(C_1-6alkyl), CON(C_1-6alkyl)₂, CONH-aryl, or CONHC_1-6alkyl aryl.

16. The compound according to claim 15, wherein R² is aryl or Het, each optionally monosubstituted or disubstituted with substituents selected from the group consisting of:

halogen, haloalkyl, or

a) (C_1-6)alkyl optionally substituted with OH, O(C_1-6)alkyl or SO₂(C_1-6alkyl);

b) (C_1-6)alkoxy; and

e) NR¹¹¹R¹¹² wherein both R¹¹¹ and R¹¹² are independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl, or R¹¹² is 6- or 10-membered aryl, Het, (C_1-6)alkyl-aryl or (C_1-6)alkyl-Het;

or both R¹¹¹ and R¹¹² are covalently bonded together and to the nitrogen to which they are attached to form a nitrogen-containing heterocycle, each of said alkyl, cycloalkyl, aryl, Het, alkyl-aryl or alkyl-Het;

or being optionally substituted with halogen or;

OR^2h or N(R^2h)₂, wherein each R^2h is independently H, (C_1-6)alkyl, or both R^2h are covalently bonded together and to the nitrogen to which they are attached to form a nitrogen-containing heterocycle.

17. The compound according to claim 16, wherein R² is phenyl or a heterocycle selected from:

18. The compound according to claim 17, wherein R² is selected from the group consisting of:

H. Br, CONHCH₃, CON(CH₃)₂, CONH₂, CH═

CH₂,

19. The compound according to claim 18, wherein R² is selected from:

20. The compound according to claim 19, wherein R² is selected from:

21. The compound according to claim 1, wherein R³ is selected from (C_3-7)cycloalkyl, (C_3-7)cycloalkenyl, (C_6-10)bicycloalkyl, (C_6-10)bicycloalkenyl, 6- or 10-membered aryl, or Het.

22. The compound according to claim 21, wherein R³ is (C_3-7)cycloalkyl.

23. The compound according to claim 22, wherein R³ is cyclopentyl, or cyclohexyl.

24. The compound according to claim 1, wherein Y¹ is O.

25. The compound according to claim 1, wherein Z is OR⁶ wherein R⁶ is (C_1-6alkyl)aryl substituted with 1 to 4 substituents selected from:

a) (C_1-6)alkyl substituted with R^150a, haloalkyl, (C_3-7)cycloalkyl, C_3-7 spirocycloalkyl optionally containing 1 or 2 heteroatom, (C_2-6)alkenyl, (C_2-8)alkynyl, (C_1-6) alkyl-(C_3-7)cycloalkyl, said haloalkyl, cycloalkyl, spirocycloalkyl, alkenyl, alkynyl and alkyl-cycloalkyl being optionally substituted with R¹⁵⁰, wherein R^150a is the same as R¹⁵⁰ but is not COOR^150b, N(R^150b)₂, NR^150bC(O)R^150b, OR^150b, SR^150b, SO₂R^150b, SO₂N(R^150b)₂, wherein R^150b is H or unsubstituted C_1-6alkyl;

b) OR¹⁰⁴ wherein R¹⁰⁴ is (C_1-6alkyl) substituted with R¹⁵⁰, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

d) SR^108a, SO₂N(R^108a)₂ or SO₂N(R¹⁰⁸)C(O)R¹⁰⁸ wherein each R¹⁰⁸ is independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or both R¹⁰⁸ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or heterocycle being optionally substituted with R¹⁵⁰, wherein R^108a is the same as R¹⁰⁸ but is not H or unsubstituted C_1-6alkyl;

e) NR¹¹¹R¹¹² wherein R¹¹¹ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, and R¹¹² is H, CN, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl, (C_1-6alkyl)Het, provided that when R¹¹¹ is H or unsubstituted alkyl, R¹¹² is not H or unsubstituted alkyl, or R¹¹² is also COOR¹¹⁵ or SO₂R^115a wherein R¹¹⁵ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, and R^115a is the same as R¹¹⁵ but is not H or unsubstituted alkyl, or both R¹¹¹ and R¹¹² are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or heterocycle being optionally substituted with R¹⁵⁰;

f) NR¹¹⁶COR¹¹⁷ wherein R¹¹⁶ and R¹¹⁷ is each (C_1-6)alkyl substituted with R¹⁵⁰ (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

g) NR¹¹⁸CONR¹¹⁹R¹²⁰, wherein R¹¹⁸, R¹¹⁹ and R¹²⁰ is each H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or R¹¹⁸ is covalently bonded to R¹¹⁹ and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle;

or R¹¹⁹ and R¹²⁰ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle;

said alkyl, cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or heterocycle being optionally substituted with R¹⁵⁰;

h) NR¹²¹COCOR¹²² wherein R¹²¹ is H or C_1-6alkyl and R¹²² is OR¹²³ or N(R¹²⁴)₂ wherein R¹²³ and each R¹²⁴ is independently H, (C_1-6alkyl), (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or R¹²⁴ is OH or O(C_1-6alkyl) or both R¹²⁴ are covalently bonded together to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, alkyl-cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het and heterocycle being optionally substituted with R¹⁵⁰;

j) COOR¹²⁸ wherein R¹²⁸ is (C_1-6)alkyl substituted with R¹⁵⁰ (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl and (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

k) CONR¹²⁹R¹³⁰ wherein R¹²⁹ and R¹³⁰ are independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, provided that when R¹²⁹ is H or unsubstituted alkyl, R¹³⁰ is not H or unsubstituted alkyl, or both R¹²⁹ and R¹³⁰ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, alkyl-cycloalkyl, aryl, Het, (C_1-6alkyl)aryl, (C_1-6alkyl)Het and heterocycle being optionally substituted with R¹⁵⁰;

l) aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, all of which being optionally substituted with R¹⁵⁰ wherein R¹⁵⁰ is;

1 to 3 substituents selected from;

halogen or azido;

or

1 to 3 substituents selected from;

a) (C_1-6) alkyl or haloalkyl, (C_3-7)cycloalkyl, C_3-7 spirocycloalkyl optionally containing 1 or 2 heteroatom, (C_2-6)alkenyl, (C_2-8)alkynyl, (C_1-6) alkyl-(C_3-7)cycloalkyl, all of which optionally substituted with R¹⁶⁰;

b) OR¹⁰⁴ wherein R¹⁰⁴ is H, (C_1-6alkyl), (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁶⁰;

d) SR¹⁰⁸, SO₂N(R¹⁰⁸)₂ or SO₂N(R¹⁰⁸)C(O)R¹⁰⁸ wherein each R¹⁰⁸ is independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or both R¹⁰⁸ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or heterocycle being optionally substituted with R¹⁶⁰;

e) NR¹¹¹R¹¹² wherein R¹¹¹ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, and R¹¹² is H, CN, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl, (C_1-6alkyl)Het, COOR¹¹⁵ or SO₂R¹¹⁵ wherein R¹¹⁵ is (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or both R¹¹¹ and R¹¹² are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or heterocycle being optionally substituted with R¹⁶⁰;

f) NR¹¹⁶COR¹¹⁷ wherein R¹¹⁶ and R¹¹⁷ is each H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁶⁰;

g) NR¹¹⁸CONR¹¹⁹R¹²⁰, wherein R¹¹⁸, R¹¹⁹ and R¹²⁰ is each H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or R¹¹⁹ and R¹²⁰ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle;

said alkyl, cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or heterocycle being optionally substituted with R¹⁶⁰;

h) NR¹²¹COCOR¹²² wherein R¹²¹ is H, (C_1-6)alkyl and R¹²² is OR¹²³ or N(R¹²⁴)₂ wherein R¹²³ and each R¹²⁴ is independently H, (C_1-6alkyl), (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or R¹²⁴ is OH or O(C_1-6alkyl) or both R¹²⁴ are covalently bonded together to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, alkyl-cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het and heterocycle being optionally substituted with R¹⁶⁰;

j) tetrazole, COOR¹²⁸ wherein R¹²⁸ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl and (C_1-6alkyl)Het being optionally substituted with R¹⁶⁰; and

k) CONR¹²⁹R¹³⁰ wherein R¹²⁹ and R¹³⁰ are independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or both R¹²⁹ and R¹³⁰ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, alkyl-cycloalkyl, aryl, Het, (C_1-6alkyl)aryl, (C_1-6alkyl)Het and heterocycle being optionally substituted with R¹⁶⁰;

wherein, R¹⁶⁰ is defined as 1 or 2 substituents selected from;

tetrazole, halogen, CN, C_1-6alkyl, haloalkyl, COOR¹⁶¹, SO₃H, SO₂¹⁶¹, OR¹⁶¹, N(R¹⁶²)₂, SO₂N(R¹⁶²)₂, N¹⁶²C¹⁶² or CON(R¹⁶²)₂, wherein R¹⁶¹ and R¹⁶² are as defined above.

26. The compound according to claim 25, wherein Z is OR⁶ wherein R⁶ is (C_1-6alkyl)aryl substituted with 1 to 4 substituents selected from:

a) (C_1-6)alkyl substituted with R¹⁵⁰, haloalkyl, (C_3-7)cycloalkyl, C_3-7 spirocycloalkyl optionally containing 1 or 2 heteroatom, (C_2-6)alkenyl, (C_2-8)alkynyl, (C_1-6) alkyl-(C_3-7)cycloalkyl, said haloalkyl, cycloalkyl, spirocycloalkyl, alkenyl, alkynyl and alkyl-cycloalkyl being optionally substituted with R¹⁵⁰ wherein R¹⁰ is the same as R¹⁵⁰ but is not COOR^150b, N(R^150b)₂, NR^150bC(O)R^150b, OR^150b, SR^150b, SO₂R^150b, SO₂N(R^150b)₂, wherein R^150b is H or unsubstituted C_1-6alkyl;

b) OR¹⁰⁴ wherein R¹⁰⁴ is (C_1-6alkyl) substituted with R¹⁵⁰, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

d) SO₃H, SO₂N(R^108a)₂ or SO₂N(R¹⁰⁸)C(O)R¹⁰⁸ wherein each R¹⁰⁸ is independently H, (C_1-6)alkyl and aryl, said alkyl and aryl being optionally substituted with R¹⁵⁰, wherein R^108a is the same as R¹⁰⁸ but is not H or unsubstituted C_1-6alkyl;

e) NR¹¹¹R¹¹² wherein R¹¹¹ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, and R¹¹² is H, (C_1-6)alkyl, provided that when R¹¹¹ is H or unsubstituted alkyl, R¹¹² is not H or unsubstituted alkyl, or R¹¹² is also COOR¹¹⁵ or SO₂R^115a wherein R¹¹⁵ is H (C_1-6)alkyl or (C_1-6alkyl)aryl, and R^115a is C_1-6alkyl substituted with R¹⁵⁰ or (C_1-6alkyl)aryl, or both R¹¹¹ and R¹¹² are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, alkyl-cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or heterocycle being optionally substituted with R¹⁵⁰;

f) NR¹¹⁶COR¹¹⁷ wherein R¹¹⁶ and R¹¹⁷ is each (C_1-6)alkyl substituted with R¹⁵⁰ (C_3-7)cycloalkyl, aryl, Het, said (C_3-7)cycloalkyl, aryl, Het being optionally substituted with R¹⁵⁰;

g) NR¹¹⁸CONR¹¹⁹R¹²⁰, wherein R¹¹⁸, R¹¹⁹ and R¹²⁰ is each H, (C_1-6)alkyl, aryl, Het, said alkyl, aryl and Het being optionally substituted with R¹⁵⁰;

h) NR¹²¹COCOR¹²² wherein R¹²¹ is H or C_1-6alkyl and R¹²² is OR¹²³ or N(R¹²⁴)₂ wherein R¹²³ and each R¹²⁴ is independently H, (C_1-6alkyl), aryl or Het, or R¹²⁴ is OH or O(C_1-6alkyl), said alkyl, aryl and Het being optionally substituted with R¹⁵⁰;

j) COOR¹²⁸ wherein R¹²⁸ is (C_1-6)alkyl substituted with R¹⁵⁰;

k) CONR¹²⁹R¹³⁰ wherein R¹²⁹ and R¹³⁰ are independently H, (C_1-6)alkyl aryl or Het, provided that when R¹²⁹ is H or unsubstituted alkyl, R¹³⁰ is not H or unsubstituted alkyl, said alkyl, aryl and Het being optionally substituted with R¹⁵⁰;

l) aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, all of which being optionally substituted with R¹⁵⁰ wherein R¹⁵⁰ is;

1 to 3 substituents selected from;

halogen or azido;

or

1 to 3 substituents selected from;

a) (C_1-6) alkyl or haloalkyl, (C_2-6)alkenyl, all of which optionally substituted with R¹⁶⁰;

b) OR¹⁰⁴ wherein R¹⁰⁴ is H, (C_1-6alkyl), aryl or Het, said alkyl, aryl and Het being optionally substituted with R¹⁶⁰;

d) SR¹⁰⁸, SO₂N(R¹⁰⁸)₂ or SO₂N(R¹⁰⁸)C(O)R¹⁰⁸ wherein each R¹⁰⁸ is independently H, (C_1-6)alkyl, aryl or Het, said alkyl, aryl and Het being optionally substituted with R¹⁶⁰;

e) NR¹¹¹R¹¹² wherein R¹¹¹ is H, (C_1-6)alkyl, aryl or Het, and R¹¹² is H, (C_1-6)alkyl, COOR¹¹⁵ or SO₂R¹¹⁵ wherein R¹¹⁵ is (C_1-6)alkyl, said alkyl, cycloalkyl, aryl or Het being optionally substituted with R¹⁶⁰;

f) NR¹¹⁶COR¹¹⁷ wherein R¹¹⁶ and R¹¹⁷ is each H, (C_1-6)alkyl, aryl or Het, said alkyl, aryl and Het being optionally substituted with R¹⁶⁰;

g) NR¹¹⁸CONR¹¹⁹R¹²⁰, wherein R¹¹⁸, R¹¹⁹ and R¹²⁰ is each H, (C_1-6)alkyl, aryl or Het, said alkyl, aryl and Het being optionally substituted with R¹⁶⁰;

h) NR¹²¹COCOR¹²² wherein R¹²¹ is H(C_1-6)alkyl and R¹²² is OR¹²³ or N(R¹²⁴)₂ wherein R¹²³ and each R¹²⁴ is independently H, (C_1-6alkyl), aryl or Het, or R¹²⁴ is OH or O(C_1-6alkyl), said alkyl, aryl and Het being optionally substituted with R¹⁶⁰;

j) tetrazole, COOR¹²⁸ wherein R¹²⁸ is H, (C_1-6)alkyl optionally substituted with R¹⁶⁰; and

k) CONR¹²⁹R¹³⁰ wherein R¹²⁹ and R¹³⁰ are independently H, (C_1-6)alkyl, aryl or Het, said alkyl, aryl and Het being optionally substituted with R¹⁶⁰; and

wherein R¹⁶⁰ is defined as 1 or 2 substituents selected from;

tetrazole, halogen, CN, C_1-6alkyl, haloalkyl, COOR¹⁶¹, SO₃H, SO₂R¹⁶¹, OR¹⁶¹, N(R¹⁶²)₂, SO₂N(R¹⁶²)₂, NR¹⁶²COR¹⁶² or CON(R¹⁶²)₂, wherein R¹⁶¹ and R¹⁶² are as defined above.

27. The compound according to claim 1, wherein Z is OR⁶ wherein R⁶ is (C_2-6)alkenyl, (C_1-6)alkyl-Het, wherein said alkenyl or alkyl-Het, is optionally substituted with R⁶⁰, wherein R⁶⁰ is:

1 to 4 substituents selected from;

halogen;

or

1 to 4 substituents selected from;

a) (C_1-6) alkyl or haloalkyl, (C_3-7)cycloalkyl, C_3-7 spirocycloalkyl optionally containing 1 or 2 heteroatom, (C_2-6)alkenyl, (C_2-8)alkynyl, (C_1-6) alkyl-(C_3-7)cycloalkyl, all of which optionally substituted with R¹⁵⁰;

b) OR¹⁰⁴ wherein R¹⁰⁴ is H(C_1-6alkyl) (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

d) SR¹⁰⁸, SO₂N(R¹⁰⁸)₂ or SO₂N(R¹⁰⁸)C(O)R¹⁰⁸ wherein each R¹⁰⁸ is independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or both R¹⁰⁸ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or heterocycle being optionally substituted with R¹⁵⁰;

e) NR¹¹¹R¹¹² wherein R¹¹¹ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, and R¹¹² is H, CN, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl, (C_1-6alkyl)Het, COOR¹¹⁵ or SO₂R¹¹⁵ wherein R¹¹⁵ is (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or both R¹¹¹ and R¹¹² are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or heterocycle being optionally substituted with R¹⁵⁰;

f) NR¹¹⁶COR¹¹⁷ wherein R¹¹⁶ and R¹¹⁷ is each (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

g) NR¹¹⁸CONR¹¹⁹R¹²⁰, wherein R¹¹⁸, R¹¹⁹ and R¹²⁰ is each H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or R¹¹⁸ is covalently bonded to R¹¹⁹ and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle;

or R¹¹⁹ and R¹²⁰ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle;

said alkyl, cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or heterocycle being optionally substituted with R¹⁵⁰;

h) NR¹²¹COCOR¹²² wherein R¹²¹ is H, (C_1-6)alkyl optionally substituted with R¹⁵⁰, and R¹²² is OR¹²³ or N(R¹²⁴)₂ wherein R¹²³ and each R¹²⁴ is independently H, (C_1-6alkyl), (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or R¹²⁴ is OH or O(C_1-6alkyl) or both R¹²⁴ are covalently bonded together to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, alkyl-cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het and heterocycle being optionally substituted with R¹⁵⁰;

i) COR¹²⁷ wherein R¹²⁷ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

j) COOR¹²⁸ wherein R¹²⁸ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl and (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

k) CONR¹²⁹R¹³⁰ wherein R¹²⁹ and R¹³⁰ are independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or both R¹²⁹ and R¹³⁰ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, alkyl-cycloalkyl, aryl, Het, (C_1-6alkyl)aryl, (C_1-6alkyl)Het and heterocycle being optionally substituted with R¹⁵⁰;

l) aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, all of which being optionally substituted with R¹⁵⁰;

wherein R¹⁵⁰ is defined as;

1 to 3 substituents selected from;

halogen or azido;

or

1 to 3 substituents selected from;

a) (C_1-6) alkyl or haloalkyl, (C_3-7)cycloalkyl, C_3-7 spirocycloalkyl optionally containing 1 or 2 heteroatom, (C_2-6)alkenyl, (C_2-8)alkynyl, (C_1-6) alkyl-(C_3-7)cycloalkyl, all of which optionally substituted with R¹⁶⁰;

b) OR¹⁰⁴ wherein R¹⁰⁴ is H, (C_1-6alkyl), (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁶⁰;

d) SR¹⁰⁸, SO₂N(R¹⁰⁸)₂ or SO₂N(R¹⁰⁸)C(O)R¹⁰⁸ wherein each R¹⁰⁸ is independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or both R¹⁰⁸ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or heterocycle being optionally substituted with R¹⁶⁰;

e) NR¹¹¹R¹¹² wherein R¹¹¹ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, and R¹¹² is H, CN, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl, (C_1-6alkyl)Het, COOR¹¹⁵ or SO₂R¹¹⁵ wherein R¹¹⁵ is (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or both R¹¹¹ and R¹¹² are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or heterocycle being optionally substituted with R¹⁶⁰;

f) NR¹¹⁶COR¹¹⁷ wherein R¹¹⁶ and R¹¹⁷ is each H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁶⁰;

g) NR¹¹⁸CONR¹¹⁹R¹²⁰, wherein R¹¹⁸, R¹¹⁹ and R¹²⁰ is each H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or R¹¹⁸ is covalently bonded to R¹¹⁹ and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, or R¹¹⁹ and R¹²⁰ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or heterocycle being optionally substituted with R¹⁶⁰;

h) NR¹²¹COCOR¹²² wherein R¹²¹ is H or (C_1-6)alkyl optionally substituted with R¹⁶⁰, and R¹²² is OR¹²³ or N(R¹²⁴)₂ wherein R¹²³ and each R¹²⁴ is independently H, (C_1-6alkyl), (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or R¹²⁴ is OH or O(C_1-6alkyl) or both R¹²⁴ are covalently bonded together to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, alkyl-cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het and heterocycle being optionally substituted with R¹⁶⁰;

j) tetrazole, COOR¹²⁸ wherein R¹²⁸ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl and (C_1-6alkyl)Het being optionally substituted with R¹⁶⁰; and

k) CONR¹²⁹R¹³⁰ wherein R¹²⁹ and R¹³⁰ are independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or both R¹²⁹ and R¹³⁰ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, alkyl-cycloalkyl, aryl, Het, (C_1-6alkyl)aryl, (C_1-6alkyl)Het and heterocycle being optionally substituted with R¹⁶⁰;

wherein R¹⁶⁰ is defined as 1 or 2 substituents selected from;

tetrazole, halogen, CN, C_1-6alkyl, haloalkyl, COOR¹⁶¹, SO₃H, SR¹⁶¹, SO₂R¹⁶¹, OR¹⁶¹N(R¹⁶²)₂, SO₂N(R¹⁶²)₂, NR¹⁶²COR¹⁶² or CON(R¹⁶²)₂, wherein R¹⁶¹ and each R¹⁶² is independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl;

or

both R¹⁶² are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle.

28. The compound according to claim 27, wherein R⁶⁰ is:

1 to 4 substituents selected from;

halogen;

or

1 to 4 substituents selected from;

a) (C_1-6) alkyl or haloalkyl, (C_3-7)cycloalkyl, C_3-7 spirocycloalkyl optionally containing 1 or 2 heteroatom, (C_2-6)alkenyl, (C_2-8)alkynyl, (C_1-6) alkyl-(C_3-7)cycloalkyl, all of which optionally substituted with R¹⁵⁰;

b) OR¹⁰⁴ wherein R¹⁰⁴ is H, (C_1-6alkyl), (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

d) SO₃H, SO₂N(R¹⁰⁸)₂ or SO₂N(R¹⁰⁸)C(O)R¹⁰⁸ wherein each R¹⁰⁸ is independently H, (C_1-6)alkyl or aryl, said alkyl and aryl being optionally substituted with R¹⁵⁰;

e) NR¹¹¹R¹¹² wherein R¹¹¹ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, and R¹¹² is H, (C_1-6)alkyl COOR¹¹⁵ or SO₂R¹¹⁵ wherein R¹¹⁵ is (C_1-6)alkyl or (C_1-6alkyl)aryl, or both R¹¹¹ and R¹¹² are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or heterocycle being optionally substituted with R¹⁵⁰;

f) NR¹¹⁶COR¹¹⁷ wherein R¹¹⁶ and R¹¹⁷ is each (C_1-6)alkyl, (C_3-7)cycloalkyl, aryl or Het, said (C_1-6)alkyl, (C_3-7)cycloalkyl, aryl or Het being optionally substituted with R¹⁵⁰;

g) NR¹¹⁸CONR¹¹⁹R¹²⁰, wherein R¹¹⁸, R¹¹⁹ and R¹²⁰ is each H, (C_1-6)alkyl, aryl or Het, said alkyl, aryl and Het being optionally substituted with R¹⁵⁰;

h) NR¹²¹COCOR¹²² wherein R¹²¹ is H or (C_1-6)alkyl, and R¹²² is OR¹²³ or N(R¹²⁴)₂ wherein R¹²³ and each R¹²⁴ is independently H, (C_1-6alkyl), aryl or Het, or R¹²⁴ is OH or O(C_1-6alkyl), said alkyl, aryl and Het being optionally substituted with R¹⁵⁰;

j) COOR¹²⁸ wherein R¹²⁸ is H or (C_1-6)alkyl optionally substituted with R¹⁵⁰;

k) CONR¹²⁹R¹³⁰ wherein R¹²⁹ and R¹³⁰ are independently H, (C_1-6)alkyl aryl or Het, said alkyl, aryl and Het being optionally substituted with R¹⁵⁰;

l) aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, all of which being optionally substituted with R¹⁵⁰;

wherein R¹⁵⁰ is defined as;

1 to 3 substituents selected from;

halogen;

or

1 to 3 substituents selected from;

a) (C_1-6) alkyl or haloalkyl, (C_2-6)alkenyl, all of which optionally substituted with R¹⁶⁰;

b) OR¹⁰⁴ wherein R¹⁰⁴ is H, (C_1-6alkyl), aryl or Het, said alkyl, aryl and Het being optionally substituted with R¹⁶⁰;

d) SR¹⁰⁸, SO₂N(R¹⁰⁸)₂ or SO₂N(R¹⁰⁸)C(O)R¹⁰⁸ wherein each R¹⁰⁸ is independently H, (C_1-6)alkyl, aryl or Het, said alkyl, aryl and Het being optionally substituted with R¹⁶⁰;

e) NR¹¹¹R¹¹² wherein R¹¹¹ is H, (C_1-6)alkyl, aryl or Het, and R¹¹² is H, (C_1-6)alkyl, COOR¹¹⁵ or SO₂R¹¹⁵ wherein R¹¹⁵ is (C_1-6)alkyl or aryl, said alkyl, aryl and Het being optionally substituted with R¹⁶⁰;

f) NR¹¹⁶COR¹¹⁷ wherein R¹¹⁶ and R¹¹⁷ is each H, (C_1-6)alkyl, aryl or Het, said alkyl, aryl and Het being optionally substituted with R¹⁶⁰;

g) NR¹¹⁸CONR¹¹⁹R¹²⁰, wherein R¹¹⁸, R¹¹⁹ and R¹²⁰ is each H, (C_1-6)alkyl, aryl or Het, said alkyl, aryl and Het being optionally substituted with R¹⁶⁰;

h) NR¹²¹COCOR¹²² wherein R¹²¹ is H or (C_1-6)alkyl optionally substituted with R¹⁶⁰, and R¹²² is OR¹²³ or N(R¹²⁴)₂ wherein R¹²³ and each R¹²⁴ is independently H, (C_1-6alkyl), aryl or Het, or R¹²⁴ is OH or O(C_1-6alkyl), said alkyl, aryl and Het being optionally substituted with R¹⁶⁰;

j) tetrazole, COOR¹²⁸ wherein R¹²⁸ is H or (C_1-6)alkyl optionally substituted with R¹⁶⁰; and

k) CONR¹²⁹R¹³⁰ wherein R¹²⁹ and R¹³⁰ are independently H, (C_1-6)alkyl, aryl or Het, said alkyl, aryl and Het being optionally substituted with R¹⁶⁰;

wherein R¹⁶⁰ is defined as 1 or 2 substituents selected from;

tetrazole, halogen, CN, C_1-6alkyl, haloalkyl, COOR¹⁶¹, SO₃H, SR¹⁶¹, SO₂R¹⁶¹, OR¹⁶¹, N(R¹⁶²)₂, SO₂N(R¹⁶²)₂, NR¹⁶²CR¹⁶² or CON(R¹⁶²)₂, wherein R¹⁶¹ and each R¹⁶² is independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl;

or

both R¹⁶² are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle.

29. The compound according to claim 1, wherein Z is N(R^6a)R⁶ wherein R^6a is H or C_1-6alkyl and R⁶ is (C_2-6)alkenyl, aryl, Het, (C_1-6)alkyl-aryl, (C_1-6)alkyl-Het, wherein said alkenyl, aryl, Het, alkyl-aryl or alkyl-Het, are all optionally substituted with:

1 to 4 substituents selected from;

halogen, OPO₃H, NO₂, cyano, azido, C(═

NH)NH₂, C(═

NH)NH(C_1-6)alkyl or C(═

NH)NHCO(C_1-6)alkyl;

or

1 to 4 substituents selected from;

a) (C_1-6) alkyl or haloalkyl, (C_3-7)cycloalkyl, C_3-7 spirocycloalkyl optionally containing 1 or 2 heteroatom, (C_2-6)alkenyl, (C_2-8)alkynyl, (C_1-6) alkyl-(C_3-7)cycloalkyl, all of which optionally substituted with R¹⁵⁰;

b) OR¹⁰⁴ wherein R¹⁰⁴ is H, (C_1-6alkyl), (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

d) SR¹⁰⁸, SO₂NH(C_1-6alkyl) or SO₂NHC(O)C_1-6alkyl;

e) NR¹¹¹R¹¹² wherein R¹¹¹ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, and R¹¹² is H, CN, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl, (C_1-6alkyl)Het, COOR¹¹⁵ or SO₂R¹¹⁵ wherein R¹¹⁵ is (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or both R¹¹¹ and R¹¹² are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or heterocycle being optionally substituted with R¹⁵⁰;

f) NR¹¹⁶COR¹¹⁷ wherein R¹¹⁶ and R¹¹⁷ is each H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

g) NR¹¹⁸CONR¹¹⁹R¹²⁰, wherein R¹¹⁸, R¹¹⁹ and R¹²⁰ is each H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or R¹¹⁸ is covalently bonded to R¹¹⁹ and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle;

or R¹¹⁹ and R¹²⁰ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle;

said alkyl, cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or heterocycle being optionally substituted with R¹⁵⁰;

h) NR¹²¹COCOR¹²² wherein R¹²¹ and R¹²² is each H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, a 6- or 10-membered aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said alkyl, cycloalkyl, alkyl-cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

or R¹²² is OR¹²³ or N(R¹²⁴)₂ wherein R¹²³ and each R¹²⁴ is independently H, (C_1-6alkyl), (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or R¹²⁴ is OH or O(C_1-6alkyl) or both R¹²⁴ are covalently bonded together to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, alkyl-cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het and heterocycle being optionally substituted with R¹⁵⁰;

i) COR¹²⁷ wherein R¹²⁷ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

j) COOR¹²⁸ wherein R¹²⁸ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl and (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

k) CONR¹²⁹R¹³⁰ wherein R¹²⁹ and R¹³⁰ are independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or both R¹²⁹ and R¹³⁰ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, alkyl-cycloalkyl, aryl, Het, (C_1-6alkyl)aryl, (C_1-6alkyl)Het and heterocycle being optionally substituted with R¹⁵⁰;

l) aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, all of which being optionally substituted with R¹⁵⁰;

wherein, R¹⁵⁰ is selected from;

1 to 3 substituents selected from;

halogen, NO₂, cyano or azido;

or

1 to 3 substituents selected from;

a) (C_1-6) alkyl or haloalkyl, (C_3-7)cycloalkyl, C_3-7 spirocycloalkyl optionally containing 1 or 2 heteroatom, (C_2-6)alkenyl, (C_2-8)alkynyl, (C_1-6) alkyl-(C_3-7)cycloalkyl, all of which optionally substituted with R¹⁶⁰;

b) OR¹⁰⁴ wherein R¹⁰⁴ is H, (C_1-6alkyl), (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁶⁰;

d) SR¹⁰⁸, SO₂N(R¹⁰⁸)₂ or SO₂N(R¹⁰⁸)C(O)R¹⁰⁸ wherein each R¹⁰⁸ is independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or both R¹⁰⁸ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or heterocycle being optionally substituted with R¹⁶⁰;

e) NR¹¹¹R¹¹² wherein R¹¹¹ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, and R¹¹² is H, CN, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl, (C_1-6alkyl)Het, COOR¹¹⁵ or SO₂R¹¹⁵ wherein R¹¹⁵ is (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or both R¹¹¹ and R¹¹² are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or heterocycle being optionally substituted with R¹⁶⁰;

f) NR¹¹⁶COR¹¹⁷ wherein R¹¹⁶ and R¹¹⁷ is each H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁶⁰;

g) NR¹¹⁸CONR¹¹⁹R¹²⁰, wherein R¹¹⁸, R¹¹⁹ and R¹²⁰ is each H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or R¹¹⁹ and R¹²⁰ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle;

said alkyl, cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or heterocycle being optionally substituted with R¹⁶⁰;

h) NR¹²¹COCOR¹²² wherein R¹²¹ is H or (C_1-6)alkyl optionally substituted with R¹⁶⁰; and

R¹²² is OR¹²³ or N(R¹²⁴)₂ wherein R¹²³ and each R¹²⁴ is independently H, (C_1-6alkyl), (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or R¹²⁴ is OH or O(C_1-6alkyl) or both R¹²⁴ are covalently bonded together to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, alkyl-cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het and heterocycle being optionally substituted with R¹⁶⁰;

j) tetrazole, COOR¹²⁸ wherein R¹²⁸ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl and (C_1-6alkyl)Het being optionally substituted with R¹⁶⁰; and

k) CONR¹²⁹R¹³⁰ wherein R¹²⁹ and R¹³⁰ are independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or both R¹²⁹ and R¹³⁰ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, alkyl-cycloalkyl, aryl, Het, (C_1-6alkyl)aryl, (C_1-6alkyl)Het and heterocycle being optionally substituted with R¹⁶⁰;

wherein R¹⁶⁰ is defined as 1 or 2 substituents selected from;

tetrazole, halogen, CN, C_1-6alkyl, haloalkyl, COOR¹⁶¹, SO₃H, SO₂R¹⁶¹, OR¹⁶¹, N(R¹⁶²)₂, SO₂N(R¹⁶²)₂, NR¹⁶²COR¹⁶² or CON(R¹⁶²)₂, wherein R¹⁶¹ and each R¹⁶² is independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl;

or

both R¹⁶² are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle.

30. The compound according to claim 29, wherein R^6a is H.

31. The compound according to claim 29, wherein R⁶ is (C_2-6)alkenyl, aryl, Het, (C_1-6)alkyl-aryl, (C_1-6)alkyl-Het, wherein said alkenyl, aryl, Het, alkyl-aryl, or alkyl-Het, are all optionally substituted with:

1 to 4 substituents selected from;

halogen, NO₂, cyano, azido;

or

1 to 4 substituents selected from;

a) (C_1-6) alkyl or haloalkyl, (C_3-7)cycloalkyl, C_3-7 spirocycloalkyl optionally containing 1 or 2 heteroatom, (C_2-6)alkenyl, (C_2-8)alkynyl, (C_1-6) alkyl-(C_3-7)cycloalkyl, all of which optionally substituted with R¹⁵⁰;

b) OR¹⁰⁴ wherein R¹⁰⁴ is H, (C_1-6alkyl), (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

d) SH, S(C_1-6alkyl), SO₃H, SO₂NH(C_1-6alkyl) or SO₂NHC(O)C_1-6alkyl;

e) NR¹¹¹R¹¹² wherein R¹¹¹ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, and R¹¹² is H, CN, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl, (C_1-6alkyl)Het COOR¹¹⁵ or SO₂R¹¹⁵ wherein R¹¹⁵ is (C_1-6)alkyl, or both R¹¹¹ and R¹¹² are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or heterocycle being optionally substituted with R¹⁵⁰;

f) NR¹¹⁶COR¹¹⁷ wherein R¹¹⁶ and R¹¹⁷ is each H, (C_1-6)alkyl, (C_3-7)cycloalkyl, said (C_1-6)alkyl, (C_3-7)cycloalkyl being optionally substituted with R¹⁵⁰;

g) NR¹¹⁸CONR¹¹⁹R¹²⁰, wherein R¹¹⁸, R¹¹⁹ and R¹²⁰ is each H, (C_1-6)alkyl, (C_3-7)cycloalkyl, or R¹¹⁹ and R¹²⁰ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle;

said alkyl, cycloalkyl or heterocycle being optionally substituted with R¹⁵⁰;

h) NR¹²¹COCOR¹²² wherein R¹²¹ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl, said alkyl, cycloalkyl being optionally substituted with R¹⁵⁰;

or R¹²² is OR¹²³ or N(R¹²⁴)₂ wherein R¹²³ and each R¹²⁴ is independently H (C_1-6alkyl) or (C_3-7)cycloalkyl, or R¹²⁴ is OH or O(C_1-6alkyl) or both R¹²⁴ are covalently bonded together to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl and heterocycle being optionally substituted with R¹⁵⁰;

j) COOR¹²⁸ wherein R¹²⁸ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl and (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

k) CONR¹²⁹R¹³⁰ wherein R¹²⁹ and R¹³⁰ are independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said alkyl, cycloalkyl, alkyl-cycloalkyl, aryl, Het, (C_1-6alkyl)aryl, and (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

l) aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, all of which being optionally substituted with R¹⁵⁰; and

wherein R¹⁵⁰ is selected from;

1 to 3 substituents selected from;

halogen, NO₂, cyano or azido;

1 to 3 substituents selected from;

a) (C_1-6) alkyl or haloalkyl, (C_3-7)cycloalkyl, C_3-7 spirocycloalkyl optionally containing 1 or 2 heteroatom, (C_2-6)alkenyl, (C_2-8)alkynyl, (C_1-6) alkyl-(C_3-7)cycloalkyl, all of which optionally substituted with R¹⁶⁰;

b) OR¹⁰⁴ wherein R¹⁰⁴ is H, (C_1-6alkyl), (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁶⁰;

d) SH, S(C_1-6alkyl), SO₃H, SO₂N(R¹⁰⁸)₂ or SO₂N(R¹⁰⁸)C(O)R¹⁰⁸ wherein each R¹⁰⁸ is independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or both R¹⁰⁸ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or heterocycle being optionally substituted with R¹⁶⁰;

e) NR¹¹¹R¹¹² wherein R¹¹¹ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, and R¹¹² is H, CN, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl, (C_1-6alkyl)Het, COOR¹¹⁵ or SO₂R¹¹⁵ wherein R¹¹⁵ is (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or both R¹¹¹ and R¹¹² are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or heterocycle being optionally substituted with R¹⁶⁰;

f) NR¹¹⁶COR¹¹⁷ wherein R¹¹⁶ and R¹¹⁷ is each H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁶⁰;

g) NR¹¹⁸CONR¹¹⁹R¹²⁰, wherein R¹¹⁸, R¹¹⁹ and R¹²⁰ is each H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or R¹¹⁹ and R¹²⁰ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle;

said alkyl, cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or heterocycle being optionally substituted with R¹⁶⁰;

h) NR¹²¹COCOR¹²² wherein R¹²¹ is H, (C_1-6)alkyl optionally substituted with R¹⁶⁰; and

R¹²² is OR¹²³ or N(R¹²⁴)₂ wherein R¹²³ and each R¹²⁴ is independently H, (C_1-6alkyl), (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or R¹²⁴ is OH or O(C_1-6alkyl) or both R¹²⁴ are covalently bonded together to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, alkyl-cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het and heterocycle being optionally substituted with R¹⁶⁰;

j) tetrazole, COOR¹²⁸ wherein R¹²⁸ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl and (C_1-6alkyl)Het being optionally substituted with R¹⁶⁰; and

k) CONR¹²⁹R¹³⁰ wherein R¹²⁹ and R¹³⁰ are independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or both R¹²⁹ and R¹³⁰ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, alkyl-cycloalkyl, aryl, Het, (C_1-6alkyl)aryl, (C_1-6alkyl)Het and heterocycle being optionally substituted with R¹⁶⁰;

wherein R¹⁶⁰ is defined as 1 or 2 substituents selected from;

tetrazole, halogen, CN, C_1-6alkyl, haloalkyl, COOR¹⁶¹, SO₃H, SO₂R¹⁶¹, OR¹⁶¹, N(R¹⁶²)₂, SO₂N(R¹⁶²)₂, NR¹⁶²COR¹⁶² or CON(R¹⁶²)₂, wherein R¹⁶¹ and each R¹⁶² is independently H or (C_1-6)alkyl.

32. The compound according to claim 31, wherein R⁶ is C_2-6alkenyl, phenyl, (C_1-6)alkyl-aryl, (C_1-6)alkyl-Het, wherein said alkenyl, phenyl and the alkyl portion of said alkyl-aryl or alkyl-Het, are optionally substituted with 1 to 3 substituents selected from:

a) (C_1-6) alkyl C_3-7 spirocycloalkyl optionally containing 1 or 2 heteroatom, (C_2-6)alkenyl, all of which optionally substituted with C_1-6alkyl or C_1-6alkoxy, NH₂, NH(Me) or N(Me)₂;

e) NHR¹¹² wherein R¹¹² is aryl, Het, (C_1-6alkyl)aryl, (C_1-6alkyl)Het, said aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, being optionally substituted with R¹⁵⁰;

j) COOH;

k) CONR¹²⁹R¹³⁰ wherein R¹²⁹ and R¹³⁰ are independently H(C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said alkyl, cycloalkyl, alkyl-cycloalkyl, aryl, Het, (C_1-6alkyl)aryl, and (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

l) phenyl or Het, both optionally substituted with R¹⁵⁰ and

wherein R¹⁵⁰ is selected from;

1 or 2 substituents selected from;

halogen, NO₂, cyano or azido;

1 or 2 substituents selected from;

a) (C_1-6) alkyl or (C_2-6)alkenyl, both optionally substituted with COOH or CONH₂;

b) OR¹⁰⁴ wherein R¹⁰⁴ is H or (C_1-6alkyl) optionally substituted with COOH;

h)NHCOCOOH;

j) COOH; and

k) CONH₂.

33. The compound according to claim 32, wherein Z is selected from:

34. The compound according to claim 29, wherein R⁶ is:

35. The compound according to claim 34, wherein R⁷ and R⁸ are each independently H, (C_1-6)alkyl, haloalkyl, (C_3-7)cycloalkyl, 6- or 10-membered aryl, Het, (C_1-6)alkyl-aryl, (C_1-6)alkyl-Het, all of which optionally substituted with from 1 to 4 substituents selected from halogen or:

a) (C_1-6)alkyl; and

b) N(R^8a′

)₂, COR^8a, or SO₂R^8a″

COOR^8a, COCOOR^8a, CON(R^8a′

)₂, COCON(R^8a′

)₂, wherein each R^8a or R^8a′

are independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl;

or each R^8a′

are independently covalently bonded together and to the nitrogen to which they are both bonded to form a 5, 6 or 7-membered saturated heterocycle;

or R^8a″

is independently (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl.

or R⁷ and R⁸ are covalently bonded together to form (C_3-7)cycloalkyl, 4,5- or 6-membered heterocycle having from 1 to 3 heteroatom selected from O, N, and S.

36. The compound according to claim 35, wherein R⁷ and R⁸ are each independently H, (C_1-6)alkyl, haloalkyl, (C_3-7)cycloalkyl, 6- or 10-membered aryl, Het, (C_1-6)alkyl-aryl, (C_1-6)alkyl-Het;

or R⁷ and R⁸ are covalently bonded together to form cyclopropyl, cyclobutyl, cyclopentyl, pyrrolidine, piperidine, tetrahydrofuran, tetrahydropyran, or pentamethylene sulfide;

wherein said alkyl, haloalkyl, (C_3-7)cycloalkyl, 6- or 10-membered aryl, Het, (C_1-6)alkyl-aryl, (C_1-6)alkyl-Het, cyclopropyl, cyclobutyl, cyclopentyl, pyrrolidine, piperidine, tetrahydrofuran, tetrahydropyran, or pentamethylene sulfide are optionally monosubstituted with substituents selected from;

a) (C_1-6)alkyl; and

b) NH₂, N(CH₂CH)₂, COCH₃, or SO₂CH₃.

37. The compound according to claim 36, wherein R⁷ and R⁸ are selected from:

38. The compound according to claim 37, wherein R⁷ and R⁸ are selected from:

39. The compound according to claim 34, wherein R⁹ is H, or R⁹ is covalently bonded to either of R⁷ or R⁸ to form a 5- or 6-membered heterocycle.

40. The compound according to claim 39, wherein R⁹ is H.

41. The compound according to claim 34, wherein Q is a 6- or 10-membered aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)-Het, all of which being optionally substituted with:

42. The compound according to claim 41, wherein Q is a 6- or 10-membered aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)-Het, all of which being optionally substituted with:

1 to 4 substituents selected from;

halogen, NO₂, cyano or azido;

or

1 to 4 substituents selected from;

a) (C_1-6) alkyl or haloalkyl, (C_3-7)cycloalkyl, (C_2-6)alkenyl, (C_2-8)alkynyl, (C_1-6) alkyl-(C_3-7)cycloalkyl, all of which optionally substituted with R¹⁵⁰;

b) OR¹⁰⁴ wherein R¹⁰⁴ is H, (C_1-6alkyl), (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

d) SR¹⁰⁸, SO₂N(R¹⁰⁸)₂ or SO₂N(R¹⁰⁸)C(O)R¹⁰⁸ wherein each R¹⁰⁸ is independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or both R¹⁰⁸ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or heterocycle being optionally substituted with R¹⁵⁰;

e) NR¹¹¹R¹¹² wherein R¹¹¹ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, and R¹¹² is H, CN, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl, (C_1-6alkyl)Het, COOR¹¹⁵ or SO₂R¹¹⁵ wherein R¹¹⁵ is (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or both R¹¹¹ and R¹¹² are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or heterocycle being optionally substituted with R¹⁵⁰;

f) NR¹¹⁶COR¹¹⁷ wherein R¹¹⁶ and R¹¹⁷ is each H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

g) NR¹¹⁸CONR¹¹⁹R¹²⁰, wherein R¹¹⁸, R¹¹⁹ and R¹²⁰ is each H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or R¹¹⁹ and R¹²⁰ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle;

said alkyl, cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het or heterocycle being optionally substituted with R¹⁵⁰;

h) NR¹²¹COCOR¹²² wherein R¹²¹ is H, (C_1-6)alkyl optionally substituted with R¹⁵⁰, and R¹²² is OR¹²³ or N(R¹²⁴)₂ wherein R¹²³ and each R¹²⁴ is independently H, (C_1-6alkyl), (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or R¹²⁴ is OH or O(C_1-6alkyl) or both R¹²⁴ are covalently bonded together to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, alkyl-cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het and heterocycle being optionally substituted with R¹⁵⁰;

j) COOR¹²⁸ wherein R¹²⁸ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said (C_1-6)alkyl, (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl and (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

k) CONR¹²⁹R¹³⁰ wherein R¹²⁹ and R¹³⁰ are independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or both R¹²⁹ and R¹³⁰ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, alkyl-cycloalkyl, aryl, Het, (C_1-6alkyl)aryl, (C_1-6alkyl)Het and heterocycle being optionally substituted with R¹⁵⁰;

l) aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, all of which being optionally substituted with R¹⁵⁰;

wherein R¹⁵⁰ is selected from;

1 to 3 substituents selected from;

halogen, NO₂, cyano or azido;

or

1 to 3 substituents selected from;

a) (C_1-6) alkyl or haloalkyl, (C_3-7)cycloalkyl, (C_2-6)alkenyl, (C_2-8)alkynyl, (C_1-6) alkyl-(C_3-7)cycloalkyl, all of which optionally substituted with R¹⁶⁰;

b) OR¹⁰⁴ wherein R¹⁰⁴ is H, (C_1-6alkyl), (C_3-7)cycloalkyl, or (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, said alkyl, cycloalkyl, aryl and Het being optionally substituted with R¹⁶⁰;

c) OCOR¹⁰⁵ wherein R¹⁰⁵ is (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁶⁰;

d) SR¹⁰⁸, SO₂N(R¹⁰⁸)₂ or SO₂N(R¹⁰⁸)C(O)R¹⁰⁸ wherein each R¹⁰⁸ is independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl or both R¹⁰⁸ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl or heterocycle being optionally substituted with R¹⁶⁰;

e) NR¹¹¹R¹¹² wherein R¹¹¹ is H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, and R¹¹² is H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl, COOR¹¹⁵ or SO₂R¹¹⁵ wherein R¹¹⁵ is (C_1-6)alkyl, (C_3-7)cycloalkyl, or both R¹¹¹ and R¹¹² are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, or heterocycle being optionally substituted with R¹⁶⁰;

f) NR¹¹⁶COR¹¹⁷ wherein R¹¹⁶ and R¹¹⁷ is each H, (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said (C_1-6)alkyl, (C_3-7)cycloalkyl, (C_1-6)alkyl-(C_3-7)cycloalkyl, aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁶⁰;

g) NR¹¹⁸CONR¹¹⁹R¹²⁰, wherein R¹¹⁸, R¹¹⁹ and R¹²⁰ is each H, (C_1-6)alkyl, (C_3-7)cycloalkyl, or R¹¹⁹ and R¹²⁰ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle;

said alkyl, cycloalkyl or heterocycle being optionally substituted with R¹⁶⁰;

h) NR¹²¹COCOR¹²² wherein R¹²¹ is H, (C_1-6)alkyl optionally substituted with R¹⁶⁰, or R¹²² is OR¹²³ or N(R¹²⁴)₂ wherein R¹²³ and each R¹²⁴ is independently H, (C_1-6alkyl) or (C_3-7)cycloalkyl, or R¹²⁴ is OH or O(C_1-6alkyl), or both R¹²⁴ are covalently bonded together to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl and heterocycle being optionally substituted with R¹⁶⁰;

j) tetrazole, COOR¹²⁸ wherein R¹²⁸ is H, (C_1-6)alkyl or (C_3-7)cycloalkyl, said (C_1-6)alkyl and (C_3-7)cycloalkyl being optionally substituted with R¹⁶⁰; and

k) CONR¹²⁹R¹³⁰ wherein R¹²⁹ and R¹³⁰ are independently H, (C_1-6)alkyl or (C_3-7)cycloalkyl, or both R¹²⁹ and R¹³⁰ are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle, said alkyl, cycloalkyl and heterocycle being optionally substituted with R¹⁶⁰;

wherein R¹⁶⁰ is defined as 1 or 2 substituents selected from;

tetrazole, halogen, CN, C_1-6alkyl, haloalkyl, COOR¹⁶¹, SO₃H, SO₂R¹⁶¹, OR¹⁶¹, N(R¹⁶²)₂, SO₂N(R¹⁶²)₂, NR¹⁶²COR¹⁶² or CON(R¹⁶²)₂, wherein R¹⁶¹ and each R¹⁶² is independently H, (C_1-6)alkyl, (C_3-7)cycloalkyl or (C_1-6)alkyl-(C_3-7)cycloalkyl;

or

both R¹⁶² are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle.

43. The compound according to claim 42, wherein Q is a 6- or 10-membered aryl or Het, both being optionally substituted with:

1 to 3 halogen, NO₂, cyano, azido;

or

1 to 3 substituents selected from;

a) (C_1-6) alkyl or haloalkyl, first (C_3-7)cycloalkyl, (C_2-6)alkenyl, (C_2-8)alkynyl, (C_1-6) alkyl-(C_3-7)cycloalkyl, all of which are optionally substituted with R¹⁵⁰;

b) OR¹⁰⁴ wherein R¹⁰⁴ is H, (C_1-6alkyl);

d) SO₂NHR¹⁰⁸ wherein R¹⁰⁸ is H or (C_1-6)alkyl;

e) NR¹¹¹R¹¹² wherein both R¹¹¹ and R¹¹² are independently H or (C_1-6)alkyl;

f) NHCOR¹¹⁷ wherein R¹¹⁶ is H or (C_1-6)alkyl;

g) NHCONR¹¹⁹R¹²⁰, wherein R¹¹⁹ and R¹²⁰ is each independently H or (C_1-6)alkyl;

h) NHCOCOR¹²² wherein R¹²² is OR¹²³ or N(R¹²⁴)₂ wherein R¹²³ and each R¹²⁴ is independently H or (C_1-6alkyl);

j) COOR¹²⁸ wherein R¹²⁸ is H, (C_1-6)alkyl;

k) CONHR¹³⁰ wherein R¹³⁰ is H, (C_1-6)alkyl;

l) 6- or 10-membered aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het, said aryl, Het, (C_1-6alkyl)aryl or (C_1-6alkyl)Het being optionally substituted with R¹⁵⁰;

wherein R¹⁵⁰ is selected from;

1 to 3 halogens;

or

1 to 3 substituents selected from;

a) first (C_1-6) alkyl or haloalkyl, first (C_3-7)cycloalkyl, (C_2-6)alkenyl, (C_2-8)alkynyl, (C_1-6) alkyl-(C_3-7)cycloalkyl, all of which are optionally substituted with tetrazole, OR¹⁰², COOR¹⁰², wherein R¹⁰² is H or (C_1-6)alkyl;

b) OR¹⁰⁴ wherein R¹⁰⁴ is H, (C_1-6alkyl);

d) SO₂NHR¹⁰⁸ wherein R¹⁰⁸ is H or (C_1-6)alkyl;

e) NR¹¹¹R¹¹² wherein both R¹¹¹ and R¹¹² are independently H or (C_1-6)alkyl;

f) NHCOR¹¹⁷ wherein R¹¹⁶ is H or (C_1-6)alkyl; and

h) NHCOCOR¹²² wherein R¹²² is OR¹²³ or N(R¹²⁴)₂ wherein R¹²³ and each R¹²⁴ is independently H or (C_1-6alkyl);

j) COOR¹²⁸ wherein R¹²⁸ is H, (C_1-6)alkyl; and

k) CONHR¹³⁰ wherein R¹³⁰ is H, (C_1-6)alkyl.

44. The compound according to claim 43, wherein Q is selected from:

45. The compound according to claim 44, wherein Q is selected from:

56. A compound of the formula I according to claim 1, or a pharmaceutically acceptable salt thereof, as an inhibitor of RNA dependent RNA polymerase activity of the enzyme NS5B, encoded by HCV.

57. A compound of the formula I according to claim 1, or a pharmaceutically acceptable salt thereof, as an inhibitor of HCV replication.

58. A pharmaceutical composition for the treatment or prevention of HCV infection, comprising an effective amount of a compound of formula I according to claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

59. A composition according to claim 58, further comprising an immunomodulatory agent.

60. A composition according to claim 59, wherein said immunomodulatory agents is selected from:

α

-, β

-, δ

- γ

-, and ω

-interferon.

61. A composition according to claim 58, further comprising another antiviral agent.

62. A composition according to claim 61, wherein said antiviral agent is selected from:

ribavirin and amantadine.

63. A composition according to claim 58, further comprising another inhibitor of HCV polymerase.

64. A composition according to claim 58, further comprising an inhibitor of:

HCV helicase, HCV protease, HCV metalloprotease or HCV IRES.

65. Use of a compound of formula I according to claim 1, as an HCV polymerase inhibitor.

66. An intermediate compound represented by formula 1c:

67. A process for producing compounds of formula I, comprising:

a) coupling, in a mixture containing an aprotic solvent, or no solvent, a coupling agent, and at a temperature of about 20°

C. to about 170°

C., and intermediate 1c;

68. An intermediate compound represented by formula 1d:

69. A process for producing compounds of formula I, comprising:

a) coupling, in a mixture containing an appropriate solvent, or no solvent, a coupling agent, and at a temperature of about 20°

C. to about 170°

C., and intermediate 1d;

70. A method of treating or preventing HCV infection in a mammal, comprising administering to the mammal an effective amount of a composition according to claim 59, or a pharmaceutically acceptable salt thereof.

71. A method of treating or preventing HCV infection in a mammal, comprising administering to the mammal an effective amount of a composition according to claim 61, or a pharmaceutically acceptable salt thereof in combination with another anti-HCV agent.

72. A method of treating or preventing HCV infection in a mammal, comprising administering to the mammal an effective amount of a composition according to claim 63, or a pharmaceutically acceptable salt thereof in combination with another anti-HCV agent.

46. A compound represented by Formula Ia:

47. A compound of the formula:

48. A compound of the formula:

49. A compound of the formula:

50. A compound of the formula:

51. A compound of the formula:

52. A compound of the formula:

53. A compound of the formula:

54. A compound of the formula:

55. A compound of the formula: