Methanogen inhibitors

Abstract

The present invention relates to a new class of methanogen inhibitors for ruminants. The invention also extends to the use of such compounds in ruminants to reduce methane production in the rumen and / or to enhance productivity in the ruminant.

Description

[0001] METHANOGEN INHIBITORS FIELD OF INVENTION The present invention relates to a new class of methanogen inhibitors for ruminants, in particular new compounds of Formula I or II; Formula I; or II; for ruminants. The invention also extends to the use of such compounds in ruminants to reduce methane production in the rumen and / or to enhance productivity in the ruminant. BACKGROUND OF INVENTION Methane is produced as a natural consequence of digestion of feed by bacteria, fungi and protozoa in ruminant animals. This fermentation leads to the production of volatile fatty acids and peptides for the host. Fermentation also produces copious quantities of CO2and H2which are used by methanogenic archaea within the rumen to produce methane, which is ultimately released from the rumen, mostly through eructation. The methane forming methanogens are members of the Archaea, and are quite different in a number of features to bacteria, fungi and protozoa. Methanogens have a number of unusual and archaeal-specific features, including cell wall structures, lipids, cofactors, and amino acid synthesis pathways, as well as their signature energy metabolism that is linked to methane production. They represent only about 1-4% of the rumen microbial community. It is known that, due to the unique metabolic pathways of methanogens and their low numbers, methanogen-specific inhibitors can be developed that do not adversely affect the fermentation of feed. It has been recognised that the release of such methane is deleterious for two reasons. One is that methane is a greenhouse gas and the other is that the methane loss represents a loss of energy for the ruminant. It has been previously recognised that if one could inhibit or reduce the release of methane from ruminants that the impact of methane on the environment and atmosphere would be reduced and productivity gains might be achieved in the ruminants. It is therefore an object of the present invention to overcome the above mentioned difficulties or to at least provide the public with a useful alternative. SUMMARY OF INVENTION In one aspect the present disclosure provides a compound of Formula I Formula I wherein R may be selected from: -C(=O)-C1-C6-C(=O)-OH, -C(=O)-C1-C6-C(=O)-O-C1-C6, -C(=O)-C1-C6-C(=O)-O-C1-C6-O- (C=O)-C1-C6, or wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or -C(=O)-C1-C6-C(=O)-NH-S(O)2-C1-C6, -C(=O)-C1-C6-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, - C(=O)-C1-C6-C(=O)-NH-S(O)2-aryl, C(=O)-C1-C6-C(=O)-NH-S(O)2-C1-C6-aryl, -C(=O)-C1- C6-C(=O)-NH-S(O)2-heteroaryl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-C1-C6-heteroaryl, or -C(=O)-C1-C6-C(=O)-NH-S(O)2-NH2, -C(=O)-C1-C6-C(=O)-NH-S(O)2-NH-C1-C6, -C(=O)- C1-C6-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-NH-aryl, - C(=O)-C1-C6-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-NH- heteroaryl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-NH- C1-C6-heteroaryl, -C(=O)-C1-C6-C(=O)-NH- S(O)2-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-C1-C6, -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-C3-C8- cycloalkyl, -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-aryl, -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2- heteroaryl, or -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-NH2, -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-NH-C1-C6, - C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C(=O)-C1-C6-NH-C(=O)-NH- S(O)2-NH-aryl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C(=O)-C1-C6-NH-C(=O)- NH-S(O)2-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH- , NC1-C6-, -S- or -O-; or -C1-C6-C(=O)-OH, -C1-C6-C(=O)-O-C1-C6, -C1-C6-C(=O)-O-C1-C6-O-(C=O)-C1-C6, -C1-C6- OH, or -C1-C6-C(=O)-NH2, -C1-C6-C(=O)-NH-C1-C6, -C1-C6-C(=O)-NH-C3-C8-cycloalkyl, -C1-C6- , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or -C1-C6-C(=O)-NH-S(O)2-C1-C6, -C1-C6-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -C1-C6-C(=O)- NH-S(O)2-aryl, -C1-C6-C(=O)-NH-S(O)2-C1-C6-aryl, -C1-C6-C(=O)-NH-S(O)2-heteroaryl, - C1-C6-C(=O)-NH-S(O)2-C1-C6-heteroaryl, or -C1-C6-C(=O)-NH-S(O)2-NH2, -C1-C6-C(=O)-NH-S(O)2-NH-C1-C6, -C1-C6-C(=O)-NH- S(O)2-NH-C3-C8-cycloalkyl, -C1-C6-C(=O)-NH-S(O)2-NH-aryl, -C1-C6-C(=O)-NH-S(O)2- NH-C1-C6-aryl, -C1-C6-C(=O)-NH-S(O)2-NH-heteroaryl, -C1-C6-C(=O)-NH-S(O)2-NH- C1- C6-heteroaryl, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or -C1-C6-NH-C(=O)-NH-S(O)2-C1-C6, -C1-C6-NH-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -C1-C6- NH-C(=O)-NH-S(O)2-aryl, -C1-C6-NH-C(=O)-NH-S(O)2-heteroaryl, or -C1-C6-NH-C(=O)-NH-S(O)2-NH2, -C1-C6-NH-C(=O)-NH-S(O)2-NH-C1-C6, -C1-C6-NH- C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C1-C6-NH-C(=O)-NH-S(O)2-NH-aryl, -C1-C6- C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C1-C6-NH-C(=O)-NH-S(O)2-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or or -C(=O)-aryl-C(=O)-OH, -C(=O)-aryl-C(=O)-O-C1-C6, -C(=O)-aryl-C(=O)-O-C1-C6-O- (C=O)-C1-C6, -C(=O)-aryl-OH, or -C(=O)-aryl-C(=O)-NH2, -C(=O)-aryl-C(=O)-NH-C1-C6, -C(=O)-aryl-C(=O)-NH-C3-C8- , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from - NH-, -NC1-C6-, -S- or -O-; or -C(=O)-aryl-C(=O)-NH-S(O)2-C1-C6, -C(=O)-aryl-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, - C(=O)-aryl-C(=O)-NH-S(O)2-aryl, -C(=O)-aryl-C(=O)-NH-S(O)2-C1-C6-aryl, -C(=O)-aryl- C(=O)-NH-S(O)2-heteroaryl, -C(=O)-aryl-C(=O)-NH-S(O)2-C1-C6-heteroaryl, or -C(=O)-aryl-C(=O)-NH-S(O)2-NH2, -C(=O)-aryl-C(=O)-NH-S(O)2-NH-C1-C6, -C(=O)-aryl- C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C(=O)-aryl-C(=O)-NH-S(O)2-NH-aryl, -C(=O)- aryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C(=O)-aryl-C(=O)-NH-S(O)2-NH-heteroaryl, - C(=O)-aryl-C(=O)-NH-S(O)2-NH-C1-C6-heteroaryl, -C(=O)-aryl-C(=O)-NH-S(O)2-N(C1- , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or -C(=O)-aryl-NH-C(=O)-NH-S(O)2-C1-C6, -C(=O)-aryl-NH-C(=O)-NH-S(O)2-C3-C8- cycloalkyl, -C(=O)-aryl-NH-C(=O)-NH-S(O)2-aryl, -C(=O)-aryl-NH-C(=O)-NH-S(O)2- heteroaryl, or -C(=O)-aryl-NH-C(=O)-NH-S(O)2-NH2, -C(=O)-aryl-NH-C(=O)-NH-S(O)2-NH-C1-C6, - C(=O)-aryl-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C(=O)-aryl-NH-C(=O)-NH-S(O)2- NH-aryl, -C(=O)-aryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C(=O)-aryl-NH-C(=O)-NH-S(O)2- N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or or -aryl-C(=O)-OH, -aryl-C(=O)-O-C1-C6, -aryl-C(=O)-O-C1-C6-O-(C=O)-C1-C6, -aryl-C1-C6- OH, -aryl-C1-C6-(C=O)OH, or -aryl-C(=O)-NH2, -aryl-C(=O)-NH-C1-C6, -aryl-C(=O)-NH-C3-C8-cycloalkyl, -aryl-C(=O)- , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or -aryl-C(=O)-NH-S(O)2-C1-C6, -aryl-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -aryl-C(=O)-NH- S(O)2-aryl, -aryl-C(=O)-NH-S(O)2-C1-C6-aryl, -aryl-C(=O)-NH-S(O)2-heteroaryl, -aryl- C(=O)-NH-S(O)2-C1-C6-heteroaryl, or -aryl-C(=O)-NH-S(O)2-NH2, -aryl-C(=O)-NH-S(O)2-NH-C1-C6, -aryl-C(=O)-NH-S(O)2-NH- C3-C8-cycloalkyl, -aryl-C(=O)-NH-S(O)2-NH-aryl, -aryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, - aryl-C(=O)-NH-S(O)2-NH-heteroaryl, -aryl-C(=O)-NH-S(O)2-NH-C1-C6-heteroaryl, -aryl- C(=O)-NH-S(O)2-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or -aryl-NH-C(=O)-NH-S(O)2-C1-C6, -aryl-NH-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -aryl-NH- C(=O)-NH-S(O)2-aryl, -aryl-NH-C(=O)-NH-S(O)2-heteroaryl, or -aryl-NH-C(=O)-NH-S(O)2-NH2, -aryl-NH-C(=O)-NH-S(O)2-NH-C1-C6, -aryl-NH-C(=O)- NH-S(O)2-NH-C3-C8-cycloalkyl, -aryl-NH-C(=O)-NH-S(O)2-NH-aryl, -aryl-C(=O)-NH- S(O)2-NH-C1-C6-aryl, -aryl-NH-C(=O)-NH-S(O)2-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or -aryl-S(O)2-OH, -aryl-S(O)2-NH2, -aryl-S(O)2-NH-C1-C6, -aryl-S(O)2-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or -aryl-S(O)2-NH-C3-C8-cycloalkyl, or ,wherein J is a 5 membered heterocycle ring containing up to 4 heteroatoms selected from _-N=, - NH-, or -O-; -C(=O)-heteroaryl-C(=O)-OH, -C(=O)-heteroaryl-C(=O)-O-C1-C6, -C(=O)-heteroaryl-C(=O)- O-C1-C6-O-(C=O)-C1-C6, -C(=O)-aryl-OH, or -C(=O)-heteroaryl-C(=O)-NH2, -C(=O)-heteroaryl-C(=O)-NH-C1-C6, -C(=O)-heteroaryl- C(=O)-NH-C3-C8-cycloalkyl, -C(=O)-heteroaryl-C(=O)-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or -C(=O)-heteroaryl-C(=O)-NH-S(O)2-C1-C6, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-C3-C8- cycloalkyl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-aryl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2- C1-C6-aryl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-heteroaryl, -C(=O)-heteroaryl-C(=O)-NH- S(O)2-C1-C6-heteroaryl, or -C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH2, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6, - C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C(=O)-heteroaryl-C(=O)-NH- S(O)2-NH-aryl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C(=O)-heteroaryl- C(=O)-NH-S(O)2-NH-heteroaryl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH- C1-C6-heteroaryl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or -C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-C1-C6, -C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2- C3-C8-cycloalkyl, -C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-aryl, -C(=O)-heteroaryl-NH- C(=O)-NH-S(O)2-heteroaryl, or -C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-NH2, -C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-NH- C1-C6, -C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C(=O)-heteroaryl- NH-C(=O)-NH-S(O)2-NH-aryl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, - C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from - NH-, -NC1-C6-, -S- or -O-; or -heteroaryl-C(=O)-NH-S(O)2-C1-C6, -heteroaryl-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, - heteroaryl-C(=O)-NH-S(O)2-aryl, -heteroaryl-C(=O)-NH-S(O)2-C1-C6-aryl, -heteroaryl- C(=O)-NH-S(O)2-heteroaryl, -heteroaryl-C(=O)-NH-S(O)2-C1-C6-heteroaryl, or -heteroaryl-C(=O)-NH-S(O)2-NH2, -heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6, -heteroaryl- C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -heteroaryl-C(=O)-NH-S(O)2-NH-aryl, -heteroaryl- C(=O)-NH-S(O)2-NH-C1-C6-aryl, -heteroaryl-C(=O)-NH-S(O)2-NH-heteroaryl, -heteroaryl- C(=O)-NH-S(O)2-NH-C1-C6-heteroaryl, -heteroaryl-C(=O)-NH-S(O)2-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or -heteroaryl-NH-C(=O)-NH-S(O)2-C1-C6, -heteroaryl-NH-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -heteroaryl-NH-C(=O)-NH-S(O)2-aryl, -heteroaryl-NH-C(=O)-NH-S(O)2-heteroaryl, or -heteroaryl-NH-C(=O)-NH-S(O)2-NH2, -heteroaryl-NH-C(=O)-NH-S(O)2-NH-C1-C6, - heteroaryl-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -heteroaryl-NH-C(=O)-NH-S(O)2- NH-aryl, -heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -heteroaryl-NH-C(=O)-NH-S(O)2- N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or -C1-C6-aryl-C(=O)-OH, -C1-C6-aryl-C(=O)-O-C1-C6, -C1-C6-aryl-C(=O)-O-C1-C6-O-(C=O)- C1-C6, -C1-C6-aryl-C1-C6-OH, or -C1-C6-aryl-C(=O)-NH2, -C1-C6-aryl-C(=O)-NH-C1-C6, -C1-C6-aryl-C(=O)-NH-C3-C8- , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from - NH-, -NC1-C6-, -S- or -O-; or -C1-C6-aryl-C(=O)-NH-S(O)2-C1-C6, -C1-C6-aryl-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -C1-C6- aryl-C(=O)-NH-S(O)2-aryl, -C1-C6-aryl-C(=O)-NH-S(O)2-C1-C6-aryl, -C1-C6-aryl-C(=O)- NH-S(O)2-heteroaryl, -C1-C6-aryl-C(=O)-NH-S(O)2-C1-C6-heteroaryl, or -C1-C6-aryl-C(=O)-NH-S(O)2-NH2, -C1-C6-aryl-C(=O)-NH-S(O)2-NH-C1-C6, -C1-C6-aryl- C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C1-C6-aryl-C(=O)-NH-S(O)2-NH-aryl, -C1-C6-aryl- C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C1-C6-aryl-C(=O)-NH-S(O)2-NH-heteroaryl, -C1-C6-aryl- C(=O)-NH-S(O)2-NH-C1-C6-heteroaryl, -C1-C6-aryl-C(=O)-NH-S(O)2-N(C1-C6)2, -C1-C6 , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or -C1-C6-aryl-NH-C(=O)-NH-S(O)2-C1-C6, -C1-C6-aryl-NH-C(=O)-NH-S(O)2-C3-C8- cycloalkyl, -C1-C6-aryl-NH-C(=O)-NH-S(O)2-aryl, -C1-C6-aryl-NH-C(=O)-NH-S(O)2- heteroaryl, or -C1-C6-aryl-NH-C(=O)-NH-S(O)2-NH2, -C1-C6-aryl-NH-C(=O)-NH-S(O)2-NH-C1-C6, -C1- C6-aryl-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C1-C6-aryl-NH-C(=O)-NH-S(O)2-NH- aryl, -C1-C6-aryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C1-C6-aryl-NH-C(=O)-NH-S(O)2-N(C1- , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or -C1-C6-aryl-S(O)2-OH, -C1-C6-aryl-S(O)2-NH2, -C1-C6-aryl-S(O)2-NH-C1-C6, -C1-C6-aryl- S(O)2-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or -C1-C6-aryl-S(O)2-NH-C3-C8-cycloalkyl, or -C1-C6-heteroaryl-C(=O)-OH, -C1-C6-heteroaryl-C(=O)-O-C1-C6, -C1-C6-heteroaryl-C(=O)- O-C1-C6-O-(C=O)-C1-C6, -C1-C6 -heteroaryl-C1-C6-OH, or -C1-C6-heteroaryl-C(=O)-NH2, -C1-C6-heteroaryl-C(=O)-NH-C1-C6, -C1-C6-heteroaryl- C(=O)-NH-C3-C8-cycloalkyl, -C1-C6-heteroaryl-C(=O)-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or -C1-C6-heteroaryl-C(=O)-NH-S(O)2-C1-C6, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-C3-C8- cycloalkyl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-aryl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-C1- C6-aryl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-heteroaryl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2- C1-C6-heteroaryl, or -C1-C6-heteroaryl-C(=O)-NH-S(O)2-NH2, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6, -- C1-C6heteroaryl-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C1-C6-heteroaryl-C(=O)-NH- S(O)2-NH-aryl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C1-C6-heteroaryl- C(=O)-NH-S(O)2-NH-heteroaryl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-heteroaryl, - C1-C6-heteroaryl-C(=O)-NH-S(O)2-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or -C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-C1-C6, -C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-C3- C8-cycloalkyl, -C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-aryl, -C1-C6-heteroaryl-NH-C(=O)- NH-S(O)2-heteroaryl, or -C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-NH2, -C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-NH- C1-C6, -C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C1-C6-heteroaryl-NH- C(=O)-NH-S(O)2-NH-aryl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C1-C6- heteroaryl-NH-C(=O)-NH-S(O)2-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; wherein P may be a 5 to 10 membered aryl ring or rings optionally containing one or more heteroatoms, and wherein P may be further substituted with one or more halo, -C1-C6-alkyl, - C1-C6-alkyl substituted with one or more halo or hydroxy; -C3-C8-cycloalkyl, -CN, hydroxy, - O-C1-C6-alkyl, -O-C1-C6-alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, - S-C1-C6-alkyl, -S-C1-C6-alkyl substituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1- C6-alkyl, -N(C1-C6-alkyl) , wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O- ; or aryl, aryl substituted with one or more, halo, -C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo or hydroxy, -C3-C8-cycloalkyl, -CN, hydroxy, -O-C1-C6-alkyl, -O-C1-C6-alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, -S-C1-C6-alkyl, -S-C1-C6-alkyl substituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1-C6-alkyl, -N(C1-C6-alkyl)2, , wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or C1-C6-aryl; C1-C6-aryl substituted with one or more halo, -C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo or hydroxy, -C3-C8-cycloalkyl, -CN, hydroxy, -O-C1-C6-alkyl, -O-C1- C6-alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, -S-C1-C6-alkyl, -S-C1- C6-alkyl substituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1-C6-alkyl, -N(C1-C6- alkyl)2, ,wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or heteroaryl; heteroaryl substituted with one or more halo, -C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo or hydroxy, -C3-C8-cycloalkyl, -CN, hydroxy, -O-C1-C6-alkyl, -O-C1- C6-alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, -S-C1-C6-alkyl, -S-C1- C6-alkyl substituted with one or more halo, -SF6, -NO2,-NH2, -NH-C1-C6-alkyl, -N(C1-C6- alkyl)2, , wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or C1-C6-heteroaryl; C1-C6-heteroaryl substituted with one or more halo, -C1-C6-alkyl, -C1-C6- alkyl substituted with one or more halo or hydroxy, -C3-C8-cycloalkyl, -CN, hydroxy, -O-C1- C6-alkyl, -O-C1-C6-alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, -S-C1- C6-alkyl, -S-C1-C6-alkyl substituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1-C6-alkyl, -N(C1-C6- , wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or -O-aryl; -O-aryl substituted with one or more halo, -C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo or hydroxy, -C3-C8-cycloalkyl, -CN, hydroxy, -O-C1-C6-alkyl, -O-C1-C6- alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, -S-C1-C6-alkyl, -S-C1-C6- alkyl substituted with one or more halo, -SF6, -NO2,-NH2, -NH-C1-C6-alkyl, -N(C1-C6-alkyl)2, , wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or -O-C1-C6-aryl; -O-C1-C6-aryl substituted with one or more halo, -C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo or hydroxy, -C3-C8-cycloalkyl, -CN, hydroxy, -O-C1-C6- alkyl, -O-C1-C6-alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, -S-C1-C6- alkyl, -S-C1-C6-alkyl substituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1-C6-alkyl, - N(C1-C6- wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or wherein Q may be selected from

[0002] and wherein R3, R4, or R6are independently selected from -H, halo, -C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo, -CN, hydroxy, -O-C1-C6-alkyl, -O-C1-C6-alkyl substituted with one or more halo; and or a salt thereof ; with the proviso that the compound excluded and with the further proviso that the compound excluded and with the further proviso that the compound excluded. In one example R is selected from -C(=O)-C1-C6-C(=O)-OH, -C(=O)-C1-C6-C(=O)-O-C1-C6, -C(=O)-C1-C6-C(=O)-O-C1-C6-O- (C=O)-C1-C6, or -C(=O)-C1-C6-C(=O)-NH2, -C(=O)-C1-C6-C(=O)-NH-C1-C6, -C(=O)-C1-C6-C(=O)-N(C1- C6)2, -C(=O)-C1-C6-C(=O)-NH-S(O)2-C1-C6, -C(=O)-C1-C6-C(=O)-NH-S(O)2-aryl, -C(=O)-C1-C6- , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from - NH-, NC1-C6-, -S- or -O-; or -C1-C6-C(=O)-OH, or -aryl-C(=O)-OH, or -aryl-C(=O)-NH-S(O)2-C1-C6. In one example R is selected from -C(=O)-C1-C6-C(=O)-OH, -C(=O)-C1-C6-C(=O)-NH- S(O)2-C1-C6, -C(=O)-C1-C6-C(=O)-NH-S(O)2-N(C1-C6)2, -C1-C6-C(=O)-OH, -aryl-C(=O)- OH, -C(=O)-C1-C6-C(=O)-NH-S(O)2-aryl, -C1-C6-C(=O)-NH-S(O)2-C1-C6,-C1-C6-C(=O)- NH-S(O)2-aryl, -C1-C6-C(=O)-NH-S(O)2-N(C1-C6)2, -aryl-C(=O)-NH-S(O)2-C1-C6, -aryl- C(=O)-NH-S(O)2-aryl, -aryl-C(=O)-NH-S(O)2-N(C1-C6)2, heteroaryl-C(=O)-OH, -heteroaryl- C(=O)-NH-S(O)2-C1-C6, -heteroaryl-C(=O)-NH-S(O)2-aryl, and -heteroaryl-C(=O)-NH- S(O)2-N(C1-C6)2. In one example R is -C(=O)-C1-C6-C(=O)-OH. In one example R is -C(=O)-C1-C6-C(=O)-NH-S(O)2-C1-C6. In one example R is -C(=O)-C1-C6-C(=O)-NH-S(O)2-aryl. In one example R is -C(=O)-C1-C6-C(=)-NH-S(O)2-N(C1-C6)2. In one example R is -C1-C6-C(=O)-OH. In one example R is -C1-C6-C(=O)-NH-S(O)2-C1-C6. In one example R is -C1-C6-C(=O)-NH-S(O)2-aryl. In one example R is -C1-C6-C(=O)-NH-S(O)2-N(C1-C6)2. In one example R is -aryl-C(=O)-OH. In one example R is -aryl-C(=O)-NH-S(O)2-C1-C6. In one example R is -aryl-C(=O)-NH-S(O)2-aryl. In one example R is -aryl-C(=O)-NH-S(O)2-N(C1-C6)2. In one example R is -heteroaryl-C(=O)-OH. In one example R is -heteroaryl-C(=O)-NH-S(O)2-C1-C6. In one example R is -heteroaryl-C(=O)-NH-S(O)2-aryl. In one example R is -heteroaryl-C(=O)-NH-S(O)2-N(C1-C6)2. In one example R is -C3-C(=O)-OH. In one example R is -C(=O)-CH2-CH2-C(=O)-OH. In one example R is -C(=O)-CH2-CH2-C(=O)-NH-S(O)2-Me. In one example R is -C(=O)-CH2-CH2-C(=O)-NH-S(O)2-iPr. In one example R is -C(=O)-CH2-CH2-C(=O)-NH-S(O)2-Ph. In one example R is -C(=O)-CH2-CH2-C(=O)-NH-S(O)2-NMe2. In one example R is -CH2-CH2-CH2-C(=O)-OH. In one example R is -CH2-CH2-CH2-C(=O)-NH-S(O)2-Me. In one example R is -CH2-CH2-CH2-C(=O)-NH-S(O)2-iPr. In one example R is -CH2-CH2-CH2-C(=O)-NH-S(O)2-Ph. In one example R is -CH2-CH2-CH2-C(=O)-NH-S(O)2-NMe2. In one example R is -phenyl-C(=O)-OH. In one example R is -phenyl-C(=O)-NH-S(O)2-Me. In one example R is -phenyl-C(=O)-NH-S(O)2-iPr. In one example R is -phenyl-C(=O)-NH-S(O)2-Ph. In one example R is -phenyl-C(=O)-NH-S(O)2-NMe2. In one example R is -pyridyl-C(=O)-OH. In one example R is -pyridyl-C(=O)-NH-S(O)2-Me. In one example R is -pyridyl-C(=O)-NH-S(O)2-iPr. In one example R is -pyridyl-C(=O)-NH-S(O)2-Ph. In one example R is -pyridyl-C(=O)-NH-S(O)2-NMe2. In one example R is selected from: -C1-C6-(C=O)OH; or In one example R is -C1-C6-(C=O)OH. In one example R is – (CH2)3-(C=O)OH.In one example R is ,wherein J is a 5 membered heterocycle ring containing up to4 heteroatoms selected from -N=, -NH-, or -O-. In one example R is -phenyl-tetrazole. In one example R is -phenyl-oxadiazolone. In one example P is selected from aryl or an aryl substituted with one or more halo, - CN, - C1-C6-alkyl, -O-C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo, or -O-C1-C6- alkyl substituted with one or more halo. In one example P is selected from aryl substituted with aryl or an aryl substituted with halo,- CN, -C1-C6-alkyl, -O-C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo, or -O-C1- C6-alkyl substituted with one or more halo. In one example P is selected from phenyl or a phenyl substituted with one or more halo, -CN, -C1-C6-alkyl, -O-C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo, or -O-C1-C6- alkyl substituted with one or more halo. In one example P is phenyl substituted with halo. In one example P is phenyl substituted with -Cl. In one example P is selected from phenyl substituted with phenyl or a phenyl substituted with halo, -CN, -C1-C6-alkyl, -O-C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo, or - O-C1-C6-alkyl substituted with one or more halo. In one example P is phenyl substituted with a phenyl. In one example P is phenyl substituted with a phenyl substituted with one or more halo. In one example P is phenyl substituted with a phenyl substituted with -Cl. In one example P is phenyl substituted with a phenyl substituted with -O-C1-C6-alkyl. In one example P is phenyl substituted with a phenyl substituted with -O-C3-alkyl. In one example P is phenyl substituted with a phenyl substituted with -OiPr. In one example P is phenyl substituted with a phenyl substituted with -OnPr. In one example P is phenyl substituted with a phenyl substituted with -O-C1-C6-alkyl substituted with one or more halo. In one example P is phenyl substituted with a phenyl substituted with -OCF3 or -OCH2CF3. In one example P is phenyl substituted with a phenyl substituted with a -C1-C6-alkyl substituted with one or more halo. In one example P is phenyl substituted with a phenyl substituted with one or more -CF3. In one example P is phenyl substituted with a phenyl substituted with -CH2CF3. In one example P is phenyl substituted with a phenyl substituted with a halo and a -O-C1-C6- alkyl. In one example P is phenyl substituted with a phenyl substituted with -F and a -O-C1-C6- alkyl. In one example P is phenyl substituted with a phenyl substituted with a -C1-C6-alkyl and a - O-C1-C6-alkyl. In one example P is phenyl substituted with a phenyl substituted with a -C1-C3-alkyl and a - O-C1-C6-alkyl. In one example P is phenyl substituted with a phenyl substituted with -CN and -O-C1-C6- alkyl. In one example P is -aryl-heteroaryl and wherein the heteroaryl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O-C1-C6-alkyl optionally substituted with one or more halo. In one example P is -phenyl-heteroaryl and wherein the heteroaryl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O-C1-C6-alkyl optionally substituted with one or more halo. In one example P is -phenyl-heteroaryl and wherein the heteroaryl is substituted with -O-C1- C6-alkyl. In one example P is -phenyl-heteroaryl and wherein the heteroaryl is substituted with -O-C3- alkyl. In one example P is -phenyl-heteroaryl and wherein the heteroaryl is substituted with -OiPr. In one example P is -phenyl-heteroaryl and wherein the heteroaryl is substituted with -OnPr. In one example P is -phenyl-heteroaryl and wherein the heteroaryl is substituted with -O-C1- C6-alkyl substituted with one or more halo. In one example P is -phenyl-heteroaryl and wherein the heteroaryl is substituted with -OCF3. In one example P is -phenyl-heteroaryl and wherein the heteroaryl is substituted with - OCH2CF3. In one example P is -aryl-pyridyl and wherein the pyridyl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O-C1-C6-alkyl optionally substituted with one or more halo. In one example P is -phenyl-pyridyl and wherein the pyridyl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O-C1-C6-alkyl optionally substituted with one or more halo. In one example P is -phenyl-pyridyl and wherein the pyridyl is optionally substituted with - O-C1-C6-alkyl. In one example P is -phenyl-pyridyl and wherein the pyridyl is optionally substituted with - OiPr. In one example P is -phenyl-pyridyl and wherein the pyridyl is substituted with -O-C1-C6- alkyl substituted with one or more halo. In one example P is -phenyl-pyridyl and wherein the pyridyl is substituted with -OCH2CF3. In one example P is –heteroaryl-aryl and wherein the aryl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O-C1-C6-alkyl optionally substituted with one or more halo. In one example P is –heteroaryl-phenyl and wherein the phenyl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O-C1-C6-alkyl optionally substituted with one or more halo. In one example P is a heteroaryl-phenyl and wherein the phenyl is substituted with -O-C1-C6- alkyl. In one example P is a heteroaryl-phenyl and wherein the phenyl is substituted with -O-C3- alkyl. In one example P is a heteroaryl-phenyl and wherein the phenyl is substituted with -OiPr. In one example P is a heteroaryl-phenyl and wherein the phenyl is substituted with -OnPr. In one example P is a heteroaryl-phenyl and wherein the phenyl is substituted with -O-C1-C6- alkyl substituted with one or more halo. In one example P is a heteroaryl-phenyl and wherein the phenyl is substituted with -OCF3. In one example P is a heteroaryl-phenyl and wherein the phenyl is substituted with - OCH2CF3. In one example P is -pyridyl-aryl and wherein the aryl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O-C1-C6-alkyl optionally substituted with one or more halo. In one example P is -pyridyl-phenyl and wherein the phenyl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O-C1-C6-alkyl optionally substituted with one or more halo. In one example P is a -pyridyl-phenyl and wherein the phenyl is substituted with -O-C1-C6- alkyl. In one example P is a -pyridyl-phenyl and wherein the phenyl is substituted with -O-C3-alkyl. In one example P is a -pyridyl-phenyl and wherein the phenyl is substituted with -OiPr. In one example P is a -pyridyl-phenyl and wherein the phenyl is substituted with -OnPr. In one example P is a -pyridyl-phenyl and wherein the phenyl is substituted with -O-C1-C6- alkyl substituted with one or more halo. In one example P is a -pyridyl-phenyl and wherein the phenyl is substituted with -OCF3. In one example P is a -pyridyl-phenyl and wherein the phenyl is substituted with -OCH2CF3. In one example P is -phenyl-phenyl- substituted with a heterocycle. In one example P is -phenyl-phenyl- substituted with a pyrrolidine. In one example Q is selected from: . In one example Q is selected from: . In one example Q is selected from: or In one example Q is . In one example the compound or salt of Formula I is selected from one or more of the following: In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: salt thereof. In one example the compound of Formula I is: salt thereof. In one example the compound of Formula I is: In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: or a salt thereof. In one example the compound of Formula I is: In another aspect, there is provided a compound of Formula II Formula II wherein R may be selected from: -C(=O)-C1-C6-C(=O)-OH, -C(=O)-C1-C6-C(=O)-O-C1-C6, -C(=O)-C1-C6-C(=O)-O-C1-C6-O- (C=O)-C1-C6, or -C(=O)-C1-C6-C(=O)-NH2, -C(=O)-C1-C6-C(=O)-NH-C1-C6, -C(=O)-C1-C6-C(=O)-NH-C3- , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or -C(=O)-C1-C6-C(=O)-NH-S(O)2-C1-C6, -C(=O)-C1-C6-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, - C(=O)-C1-C6-C(=O)-NH-S(O)2-aryl, C(=O)-C1-C6-C(=O)-NH-S(O)2-C1-C6-aryl, -C(=O)-C1- C6-C(=O)-NH-S(O)2-heteroaryl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-C1-C6-heteroaryl, or -C(=O)-C1-C6-C(=O)-NH-S(O)2-NH2, -C(=O)-C1-C6-C(=O)-NH-S(O)2-NH-C1-C6, -C(=O)- C1-C6-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-NH-aryl, - C(=O)-C1-C6-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-NH- heteroaryl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-NH- C1-C6-heteroaryl, -C(=O)-C1-C6-C(=O)-NH- , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-C1-C6, -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-C3-C8- cycloalkyl, -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-aryl, -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2- heteroaryl, or -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-NH2, -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-NH-C1-C6, - C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C(=O)-C1-C6-NH-C(=O)-NH- S(O)2-NH-aryl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C(=O)-C1-C6-NH-C(=O)- , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH- , NC1-C6-, -S- or -O-; or -C1-C6-C(=O)-OH, -C1-C6-C(=O)-O-C1-C6, -C1-C6-C(=O)-O-C1-C6-O-(C=O)-C1-C6, -C1-C6- OH, or -C1-C6-C(=O)-NH2, -C1-C6-C(=O)-NH-C1-C6, -C1-C6-C(=O)-NH-C3-C8-cycloalkyl, -C1-C6- , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or -C1-C6-C(=O)-NH-S(O)2-C1-C6, -C1-C6-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -C1-C6-C(=O)- NH-S(O)2-aryl, -C1-C6-C(=O)-NH-S(O)2-C1-C6-aryl, -C1-C6-C(=O)-NH-S(O)2-heteroaryl, - C1-C6-C(=O)-NH-S(O)2-C1-C6-heteroaryl, or -C1-C6-C(=O)-NH-S(O)2-NH2, -C1-C6-C(=O)-NH-S(O)2-NH-C1-C6, -C1-C6-C(=O)-NH- S(O)2-NH-C3-C8-cycloalkyl, -C1-C6-C(=O)-NH-S(O)2-NH-aryl, -C1-C6-C(=O)-NH-S(O)2- NH-C1-C6-aryl, -C1-C6-C(=O)-NH-S(O)2-NH-heteroaryl, -C1-C6-C(=O)-NH-S(O)2-NH- C1- , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or -C1-C6-NH-C(=O)-NH-S(O)2-C1-C6, -C1-C6-NH-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -C1-C6- NH-C(=O)-NH-S(O)2-aryl, -C1-C6-NH-C(=O)-NH-S(O)2-heteroaryl, or -C1-C6-NH-C(=O)-NH-S(O)2-NH2, -C1-C6-NH-C(=O)-NH-S(O)2-NH-C1-C6, -C1-C6-NH- C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C1-C6-NH-C(=O)-NH-S(O)2-NH-aryl, -C1-C6- C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C1-C6-NH-C(=O)-NH-S(O)2-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or -C(=O)-aryl-C(=O)-OH, -C(=O)-aryl-C(=O)-O-C1-C6, -C(=O)-aryl-C(=O)-O-C1-C6-O- (C=O)-C1-C6, -C(=O)-aryl-OH, or -C(=O)-aryl-C(=O)-NH2, -C(=O)-aryl-C(=O)-NH-C1-C6, -C(=O)-aryl-C(=O)-NH-C3-C8- cycloalkyl, -C(=O)-aryl-C(=O)-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from - NH-, -NC1-C6-, -S- or -O-; or -C(=O)-aryl-C(=O)-NH-S(O)2-C1-C6, -C(=O)-aryl-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, - C(=O)-aryl-C(=O)-NH-S(O)2-aryl, -C(=O)-aryl-C(=O)-NH-S(O)2-C1-C6-aryl, -C(=O)-aryl- C(=O)-NH-S(O)2-heteroaryl, -C(=O)-aryl-C(=O)-NH-S(O)2-C1-C6-heteroaryl, or -C(=O)-aryl-C(=O)-NH-S(O)2-NH2, -C(=O)-aryl-C(=O)-NH-S(O)2-NH-C1-C6, -C(=O)-aryl- C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C(=O)-aryl-C(=O)-NH-S(O)2-NH-aryl, -C(=O)- aryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C(=O)-aryl-C(=O)-NH-S(O)2-NH-heteroaryl, - C(=O)-aryl-C(=O)-NH-S(O)2-NH-C1-C6-heteroaryl, -C(=O)-aryl-C(=O)-NH-S(O)2-N(C1- , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or -C(=O)-aryl-NH-C(=O)-NH-S(O)2-C1-C6, -C(=O)-aryl-NH-C(=O)-NH-S(O)2-C3-C8- cycloalkyl, -C(=O)-aryl-NH-C(=O)-NH-S(O)2-aryl, -C(=O)-aryl-NH-C(=O)-NH-S(O)2- heteroaryl, or -C(=O)-aryl-NH-C(=O)-NH-S(O)2-NH2, -C(=O)-aryl-NH-C(=O)-NH-S(O)2-NH-C1-C6, - C(=O)-aryl-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C(=O)-aryl-NH-C(=O)-NH-S(O)2- NH-aryl, -C(=O)-aryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C(=O)-aryl-NH-C(=O)-NH-S(O)2- , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or or -aryl-C(=O)-OH, -aryl-C(=O)-O-C1-C6, -aryl-C(=O)-O-C1-C6-O-(C=O)-C1-C6, -aryl-C1-C6- OH, -aryl-C1-C6-(C=O)OH, or -aryl-C(=O)-NH2, -aryl-C(=O)-NH-C1-C6, -aryl-C(=O)-NH-C3-C8-cycloalkyl, -aryl-C(=O)- N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or -aryl-C(=O)-NH-S(O)2-C1-C6, -aryl-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -aryl-C(=O)-NH- S(O)2-aryl, -aryl-C(=O)-NH-S(O)2-C1-C6-aryl, -aryl-C(=O)-NH-S(O)2-heteroaryl, -aryl- C(=O)-NH-S(O)2-C1-C6-heteroaryl, or -aryl-C(=O)-NH-S(O)2-NH2, -aryl-C(=O)-NH-S(O)2-NH-C1-C6, -aryl-C(=O)-NH-S(O)2-NH- C3-C8-cycloalkyl, -aryl-C(=O)-NH-S(O)2-NH-aryl, -aryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, - aryl-C(=O)-NH-S(O)2-NH-heteroaryl, -aryl-C(=O)-NH-S(O)2-NH-C1-C6-heteroaryl, -aryl- , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or -aryl-NH-C(=O)-NH-S(O)2-C1-C6, -aryl-NH-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -aryl-NH- C(=O)-NH-S(O)2-aryl, -aryl-NH-C(=O)-NH-S(O)2-heteroaryl, or -aryl-NH-C(=O)-NH-S(O)2-NH2, -aryl-NH-C(=O)-NH-S(O)2-NH-C1-C6, -aryl-NH-C(=O)- NH-S(O)2-NH-C3-C8-cycloalkyl, -aryl-NH-C(=O)-NH-S(O)2-NH-aryl, -aryl-C(=O)-NH- S(O)2-NH-C1-C6-aryl, -aryl-NH-C(=O)-NH-S(O)2-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or -aryl-S(O)2-OH, -aryl-S(O)2-NH2, -aryl-S(O)2-NH-C1-C6, -aryl-S(O)2-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or -aryl-S(O)2-NH-C3-C8-cycloalkyl, or -C(=O)-heteroaryl-C(=O)-OH, -C(=O)-heteroaryl-C(=O)-O-C1-C6, -C(=O)-heteroaryl-C(=O)- O-C1-C6-O-(C=O)-C1-C6, -C(=O)-aryl-OH, or -C(=O)-heteroaryl-C(=O)-NH2, -C(=O)-heteroaryl-C(=O)-NH-C1-C6, -C(=O)-heteroaryl- C(=O)-NH-C3-C8-cycloalkyl, -C(=O)-heteroaryl-C(=O)-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or -C(=O)-heteroaryl-C(=O)-NH-S(O)2-C1-C6, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-C3-C8- cycloalkyl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-aryl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2- C1-C6-aryl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-heteroaryl, -C(=O)-heteroaryl-C(=O)-NH- S(O)2-C1-C6-heteroaryl, or -C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH2, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6, - C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C(=O)-heteroaryl-C(=O)-NH- S(O)2-NH-aryl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C(=O)-heteroaryl- C(=O)-NH-S(O)2-NH-heteroaryl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH- C1-C6-heteroaryl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or -C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-C1-C6, -C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2- C3-C8-cycloalkyl, -C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-aryl, -C(=O)-heteroaryl-NH- C(=O)-NH-S(O)2-heteroaryl, or -C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-NH2, -C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-NH- C1-C6, -C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C(=O)-heteroaryl- NH-C(=O)-NH-S(O)2-NH-aryl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, - C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or or -heteroaryl-C(=O)-OH, -heteroaryl-C(=O)-O-C1-C6, -heteroaryl-C(=O)-O-C1-C6-O-(C=O)- C1-C6, -heteroaryl-C1-C6-OH, -heteroaryl-C1-C6-(C=O)OH, or -heteroaryl-C(=O)-NH2, -heteroaryl-C(=O)-NH-C1-C6, -heteroaryl-C(=O)-NH-C3-C8- cycloalkyl, -heteroaryl-C(=O)-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from - NH-, -NC1-C6-, -S- or -O-; or -heteroaryl-C(=O)-NH-S(O)2-C1-C6, -heteroaryl-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, - heteroaryl-C(=O)-NH-S(O)2-aryl, -heteroaryl-C(=O)-NH-S(O)2-C1-C6-aryl, -heteroaryl- C(=O)-NH-S(O)2-heteroaryl, -heteroaryl-C(=O)-NH-S(O)2-C1-C6-heteroaryl, or -heteroaryl-C(=O)-NH-S(O)2-NH2, -heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6, -heteroaryl- C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -heteroaryl-C(=O)-NH-S(O)2-NH-aryl, -heteroaryl- C(=O)-NH-S(O)2-NH-C1-C6-aryl, -heteroaryl-C(=O)-NH-S(O)2-NH-heteroaryl, -heteroaryl- C(=O)-NH-S(O)2-NH-C1-C6-heteroaryl, -heteroaryl-C(=O)-NH-S(O)2-N(C1-C6)2, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or -heteroaryl-NH-C(=O)-NH-S(O)2-C1-C6, -heteroaryl-NH-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -heteroaryl-NH-C(=O)-NH-S(O)2-aryl, -heteroaryl-NH-C(=O)-NH-S(O)2-heteroaryl, or -heteroaryl-NH-C(=O)-NH-S(O)2-NH2, -heteroaryl-NH-C(=O)-NH-S(O)2-NH-C1-C6, - heteroaryl-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -heteroaryl-NH-C(=O)-NH-S(O)2- NH-aryl, -heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -heteroaryl-NH-C(=O)-NH-S(O)2- , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or -C1-C6-aryl-C(=O)-OH, -C1-C6-aryl-C(=O)-O-C1-C6, -C1-C6-aryl-C(=O)-O-C1-C6-O-(C=O)- C1-C6, -C1-C6-aryl-C1-C6-OH, or -C1-C6-aryl-C(=O)-NH2, -C1-C6-aryl-C(=O)-NH-C1-C6, -C1-C6-aryl-C(=O)-NH-C3-C8- , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from - NH-, -NC1-C6-, -S- or -O-; or -C1-C6-aryl-C(=O)-NH-S(O)2-C1-C6, -C1-C6-aryl-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -C1-C6- aryl-C(=O)-NH-S(O)2-aryl, -C1-C6-aryl-C(=O)-NH-S(O)2-C1-C6-aryl, -C1-C6-aryl-C(=O)- NH-S(O)2-heteroaryl, -C1-C6-aryl-C(=O)-NH-S(O)2-C1-C6-heteroaryl, or -C1-C6-aryl-C(=O)-NH-S(O)2-NH2, -C1-C6-aryl-C(=O)-NH-S(O)2-NH-C1-C6, -C1-C6-aryl- C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C1-C6-aryl-C(=O)-NH-S(O)2-NH-aryl, -C1-C6-aryl- C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C1-C6-aryl-C(=O)-NH-S(O)2-NH-heteroaryl, -C1-C6-aryl- C(=O)-NH-S(O)2-NH-C1-C6-heteroaryl, -C1-C6-aryl-C(=O)-NH-S(O)2-N(C1-C6)2, -C1-C6 , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or -C1-C6-aryl-NH-C(=O)-NH-S(O)2-C1-C6, -C1-C6-aryl-NH-C(=O)-NH-S(O)2-C3-C8- cycloalkyl, -C1-C6-aryl-NH-C(=O)-NH-S(O)2-aryl, -C1-C6-aryl-NH-C(=O)-NH-S(O)2- heteroaryl, or -C1-C6-aryl-NH-C(=O)-NH-S(O)2-NH2, -C1-C6-aryl-NH-C(=O)-NH-S(O)2-NH-C1-C6, -C1- C6-aryl-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C1-C6-aryl-NH-C(=O)-NH-S(O)2-NH- aryl, -C1-C6-aryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C1-C6-aryl-NH-C(=O)-NH-S(O)2-N(C1- C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or -C1-C6-aryl-S(O)2-OH, -C1-C6-aryl-S(O)2-NH2, -C1-C6-aryl-S(O)2-NH-C1-C6, -C1-C6-aryl- S(O)2-N(C1-C6)2 , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or -C1-C6-aryl-S(O)2-NH-C3-C8-cycloalkyl, or -C1-C6-heteroaryl-C(=O)-OH, -C1-C6-heteroaryl-C(=O)-O-C1-C6, -C1-C6-heteroaryl-C(=O)- O-C1-C6-O-(C=O)-C1-C6, -C1-C6 -heteroaryl-C1-C6-OH, or -C1-C6-heteroaryl-C(=O)-NH2, -C1-C6-heteroaryl-C(=O)-NH-C1-C6, -C1-C6-heteroaryl- C(=O)-NH-C3-C8-cycloalkyl, -C1-C6-heteroaryl-C(=O)-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or -C1-C6-heteroaryl-C(=O)-NH-S(O)2-C1-C6, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-C3-C8- cycloalkyl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-aryl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-C1- C6-aryl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-heteroaryl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2- C1-C6-heteroaryl, or -C1-C6-heteroaryl-C(=O)-NH-S(O)2-NH2, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6, -- C1-C6heteroaryl-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C1-C6-heteroaryl-C(=O)-NH- S(O)2-NH-aryl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C1-C6-heteroaryl- C(=O)-NH-S(O)2-NH-heteroaryl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-heteroaryl, - C1-C6-heteroaryl-C(=O)-NH-S(O)2-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or -C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-C1-C6, -C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-C3- C8-cycloalkyl, -C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-aryl, -C1-C6-heteroaryl-NH-C(=O)- NH-S(O)2-heteroaryl, or -C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-NH2, -C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-NH- C1-C6, -C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C1-C6-heteroaryl-NH- C(=O)-NH-S(O)2-NH-aryl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C1-C6- heteroaryl-NH-C(=O)-NH-S(O)2-N(C1-C6)2, , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; wherein P may be a 5 to 10 membered aryl ring or rings optionally containing one or more heteroatoms, and wherein P may be further substituted with one or more halo, -C1-C6-alkyl, - C1-C6-alkyl substituted with one or more halo or hydroxy; -C3-C8-cycloalkyl, -CN, hydroxy, - O-C1-C6-alkyl, -O-C1-C6-alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, - S-C1-C6-alkyl, -S-C1-C6-alkyl substituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1- , wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or aryl, aryl substituted with one or more, halo, -C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo or hydroxy, -C3-C8-cycloalkyl, -CN, hydroxy, -O-C1-C6-alkyl, -O-C1-C6-alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, -S-C1-C6-alkyl, -S-C1-C6-alkyl substituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1-C6-alkyl, -N(C1-C6-alkyl)2, , wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or C1-C6-aryl; C1-C6-aryl substituted with one or more halo, -C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo or hydroxy, -C3-C8-cycloalkyl, -CN, hydroxy, -O-C1-C6-alkyl, -O-C1- C6-alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, -S-C1-C6-alkyl, -S-C1- C6-alkyl substituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1-C6-alkyl, -N(C1-C6- alkyl)2, , wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or heteroaryl; heteroaryl substituted with one or more halo, -C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo or hydroxy, -C3-C8-cycloalkyl, -CN, hydroxy, -O-C1-C6-alkyl, -O-C1- C6-alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, -S-C1-C6-alkyl, -S-C1- C6-alkyl substituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1-C6-alkyl, -N(C1-C6- wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or C1-C6-heteroaryl; C1-C6-heteroaryl substituted with one or more halo, -C1-C6-alkyl, -C1-C6- alkyl substituted with one or more halo or hydroxy, -C3-C8-cycloalkyl, -CN, hydroxy, -O-C1- C6-alkyl, -O-C1-C6-alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, -S-C1- C6-alkyl, -S-C1-C6-alkyl substituted with one or more halo, -SF6, -NO2,-NH2, -NH-C1-C6-alkyl, -N(C1-C6-alkyl)2, , wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or -O-aryl; -O-aryl substituted with one or more halo, -C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo or hydroxy, -C3-C8-cycloalkyl, -CN, hydroxy, -O-C1-C6-alkyl, -O-C1-C6- alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, -S-C1-C6-alkyl, -S-C1-C6- alkyl substituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1-C6-alkyl, -N(C1-C6-alkyl)2, , wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or -O-C1-C6-aryl; -O-C1-C6-aryl substituted with one or more halo, -C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo or hydroxy, -C3-C8-cycloalkyl, -CN, hydroxy, -O-C1-C6- alkyl, -O-C1-C6-alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, -S-C1-C6- alkyl, -S-C1-C6-alkyl substituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1-C6-alkyl, - N(C1-C6- , wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or wherein Q may be selected from and wherein R3, R4, or R6 are independently selected from -H, halo, -C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo, -CN, hydroxy, -O-C1-C6-alkyl, -O-C1-C6-alkyl substituted with one or more halo; and or a salt thereof. In one example R is selected from -C(=O)-C1-C6-C(=O)-OH, -C(=O)-C1-C6-C(=O)-O-C1-C6, -C(=O)-C1-C6-C(=O)-O-C1-C6-O- (C=O)-C1-C6, or -C(=O)-C1-C6-C(=O)-NH2, -C(=O)-C1-C6-C(=O)-NH-C1-C6, -C(=O)-C1-C6-C(=O)-N(C1- C6)2, -C(=O)-C1-C6-C(=O)-NH-S(O)2-C1-C6, -C(=O)-C1-C6-C(=O)-NH-S(O)2-aryl, -C(=O)-C1-C6- , wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from - NH-, NC1-C6-, -S- or -O-; or -C1-C6-C(=O)-OH, or -aryl-C(=O)-OH, or -aryl-C(=O)-NH-S(O)2-C1-C6. In one example R is selected from -C(=O)-C1-C6-C(=O)-OH, -C(=O)-C1-C6-C(=O)-NH- S(O)2-C1-C6, -C(=O)-C1-C6-C(=O)-NH-S(O)2-N(C1-C6)2, -C1-C6-C(=O)-OH, -aryl-C(=O)- OH, -C(=O)-C1-C6-C(=O)-NH-S(O)2-aryl, -C1-C6-C(=O)-NH-S(O)2-C1-C6,-C1-C6-C(=O)- NH-S(O)2-aryl, -C1-C6-C(=O)-NH-S(O)2-N(C1-C6)2, -aryl-C(=O)-NH-S(O)2-C1-C6, -aryl- C(=O)-NH-S(O)2-aryl, -aryl-C(=O)-NH-S(O)2-N(C1-C6)2, heteroaryl-C(=O)-OH, -heteroaryl- C(=O)-NH-S(O)2-C1-C6, -heteroaryl-C(=O)-NH-S(O)2-aryl, -heteroaryl-C(=O)-NH-S(O)2- N(C1-C6)2. In one example R is -C(=O)-C1-C6-C(=O)-OH. In one example R is -C(=O)-C1-C6-C(=O)-NH-S(O)2-C1-C6. In one example R is -C(=O)-C1-C6-C(=O)-NH-S(O)2-aryl. In one example R is -C(=O)-C1-C6-C(=)-NH-S(O)2-N(C1-C6)2. In one example R is -C1-C6-C(=O)-OH. In one example R is -C1-C6-C(=O)-NH-S(O)2-C1-C6. In one example R is -C1-C6-C(=O)-NH-S(O)2-aryl. In one example R is -C1-C6-C(=O)-NH-S(O)2-N(C1-C6)2. In one example R is -aryl-C(=O)-OH. In one example R is -aryl-C(=O)-NH-S(O)2-C1-C6. In one example R is -aryl-C(=O)-NH-S(O)2-aryl. In one example R is -aryl-C(=O)-NH-S(O)2-N(C1-C6)2. In one example R is -heteroaryl-C(=O)-OH. In one example R is -heteroaryl-C(=O)-NH-S(O)2-C1-C6. In one example R is -heteroaryl-C(=O)-NH-S(O)2-aryl. In one example R is -heteroaryl-C(=O)-NH-S(O)2-N(C1-C6)2. In one example R is -C3-C(=O)-OH. In one example R is -C(=O)-CH2-CH2-C(=O)-OH. In one example R is -C(=O)-CH2-CH2-C(=O)-NH-S(O)2-Me. In one example R is -C(=O)-CH2-CH2-C(=O)-NH-S(O)2-iPr. In one example R is -C(=O)-CH2-CH2-C(=O)-NH-S(O)2-Ph. In one example R is -C(=O)-CH2-CH2-C(=O)-NH-S(O)2-NMe2. In one example R is -CH2-CH2-CH2-C(=O)-OH. In one example R is -CH2-CH2-CH2-C(=O)-NH-S(O)2-Me. In one example R is -CH2-CH2-CH2-C(=O)-NH-S(O)2-iPr. In one example R is -CH2-CH2-CH2-C(=O)-NH-S(O)2-Ph. In one example R is -CH2-CH2-CH2-C(=O)-NH-S(O)2-NMe2. In one example R is -phenyl-C(=O)-OH. In one example R is -phenyl-C(=O)-NH-S(O)2-Me. In one example R is -phenyl-C(=O)-NH-S(O)2-iPr. In one example R is -phenyl-C(=O)-NH-S(O)2-Ph. In one example R is -phenyl-C(=O)-NH-S(O)2-NMe2. In one example R is -pyridyl-C(=O)-OH. In one example R is -pyridyl-C(=O)-NH-S(O)2-Me. In one example R is -pyridyl-C(=O)-NH-S(O)2-iPr. In one example R is -pyridyl-C(=O)-NH-S(O)2-Ph. In one example R is -pyridyl-C(=O)-NH-S(O)2-NMe2. In one example R is selected from: -C1-C6-(C=O)OH; or In one example R is -C1-C6-(C=O)OH. In one example R is – (CH2)3-(C=O)OH.In one example R is ,wherein J is a 5 membered heterocycle ring containing up to4 heteroatoms selected from -N=, -NH-, or -O-. In one example R is -phenyl-tetrazole. In one example R is -phenyl-oxadiazolone. In one example P is selected from aryl or an aryl substituted with one or more halo, - CN, - C1-C6-alkyl, -O-C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo, or -O-C1-C6- alkyl substituted with one or more halo. In one example P is selected from aryl substituted with aryl or an aryl substituted with halo,- CN, -C1-C6-alkyl, -O-C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo, or -O-C1- C6-alkyl substituted with one or more halo. In one example P is selected from phenyl or a phenyl substituted with one or more halo, -CN, -C1-C6-alkyl, -O-C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo, or -O-C1-C6- alkyl substituted with one or more halo. In one example P is phenyl substituted with halo. In one example P is phenyl substituted with -Cl. In one example P is selected from phenyl substituted with phenyl or a phenyl substituted with halo, -CN, -C1-C6-alkyl, -O-C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo, or - O-C1-C6-alkyl substituted with one or more halo. In one example P is phenyl substituted with a phenyl. In one example P is phenyl substituted with a phenyl substituted with one or more halo. In one example P is phenyl substituted with a phenyl substituted with -Cl. In one example P is phenyl substituted with a phenyl substituted with -O-C1-C6-alkyl. In one example P is phenyl substituted with a phenyl substituted with -O-C3-alkyl. In one example P is phenyl substituted with a phenyl substituted with -OiPr. In one example P is phenyl substituted with a phenyl substituted with -OnPr. In one example P is phenyl substituted with a phenyl substituted with -O-C1-C6-alkyl substituted with one or more halo. In one example P is phenyl substituted with a phenyl substituted with -OCF3or -OCH2CF3. In one example P is phenyl substituted with a phenyl substituted with a -C1-C6-alkyl substituted with one or more halo. In one example P is phenyl substituted with a phenyl substituted with one or more -CF3. In one example P is phenyl substituted with a phenyl substituted with -CH2CF3. In one example P is phenyl substituted with a phenyl substituted with a halo and a -O-C3- alkyl. In one example P is phenyl substituted with a phenyl substituted with -F and a -O-C3-alkyl. In one example P is phenyl substituted with a phenyl substituted with a -C1-C6-alkyl and a - O-C1-C6-alkyl. In one example P is phenyl substituted with a phenyl substituted with a -C1-C3-alkyl and a - O-C3-alkyl. In one example P is phenyl substituted with a phenyl substituted with -CN and -O-C1-C6- alkyl. In one example P is -aryl-heteroaryl and wherein the heteroaryl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O-C1-C6-alkyl optionally substituted with one or more halo. In one example P is -phenyl-heteroaryl and wherein the heteroaryl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O-C1-C6-alkyl optionally substituted with one or more halo. In one example P is -phenyl-heteroaryl and wherein the heteroaryl is substituted with -O-C1- C6-alkyl. In one example P is -phenyl-heteroaryl and wherein the heteroaryl is substituted with -O-C3- alkyl. In one example P is -phenyl-heteroaryl and wherein the heteroaryl is substituted with -OiPr. In one example P is -phenyl-heteroaryl and wherein the heteroaryl is substituted with -OnPr. In one example P is -phenyl-heteroaryl and wherein the heteroaryl is substituted with -O-C1- C6-alkyl substituted with one or more halo. In one example P is -phenyl-heteroaryl and wherein the heteroaryl is substituted with -OCF3. In one example P is -phenyl-heteroaryl and wherein the heteroaryl is substituted with - OCH2CF3. In one example P is -aryl-pyridyl and wherein the pyridyl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O-C1-C6-alkyl optionally substituted with one or more halo. In one example P is -phenyl-pyridyl and wherein the pyridyl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O-C1-C6-alkyl optionally substituted with one or more halo. In one example P is -phenyl-pyridyl and wherein the pyridyl is optionally substituted with - O-C1-C6-alkyl. In one example P is -phenyl-pyridyl and wherein the pyridyl is optionally substituted with - OiPr. In one example P is -phenyl-pyridyl and wherein the pyridyl is substituted with -O-C1-C6- alkyl substituted with one or more halo. In one example P is -phenyl-pyridyl and wherein the pyridyl is substituted with -OCH2CF3. In one example P is –heteroaryl-aryl and wherein the aryl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O-C1-C6-alkyl optionally substituted with one or more halo. In one example P is –heteroaryl-phenyl and wherein the phenyl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O-C1-C6-alkyl optionally substituted with one or more halo. In one example P is a heteroaryl-phenyl and wherein the phenyl is substituted with -O-C1-C6- alkyl. In one example P is a heteroaryl-phenyl and wherein the phenyl is substituted with -O-C3- alkyl. In one example P is a heteroaryl-phenyl and wherein the phenyl is substituted with -OiPr. In one example P is a heteroaryl-phenyl and wherein the phenyl is substituted with -OnPr. In one example P is a heteroaryl-phenyl and wherein the phenyl is substituted with -O-C1-C6- alkyl substituted with one or more halo. In one example P is a heteroaryl-phenyl and wherein the phenyl is substituted with -OCF3. In one example P is a heteroaryl-phenyl and wherein the phenyl is substituted with - OCH2CF3. In one example P is -pyridyl-aryl and wherein the aryl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O-C1-C6-alkyl optionally substituted with one or more halo. In one example P is -pyridyl-phenyl and wherein the phenyl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O-C1-C6-alkyl optionally substituted with one or more halo. In one example P is a -pyridyl-phenyl and wherein the phenyl is substituted with -O-C1-C6- alkyl. In one example P is a -pyridyl-phenyl and wherein the phenyl is substituted with -O-C3-alkyl. In one example P is a -pyridyl-phenyl and wherein the phenyl is substituted with -OiPr. In one example P is a -pyridyl-phenyl and wherein the phenyl is substituted with -OnPr. In one example P is a -pyridyl-phenyl and wherein the phenyl is substituted with -O-C1-C6- alkyl substituted with one or more halo. In one example P is a -pyridyl-phenyl and wherein the phenyl is substituted with -OCF3. In one example P is a -pyridyl-phenyl and wherein the phenyl is substituted with -OCH2CF3. In one example P is -phenyl-phenyl- substituted with a heterocycle. In one example P is -phenyl-phenyl- substituted with a pyrrolidine. In one example Q is selected from: . In one example Q is selected from: . In one example In one example the compound or salt of Formula II is selected from one or more of the following: In one example the compound of Formula II is: or a salt thereof. In one example the compound of Formula II is: or a salt thereof. In one example the compound of Formula II is: or a salt thereof. In one example the compound of Formula II is: or a salt thereof. In one example the compound of Formula II is: or a salt thereof. In one example the compound of Formula II is: or a salt thereof. In one example the compound of Formula II is: or a salt thereof. In one example the compound of Formula II is: or a salt thereof. In one example the compound of Formula II is: or a salt thereof. In one example the compound of Formula II is: or a salt thereof. In one example the compound of Formula II is: or a salt thereof. In one example the compound of Formula II is: or a salt thereof. In one example the compound of Formula II is: or a salt thereof. In one example the compound of Formula II is: or a salt thereof. In one example the compound of Formula II is: or a salt thereof. In one example the compound of Formula II is: or a salt thereof. In one example the compound of Formula II is: or a salt thereof. In one example the compound of Formula II is: or a salt thereof. In one example the compound of Formula II is: or a salt thereof. In one example the compound of Formula II is: or a salt thereof. In another aspect, the present invention provides the compound of Formula I or II as defined above for reducing the formation of methane from the digestive actions of ruminants and / or for improving ruminant performance. In one example a compound of Formula I or II as defined above is for reducing the formation of methane from the digestive actions of ruminants. In one example a compound of Formula I or II as defined above is for reducing the formation of methane from the digestive actions of ruminants by at least 10%. In another example of a compound of Formula I or II as defined above is for reducing the formation of methane from the digestive actions of ruminants by at least 15%. In yet another example the compound of Formula I, or II as defined above is for reducing the formation of methane from the digestive actions of ruminants by at least 20%. In one aspect the present invention further provides a method for reducing the production of methane emanating from a ruminant and / or for improving ruminant animal performance, comprising administering orally to the ruminant an effective amount of at least one compound of Formula I or II or a salt thereof to the ruminant. Oral administration is to be understood as a route involving drenching, addition to feed, water source or pasture; or manual administration of a bolus or a capsule. In one example the effective amount of at least one compound of Formula I or II or a salt thereof is administered at least once-daily to the ruminant. In one example the effective amount of at least one compound of Formula I or II or a salt thereof reduces the production of methane emanating from the ruminant by at least 10% per day. In one example the effective amount of at least one compound of Formula I or II or a salt thereof reduces the production of methane emanating from the ruminant by at least 15% per day. In one example the effective amount of at least one compound of Formula I or II or a salt thereof reduces the production of methane emanating from the ruminant by at least 20% per day. In a further aspect of the present invention there is provided a composition for oral administration comprising at least one compound of Formula I or II or a salt thereof for reducing the production of methane emanating from a ruminant, and the composition further including at least one agriculturally and orally acceptable excipient. In one example the composition is adapted for use as a feed additive. In one example the composition is adapted for use as a water additive. In another example the composition is adapted for use as a ruminant lick. In one example the composition is adapted for use as an oral drench. In another example the composition is adapted for use as a rumen bolus or capsule. In one example the composition is adapted to reduce the production of methane emanating from the ruminant by at least 10% per day. In one example the composition is adapted to reduce the production of methane emanating from the ruminant by at least 15% per day. In one example the composition is adapted to reduce the production of methane emanating from the ruminant by at least 20% per day. In one example the excipient may include one or more minerals and / or one or more vitamins. In one example the excipient may include one or more vitamins selected from vitamin A, vitamin D3, vitamin E, and vitamin K, e.g. vitamin K3, vitamin B12, biotin and choline, vitamin B1, vitamin B2, vitamin B6, niacin, folic acid or the like. In one example the excipient may include one or more minerals selected from calcium, phosphorus, sodium, manganese, zinc, iron, copper, chlorine, sulphur, magnesium, iodine, selenium, and cobalt or the like. In one example the composition may further include sunflower oil, electrolytes such as ammonium chloride, calcium carbonates, starch, proteins or the like. The compounds of the present invention have potential for use in a ruminant to reduce the formation of methane without affecting microbial fermentation in a way that would be detrimental to the ruminant. DETAILED DESCRIPTION OF INVENTION DEFINTIONS The term “ruminant” as used herein is a mammal that is able to acquire nutrients from plant- based food by fermenting it in a specialized foregut (the rumen) prior to digestion, principally through microbial activity. Representative examples of ruminants and other foregut fermenters include cattle, goats, sheep, giraffes, bison, moose, elk, yaks, water buffalo, deer, camels, alpacas, llamas, and antelope. The term “effective amount” as used herein refers to an amount of at least one compound of Formula I or a salt thereof that either reduces the production of methane emanating from the ruminant or improves ruminant performance. The term “ruminant performance” as used herein refers to improving the productivity of the ruminant, such as increased weight gain, milk yield or quality, wool growth or quality, surviving offspring per parturition, or the like. The term -C1-C6– means a carbon chain having from 1 to 6 carbons and being straight chained or branched, saturated or unsaturated, including but not limited to methyl, ethyl, ethylene, propyl, isopropyl, propylene, butyl, tert-butyl, butylene, pentyl, pentene, hexyl, hexene and the like, wherein the -C1-C6group is optionally substituted with one or more halo. The term -C1-C6alkyl – means an alkyl chain having from 1 to 6 carbons, being straight chained or branched including but not limited to methyl, ethyl, propyl, isopropyl, butyl, tertiary butyl, pentyl and hexyl, wherein the -C1-C6alkyl group is optionally substituted with one or more halo. The term “halo” as used herein refers to a halogen atom selected from Cl, Br, or F. The term “aryl” as used herein refers to “aryl”, unless specifically limited, denotes a C5-12 aryl group, suitably a C6-10aryl group, more suitably a C6-8aryl group. Aryl groups will contain at least one aromatic ring (e.g. one, two or three rings). Examples of a typical aryl group with one aromatic ring is phenyl. An example of a typical aryl group with two aromatic rings is naphthyl. The aryl group is optionally substituted with one or more -CN, -halo, -C(halo)3,- NH2, -NO2, -NH-( C1-C6alkyl), -N(C1-C6alkyl)2, -C1-C6alkyl, -C1-C6alkyl substituted with one or more halo, -C1-C6 alkenyl, -C1-C6 alkynyl, -O-C1-C6-alkyl, -O-C1-C6-alkyl substituted with one or more halo, aryl or substituted aryl, the substituted aryl, may include a substituted phenyl (benzyl group), a substituted thiophenol, a tosyl group, the substituted aryl group being substituted with one or more -CN, -halo, -C(halo)3,-NH2, -NO2 -NH-( C1-C6 alkyl), - N(C1-C6 alkyl)2, C1-C6 alkyl, C1-C6 alkenyl and C1-C6 alkynyl. The term “heteroaryl” as used herein refers to ”, unless specifically limited, denotes an aryl residue, wherein one or more (e.g., 1, 2, 3, or 4, suitably 1, 2 or 3) ring atoms are replaced by heteroatoms selected from N, S and O, or else a 5-membered aromatic ring containing one or more (e.g., 1, 2, 3, or 4, suitably 1, 2 or 3) ring atoms selected from N, S and O. Exemplary monocyclic heteroaryl groups having one heteroatom include: five membered rings (e.g., pyrrole, furan, thiophene,); and six membered rings (e.g., pyridine, such as pyridin-2-yl, pyridin-3-yl and pyridin-4-yl). Exemplary monocyclic heteroaryl groups having two heteroatoms include: five membered rings (e.g., pyrazole, oxazole, isoxazole, thiazole, isothiazole, imidazole, such as imidazol-1-yl, imidazol-2-yl imidazol-4-yl); six membered rings (e.g., pyridazine, pyrimidine, pyrazine). Exemplary monocyclic heteroaryl groups having three heteroatoms include: 1,2,3-triazole and 1,2,4-triazole, oxadiazole, oxadiazolone;. Exemplary monocyclic heteroaryl groups having four heteroatoms include tetrazole. Exemplary bicyclic heteroaryl groups include: indole (e.g., indol-6-yl), benzofuran, benzothiophene, quinoline, isoquinoline, indazole, benzimidazole, benzthiazole, quinazoline and purine. The heteroaryl group is optionally substituted with one or more -CN, -halo, - C(halo)3,-NH2, -NH-(C1-C6 alkyl), -N(C1-C6 alkyl)2, -NO2, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkynyl, aryl or substituted aryl, the substituted aryl, may include a substituted phenyl (benzyl group), a substituted thiophenol, a tosyl group, the substituted aryl group being substituted with one or more -CN, -halo, -C(halo)3,-NH2, -NH-( C1-C6 alkyl), -N(C1-C6 alkyl)2, alkyl, alkenyl and alkynyl. The term “heterocyclyl” as used herein includes a “carbocycle” as defined herein, wherein one or more (e.g.1, 2, 3, or 4) carbon atoms have been replaced with a heteroatom (e.g. O, N, or S). The terms “heterocycle” or “heterocyclyl” includes saturated rings (i.e., heterocycloalkyls), partially unsaturated rings, and aromatic rings (i.e., heteroaromatic rings). Substituted heterocyclyls include, for example, heterocyclic rings substituted with any of the substituents disclosed herein including carbonyl groups. Examples of heterocycles include by way of example and not limitation pyridyl, dihydroypyridyl, tetrahydropyridyl (piperidyl), thiazolyl,thiazolidine-dione; tetrahydrothiophenyl, sulfur oxidized tetrahydrothiophenyl, pyrimidinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, tetrazolyl, oxadiazolyl, oxadiazolone, benzofuranyl, thianaphthalenyl, indolyl, indolenyl, quinolinyl, isoquinolinyl, benzimidazolyl, piperidirtyl, 4-piperidonyl, pyrrolidinyl, 2-pyrrolidonyl, pyrrolinyl, tetrahydrofuranyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, octahydroisoquinolinyl, azocinyl, triazinyl, 6H-1,2,5-thiadiazinyl, 2H,6H-1,5,2-dithiazinyl, thienyl, thianthrenyl, pyranyl, isobenzofuranyl, chromenyl, xanthenyl, phenoxathinyl, 2H-pyrrolyl, isothiazolyl, isoxazolyl, pyrazinyl, pyridazinyl, indolizinyl, isoindolyl, 3H-indolyl, 1H-indazoly, purinyl, 4H-quinolizinyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, pteridinyl, 4aH-carbazolyl, carbazolyl, β-carbolinyl, phenanthridinyl, acridinyl, pyrimidinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, furazanyl, phenoxazinyl, isochromanyl, chromanyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperazinyl, indolinyl, isoindolinyl, quinuclidinyl, morpholinyl, oxazolidinyl, benzotriazolyl, benzisoxazolyl, oxindolyl, benzoxazolinyl. By way of example and not limitation, carbon bonded heterocycles are bonded at position 2, 3, 4, 5, or 6 of a pyridine, position 3, 4, 5, or 6 of a pyridazine, position 2, 4, 5, or 6 of a pyrimidine, position 2, 3, 5, or 6 of a pyrazine, position 2, 3, 4, or 5 of a furan, tetrahydrofuran, thiofuran, thiophene, pyrrole or tetrahydropyrrole, position 2, 4, or 5 of an oxazole, imidazole or thiazole, position 3, 4, or 5 of an isoxazole, pyrazole, or isothiazole, position 2 or 3 of an aziridine, position 2, 3, or 4 of an azetidine, position 2, 3, 4, 5, 6, 7, or 8 of a quinoline or position 1, 3, 4, 5, 6, 7, or 8 of an isoquinoline. Still more typically, carbon bonded heterocycles include 2-pyridyl, 3-pyridyl, 4-pyridyl, 5-pyridyl, 6-pyridyl, 3- pyridazinyl, 4-pyridazinyl, 5-pyridazinyl, 6-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5- pyrimidinyl, 6-pyrimidinyl, 2-pyrazinyl, 3-pyrazinyl, 5-pyrazinyl, 6-pyrazinyl, 2-thiazolyl, 4- thiazolyl, or 5-thiazolyl. By way of example and not limitation, nitrogen bonded heterocycles are bonded at position 1 of an aziridine, azetidine, pyrrole, pyrrolidine, 2-pyrroline, 3-pyrroline, imidazole, imidazolidine, 2-imidazoline, 3-imidazoline, pyrazole, pyrazoline, 2-pyrazoline, 3- pyrazoline, piperidine, piperazine, indole, indoline, 1H-indazole, position 2 of a isoindole, or isoindoline, position 4 of a morpholine, and position 9 of a carbazole, or β-carboline. Still more typically, nitrogen bonded heterocycles include 1-aziridyl, 1-azetedyl, 1-pyrrolyl, 1- imidazolyl, 1-pyrazolyl, and 1-piperidinyl. All possible stereoisomers of the claimed compounds are included in the present disclosure. Where a compound described herein has at least one chiral center, it may accordingly exist as enantiomers. Where a compound possesses two or more chiral centers it may additionally exist as diastereomers. It is to be understood that all such isomers and mixtures thereof are encompassed within the scope of the present disclosure. Some of the crystalline forms of the compounds may exist in more than one polymorphic form and as such all forms are intended to be included in the present disclosure. In addition, some of the compounds may form solvates with water (i.e., hydrates) or common organic solvents, and such solvates are also intended to be encompassed within the scope of this disclosure. The compounds, including their salts, can also be obtained in the form of their hydrates, or include other solvents used for their crystallization. The present disclosure further includes within its scope prodrugs of the compounds described herein. In general, such prodrugs will be functional derivatives of the compounds which are readily convertible in vivo into the desired active compound. Thus, in these cases, the methods of treatment of the present invention, the term “administering” shall encompass the treatment of the various disorders described with prodrug versions of one or more of the claimed compounds, but which converts to the above specified compound in vivo after administration to the subject. As used herein, the term “composition” is intended to encompass a product comprising a claimed compound(s) in a therapeutically effective amount, as well as any product which results, directly or indirectly, from combinations of the claimed compounds. The term “or a salt thereof,” as used herein, is a salt of an acid or a basic nitrogen atom. Illustrative salts include, but are not limited, to sodium salt, potassium salt, lithium salt, calcium salt, ammonium salt, sulfate, citrate, acetate, oxalate, chloride, bromide, iodide, nitrate, bisulfate, phosphate, and the like. Methods of making Compounds of Formula I The following compounds were prepared as follows: 4-(3-(4-Chlorophenyl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)butanoic acid (Compound 1) To a solution of ethyl 4-(3-(4-chlorophenyl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1- yl)butanoate (60 mg, 0.14 mmol) in THF-H2O (2.5 mL, 4:1 v / v) was added LiOH·H2O (12 mg, 0.28 mmol). The reaction mixture was then stirred at RT for 18 h, diluted with H2O (50 mL), acidified to pH 1 with 1 M aq. HCl and extracted with EtOAc (2 × 30 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (50% EtOAc in Pet. Ether, then EtOAc) afforded Compound 1 (40 mg, 73%) as a pale-yellow solid.1H NMR (400 MHz, DMSO-d6) δ 9.09 – 9.05 (br s, 2H), 8.51 (d, J = 1.3 Hz, 1H), 8.29 (d, J = 8.7 Hz, 1H), 8.24 (dd, J = 8.7, 1.7 Hz, 1H), 8.11 (d, J = 8.5 Hz, 2H), 7.57 (d, J = 8.5 Hz, 2H), 4.42 (t, J = 7.1 Hz, 2H), 2.30 (t, J = 7.0 Hz, 2H), 2.18 – 2.05 (m, 2H);13C NMR (101 MHz, DMSO-d6) δ 173.7 (C), 159.3 (C), 154.2 (C), 147.0 (CH), 146.8 (CH), 142.6 (C), 141.8 (C), 133.9 (C), 130.3 (CH), 130.0 (CH), 129.6 (CH), 129.1 (C), 129.0 (CH), 127.6 (CH), 48.6 (CH2), 30.3 (CH2), 24.7 (CH2). HRMS (ESI₋ / Q- TOF) m / z: [M₋H]₋calcd for C20H1535ClN5O2392.0920; found 392.0920. 4-(3-([1,1'-Biphenyl]-4-yl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)butanoic acid (Compound 2) To a solution of ethyl 4-(3-([1,1'-biphenyl]-4-yl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1- yl)butanoate (63 mg, 0.14 mmol) in THF-H2O (3 mL, 4:1 v / v) was added 1 M aq. LiOH (0.28 mL). The reaction mixture was then stirred at RT for 17 h, diluted with H2O (20 mL), acidified to pH 1 with 1 M aq. HCl and extracted with EtOAc (3 × 10 mL). The combined organic extracts were washed with brine (2 × 10 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (0 → 20% MeOH in EtOAc) afforded Compound 2 (12 mg, 18%) as a pale-yellow solid.1H NMR (400 MHz, DMSO-d6) δ 12.13 (br s, 1H), 9.10 – 9.06 (m, 2H), 8.53 (d, J = 1.5 Hz, 1H), 8.31 (d, J = 8.5 Hz, 1H), 8.27 (dd, J = 8.5, 1.6 Hz, 1H), 8.19 (d, J = 8.4 Hz, 2H), 7.83 (d, J = 8.4 Hz, 2H), 7.75 (d, J = 7.4 Hz, 2H), 7.50 (t, J = 7.6 Hz, 2H), 7.40 (t, J = 7.4 Hz, 1H), 4.47 (t, J = 7.1 Hz, 2H), 2.32 (t, J = 7.1 Hz, 2H), 2.18 – 2.09 (m, 2H);13C NMR (125 MHz, DMSO-d6) δ 173.8 (C), 160.1 (C), 154.1 (C), 147.1 (CH), 146.9 (CH), 142.6 (C), 141.9 (C), 140.9 (C), 139.5 (C), 130.4 (CH), 130.1 (CH), 129.8 (C), 129.6 (CH), 129.3 (C), 129.1 (CH), 127.9 (CH), 127.1 (CH), 126.7 (CH), 126.5 (CH), 48.6 (CH2), 30.4 (CH2), 24.8 (CH2); HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C26H22N5O2436.1768; found 436.1768. 4-(3-(4'-Isopropoxy-[1,1'-biphenyl]-4-yl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1- yl)butanoic acid (Compound 3) To a solution of ethyl 4-(3-(4'-isopropoxy-[1,1'-biphenyl]-4-yl)-5-(quinoxalin-6-yl)-1H-1,2,4- triazol-1-yl)butanoate (64 mg, 0.12 mmol) in THF-H2O (3 mL, 4:1 v / v) was added 1 M aq. LiOH (0.25 mL). The reaction mixture was then stirred at RT for 6 h, diluted with H2O (20 mL), acidified to pH 1 with 1 M aq. HCl and extracted with EtOAc (3 × 10 mL). The combined organic extracts were washed with brine (2 × 10 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford Compound 3 (57 mg, 94%) as a yellow solid.1H NMR (400 MHz, DMSO-d6) δ 12.11 (br s, 1H), 9.09 – 9.07 (m, 2H), 8.52 (d, J = 1.5 Hz, 1H), 8.30 (d, J = 8.5 Hz, 1H), 8.26 (dd, J = 8.8, 2.0 Hz, 1H), 8.14 (d, J = 8.4 Hz, 2H), 7.76 (d, J = 8.4 Hz, 2H), 7.67 (d, J = 8.8 Hz, 2H), 7.02 (d, J = 8.8 Hz, 2H), 4.71 – 4.64 (m, 1H), 4.46 (t, J = 7.1 Hz, 2H), 2.32 (t, J = 7.0 Hz, 2H), 2.17 – 2.09 (m, 2H), 1.30 (d, J = 6.0 Hz, 6H);13C NMR (101 MHz, DMSO-d6) δ 173.7 (C), 160.1 (C), 157.4 (C), 154.0 (C), 147.0 (CH), 146.8 (CH), 142.5 (C), 141.8 (C), 140.5 (C), 131.5 (C), 130.3 (CH), 130.0 (CH), 129.5 (CH), 129.3 (C), 129.0 (C), 127.8 (CH), 126.4 (CH), 116.0 (CH), 69.2 (CH), 48.5 (CH2), 30.3 (CH2), 24.7 (CH2), 21.8 (CH3); HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C29H28N5O3494.2187; found 494.2187. 3-(3-(4-Chlorophenyl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)benzoic acid (Compound 5) A solution of ethyl-4-chloro-N-(quinoxaline-6-carbonyl)benzimidate (20 mg, 0.059 mmol) and 3-hydrazinobenzoic acid (18 mg, 0.12 mmol) in THF (2 mL) was heated at 100 °C in a microwave for 30 min. The solution was diluted with EtOAc (25 mL), washed with 0.1 M aq. HCl (25 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (EtOAc, then 15% MeOH in DCM) afforded Compound 5 (10 mg, 40%) as an off-white solid.1H NMR (500 MHz, DMSO-d6) δ 9.01 – 8.97 (m, 2H), 8.19 (d, J = 8.5 Hz, 2H), 8.18 (d, J = 8.6 Hz, 1H), 8.13 (d, J = 1.7 Hz, 1H), 8.11 – 8.09 (m, 1H), 8.08 (d, J = 7.8 Hz, 1H), 8.06 (dd, J = 8.6, 1.8 Hz, 1H), 7.68 (d, J = 7.8 Hz), 1H, 7.61 (d, J = 8.5 Hz, 2H), 7.57 (t, J = 7.8 Hz, 1H);13C NMR (125 MHz, DMSO-d6) δ 167.3 (C), 160.2 (C), 153.6 (C), 147.1 (CH), 146.9 (CH), 142.5 (C), 141.5 (C), 137.5 (C), 134.4 (C), 130.1 (CH), 130.0 (CH), 129.8 (CH), 129.7 (CH), 129.5 (CH), 129.1 (CH), 128.8 (C), 127.8 (CH), 126.4 (CH). HRMS (ESI₋ / Q-TOF) m / z: [M₋H]₋calcd for C23H1335ClN5O2426.0763; found 426.0760. 3-(3-(4'-Isopropoxy-[1,1'-biphenyl]-4-yl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1- yl)benzoic acid (Compound 7) A solution of ethyl-4'-isopropoxy-N-(quinoxaline-6-carbonyl)-[1,1'-biphenyl]-4-carbimidate (200 mg, 0.46 mmol) and 3-hydrazinobenzoic acid (140 mg, 0.92 mmol) in THF (5 mL) was heated at 100 °C in a microwave for 30 minutes. The mixture was then diluted with EtOAc (25 mL) and washed with 1 M aq. HCl (25 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (EtOAc, then 20% MeOH in EtOAc) afforded Compound 7 (50 mg, 21%) as an off-white solid.1H NMR (500 MHz, DMSO-d6) δ 9.01 (d, J = 2.0 Hz, 1H), 8.97 (d, J = 2.0 Hz, 1H), 8.22 (d, J = 8.3 Hz, 2H), 8.18 (d, J = 2.0 Hz, 1H), 8.19 – 8.13 (m, 3H), 8.10 – 8.05 (m, 2H), 7.80 (d, J = 8.4 Hz, 2H), 7.73 (d, J = 7.9 Hz, 1H), 7.68 (d, J = 8.6 Hz, 2H), 7.60 (t, J = 7.8 Hz, 1H), 7.03 (d, J = 8.7 Hz, 2H), 4.67 (hept, J = 6.0 Hz, 1H), 1.30 (d, J 6.0 Hz, 6H);13C NMR (125 MHz, DMSO-d6) δ 167.0 (C), 160.9 (C), 157.4 (C), 153.4 (C), 147.1 (CH), 146.8 (CH), 142.5 (C), 141.5 (C), 140.9 (C), 137.7 (C), 131.4 (C), 130.1 (CH), 130.0 (CH), 129.8 (CH), 129.7 (CH), 129.6 (CH), 129.1 (CH), 128.9 (C), 128.4 (C), 127.8 (CH), 126.6 (CH), 126.5 (CH), 126.3 (CH), 116.0 (CH), 69.2 (CH), 21.8 (CH3); HRMS (ESI₋ / Q-TOF) m / z: [M₋H]₋calcd for C32H24N5O3526.1885; found 526.1882. 4-(3-(4-Chlorophenyl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)benzoic acid (Compound 9) A solution of ethyl-4-chloro-N-(quinoxaline-6-carbonyl)benzimidate (80 mg, 0.24 mmol) and 4-hydrazinobenzoic acid (72 mg, 0.47 mmol) in THF (2 mL) was heated at 100 °C in a microwave for 30 min. The solution was diluted with EtOAc (50 mL), washed with 0.1 M aq. HCl (25 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (EtOAc, then 20% MeOH in EtOAc) afforded Compound 9 (88 mg, 87%) as an off-white solid.1H NMR (400 MHz, DMSO-d6) δ 9.02 – 8.97 (m, 2H), 8.19 – 8.15 (m, 4H), 8.07 – 8.01 (m, 3H), 7.67 (d, J = 8.5 Hz, 2H), 7.61 (d, J = 8.6 Hz, 2H);13C NMR (100 MHz, DMSO-d6) δ 166.6 (C), 160.4 (C), 153.8 (C), 147.2 (CH), 146.9 (CH), 142.6 (C), 141.5 (C), 140.6 (C), 134.5 (C), 132.2 (C), 130.7 (CH), 130.0 (CH), 129.9 (CH), 129.1 (CH), 129.0 (C), 128.7 (C), 127.9 (CH), 125.8 (CH); HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C23H15ClN5O2428.0909; found 428.0908. 3-(3-(4-Chlorophenyl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)-N- (methylsulfonyl)benzamide (Compound 21) A solution of 3-(3-(4-chlorophenyl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)benzoic acid (19 mg, 0.04 mmol), methanesulfonamide (7 mg, 0.07 mmol), EDCI·HCl (14 mg, 0.07 mmol) and DMAP (7 mg, 0.05 mmol) was stirred at RT for 24 h. Additional portions of methanesulfonamide (4 mg, 0.04 mmol), EDCI·HCl (9 mg, 0.05 mmol) and DMAP (6 mg, 0.05 mmol) were added to the reaction mixture and stirred for a further 24 h. The reaction mixture was diluted with EtOAc (25 mL) then washed with 0.2 M aq. HCl (5 × 10 mL). The organic phase was dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (0 → 5% MeOH in EtOAc) afforded Compound 21 (12 mg, 56%) as a pale-pink solid.1H NMR (400 MHz, DMSO-d6) δ 11.94 (br s, 1H), 9.00 – 8.96 (m, 2H), 8.21 – 8.16 (m, 4H), 8.14 (d, J = 1.4 Hz, 1H), 8.11 – 8.04 (m, 2H), 7.61 (d, J = 8.5 Hz, 2H), 7.57 – 7.49 (m, 2H), 2.95 (s, 3H);13C NMR (100 MHz, DMSO-d6) δ 160.1 (C), 153.5 (C), 147.1 (CH), 146.8 (CH), 142.5 (C), 141.5 (C), 137.3 (C), 134.3 (C), 129.9 (CH), 129.8 (CH), 129.6 (CH), 129.3 (CH), 129.14, 129.06 (CH), 128.7 (C), 127.9 (CH), 125.7 (CH), 40.4 (CH3); HRMS (ESI₋ / Q-TOF) m / z: [M₋H]₋calcd for C24H16ClN6O3S 503.0699; found 503.0701. 6-(1-(3-(Tetrazol-5-yl)phenyl)-3-(4-chlorophenyl)-1H-1,2,4-triazol-5-yl)quinoxaline (Compound 22) A solution of 3-(3-(4-chlorophenyl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)benzonitrile (100 mg, 0.25 mmol), sodium azide (37 mg, 0.56 mmol) and Et3N·HCl (81 mg, 0.59 mmol) in toluene (5 mL) was heated at reflux for 4 d. The reaction mixture was cooled to RT and diluted with EtOAc (50 mL) then washed with 0.1 M aq. HCl (25 mL). The aqueous phase was further extracted with EtOAc (4 × 50 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (EtOAc, then 20% MeOH in EtOAc) afforded Compound 22 (44 mg, 39%) as an off-white solid.1H NMR (400 MHz, DMSO-d6) δ 9.01 – 8.97 (m, 2H), 8.31 (br s, 1H), 8.22 – 8.17 (m, 5H), 8.10 – 8.08 (m, 1H), 7.72 – 7.65 (m, 2H), 7.63 (d, J = 8.6 Hz, 2H);13C NMR (100 MHz, DMSO-d6) δ 160.3 (C), 153.8 (C), 147.1 (CH), 146.8 (CH), 142.6 (C), 141.5 (C), 138.3 (C), 134.4 (C), 130.7, 129.9, 129.8 (CH), 129.1 (CH), 129.0 (C), 128.6 (C), 127.9 (CH), 127.7 (CH), 124.0; HRMS (ESI₋ / Q-TOF) m / z: [M₋H]₋calcd for C23H13ClN9450.0988; found 450.0991. 3-(3-(3-(4-Chlorophenyl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)phenyl)-1,2,4- oxadiazol-5-one (Compound 23) A solution of 3-(3-(4-chlorophenyl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)-N'- hydroxybenzimidamide (35 mg, 0.08 mmol), CDI (19 mg, 0.12 mmol) and DBU (13 μL, 0.09 mmol) in 1,4-dioxane (1 mL) was heated at 110 °C in a microwave for 1 h. The solution was diluted with EtOAc (30 mL) and washed with 1 M aq. HCl (10 mL). The organic phase was dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (80 → 100% EtOAc in Pet. Ether) afforded Compound 23 (27 mg, 72%) as an off-white solid.1H NMR (400 MHz, DMSO-d6) δ 9.02 – 8.97 (m, 2H), 8.21 – 8.17 (m, 4H), 8.14 – 8.12 (m, 1H), 8.06 (dt, J = 8.9, 1.7 Hz, 1H), 7.98 (dt, J = 7.6, 1.3 Hz, 1H), 7.78 – 7.75 (m, 1H), 7.71 (t, J = 7.8 Hz, 1H), 7.63 (d, J = 8.5 Hz, 2H); HRMS (ESI₋ / Q-TOF) m / z: [M₋H]₋calcd for C24H13ClN7O2466.0825; found 466.0822. 3-(3-(4-Chlorophenyl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)benzenesulfonamide (Compound 24) A solution of ethyl 4-chlorobenzimidate hydrochloride (100 mg, 0.45 mmol), quinoxaline-6- carbonyl chloride (175 mg, 0.91 mmol) and Et3N (190 µL, 1.36 mmol) in THF (1.5 mL) was heated at 100 °C in a microwave for 15 min.3-Hydrazinobenzenesulfonamide (170 mg, 0.91 mmol) was then added to the mixture and heated at 100 °C in a microwave for a further 30 min. The reaction mixture was diluted with EtOAc (100 mL) and washed with H2O (50 mL). The aqueous phase was further extracted with EtOAc (3 × 100 mL) then the combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (70% EtOAc in Pet. Ether) afforded Compound 24 (63 mg, 30%) as an off-white solid.1H NMR (400 MHz, DMSO-d6) δ 9.03 – 8.99 (m, 2H), 8.21 – 8.18 (m, 4H), 8.12 (br s, 1H), 8.05 (dd, J = 8.7, 1.8 Hz, 1H), 7.98 (d, J = 7.2 Hz, 1H), 7.74 – 7.67 (m, 2H), 7.62 (d, J = 8.5 Hz, 2H), 7.57 (br s, 2H);13C NMR (100 MHz, DMSO-d6) δ 160.3 (C), 153.8 (C), 147.1 (CH), 146.9 (CH), 145.6 (C), 142.6 (C), 141.5 (C), 137.8 (C), 134.5 (C), 130.5 (CH), 129.9 (CH), 129.1 (CH), 128.9 (CH), 128.5 (C), 127.9 (CH), 126.5 (CH), 122.9 (CH); HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C22H16ClN6O2S 463.0739; found 463.0738. 3-(3-(4-Isopropoxyphenyl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)benzoic acid (Compound 25) To a stirred suspension of ethyl-4-isopropoxy-N-(quinoxaline-6-carbonyl)benzimidate (48.3 mg, 0.043 mmol) in THF (0.65 mL) was added 3-hydrazinobenzoic acid (35.5 mg, 0.284 mmol). The reaction mixture was heated in a microwave at 100 °C for 30 min then cooled to RT. The reaction was then quenched with 0.1 M aq. HCl (5 mL) and the aqueous layer was extracted with EtOAc (10 mL). The combined organic layers were diluted with MeOH (20 mL) then concentrated in vacuo onto Celite®and purified by flash column chromatography (EtOAc, then 20% MeOH in EtOAc) to afford Compound 25 (27.1 mg, 45%) as an amorphous yellow solid.1H NMR (500 MHz, DMSO-d6) δ 9.02‒8.98 (m, 2H), 8.19‒8.04 (m, 7H), 7.77‒7.75 (m, 1H), 7.63 (t, J = 7.9 Hz, 1H), 7.08‒7.06 (m, 2H), 4.72 (hept, J = 6.0 Hz, 1H), 1.32 (d, J = 6.1 Hz, 6H);13C NMR (125 MHz, DMSO-d6) δ 166.6 (C), 161.6 (C), 159.2 (C), 153.8 (C), 147.5 (CH), 147.3 (CH), 143.0 (C), 142.0 (C), 138.4 (C), 130.5 (CH), 130.4 (CH), 130.3 (CH), 130.2 (CH), 129.5 (C), 128.2 (CH), 126.8 (CH), 122.8 (C), 116.2 (CH), 69.8 (CH), 22.3 (CH3); HRMS (ESI+ / TOF-Q) m / z: [M+H]+calcd for C26H22N5O3, 452.17172; found, 452.1715. 3-(3-(6-(4-Isopropoxyphenyl)pyridin-3-yl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1- yl)benzoic acid (Compound 26) To a solution of methyl 3-(3-(6-(4-isopropoxyphenyl)pyridin-3-yl)-5-(quinoxalin-6-yl)-1H- 1,2,4-triazol-1-yl)benzoate (16 mg, 29 µmol) in THF (1.6 mL) was added 1 M aq. LiOH (0.55 mL). The reaction mixture was stirred at RT for 18 h then quenched with 0.1 M aq. HCl (5 mL). The resultant solid was collected by filtration to afford Compound 26 (14.9 mg, 96%) as an amorphous pale yellow solid.1H NMR (500 MHz, DMSO-d6) δ 9.36‒9.35 (m, 1H), 9.03‒ 8.99 (m, 2H), 8.58 (dd, J = 8.4, 2.3 Hz, 1H), 8.21‒8.18 (m, 3H), 8.16‒8.07 (m, 5H), 7.83‒7.80 (m, 1H), 7.67 (t, J = 7.9 Hz, 1H), 7.07 (d, J = 9.0 Hz, 2H), 4.74 (hept, J = 6.0 Hz, 1H), 1.32 (d, J = 6.0 Hz, 6H);13C NMR (100 MHz, CDCl3) δ 166.1 (C), 159.0 (C), 158.9 (C), 156.2 (C), 153.9 (C), 147.2 (CH), 146.9 (CH), 146.2 (CH), 142.6 (C), 141.5 (C), 137.8 (C), 135.1 (CH), 132.4 (C), 130.2 (CH), 130.1 (CH), 130.0 (CH), 129.9 (CH), 129.8 (CH), 128.6 (C), 128.4 (CH), 126.5 (CH), 124.1 (C), 119.9 (CH), 115.7 (CH), 69.3 (CH), 21.8 (CH3); HRMS (ESI+ / TOF-Q) m / z: [M+H]+calcd for C31H25N6O3, 529.1983; found, 529.1981. 3-(3-(4-(6-Isopropoxypyridin-3-yl)phenyl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1- yl)benzoic acid (Compound 27) To a stirred suspension of ethyl-4-(6-isopropoxypyridin-3-yl)-N-(quinoxaline-6- carbonyl)benzimidate (19.0 mg, 0.043 mmol) in THF (0.5 mL) was added 3-hydrazinobenzoic acid (10.8 mg, 0.086 mmol). The reaction mixture was heated in a microwave at 100 °C for 30 min then cooled to RT. The reaction was then concentrated in vacuo onto Celite®and purified by flash column chromatography (EtOAc, then 20% MeOH in EtOAc) to afford Compound 27 (18 mg, 79%) as an amorphous off-white solid.1H NMR (400 MHz, DMSO-d6) δ 9.01‒ 8.97 (m, 2H), 8.57 (d, J = 2.7 Hz, 1H), 8.25 (d, J = 8.3 Hz, 2H), 8.18 (d, J = 8.8 Hz, 1H), 8.15 (d, J = 1.6 Hz, 1H), 8.11‒8.05 (m, 4H), 7.85 (d, J = 8.4 Hz, 2H), 7.65‒7.63 (m, 1H), 7.54 (t, J = 7.7 Hz, 1H), 6.86 (d, J = 8.7 Hz, 1H), 5.32 (hept, J = 6.2 Hz, 1H), 1.33 (d, J = 6.2 Hz, 6H);13C NMR (100 MHz, DMSO-d6) δ 162.6 (C), 160.7 (C), 153.4 (C), 147.0 (CH), 146.8 (CH), 144.8 (CH), 142.5 (C), 141.5 (C), 138.2 (C), 137.5 (CH), 137.4 (C), 130.0 (CH), 129.9 (CH), 129.7 (CH), 129.6 (CH), 129.2 (CH), 129.1 (C), 128.9 (C), 128.1 (C), 126.7 (CH), 126.6 (CH), 126.3 (C), 111.3 (CH), 67.7 (CH), 21.9 (CH3); HRMS (ESI+ / TOF-Q) m / z: [M+H]+calcd for C31H25N6O3, 529.1983; found, 529.1980. 3-(3-(3'-Fluoro-4'-isopropoxy-[1,1'-biphenyl]-4-yl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol- 1-yl)benzoic acid (Compound 28) To a solution of methyl 3-(3-(3'-fluoro-4'-isopropoxy-[1,1'-biphenyl]-4-yl)-5-(quinoxalin-6- yl)-1H-1,2,4-triazol-1-yl)benzoate (25.0 mg, 0.045 mmol) in THF-MeOH (2.5 mL, 4:1 v / v) was added 1 M aq. NaOH (0.22 mL). The reaction mixture was heated to 40 °C and stirred overnight then quenched with 1 M aq. HCl (5 mL) and extracted with EtOAc (2 × 10 mL). The combined organic extracts were washed with brine (10 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford Compound 28 (19.6 mg, 80%) as an amorphous off white solid.1H NMR (500 MHz, DMSO-d6) δ 13.37 (br s, 1H), 9.02‒8.99 (m, 2H), 8.24 (d, J = 8.4 Hz, 2H), 8.20‒8.16 (m, 3H), 8.10‒8.07 (m, 2H), 7.86 (d, J = 8.4 Hz, 2H), 7.81‒7.79 (m, 1H), 7.69‒7.64 (m, 2H), 7.57‒7.55 (m, 1H), 7.29 (t, J = 8.8 Hz, 1H), 4.71 (hept, J = 6.0 Hz, 1H), 1.33 (d, J = 5.5 Hz, 6H);13C NMR (125 MHz, DMSO-d6) δ 166.2 (C), 160.9 (C), 153.6 (C), 152.8 (C, d, J = 243 Hz), 147.1 (CH), 146.9 (CH), 145.0 (C, d, J = 10.8 Hz), 142.5 (C), 141.5 (C), 139.7 (C), 137.9 (C), 132.4 (C, d, J = 6.4 Hz), 130.08 (CH), 130.05 (CH), 129.99 (CH), 129.8 (CH), 129.0 (C), 128.9 (C), 126.74 (CH), 126.66 (CH), 126.4 (CH), 122.8 (CH, d, J = 3.6 Hz), 117.2 (CH, d, J = 1.8 Hz), 114.3 (CH, d, J = 19.5 Hz), 71.3 (CH), 21.8 (CH3); HRMS (ESI+ / TOF-Q) m / z: [M+H]+calcd for C32H25FN5O3, 546.1936; found, 546.1934. 3-(5-(Quinoxalin-6-yl)-3-(4'-(trifluoromethoxy)-[1,1'-biphenyl]-4-yl)-1H-1,2,4-triazol-1- yl)benzoic acid (Compound 29) To a stirred suspension of 4'-(trifluoromethoxy)-[1,1'-biphenyl]-4-carbonitrile (2.09 g, 7.92 mmol) in EtOH (15 mL) at 0°C was added AcCl (10 mL, 140 mmol) dropwise. The mixture was warmed to RT and stirred for 3 d then concentrated in vacuo. The resultant solid was washed with Et2O and collected by filtration to afford ethyl 4'-(trifluoromethoxy)-[1,1'- biphenyl]-4-carbimidate hydrochloride (2.71 g, quant.) as a grey solid, which was used in the next step without further purification. To a suspension of ethyl 4'-(trifluoromethoxy)-[1,1'- biphenyl]-4-carbimidate hydrochloride (506 mg, 1.46 mmol) and Et3N (0.6 mL, 4.30 mmol) in anhydrous THF (7 mL) was added quinoxaline-6-carbonyl chloride (564 mg, 2.93 mmol) in a single portion. The reaction mixture was heated in a microwave at 100 °C for 15 min then cooled to RT.3-Hydrazinobenzoic acid (371 mg, 2.96 mmol) was then added and the reaction mixture was heated in a microwave at 100 °C for a further 30 min. The reaction mixture was diluted with EtOAc (100 mL), washed with 0.1 M aq. HCl (50 mL), then dried over anhydrous Na2SO4, filtered and concentrated in vacuo onto Celite®. The crude residue was purified by flash column chromatography (EtOAc, then 20% MeOH in EtOAc) to afford Compound 29 (69.5 mg, 9%) as an amorphous yellow solid.1H NMR (400 MHz, DMSO-d6) δ 9.02‒8.99 (m, 2H), 8.29 (d, J = 8.4 Hz, 2H), 8.21‒8.16 (m, 3H), 8.11‒8.07 (m, 2H), 7.92‒7.88 (m, 4H), 7.81‒ 7.79 (m, 1H), 7.65 (t, J = 7.9 Hz, 1H), 7.50 (d, J = 8.1 Hz, 2H):13C NMR (100 MHz, DMSO- d6) δ 166.1 (C), 160.8 (C), 153.6 (C), 148.1 (C), 147.1 (CH), 146.9 (CH), 142.5 (C), 141.5 (C), 139.8 (C), 138.7 (C), 137.9 (C), 130.1 (CH), 130.02 (CH), 129.96 (CH), 129.8 (CH), 129.6 (C), 128.8 (C), 128.6 (CH), 127.3 (CH), 126.8 (CH), 126.4 (CH), 121.5 (CH), 120.1 (q, J = 256 Hz, CF3); HRMS (ESI₋ / TOF-Q) m / z: [M₋H]₋calcd for C30H17F3N5O3, 552.12890; found, 552.1290. 3-(3-(4'-Isopropyl-[1,1'-biphenyl]-4-yl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)benzoic acid (Compound 30) To a solution of methyl 3-(3-(4'-isopropyl-[1,1'-biphenyl]-4-yl)-5-(quinoxalin-6-yl)-1H-1,2,4- triazol-1-yl)benzoate (114 mg, 0.216 mmol) in THF (6.2 mL) was added 1 M aq. LiOH (2.16 mL). The reaction mixture was stirred at RT overnight then quenched with 1 M aq. HCl (7 mL). The resultant solid was collected by filtration to afford Compound 30 (84.4 mg, 76%) as an amorphous white solid.1H NMR (400 MHz, DMSO-d6) δ 9.02‒8.98 (m, 2H), 8.25 (d, J = 8.4 Hz, 2H), 8.20‒8.16 (m, 3H), 8.11‒8.06 (m, 2H), 7.83 (d, J = 8.4 Hz, 2H), 7.81‒7.79 (m, 1H), 7.70‒7.63 (m, 3H), 7.37 (d, J = 8.3 Hz, 2H), 2.95 (hept, J = 6.9 Hz, 1H), 1.25 (d, J = 6.9 Hz, 6H);13C NMR (100 MHz, DMSO-d6) δ 166.1 (C), 161.0 (C), 153.6 (C), 148.1 (C), 147.1 (CH), 146.8 (CH), 142.5 (C), 141.5 (C), 141.2 (C), 137.9 (C), 136.9 (C), 132.4 (C), 130.08 (CH), 130.06 (CH), 130.02 (CH), 130.00 (CH), 129.8 (CH), 128.90 (C), 128.87 (C), 127.0 (CH), 126.9 (CH), 126.7 (CH), 126.6 (CH), 126.4 (CH), 33.1 (CH), 23.8 (CH3); HRMS (ESI+ / TOF-Q) m / z: [M+H]+calcd for C30H26N5O2, 512.2081; found, 512.2078. 3-(3-(3',5'-Bis(trifluoromethyl)-[1,1'-biphenyl]-4-yl)-5-(quinoxalin-6-yl)-1H-1,2,4- triazol-1-yl)benzoic acid (Compound 31) To a solution of methyl 3-(3-(3',5'-bis(trifluoromethyl)-[1,1'-biphenyl]-4-yl)-5-(quinoxalin-6- yl)-1H-1,2,4-triazol-1-yl)benzoate (20 mg, 32 µmol) in THF (1.0 mL) and MeOH (0.16 mL) was added 1 M aq. LiOH (0.65 mL). The reaction mixture was stirred at RT for 7 h then quenched with 1 M aq. HCl (4 mL). The resulting mixture was extracted with EtOAc (4 × 5 mL) and the combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford Compound 31 (16 mg, 82%) as an amorphous off-white solid.1H NMR (500 MHz, DMSO-d6) δ 13.37 (br s, 1H), 9.01‒8.97 (m, 2H), 8.42 (s, 2H), 8.30 (d, J = 8.4 Hz, 2H), 8.19‒8.16 (m, 3H), 8.12‒8.06 (m, 5H), 7.82‒7.80 (m, 1H), 7.65 (t, J = 7.9 Hz, 1H);13C NMR (100 MHz, CDCl3) δ 166.1 (C), 160.6 (C), 153.7 (C), 147.1 (CH), 146.9 (CH), 142.5 (C), 141.9 (C), 141.5 (C), 137.9 (C), 132.4 (C), 131.0 (C, q, J = 32.3 Hz), 130.6 (C), 130.15 (CH), 130.11 (CH), 130.07 (CH), 130.02 (CH), 129.82 (CH), 129.79 (CH), 128.8 (C), 128.3 (CH), 128.0 (CH), 127.4 (CH), 127.3 (CH), 126.8 (CH), 126.4 (CH), 123.4 (C, q, J = 273 Hz), 121.2 (CH); HRMS (ESI₋ / TOF-Q) m / z: [M₋H]₋calcd for C31H16F6N5O2, 604.1214; found, 604.1214. 3-(3-(4'-(Pyrrolidin-1-yl)-[1,1'-biphenyl]-4-yl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1- yl)benzoic acid (Compound 32) To a solution of methyl 3-(3-(4'-(pyrrolidin-1-yl)-[1,1'-biphenyl]-4-yl)-5-(quinoxalin-6-yl)- 1H-1,2,4-triazol-1-yl)benzoate (85.1 mg, 1.54 mmol) in THF (4.4 mL) was added 1 M aq. LiOH (1.5 mL). The reaction mixture was stirred at RT for 17 h then quenched with 1 M aq. HCl (5 mL) and extracted with EtOAc (2 × 10 mL). The combined organic extracts were washed with brine (10 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford Compound 32 (78.9 mg, 95%) as an amorphous orange solid.1H NMR (400 MHz, DMSO-d6) δ 9.06‒8.98 (m, 2H), 8.20‒8.15 (m, 5H), 8.10‒8.06 (m, 2H), 7.81‒7.76 (m, 3H), 7.67‒7.61 (m, 3H), 6.65 (d, J = 8.9 Hz, 2H), 3.33‒3.28 (m, 4H), 2.00‒1.97 (m, 4H);13C NMR (100 MHz, DMSO-d6) δ 166.1 (C), 161.2 (C), 153.5 (C), 147.4 (C), 147.1 (CH), 146.8 (CH), 142.5 (C), 141.6 (C), 141.5 (C), 138.0 (C), 132.3 (C), 130.1 (CH), 130.0 (CH), 129.8 (CH), 129.7 (CH), 128.9 (C), 127.3 (C), 127.2 (CH), 126.6 (CH), 126.4 (CH), 125.7 (C), 125.5 (CH), 112.1 (CH), 47.3 (CH2), 25.0 (CH2); HRMS (ESI₋ / Q-TOF) m / z: [M₋H]₋calcd for C33H25N6O2, 537.2045; found, 537.2042. 3-(3-(4'-Isopropoxy-[1,1'-biphenyl]-4-yl)-5-(pyrazin-2-yl)-1H-1,2,4-triazol-1-yl)benzoic acid (Compound 33) To a solution of methyl 3-(3-(4'-isopropoxy-[1,1'-biphenyl]-4-yl)-5-(pyrazin-2-yl)-1H-1,2,4- triazol-1-yl)benzoate (50 mg, 101 µmol) in THF (3 mL) was added 1 M aq. LiOH (1 mL). The reaction mixture was stirred at RT overnight then quenched with 0.1 M aq. HCl (50 mL). The resulting mixture was extracted with EtOAc (4 × 10 mL) and the combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford Compound 33 (47 mg, 97%) as an amorphous off-white solid.1H NMR (400 MHz, DMSO-d6) δ 13.27 (s, 1H), 9.36 (d, J = 1.5 Hz, 1H), 8.76 (d, J = 2.5 Hz, 1H), 8.53 (dd, J = 2.5, 1.5 Hz, 1H), 8.21 (d, J = 8.5 Hz, 2H), 8.10 – 8.03 (m, 2H), 7.84 – 7.74 (m, 3H), 7.68 (d, J = 8.8 Hz, 2H), 7.66 – 7.61 (m, 1H), 7.07 – 6.98 (m, 2H), 4.67 (hept, J = 6.0 Hz, 1H), 1.29 (d, J = 6.0 Hz, 6H);13C NMR (101 MHz, DMSO-d6) δ 166.31, 160.95, 157.45, 151.08, 145.80, 145.04, 143.63, 142.61, 141.10, 138.52, 131.76, 131.33, 129.92, 129.65, 129.43, 128.09, 127.83, 126.70, 126.48, 126.14, 116.02, 69.23, 21.83; HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C28H24N5O3 478.18737; found 478.1871. 3-(5-(Benzo[c][1,2,5]oxadiazol-5-yl)-3-(4'-isopropoxy-[1,1'-biphenyl]-4-yl)-1H-1,2,4- triazol-1-yl)benzoic acid (Compound 34) To a solution of methyl 3-(5-(benzo[c][1,2,5]oxadiazol-5-yl)-3-(4'-isopropoxy-[1,1'-biphenyl]- 4-yl)-1H-1,2,4-triazol-1-yl)benzoate (44 mg, 82 µmol) in THF (3 mL) was added 1 M aq. NaOH (1.5 mL). The reaction mixture was stirred at 50 °C overnight then quenched with 0.1 M aq. HCl (50 mL). The resulting mixture was extracted with EtOAc (4 × 10 mL) and the combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford Compound 34 (42 mg, 99%) as an amorphous orange-brown solid.1H NMR (300 MHz, DMSO-d6) δ 13.35 (s, 1H), 8.24 – 8.14 (m, 5H), 8.09 (dt, J = 7.8, 1.3 Hz, 1H), 7.84 – 7.74 (m, 4H), 7.73 – 7.62 (m, 3H), 7.04 (d, J = 8.9 Hz, 2H), 4.68 (hept, J = 6.1 Hz, 1H), 1.30 (d, J = 6.0 Hz, 6H);13C NMR (126 MHz, DMSO-d6) δ 166.16, 161.03, 157.45, 152.71, 148.45, 141.08, 137.51, 132.78, 131.45, 131.31, 130.09, 129.66, 128.16, 127.83, 126.67, 126.50, 126.17, 117.47, 116.92, 116.01, 69.22, 67.01, 25.12, 21.84; HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C30H24N5O4518.1823; found 518.1821. Methods of making Compounds of Formula II The following compounds were prepared as follows: 4-(5-(4-Chlorophenyl)-3-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)butanoic acid (Compound 35) To a solution of ethyl 4-(5-(4-chlorophenyl)-3-(quinoxalin-6-yl)-1H-1,2,4-triazol-1- yl)butanoate (60 mg, 0.14 mmol) in THF-H2O (2.5 mL, 4:1 v / v) was added LiOH·H2O (12 mg, 0.28 mmol). The reaction mixture was then stirred at RT for 18 h, diluted with H2O (50 mL), acidified to pH 1 with 1 M aq. HCl and extracted with EtOAc (2 × 30 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (50% EtOAc in Pet. Ether, then EtOAc) afforded Compound 35 (28 mg, 51%) as a pale-yellow solid.1H NMR (400 MHz, DMSO-d6) δ 12.16 (br s, 1H), 9.02 – 8.97 (m, 2H), 8.68 (d, J = 1.5 Hz, 1H), 8.52 (dd, J = 8.7, 1.5 Hz, 1H), 8.22 (d, J = 8.7 Hz, 1H), 7.87 (d, J = 8.4 Hz, 2H), 7.68 (d, J = 8.4 Hz, 2H), 4.37 (t, J = 7.2 Hz, 2H), 2.33 (t, J = 7.0 Hz, 2H), 2.16 – 2.06 (m, 2H);13C NMR (101 MHz, DMSO-d6) δ 173.7 (C), 159.0 (C), 154.7 (C), 146.5 (CH), 146.0 (CH), 142.7 (C), 142.4 (C), 135.2 (C), 132.2 (C), 130.7 (CH), 129.9 (CH), 129.1 (CH), 127.7 (CH), 126.4 (C), 125.5 (CH), 48.5 (CH2), 30.4 (CH2), 24.7 (CH2). ); HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C20H1735ClN5O2394.1065; found 394.1063. 4-(5-([1,1'-Biphenyl]-4-yl)-3-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)butanoic acid (Compound 36) To a solution of ethyl 4-(5-([1,1'-biphenyl]-4-yl)-3-(quinoxalin-6-yl)-1H-1,2,4-triazol-1- yl)butanoate (67 mg, 0.14 mmol) in THF-H2O (3 mL, 4:1 v / v) was added 1 M aq. LiOH (0.29 mL). The reaction mixture was then stirred at rt for 17 h, diluted with H2O (20 mL), acidified to pH 1 with 1 M aq. HCl and extracted with EtOAc (3 × 10 mL). The combined organic extracts were washed with brine (2 × 10 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (0 → 20% MeOH in EtOAc) afforded Compound 36 (19 mg, 31%) as an off-white solid.1H NMR (400 MHz, DMSO-d6) δ 12.18 (br s, 1H), 9.01 – 8.99 (2H, m), 8.71 (d, J = 1.8 Hz, 1H), 8.54 (dd, J = 8.7, 1.9 Hz, 1H), 8.23 (d, J = 8.7 Hz, 1H), 7.96 – 7.89 (m, 4H), 7.81 – 7.77 (m, 2H), 7.56 – 7.51 (m, 2H), 7.46 – 7.42 (m, 1H), 4.43 (t, J = 7.1 Hz, 2H), 2.35 (t, J = 7.1 Hz, 2H), 2.20 – 2.12 (m, 2H);13C NMR (101 MHz, DMSO-d6) δ 173.7 (C), 159.0 (C), 155.4 (C), 146.5 (CH), 146.0 (CH), 142.6 (C), 142.4 (C), 141.8 (C), 139.1 (C), 132.3 (C), 129.9 (CH), 129.4 (CH), 129.1 (CH), 128.1 (CH), 127.8 (CH), 127.1 (CH), 126.8 (CH), 126.5 (C), 125.5 (CH), 48.6 (CH2), 30.4 (CH2), 24.7 (CH2); HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C26H22N5O2436.1768; found 436.1768. 4-(5-(4'-Isopropoxy-[1,1'-biphenyl]-4-yl)-3-(quinoxalin-6-yl)-1H-1,2,4-triazol-1- yl)butanoic acid (Compound 37) To a solution of ethyl 4-(5-(4'-isopropoxy-[1,1'-biphenyl]-4-yl)-3-(quinoxalin-6-yl)-1H-1,2,4- triazol-1-yl)butanoate (52 mg, 0.10 mmol) in THF-H2O (3 mL, 4:1 v / v) was added 1 M aq. LiOH (0.20 mL). The reaction mixture was then stirred at RT for 16 h, diluted with H2O (20 mL), acidified to pH 1 with 1 M aq. HCl and extracted with EtOAc (3 × 10 mL). The combined organic extracts were washed with brine (2 × 10 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford Compound 37 (49 mg, quant.) as a yellow solid.1H NMR (400 MHz, DMSO-d6) δ 12.19 (br s, 1H), 8.99 (d, J = 2.0 Hz, 1H), 8.98 (d, J = 2.0 Hz, 1H), 8.69 (d, J = 1.8 Hz, 1H), 8.53 (dd, J = 8.7, 1.9 Hz, 1H), 8.21 (d, J = 8.7 Hz, 1H), 7.88 (d, J = 8.8 Hz, 2H), 7.84 (d, J = 8.8 Hz, 2H), 7.70 (d, J = 8.8 Hz, 2H), 7.04 (d, J = 8.8 Hz, 2H), 4.73 – 4.64 (m, 1H), 4.42 (t, J = 7.2 Hz, 2H), 2.37 (t, J = 7.1 Hz, 2H), 2.20 – 2.11 (m, 2H), 1.30 (d, J = 6.0 Hz, 6H);13C NMR (101 MHz, DMSO-d6) δ 173.9 (C), 158.9 (C), 157.7 (C), 155.5 (C), 146.5 (CH), 146.0 (CH), 142.6 (C), 142.4 (C), 141.5 (C), 132.4 (C), 131.0 (C), 129.9 (CH), 129.3 (CH), 128.0 (CH), 127.8 (CH), 126.4 (CH), 125.6 (C), 125.5 (CH), 116.1 (CH), 69.3 (CH), 48.5 (CH2), 30.4 (CH2), 24.8 (CH2), 21.8 (CH3); HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C29H28N5O3494.2187; found 494.2184. 3-(5-(4-Chlorophenyl)-3-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)benzoic acid (Compound 38) To a solution of ethyl 3-(5-(4-chlorophenyl)-3-(quinoxalin-6-yl)-1H-1,2,4-triazol-1- yl)benzoate (30 mg, 0.07 mmol) in MeOH (1 mL) was added 1 M aq. NaOH (0.2 mL). The reaction mixture was stirred at RT for 5 h, then carefully neutralized with 1 M aq. HCl to pH 3. The resulting solid was filtered, washed with H2O and lyophilized to afford Compound 38 (19 mg, 64%) as a light-yellow solid.1H NMR (400 MHz, DMSO-d6) δ 9.04 (d, J = 2.0 Hz, 1H), 9.02 (d, J = 2.0 Hz, 1H), 8.79 (d, J = 1.8 Hz, 1H), 8.60 (dd, J = 8.5, 1.5 Hz, 1H), 8.27 (d, J = 8.5 Hz, 1H), 8.13 – 8.09 (m, 2H), 7.80 – 7.75 (m, 1H), 7.69 (t, J = 7.8 Hz, 1H), 7.64 – 7.54 (m, 4H);13C NMR (101 MHz, DMSO-d6) δ 166.3 (C), 160.0 (C), 154.5 (C), 146.8 (CH), 146.4 (CH), 143.0 (C), 142.4 (C), 137.8 (C), 135.5 (C), 131.8 (C), 130.9 (CH), 130.3 (CH), 130.2 (CH), 129.9 (C), 129.1 (CH), 127.9 (CH), 126.4 (CH), 126.3 (CH), 126.2 (CH), 126.1 (CH); HRMS (ESI+ / Q-TOF) m / z [M+H]+calcd for C23H15N5ClO2428.0914; found 428.0909. The following precursor or intermediate compounds referred to above were prepared as follows: Ethyl 4-(3-(4-chlorophenyl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)butanoate (left structure) and ethyl 4-(5-(4-chlorophenyl)-3-(quinoxalin-6-yl)-1H-1,2,4-triazol-1- yl)butanoate (right structure) To a solution of 6-(5-(4-chlorophenyl)-4H-1,2,4-triazol-3-yl)quinoxaline (308 mg, 1.00 mmol) in DMF (2 mL) was added ethyl 4-bromobutyrate (143 µL, 1.00 mmol) and K2CO3 (415 mg, 3 mmol). The reaction mixture was then stirred at 160 °C for 5 h, cooled to RT, quenched with 1 M aq. HCl (50 mL) and extracted with EtOAc (3 × 40 mL). The combined organic extracts were washed with brine (3 × 50 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (25% EtOAc in Pet. Ether) afforded ethyl 4-(3-(4-chlorophenyl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)butanoate (brown solid; 89 mg, 21%):1H NMR (400 MHz, CDCl3) δ 8.94 (br s, 2H), 8.43 (d, J = 1.6 Hz, 1H), 8.28 (d, J = 8.7 Hz, 1H), 8.18 (dd, J = 8.7, 1.9 Hz, 1H), 8.15 – 8.10 (m, 2H), 7.45 – 7.40 (m, 2H), 4.45 (t, J = 6.9 Hz, 2H), 4.03 (q, J = 7.1 Hz, 2H), 2.42 (t, J = 7.0 Hz, 2H), 2.37 – 2.27 (m, 2H), 1.16 (t, J = 7.1 Hz, 3H);13C NMR (101 MHz, CDCl3) δ 172.4, 161.0, 154.6, 146.5, 146.2, 143.5, 142.7, 135.4, 130.8, 130.5, 130.0, 129.7, 129.5, 129.0, 127.9, 60.8, 48.9, 31.0, 25.2, 14.2; and ethyl 4-(5-(4-chlorophenyl)-3-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)butanoate butanoate (brown solid; 148 mg, 35%):1H NMR (400 MHz, CDCl3) δ 8.91-8.87 (m, 2H), 8.84 (d, J = 1.8 Hz, 1H), 8.57 (dd, J = 8.8, 1.8 Hz, 1H), 8.17 (d, J = 8.8 Hz, 1H), 7.74 – 7.68 (m, 2H), 7.57 – 7.51 (m, 2H), 4.37 (t, J = 7.0 Hz, 2H), 4.08 (q, J = 7.1 Hz, 2H), 2.43 (t, J = 7.0 Hz, 2H), 2.35 – 2.26 (m, 2H), 1.22 (t, J = 7.1 Hz, 3H);13C NMR (101 MHz, CDCl3) δ 172.3, 160.3, 155.1, 145.5, 145.0, 143.4, 143.2, 136.6, 132.6, 130.2, 129.7, 129.3, 128.4, 126.7, 126.3, 60.7, 48.6, 30.8, 25.1, 14.1. 6-(5-(4-Chlorophenyl)-4H-1,2,4-triazol-3-yl)quinoxaline To a solution of 4-chlorobenzohydrazide (324 mg, 1.90 mmol) in n-BuOH (6 mL) was added quinoxaline-6-carbonitrile (295 mg, 1.90 mmol) and K2CO3(290 mg, 2.10 mmol). The reaction mixture was then stirred at 130 °C for 3 h, cooled to RT, quenched with 1 M aq. HCl (50 mL) and extracted with EtOAc (3 × 40 mL). The combined organic extracts were washed with aqueous HCl (3 × 30 mL, 1 M), brine (2 × 30 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (50% EtOAc in Pet. Ether) afforded 6-(5-(4-chlorophenyl)-4H-1,2,4-triazol-3-yl)quinoxaline (368 mg, 63%) as a pale-brown solid.1H NMR (400 MHz, DMSO) δ 9.00 (d, J = 1.8 Hz, 1H), 8.98 (d, J = 1.8 Hz, 1H), 8.74 (d, J = 1.7 Hz, 1H), 8.52 (dd, J = 8.7, 1.9 Hz, 1H), 8.22 (d, J = 8.7 Hz, 1H), 8.14 – 8.10 (m, 2H), 7.61 (d, J = 8.5 Hz, 2H). 4-Chlorobenzohydrazide To a solution of methyl 4-chlorobenzoate (1.69 g, 9.89 mmol) in MeOH (40 mL) was added hydrazine hydrate (6.20 mL, 0.20 mol). The reaction mixture was stirred at 85 °C for 21 h and then cooled to 0 °C. The resulting solid was collected via vacuum filtration, washed with cold MeOH (2 × 20 mL) and dried in vacuo to afford 4-chlorobenzohydrazide (1.23 g, 73%) as a white solid.1H NMR (400 MHz, DMSO-d6) δ 9.85 (s, 1H), 7.89 – 7.80 (m, 2H), 7.58 – 7.48 (m, 2H), 4.51 (br s, 2H);13C NMR (101 MHz, DMSO-d6) δ 164.7 (C), 135.8 (C), 132.0 (C), 128.8 (CH), 128.4 (CH). Ethyl 4-(3-([1,1'-biphenyl]-4-yl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)butanoate (left structure) and ethyl 4-(5-([1,1'-biphenyl]-4-yl)-3-(quinoxalin-6-yl)-1H-1,2,4-triazol-1- yl)butanoate (right structure) To a solution of 6-(5-([1,1'-biphenyl]-4-yl)-4H-1,2,4-triazol-3-yl)quinoxaline (200 mg, 0.57 mmol) in DMF (5 mL) was added ethyl 4-bromobutyrate (0.08 mL, 0.57 mmol) and K2CO3(236 mg, 1.71 mmol). The reaction mixture was then stirred at 160 °C for 5 h, cooled to RT, quenched with 1 M aq. HCl (50 mL) and extracted with EtOAc (3 × 40 mL). The combined organic extracts were washed with brine (3 × 50 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (40 → 50% EtOAc in Pet. Ether) afforded ethyl 4-(3-([1,1'-biphenyl]-4-yl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol- 1-yl)butanoate (brown solid; 90 mg, 34%):1H NMR (400 MHz, CDCl3) δ 8.94 (br s, 2H), 8.45 (d, J = 1.8 Hz, 1H), 8.29 (d, J = 8.7 Hz, 1H), 8.26 (d, J = 8.4 Hz, 2H), 8.21 (dd, J = 8.4, 2.1 Hz, 1H), 7.71 (d, J = 8.0 Hz, 2H), 7.66 (d, J = 7.2 Hz, 2H), 7.46 (t, J = 7.7 Hz, 2H), 7.36 (t, J = 7.3 Hz, 1H), 4.47 (t, J = 6.8 Hz, 2H), 4.03 (q, J = 14.4, 7.1 Hz, 2H), 2.46 – 2.40 (m, 2H), 2.39 – 2.30 (m, 2H), 1.16 (t, J = 7.1 Hz, 3H);13C NMR (101 MHz, CDCl3) δ 172.5 (C), 161.7 (C), 154.5 (C), 146.3 (CH), 146.1 (CH), 143.5 (C), 142.7 (C), 142.2 (C), 140.8 (C), 130.7 (CH), 130.6 (CH), 129.94 (CH), 129.91 (C), 128.9 (CH), 127.6 (CH), 127.4 (CH), 127.2 (CH), 127.0 (CH), 60.8 (CH2), 48.8 (CH2), 31.0 (CH2), 25.3 (CH2), 14.2 (CH3); HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C28H26N5O2464.2081; found 464.2079; and ethyl 4-(5-([1,1'-biphenyl]-4- yl)-3-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)butanoate (brown solid; 92 mg, 35%):1H NMR (400 MHz, CDCl3) δ 8.93 (d, J = 1.7 Hz, 1H), 8.88 (d, J = 1.8 Hz, 1H), 8.83 (d, J = 1.7 Hz, 1H), 8.61 (dd, J = 8.8, 1.9 Hz, 1H), 8.18 (d, J = 8.8 Hz, 1H), 7.85 – 7.75 (m, 4H), 7.67 – 7.63 (m, 2H), 7.49 (t, J = 7.3 Hz, 2H), 7.40 (t, J = 7.3 Hz, 1H), 4.43 (t, J = 6.9 Hz, 2H), 4.07 (q, J = 14.2, 7.4 Hz, 2H), 2.45 (t, J = 6.4 Hz, 2H), 2.39 – 2.29 (m, 2H), 1.20 (t, J = 7.2 Hz, 3H);13C NMR (101 MHz, CDCl3) δ 172.5 (C), 160.5 (C), 156.2 (C) 145.6 (CH), 145.1 (CH), 143.6 (C), 143.4 (C), 143.3 (C), 140.1 (C), 133.0 (C), 129.8 (CH), 129.4 (CH), 129.1 (CH), 128.6 (CH), 128.1 (CH), 127.8 (CH), 127.3 (CH), 126.9 (CH), 126.8 (C), 60.8 (CH2), 48.7 (CH2), 31.1 (CH2), 25.3 (CH2), 14.3 (CH3); HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C28H26N5O2 464.2081; found 464.2077; 6-(5-([1,1'-Biphenyl]-4-yl)-4H-1,2,4-triazol-3-yl)quinoxaline To a solution of [1,1'-biphenyl]-4-carbohydrazide (410 mg, 1.93 mmol) in n-BuOH (10 mL) was added quinoxaline-6-carbonitrile (300 mg, 1.93 mmol) and K2CO3 (294 mg, 2.13 mmol). The reaction mixture was then stirred at 130 °C for 3 h, cooled to RT, quenched with 1 M aq. HCl (50 mL) and extracted with EtOAc (3 × 30 mL). The combined organic extracts were washed with 1 M aq. HCl (2 × 30 mL), brine (2 × 30 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (50 → 90% EtOAc in Pet. Ether) afforded 6-(3-([1,1'-biphenyl]-4-yl)-1H-1,2,4-triazol-5-yl)quinoxaline (312 mg, 46%) as a yellow solid.1H NMR (400 MHz, DMSO-d6) δ 9.03 (d, J = 1.8 Hz, 1H), 8.99 (d, J = 1.7 Hz, 1H), 8.78 (d, J = 1.6 Hz, 1H), 8.58 (dd, J = 8.8, 1.9 Hz, 1H), 8.25 (d, J = 8.5 Hz, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.89 (d, J = 8.3 Hz, 2H), 7.77 (d, J = 7.1 Hz, 2H), 7.51 (t, J = 7.6 Hz, 2H), 7.42 (tt, J = 7.3, 2.0 Hz, 1H); HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C22H16N5350.1400; found 350.1399. [1,1'-Biphenyl]-4-carbohydrazide To a solution of methyl [1,1′-biphenyl]-4-carboxylate (2.10 g, 9.89 mmol) in MeOH (40 mL) was added hydrazine hydrate (6.20 mL, 0.20 mol). The reaction mixture was stirred at 85 °C for 21 h and then cooled to 0 °C. The resulting solid was collected via vacuum filtration, washed with cold MeOH (2 × 20 mL) and dried in vacuo to afford [1,1'-biphenyl]-4-carbohydrazide (1.38 g, 66%) as a white solid.1H NMR (400 MHz, DMSO-d6) δ 9.82 (s, 1H), 7.92 (d, J = 8.4 Hz, 2H), 7.75 (d, J = 8.4 Hz, 2H), 7.72 (d, J = 8.4 Hz, 2H), 7.49 (t, J = 7.5 Hz, 2H), 7.40 (t, J = 7.3 Hz, 1H), 4.52 (s, 2H);13C NMR (101 MHz, DMSO-d6) δ 165.5 (C), 142.6 (C), 139.2 (C), 132.1 (C), 129.0 (CH), 128.0 (CH), 127.6 (CH), 126.8 (CH), 126.5 (CH); HRMS (ESI+ / Q- TOF) m / z: [M+Na]+calcd for C13H12N2ONa 235.0842; found 235.0481. Methyl [1,1′-biphenyl]-4-carboxylate To a solution of biphenyl-4-carboxylic acid (2.00 g, 10.1 mmol) in MeOH (20 mL) was added H2SO4(0.76 mL, 14.1 mmol). The reaction mixture was then stirred at 80 °C for 3 h, cooled to RT and neutralised with sat. aq. NaHCO3. The mixture was then extracted with EtOAc (3 × 50 mL) and the combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (3 → 5% EtOAc in Pet. Ether) afforded methyl [1,1′-biphenyl]-4-carboxylate (2.14 g, 98%) as a white solid.1H NMR (400 MHz, CDCl3) δ 8.11 (d, J = 8.3 Hz, 2H), 7.67 (d, J = 8.7 Hz, 2H), 7.65 – 7.61 (m, 2H), 7.47 (t, J = 7.5 Hz, 2H), 7.43 – 7.37 (m, 1H), 3.95 (s, 3H);13C NMR (101 MHz, CDCl3) δ 167.1 (C), 145.8 (C), 140.1 (C), 130.2 (CH), 129.1 (CH), 128.3 (C), 127.4 (CH), 127.2 (CH), 52.2 (CH3); HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C14H13O2213.0910; found 213.0910. Ethyl 4-(3-(4'-isopropoxy-[1,1'-biphenyl]-4-yl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1- yl)butanoate (left structure) and ethyl 4-(5-(4'-isopropoxy-[1,1'-biphenyl]-4-yl)-3- (quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)butanoate (right structure) To a solution of 6-(5-(4'-isopropoxy-[1,1'-biphenyl]-4-yl)-4H-1,2,4-triazol-3-yl)quinoxaline (200 mg, 0.49 mmol) in DMF (8 mL) was added ethyl 4-bromobutyrate (0.07 mL, 0.49 mmol) and K2CO3(203 mg, 1.47 mmol). The reaction mixture was then stirred at 160 °C for 6 h, cooled to rt, quenched with 1 M aq. HCl (50 mL) and extracted with EtOAc (3 × 40 mL). The combined organic extracts were washed with brine (3 × 50 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (30 → 50% EtOAc in Pet. Ether) afforded ethyl 4-(3-(4'-isopropoxy-[1,1'-biphenyl]-4-yl)-5-(quinoxalin-6- yl)-1H-1,2,4-triazol-1-yl)butanoate (brown solid; 59 mg, 23%):1H NMR (400 MHz, CDCl3) δ 8.94 (br s, 2H), 8.45 (d, J = 1.8 Hz, 1H), 8.29 (d, J = 8.7 Hz, 1H), 8.22 (d, J = 8.5 Hz, 2H), 8.21 (dd, J = 8.7, 1.9 Hz, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.59 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.7 Hz, 2H), 4.66 – 4.55 (m, 1H), 4.46 (t, J = 6.8 Hz, 2H), 4.03 (q, J = 14.2, 7.2 Hz, 2H), 2.47 – 2.39 (m, 2H), 2.38 – 2.30 (m, 2H), 1.37 (d, J = 6.1 Hz, 6H), 1.16 (t, J = 7.1 Hz, 3H);13C NMR (101 MHz, CDCl3) δ 172.5 (C), 161.8 (C), 157.8 (C), 154.5 (C), 146.3 (CH), 146.1 (CH), 143.5 (C), 142.7 (C), 141.8 (C), 133.0 (C), 130.7 (CH), 130.6 (CH), 129.9 (CH), 129.2 (C), 128.2 (CH), 126.94 (CH), 126.89 (CH), 116.3 (CH), 70.1 (CH), 60.8 (CH2), 48.8 (CH2), 31.0 (CH2), 25.3 (CH2), 22.2 (CH3), 14.2 (CH3); HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C31H32N5O3522.2500; found 522.2496; and ethyl 4-(5-(4'-isopropoxy-[1,1'-biphenyl]-4-yl)-3- (quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)butanoate (brown solid; 87 mg, 34%):1H NMR (400 MHz, CDCl3) δ 8.92 (d, J = 1.6 Hz, 1H), 8.88 (d, J = 1.6 Hz, 1H), 8.83 (d, J = 1.7 Hz, 1H), 8.61 (dd, J = 8.8, 1.8 Hz, 1H), 8.17 (d, J = 9.0 Hz, 1H), 7.79 (d, J = 8.5 Hz, 2H), 7.73 (d, J = 8.4 Hz, 2H), 7.58 (d, J = 8.7 Hz, 2H), 6.99 (d, J = 9.0 Hz, 2H), 4.67 – 4.55 (m, 1H), 4.42 (t, J = 6.9 Hz, 2H), 4.07 (q, J = 14.0, 7.1 Hz, 2H), 2.44 (t, J = 6.9 Hz, 2H), 2.39 – 2.29 (m, 2H), 1.38 (d, J = 6.1 Hz, 6H), 1.20 (t, J = 7.1 Hz, 3H);13C NMR (101 MHz, CDCl3) δ 172.6 (C), 160.4 (C), 158.2 (C), 156.2 (C), 145.6 (CH), 145.1 (CH), 143.6 (C), 143.4 (C), 142.9 (C), 133.1 (C), 132.2 (C), 129.8 (CH), 129.4 (CH), 128.7 (CH), 128.3 (CH), 127.2 (CH), 126.9 (CH), 126.0 (C), 116.3 (CH), 70.2 (CH), 60.8 (CH2), 48.7 (CH2), 31.1 (CH2), 25.3 (CH2), 22.2 (CH3), 14.3 (CH3); HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C31H32N5O3522.2500; found 522.2496; 6-(5-(4'-Isopropoxy-[1,1'-biphenyl]-4-yl)-4H-1,2,4-triazol-3-yl)quinoxaline To a solution of 4'-isopropoxy-[1,1'-biphenyl]-4-carbohydrazide (323 mg, 1.19 mmol) in n- BuOH (15 mL) was added quinoxaline-6-carbonitrile (185 mg, 1.19 mmol) and K2CO3(182 mg, 1.31 mmol). The reaction mixture was then stirred at 130 °C for 3 h, cooled to RT, quenched with 1 M aq. HCl (50 mL) and extracted with EtOAc (3 × 30 mL). The combined organic extracts were washed with 1 M aq. HCl (2 × 30 mL), brine (2 × 30 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (40 → 90% EtOAc in Pet. Ether) afforded 6-(5-(4'-isopropoxy-[1,1'- biphenyl]-4-yl)-4H-1,2,4-triazol-3-yl)quinoxaline (314 mg, 65%) as a yellow solid.1H NMR (400 MHz, DMSO-d6) δ 14.82 (br s, 1H), 9.03 (d, J = 2.1 Hz, 1H), 8.99 (d, J = 1.5 Hz, 1H), 8.77 (br s, 1H), 8.58 (dd, J = 8.8, 1.6 Hz, 1H), 8.25 (d, J = 8.7 Hz, 1H), 8.18 (d, J = 8.4 Hz, 2H), 7.83 (d, J = 8.7 Hz, 2H), 7.69 (d, J = 8.7 Hz, 2H), 7.03 (d, J = 8.7 Hz, 2H), 4.72 – 4.62 (m, 1H), 1.30 (d, J = 6.0 Hz, 6H); HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C25H22N5O 408.1819; found 408.1822. 4'-Isopropoxy-[1,1'-biphenyl]-4-carbohydrazide To a solution of methyl 4'-isopropoxy-[1,1'-biphenyl]-4-carboxylate (386 mg, 1.43 mmol) in MeOH (10 mL) was added hydrazine hydrate (0.90 mL, 28.6 mmol). The reaction mixture was stirred at 85 °C for 18 h and then cooled to 0 °C. The resulting solid was collected via vacuum filtration, washed with cold MeOH (2 × 10 mL) and dried in vacuo to afford 4'-isopropoxy- [1,1'-biphenyl]-4-carbohydrazide (323 mg, 84%) as a white solid.1H NMR (400 MHz, DMSO- d6) δ 9.77 (s, 1H), 7.88 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H), 7.64 (d, J = 8.8 Hz, 2H), 7.01 (d, J = 8.8 Hz, 2H), 4.72 – 4.61 (m, 1H), 4.49 (s, 2H), 1.29 (d, J = 6.0 Hz, 6H);13C NMR (101 MHz, DMSO-d6) δ 165.6 (C), 157.5 (C), 142.3 (C), 131.3 (C), 131.1 (C), 128.0 (CH), 127.5 (CH), 125.8 (CH), 116.0 (CH), 69.2 (CH), 21.8 (CH3); HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C16H19N2O2271.1441; found 271.1440. Methyl 4'-isopropoxy-[1,1'-biphenyl]-4-carboxylate To a solution of 4-isopropoxyphenylboronic acid (1.15 g, 6.39 mmol) in DMF-H2O (64 mL, 1:1 v / v) was added methyl 4-iodobenzoate (1.67 g, 6.39 mmol), Pd(OAc)2(144 mg, 0.64 mmol) and K3PO4(2.71 g, 12.8 mmol). The mixture was stirred at RT for 20 h, diluted with EtOAc (50 mL) and washed with H2O (30 mL). The separated aqueous layer was further extracted with EtOAc (3 × 50 mL). The combined organic extracts were washed with H2O (3 × 50 mL) and brine (3 × 50 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (5% EtOAc in Pet. Ether) afforded methyl 4'- isopropoxy-[1,1'-biphenyl]-4-carboxylate (386 mg, 22%) as a white solid.1H NMR (400 MHz, CDCl3) δ 8.07 (d, J = 8.5 Hz, 2H), 7.62 (d, J = 8.5 Hz, 2H), 7.55 (d, J = 8.8 Hz, 2H), 6.97 (d, J = 8.8 Hz, 2H), 4.66 – 4.55 (m, 1H), 3.93 (s, 3H), 1.37 (d, J = 6.0 Hz, 6H);13C NMR (101 MHz, CDCl3) δ 167.2 (C), 158.4 (C), 145.4 (C), 132.3 (C), 130.2 (CH), 128.5 (CH), 128.3 (C), 126.6 (CH), 116.3 (CH), 70.1 (CH), 52.2 (CH3), 22.2 (CH3); HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C17H19O3271.1329; found 271.1330. Ethyl-4-chloro-N-(quinoxaline-6-carbonyl)benzimidate A solution of ethyl 4-chlorobenzimidate hydrochloride (500 mg, 2.27 mmol), quinoxaline-6- carbonyl chloride (600 mg, 3.12 mmol) and Et3N (0.65 mL, 4.66 mmol) in THF (8 mL) was heated at 100 °C in a microwave for 15 min, then concentrated in vacuo. Purification by flash column chromatography (20% EtOAc in Pet. Ether) afforded ethyl-4-chloro-N-(quinoxaline- 6-carbonyl)benzimidate (491 mg, 64%) as an off-white solid.1H NMR (400 MHz, CDCl3) δ 8.93 – 8.92 (m, 2H), 8.70 (d, J = 1.9 Hz, 1H), 8.42 (dd, J = 8.7, 1.8 Hz, 1H), 8.19 (d, J = 8.8 Hz, 1H), 7.58 (d, J = 8.6 Hz, 2H), 7.30 (d, J = 9.1 Hz, 2H), 4.53 (q, J = 7.1 Hz, 2H), 1.52 (t, J = 7.2 Hz, 3H);13C NMR (100 MHz, CDCl3) δ 174.8 (C), 158.8 (C), 146.7 (CH), 146.0 (CH), 145.3 (C), 142.6 (C), 138.4 (C), 135.6 (C), 132.0 (CH), 130.3 (CH), 130.1 (CH), 129.6 (CH), 129.10 (CH), 129.07 (C), 64.8 (CH2), 14.3 (CH3); HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C18H15ClN3O2340.0847; found 340.0846. Ethyl 4-chlorobenzimidate hydrochloride To a stirred solution of 4-chlorobenzonitrile (1.57 g, 11.4 mmol) in EtOH (20 mL) at 0 °C was added acetyl chloride (14 mL) dropwise. The mixture was warmed to RT and stirred for 18 h then concentrated in vacuo. The resultant solid was washed with Et2O and filtered to afford ethyl 4-chlorobenzimidate hydrochloride (2.51 g, quant.) as a white solid, which was used in the next step without further purification.1H NMR (400 MHz, DMSO-d6) δ 8.14 (d, J = 9.3 Hz, 2H), 7.74 (d, J = 9.2 Hz, 2H), 4.62 (q, J = 7.0 Hz, 2H), 1.47 (t, J = 7.0 Hz, 3H);13C NMR (100 MHz, DMSO-d6) δ 169.8 (C), 140.1 (C), 130.9 (CH), 129.3 (CH), 125.2 (C), 69.6 (CH2), 13.5 (CH3); HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C9H11ClNO 184.0524; found 184.0522. Ethyl-4'-isopropoxy-N-(quinoxaline-6-carbonyl)-[1,1'-biphenyl]-4-carbimidate A solution of ethyl 4'-isopropoxy-[1,1'-biphenyl]-4-carbimidate hydrochloride (0.50 g, 1.56 mmol), quinoxaline-6-carbonyl chloride (0.45 g, 2.35 mmol) and Et3N (0.55 mL, 3.91 mmol) in THF (10 mL) was heated at 100 °C in a microwave for 15 minutes. The mixture was then diluted with EtOAc and washed with H2O, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (10 → 40% EtOAc in Pet. Ether) afforded ethyl-4'-isopropoxy-N-(quinoxaline-6-carbonyl)-[1,1'-biphenyl]-4- carbimidate (200 mg, 29%) as a white solid.1H NMR (400 MHz, CDCl3) δ 8.93 – 8.89 (m, 2H), 8.75 (d, J = 1.9 Hz, 1H), 8.47 (dd, J = 8.7, 1.9 Hz, 1H), 8.23 – 8.18 (m, 1H), 7.68 (d, J = 8.3 Hz, 2H), 7.49 (d, J = 8.2 Hz, 2H), 7.45 (d, J = 8.5 Hz, 2H), 6.91 (d, J = 8.6 Hz, 2H), 4.61 – 4.50 (m, 3H), 1.55 (t, J = 7.1 Hz, 3H), 1.34 (d, J = 6.0 Hz, 6H);13C NMR (101 MHz, CDCl3) δ 174.88, 159.62, 158.19, 146.49, 145.82, 145.06, 144.37, 142.53, 135.81, 131.86, 130.03, 129.65, 129.14, 128.26, 126.67, 116.14, 69.98, 64.37, 22.04, 14.26. Ethyl 4'-isopropoxy-[1,1'-biphenyl]-4-carbimidate hydrochloride To a solution of 4'-isopropoxy-[1,1'-biphenyl]-4-carbonitrile (0.5 g, 1.76 mmol) in EtOH (20 mL) at 0 °C was carefully added dropwise acetyl chloride (14 mL), and the mixture stirred at RT overnight. The solvents were then removed in vacuo to afford ethyl 4'-isopropoxy-[1,1'- biphenyl]-4-carbimidate hydrochloride (0.56 g, quant.) as a yellow solid, which was used in the next step without further purification.1H NMR (400 MHz, CDCl3) δ 12.54 (s, 1H), 11.84 (s, 1H), 8.46 (d, J = 8.2 Hz, 2H), 7.74 (d, J = 8.1 Hz, 2H), 7.56 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.7 Hz, 2H), 4.97 (q, J = 6.8 Hz, 2H), 4.61 (hept, J = 6.0 Hz, 1H), 1.63 (t, J = 6.3 Hz, 3H), 1.37 (d, J = 6.0 Hz, 6H);13C NMR (101 MHz, CDCl3) δ 170.78, 158.96, 148.09, 131.15, 130.42, 128.65, 127.13, 123.10, 116.41, 71.27, 70.17, 22.16, 14.06; HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C18H22NO2284.1645; found 284.1642. 4'-Isopropoxy-[1,1'-biphenyl]-4-carbonitrile A mixture of 4-bromobenzonitrile (1.50 g, 8.24 mmol), 4-isopropoxyphenylboronic acid (1.48 g, 8.24 mmol), potassium phosphate tribasic (3.50 g, 16.5 mmol) and palladium acetate (185 mg, 0.82 mmol) in DMF-H2O (80 mL, 1:1 v / v) was stirred at RT for 2 h. The solution was then diluted with Et2O (100 mL) and the separated organic phase washed with H2O (2 × 100 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford 4'-isopropoxy-[1,1'- biphenyl]-4-carbonitrile (1.95 g, quant.) as a white solid, which was used in the next step without further purification.1H NMR (300 MHz, CDCl3) δ 7.71 – 7.61 (m, 4H), 7.55 – 7.49 (m, 2H), 7.01 – 6.95 (m, 2H), 4.61 (hept, J = 6.0 Hz, 1H), 1.38 (d, J = 6.0 Hz, 6H). 3-(3-(4-Chlorophenyl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)benzonitrile A solution of ethyl 4-chlorobenzimidate hydrochloride (300 mg, 1.36 mmol), quinoxaline-6- carbonyl chloride (525 mg, 2.73 mmol) and Et3N (570 µL, 4.09 mmol) in THF (3 mL) was heated at 100 °C in a microwave for 15 min. Additional portions of quinoxaline-6-carbonyl chloride (131 mg, 0.68 mmol) and Et3N (95 µL, 0.68 mmol) were added to the mixture and heated at 100 °C in a microwave for a further 10 min before the addition of 3- cyanophenylhydrazine hydrochloride (462 mg, 2.73 mmol) and Et3N (380 µL, 2.73 mmol). The resultant mixture and heated at 100 °C in a microwave for a further 30 min. The reaction mixture was diluted with EtOAc (100 mL) and washed with H2O (2 × 100 mL). The aqueous phase was further extracted with EtOAc (3 × 100 mL) then the combined organic extracts were washed with brine (50 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (50% EtOAc in Pet. Ether) afforded 3-(3- (4-chlorophenyl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)benzonitrile (246 mg, 44%) as a yellow solid.1H NMR (400 MHz, DMSO-d6) δ 9.03 – 8.99 (m, 2H), 8.22 – 8.16 (m, 5H), 8.06 – 8.02 (m, 2H), 7.94 – 7.87 (m, 1H), 7.74 (t, J = 8.0 Hz, 1H), 7.62 (d, J = 8.6 Hz, 2H);13C NMR (100 MHz, DMSO-d6) δ 160.4 (C), 154.0 (C), 147.2 (CH), 146.9 (CH), 142.6 (C), 141.5 (C), 138.2 (C), 134.5 (C), 133.4 (CH), 131.1 (CH), 130.9 (CH), 129.95 (CH), 129.88 (CH), 129.6 (CH), 129.1 (CH), 128.9 (C), 128.4 (C), 127.9 (CH), 117.6 (C), 112.6 (C); HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C23H14ClN6409.0963; found 409.0962. 3-(3-(4-Chlorophenyl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)-N'- hydroxybenzimidamide A solution of 3-(3-(4-chlorophenyl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)benzonitrile (100 mg, 0.25 mmol), hydroxylamine hydrochloride (25 mg, 0.37 mmol) and DIPEA (128 μL, 0.73 mmol) in EtOH (2 mL) was heated at 80 °C in a microwave for 1 h. Purification by flash column chromatography (80% EtOAc in Pet. Ether) afforded 3-(3-(4-chlorophenyl)-5- (quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)-N'-hydroxybenzimidamide (70 mg, 64%) as an off- white solid.1H NMR (500 MHz, DMSO-d6) δ 9.80 (s, 1H), 9.01 – 8.97 (m, 2H), 8.20 – 8.17 (m, 3H), 8.14 (d, J = 1.9 Hz, 1H), 8.07 (dd, J = 8.8, 2.1 Hz, 1H), 7.95 – 7.93 (m, 1H), 7.89 – 7.86 (m, 1H), 7.62 (d, J = 8.5 Hz, 2H), 7.56 – 7.52 (m, 2H), 5.92 (s, 2H);13C NMR (125 MHz, DMSO-d6) δ 160.1 (C), 153.6 (C), 149.5 (C), 147.1 (CH), 146.9 (CH), 142.5 (C), 141.5 (C), 137.6 (C), 134.9 (C), 134.4 (C), 129.9 (CH), 129.8 (CH), 129.60 (CH), 129.56 (CH), 129.12 (CH), 129.09 (C), 128.7 (C), 127.8 (CH), 126.4 (CH), 126.3 (CH), 122.8 (CH); HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C23H17ClN7O 442.1178; found 442.1176. Ethyl-4-isopropoxy-N-(quinoxaline-6-carbonyl)benzimidate To a suspension of ethyl 4-isopropoxybenzimidate hydrochloride (208 mg, 0.853 mmol) and Et3N (0.40 mL, 2.09 mmol) in THF (3 mL) was added quinoxaline-6-carbonyl chloride (403 mg, 2.09 mmol) in a single portion. The reaction mixture was heated in a microwave at 100 °C for 15 min then cooled to RT. The reaction was then concentrated in vacuo onto Celite®and purified by flash column chromatography (0 → 15% EtOAc in Pet. Ether) to afford ethyl-4- isopropoxy-N-(quinoxaline-6-carbonyl)benzimidate (120 mg, 39%) as an amorphous light pink solid.1H NMR (400 MHz, DMSO-d6) δ 8.91 (s, 2H), 8.72 (d, J = 1.9 Hz, 1H), 8.45 (dd, J = 8.8, 1.9 Hz, 1H), 8.18 (d, J = 8.7 Hz, 1H), 7.59 (d, J = 9.0 Hz, 2H), 6.77 (d, J = 8.9 H, 2H), 4.55–4.48 (m, 3H), 1.51 (t, J = 7.1 Hz, 3H), 1.28 (d, J = 6.0 Hz, 6H);13C NMR (100 MHz, DMSO-d6) δ 174.9 (C) 161.1 (C), 159.4 (C), 146.5 (CH), 145.9 (CH), 145.1 (C), 142.7 (C), 136.1 (C), 131.9 (CH), 130.8 (CH), 130.1 (CH), 129.8 (CH), 122.0 (C), 115.5 (CH), 70.2 (CH), 64.3 (CH2), 22.0 (CH3), 14.4 (CH3); HRMS (ESI / Q-TOF) m / z: molecular ion not observed. Ethyl 4-isopropoxybenzimidate hydrochloride To a stirred solution of 4-isopropoxybenzonitrile (0.677 g, 4.20 mmol) in EtOH (7.5 mL) at 0 °C was added AcCl (5.2 mL, 73.1 mmol) dropwise. The mixture was warmed to RT and stirred for 3 d then concentrated in vacuo to afford ethyl 4-isopropoxybenzimidate hydrochloride (0.967 g, 95%) as an amorphous light brown solid, which was used in the next step without further purification.1H NMR (400 MHz, DMSO-d6) δ 8.15 (d, J = 8.7 Hz, 2H), 7.13 (d, J = 8.7 Hz, 2H), 4.84 (hept, J = 6.2 Hz, 1H), 4.62 (q, J = 6.8 Hz, 2H), 1.46 (t, J = 6.9 Hz, 3H), 1.29 (d, J = 5.9 Hz, 6H);13C NMR (400 MHz, DMSO-d6) δ 169.8 (C), 163.3 (C), 131.6 (CH), 116.9 (C), 115.7 (CH), 70.2 (CH), 69.3 (CH2), 21.6 (CH3), 13.5 (CH3); HRMS (ESI+ / TOF-Q) m / z: [M+H]+calcd for C12H18NO2, 208.1332; found, 208.1331. Methyl 3-(3-(6-(4-isopropoxyphenyl)pyridin-3-yl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1- yl)benzoate To a suspension of methyl 6-(4-isopropoxyphenyl)nicotinimidate (79.3 mg, 0.293 mmol) and Et3N (0.22 mL, 1.58 mmol) in THF (1.3 mL) was added quinoxaline-6-carbonyl chloride (106 mg, 0.550 mmol) in a single portion. The reaction mixture was heated in a microwave at 100 °C for 15 min then cooled to RT. Methyl 3-hydrazineylbenzoate hydrochloride (96.0 mg, 0.578 mmol) was then added and the reaction mixture was heated in a microwave at 100 °C for a further 30 min. The reaction mixture was diluted with EtOAc (2 mL), washed with 0.1 M aq. HCl (1.5 mL), then dried over anhydrous Na2SO4, filtered and concentrated in vacuo onto Celite®. The crude residue was purified by flash column chromatography (0 → 40% EtOAc in Pet. Ether) to afford methyl 3-(3-(6-(4-isopropoxyphenyl)pyridin-3-yl)-5-(quinoxalin-6-yl)- 1H-1,2,4-triazol-1-yl)benzoate (69.5 mg, 9%) as an amorphous yellow solid.1H NMR (500 MHz, CDCl3) δ 9.50 (d, J = 1.6 Hz, 1H), 8.90‒8.88 (m, 2H), 8.53 (dd, J = 8.3, 2.2 Hz, 1H), 8.28 (d, J = 1.9 Hz, 1H), 8.244‒8.237 (m, 1H), 8.18‒8.15 (m, 2H), 8.06‒8.03 (m, 3H), 7.81 (d, J = 8.6 Hz, 1H), 7.64‒7.62 (m, 1H), 7.56 (t, J = 7.9 Hz, 1H), 7.01 (d, J = 8.7 Hz, 2H), 4.65 (hept, J = 6.1 Hz, 1H), 3.91 (s, 3H), 1.38 (d, J = 6.1 Hz, 6H);13C NMR (125 MHz, CDCl3) δ 165.7 (C), 160.7 (C), 159.3 (C), 158.1 (C), 154.0 (C), 148.1 (CH), 146.4 (CH), 146.2 (CH), 143.6 (C), 142.6 (C), 138.3 (C), 134.7 (CH), 132.2 (C), 131.4 (C), 130.7 (CH), 130.6 (CH), 130.5 (CH), 130.1 (CH), 130.0 (CH), 129.8 (CH), 129.2 (C), 128.5 (CH), 126.8 (CH), 124.0 (C), 119.6 (CH), 116.1 (CH), 70.1 (CH), 52.7 (CH3), 22.2 (CH3); HRMS (ESI+ / TOF-Q) m / z: [M+H]+calcd for C32H27N6O3, 543.2139; found, 543.2138. Methyl 6-(4-isopropoxyphenyl)nicotinimidate To a stirred solution of 6-(4-isopropoxyphenyl)nicotinonitrile (1.12 g, 4.70 mmol) in MeOH (12 mL) at RT was added DBU (0.25 mL, 1.67 mmol) dropwise. The mixture was heated to reflux and stirred for 25 h then another portion of DBU (0.52 mL, 3.48 mmol) was added, and the reaction stirred for a further 24 h. The reaction was then concentrated in vacuo to onto Celite®and purified by flash column chromatography (0 → 20% EtOAc in Pet. Ether) to afford methyl 6-(4-isopropoxyphenyl)nicotinimidate (79.3 mg, 6%) as an amorphous yellow solid.1H NMR (400 MHz, CDCl3) δ 8.99 (br s, 1H), 7.99‒7.91 (m, 3H), 7.72‒7.70 (m, 1H), 6.98 (d, J = 8.9 Hz, 2H), 4.64 (hept, J = 6.1 Hz, 1H), 3.96 (br s, 3H), 1.37 (d, J = 6.0 Hz, 6H); HRMS (ESI+ / TOF-Q) m / z: [M+H]+calcd for C16H19N2O2, 271.1441; found, 271.1438. 6-(4-Isopropoxyphenyl)nicotinonitrile To a stirred suspension of 6-bromonicotinonitrile (2.04 g, 11.1 mmol), 4- isopropoxyphenylboronic acid (2.01 g, 11.2 mmol) and K3PO4(4.70 g, 22.2 mmol) in a mixture of DMF-H2O (109 mL, 1:1 v / v) was added Pd(OAc)2 (28.0 mg, 1.25 mmol) in a single portion. The reaction was stirred at RT for 2 h then diluted with H2O (100 mL) and extracted with Et2O (2 × 100 mL). The combined organic extracts were diluted with EtOAc (200 mL) washed with H2O (5 × 300 mL) and brine (5 × 300 mL) then dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford 6-(4-isopropoxyphenyl)nicotinonitrile (2.60 g, 89%) as an amorphous yellow solid.1H NMR (400 MHz, CDCl3) δ 8.89‒8.88 (m, 1H), 8.02‒7.98 (m, 2H), 7.94 (dd, J = 8.4, 2.0 Hz, 1H), 7.77 (dd, J = 8.5, 0.9 Hz, 1H), 7.01‒6.97 (m, 2H), 4.65 (hept, J = 7.3 Hz, 1H), 1.38 (d, J = 6.0 Hz, 6H);13C NMR (100 MHz, CDCl3) δ 160.4 (C), 160.3 (C), 152.6 (CH), 139.8 (CH), 129.6 (C), 129.1 (CH), 119.1 (CH), 117.4 (C), 116.2 (CH), 106.9 (C), 70.2 (CH), 22.1 (CH3); HRMS (ESI+ / TOF-Q) m / z: [M+H]+calcd for C15H15N2O, 239.11789; found, 239.1179. Ethyl-4-(6-isopropoxypyridin-3-yl)-N-(quinoxaline-6-carbonyl)benzimidate To a stirred solution of 4-(6-isopropoxypyridin-3-yl)benzonitrile (0.559 g, 2.34 mmol) in EtOH (4.2 mL) at 0 °C was added AcCl (2.9 mL, 40.6 mmol) dropwise. The mixture was warmed to RT and stirred for 18 h then concentrated in vacuo. The resultant solid was washed with Et2O and collected by filtration to afford ethyl 4-(6-isopropoxypyridin-3-yl)benzimidate hydrochloride (0.751 g, quant.) as a brown solid, which was used in the next step without further purification. To a suspension of ethyl 4-(6-isopropoxypyridin-3-yl)benzimidate hydrochloride (194 mg, 0.603 mmol) and Et3N (0.26 mL, 1.87 mmol) in anhydrous THF (3 mL) was added quinoxaline-6-carbonyl chloride (247 mg, 1.28 mmol) in a single portion. The reaction mixture was heated in a microwave at 100 °C for 15 min then cooled to RT. The reaction was then concentrated in vacuo onto Celite®and purified by flash column chromatography (0 → 30% EtOAc in Pet. Ether) to afford ethyl-4-(6-isopropoxypyridin-3-yl)- N-(quinoxaline-6-carbonyl)benzimidate (19 mg, 7%) as an amorphous off-white solid.1H NMR (400 MHz, DMSO-d6) δ 9.07 (s, 2H), 8.66 (d, J = 1.9 Hz, 1H), 8.47 (d, J = 2.5 Hz, 1H), 8.38 (dd, J = 8.8, 2.0 Hz, 1H), 8.24 (d, J = 8.8 Hz, 1H), 7.98 (dd, J = 8.6, 2.6 Hz, 1H), 7.73 (d, J = 8.5 Hz, 2H), 7.63 (d, J = 8.6 Hz, 2H), 6.81 (d, J = 8.9 Hz, 1H), 5.27 (hept, J = 6.2 Hz, 1H), 4.53 (q, J = 7.1 Hz, 2H), 1.49 (t, J = 7.1 Hz, 3H), 1.29 (d, J = 6.1 Hz, 6H); HRMS (ESI+ / TOF- Q) m / z: [M+H]+calcd for C26H25N4O3, 441.19212; found, 441.1931. 4-(6-Isopropoxypyridin-3-yl)benzonitrile To a stirred suspension of 5-bromo-2-isopropoxypyridine (0.576 g, 2.66 mmol), 4- cyanophenylboronic acid (0.402 g, 2.73 mmol) and K3PO4 (1.11 g, 5.24 mmol) in a mixture of DMF-H2O (26 mL, 1:1 v / v) was added Pd(OAc)2 (62.1 mg, 0.277 mmol) in a single portion. The reaction was stirred at RT for 2 h then diluted with H2O (50 mL) and extracted with Et2O (2 × 100 mL). The combined organic extracts were washed with H2O (2 × 100 mL) and brine (2 × 100 mL) then dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford 4-(6-isopropoxypyridin-3-yl)benzonitrile (0.559 g, 88%) as an amorphous yellow solid.1H NMR (400 MHz, CDCl3) δ 8.39‒8.38 (m, 1H), 7.79‒7.76 (m, 1H), 7.74‒7.70 (m, 2H), 7.64‒ 7.61 (m, 2H), 6.79‒6.77 (m, 1H), 5.36 (hept, J = 6.2 Hz, 1H), 1.38 (d, J = 6.3 Hz, 6H);13C NMR (100 MHz, CDCl3) δ 164.0 (C), 145.6 (CH), 142.8 (C), 137.3 (CH), 132.9 (CH), 127.7 (C), 127.2 (CH), 119.0 (C), 112.1 (CH), 111.0 (C), 68.8 (CH), 22.2 (CH3); HRMS (ESI+ / TOF- Q) m / z: [M+H]+calcd for C15H15N2O, 239.11789; found, 239.1178. Methyl 3-(3-(3'-fluoro-4'-isopropoxy-[1,1'-biphenyl]-4-yl)-5-(quinoxalin-6-yl)-1H-1,2,4- triazol-1-yl)benzoate To a suspension of ethyl 3'-fluoro-4'-isopropoxy-[1,1'-biphenyl]-4-carbimidate hydrochloride (303 mg, 0.898 mmol) and Et3N (0.74 mL, 1.9 mmol) in THF (5 mL) was added quinoxaline- 6-carbonyl chloride (0.367 mg, 1.91 mmol) in a single portion. The reaction mixture was heated in a microwave at 100 °C for 15 min then cooled to RT. Methyl 3-hydrazineylbenzoate hydrochloride (0.363 mg, 1.80 mmol) was then added and the reaction mixture heated in a microwave at 100 °C for a further 30 min. The reaction mixture was diluted with EtOAc (150 mL), washed with H2O (50 mL), brine (3 × 100 mL) then dried over anhydrous Na2SO4, filtered and concentrated in vacuo onto Celite®. The crude residue was purified by flash column chromatography (0 → 40% EtOAc in Pet. Ether) then recrystallised from MeOH to afford methyl 3-(3-(3'-fluoro-4'-isopropoxy-[1,1'-biphenyl]-4-yl)-5-(quinoxalin-6-yl)-1H-1,2,4- triazol-1-yl)benzoate (25.9 mg, 5%) as an amorphous pale yellow solid.1H NMR (400 MHz, CDCl3) δ 8.88‒8.86 (m, 2H), 8.31 (d, J = 8.4 Hz, 2H), 8.28 (d, J = 1.8 Hz, 1H), 8.24‒8.23 (m, 1H), 8.17‒8.13 (m, 2H), 8.05 (dd, J = 8.8, 1.9 Hz, 1H), 7.67 (d, J = 8.4 Hz, 2H), 7.63‒7.60 (m, 1H), 7.53 (t, J = 7.9 Hz, 1H), 7.41 (dd, J = 12.4, 2.2 Hz, 1H), 7.38‒7.35 (m, 1H), 7.06 (app t, J = 8.5 Hz, 1H), 4.60 (hept, J = 6.1 Hz, 1H), 3.90 (s, 3H), 1.40 (d, J = 6.0 Hz, 6H);13C NMR (100 MHz, CDCl3) δ 165.7 (C), 162.4 (C), 154.0 (C, d, J = 245.6 Hz), 153.8 (C), 146.3 (CH), 146.1 (CH), 145.6 (C, d, J = 10.8 Hz), 143.5 (C), 142.6 (C), 141.1 (C), 138.4 (C), 134.2 (C, d, J = 6.6 Hz), 132.2 (C), 130.5 (CH), 130.4 (CH), 130.1 (CH), 129.9 (CH), 129.8 (CH), 129.4 (C), 129.3 (C), 127.3 (CH), 127.0 (CH), 126.8 (CH), 122.7 (CH, d, J = 2.9 Hz), 118.0 (CH, d, J = 2.2 Hz), 115.1 (CH, d, J = 19.8 Hz), 72.6 (CH), 52.6 (CH3), 22.2 (CH3); HRMS (ESI+ / TOF- Q) m / z: [M+H]+calcd for C33H27FN5O3, 560.2092; found, 560.2089. Ethyl 3'-fluoro-4'-isopropoxy-[1,1'-biphenyl]-4-carbimidate hydrochloride To a stirred solution of 3'-fluoro-4'-isopropoxy-[1,1'-biphenyl]-4-carbonitrile (0.480 g, 1.88 mmol) in EtOH (3.5 mL) at 0 °C was added AcCl (2.3 mL, 32.5 mmol) dropwise. The mixture was warmed to RT and stirred for 17 h then concentrated in vacuo to afford ethyl 3'-fluoro-4'- isopropoxy-[1,1'-biphenyl]-4-carbimidate hydrochloride (0.553 g, 87%) as an amorphous pale orange solid, which was used in the next step without further purification.1H NMR (400 MHz, CDCl3) δ 12.58 (br s, 1H), 11.88 (br s, 1H), 8.46 (d, J = 8.4 Hz, 2H), 7.72 (d, J = 8.3 Hz, 2H), 7.38‒7.32 (m, 2H), 7.07 (app t, J = 8.4 Hz, 1H), 4.99‒4.94 (m, 2H), 4.62 (hept, J = 6.2 Hz, 1H), 1.66‒1.62 (m, 3H), 1.40 (d, J = 6.0 Hz, 6H);13C NMR (100 MHz, CDCl3) δ 170.7 (C), 153.9 (C, d, J = 246.6 Hz), 146.9 (C), 146.8 (C, d, J = 11.0 Hz), 132.2 (C, d, J = 6.6 Hz), 130.5 (CH), 127.3 (CH), 123.8 (C), 123.3 (CH, d, J = 3.7 Hz), 117.6 (CH, d, J = 2.2 Hz), 115.4 (CH, d, J = 20.1 Hz), 72.5 (CH), 71.4 (CH2), 22.2 (CH3), 14.0 (CH3); HRMS (ESI / TOF-Q) m / z: molecular ion not observed. 3'-Fluoro-4'-isopropoxy-[1,1'-biphenyl]-4-carbonitrile To a stirred suspension of 4-bromobenzonitrile (0.380 g, 2.09 mmol), (3-fluoro-4- isopropoxyphenyl)boronic acid (0.447 g, 2.26 mmol) and K3PO4 (0.923 g, 4.35 mmol) in a mixture of DMF-H2O (22 mL, 1:1 v / v) was added Pd(OAc)2(56 mg, 0.249 mmol) in a single portion. The reaction was stirred at RT for 5 d then diluted with H2O (20 mL) and extracted with EtOAc (20 mL). The combined organic extracts were washed with H2O (20 mL) and brine (5 × 20 mL) then dried over anhydrous Na2SO4, filtered and concentrated in vacuo onto Celite®. The crude residue was purified by flash column chromatography (5% EtOAc in Pet. Ether) to afford 3'-fluoro-4'-isopropoxy-[1,1'-biphenyl]-4-carbonitrile (0.489 g, 92 %) as an amorphous white solid.1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 8.7 Hz, 2H), 7.62 (d, J = 8.7 Hz, 2H), 7.33 (dd, J = 12.1, 2.3 Hz, 1H), 7.32‒7.28 (m, 1H), 7.06 (app t, J = 8.5 Hz, 1H), 4.62 (hept, J = 6.07 Hz, 1H), 1.40 (d, J = 6.03 Hz, 6H);13C NMR (100 MHz, CDCl3) δ 153.9 (C, d, J = 246.8 Hz), 146.6 (C, d, J = 10.6 Hz), 144.3 (C), 132.8 (CH), 132.4 (C, d, J = 6.7 Hz), 127.3 (CH), 123.1 (CH, d, J = 3.2 Hz), 119.0 (C), 117.7 (CH, d, J = 2.2 Hz), 115.3 (CH, d, J = 20.0 Hz), 110.9 (C), 72.6 (CH), 22.2 (CH3); HRMS (ESI+ / TOF-Q) m / z: [M+H]+calcd for C16H15FNO, 256.1132; found, 256.1133. 4'-(Trifluoromethoxy)-[1,1'-biphenyl]-4-carbonitrile To a stirred suspension of 4-bromobenzonitrile (1.510 g, 8.29 mmol), 4- (trifluoromethoxy)phenylboronic acid (1.72 g, 8.35 mmol) and K3PO4 (3.70 g, 17.4 mmol) in a mixture of DMF-H2O (80 mL, 1:1 v / v) was added Pd(OAc)2(190 mg, 0.847 mmol) in a single portion. The reaction was stirred at RT for 90 min then diluted with H2O (200 mL) and extracted with Et2O (200 mL). The combined organic extracts were washed with H2O (2 × 100 mL) and brine (2 × 100 mL) then dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford 4'-(trifluoromethoxy)-[1,1'-biphenyl]-4-carbonitrile (2.10 g, 96 %) as an amorphous grey solid.1H NMR (400 MHz, CDCl3) δ 7.76‒7.75 (m, 2H), 7.67‒7.65 (m, 2H), 7.62‒7.60 (m, 2H), 7.35‒7.32 (m, 2H);13C NMR (100 MHz, CDCl3) δ 149.8 (C), 144.4 (C), 138.0 (C), 132.9 (CH), 128.9 (CH), 127.9 (CH), 121.7 (CH), 118.8 (C), 111.6 (C). HRMS (ESI+ / TOF-Q) m / z: [M+Na]+calcd for C14H8F3NONa, 286.04502; found, 286.0450. Methyl 3-(3-(4'-isopropyl-[1,1'-biphenyl]-4-yl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1- yl)benzoate To a stirred solution of 3',5'-bis(trifluoromethyl)-[1,1'-biphenyl]-4-carbonitrile (0.739 g, 2.34 mmol) in EtOH (4.5 mL) at 0 °C was added AcCl (3.1 mL, 43.6 mmol) dropwise. The mixture was warmed to RT and stirred for 2 d then concentrated in vacuo to afford ethyl 4'-isopropyl- [1,1'-biphenyl]-4-carbimidate hydrochloride (0.890 g, 95%) as an amorphous brown solid, which was used in the next step without further purification.1H NMR (400 MHz DMSO-d6) δ 8.16 (d, J = 8.7 Hz, 2H), 7.95 (d, J = 8.7 Hz, 2H), 7.73 (d, J = 8.3 Hz, 2H), 7.40 (d, J = 8.3 Hz, 2H), 4.63 (q, J = 7.0 Hz, 2H), 2.96 (hept, J = 6.6 Hz, 1H), 1.51 (t, J = 7.0 Hz, 3H), 1.24 (d, J = 6.9 Hz, 6H). To a suspension of ethyl 4'-isopropyl-[1,1'-biphenyl]-4-carbimidate hydrochloride (307 mg, 1.01 mmol) and Et3N (0.83 mL, 6.0 mmol) in THF (5 mL) was added quinoxaline-6- carbonyl chloride (370 mg, 1.92 mmol) in a single portion. The reaction mixture was heated in a microwave at 100 °C for 15 min then cooled to RT. Methyl 3-hydrazineylbenzoate hydrochloride (399 mg, 1.97 mmol) was then added and the reaction mixture was heated in a microwave at 100 °C for a further 30 min. The reaction mixture was diluted with EtOAc (30 mL), washed with H2O (15 mL), then dried over anhydrous Na2SO4, filtered and concentrated in vacuo onto Celite®. The crude residue was purified by flash column chromatography (0 → 40% EtOAc in Pet. Ether) then recrystallised from MeOH to afford methyl 3-(3-(4'-isopropyl- [1,1'-biphenyl]-4-yl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)benzoate (0.261 g, 49%) as an amorphous off-white solid.1H NMR (400 MHz, CDCl3) δ 8.89‒8.87 (m, 2H), 8.32 (d, J = 8.3 Hz, 2H), 8.28 (d, J = 1.8 Hz, 1H), 8.25‒8.24 (m, 1H), 8.17‒8.14 (m, 2H), 8.07‒8.05 (m, 1H), 7.73 (d, J = 8.3 Hz, 2H), 7.64‒7.61 (m, 3H), 7.54 (t, J = 7.8 Hz, 1H), 7.34 (d, J = 8.2 Hz, 2H), 3.91 (s, 3H), 2.98 (hept, J = 6.9 Hz, 1H), 1.31 (d, J = 7.0 Hz, 6H);13C NMR (100 MHz, CDCl3) δ 165.7 (C), 162.6 (C), 153.8 (C), 148.6 (C), 146.3 (CH), 146.1 (CH), 143.5 (C), 142.6 (C), 142.5 (C), 138.5 (C), 138.2 (C), 132.2 (C), 130.5 (CH), 130.4 (CH), 130.2 (CH), 129.9 (CH), 129.8 (CH), 129.5 (C), 129.1 (C), 127.4 (CH), 127.21 (CH), 127.17 (CH), 127.1 (CH), 126.8 (CH), 52.7 (CH3), 34.0 (CH), 24.1 (CH3); HRMS (ESI+ / TOF-Q) m / z: [M+H]+calcd for C33H28N5O2, 526.2238; found, 526.2234. 4'-Isopropyl-[1,1'-biphenyl]-4-carbonitrile To a stirred suspension of 4-bromobenzonitrile (1.07 g, 5.88 mmol), (4- isopropylphenyl)boronic acid (0.918 g, 5.60 mmol) and K3PO4 (2.50 g, 11.8 mmol) in a mixture of DMF-H2O (60 mL, 1:1 v / v) was added Pd(OAc)2(14.3 mg, 0.64 mmol) in a single portion. The reaction was stirred at RT for 3 h then diluted with H2O (100 mL) and extracted with Et2O (100 mL). The combined organic extracts were washed with H2O (2 × 50 mL) and brine (2 × 50 mL) then dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford 4'-isopropyl-[1,1'-biphenyl]-4-carbonitrile (1.30 g, 74 %) as an amorphous grey solid.1H NMR (400 MHz, CDCl3) δ 7.72‒7.65 (m, 4H), 7.55‒7.51 (m, 2H), 7.36‒7.33 (m, 2H), 2.98 (hept, J = 6.9 Hz, 1H), 1.30 (d, J = 6.9 Hz, 6H);13C NMR (100 MHz, CDCl3) δ 149.8 (C), 145.8 (C), 136.8 (C), 132.7 (CH), 127.6 (CH), 127.4 (CH), 127.3 (CH), 119.2 (C), 110.7 (C), 34.0 (CH), 24.1 (CH3); HRMS (ESI+ / TOF-Q) m / z: [M+Na]+calcd for C16H15NNa, 244.10967; found, 244.1096. Methyl 3-(3-(3',5'-bis(trifluoromethyl)-[1,1'-biphenyl]-4-yl)-5-(quinoxalin-6-yl)-1H- 1,2,4-triazol-1-yl)benzoate To a stirred solution of 3',5'-bis(trifluoromethyl)-[1,1'-biphenyl]-4-carbonitrile (0.739 g, 2.34 mmol) in EtOH (4.5 mL) at 0 °C was added AcCl (3.1 mL, 43.6 mmol) dropwise. The mixture was warmed to RT and stirred for 2 d then concentrated in vacuo to afford ethyl 3',5'- bis(trifluoromethyl)-[1,1'-biphenyl]-4-carbimidate hydrochloride (0.890 g, 95%) as an amorphous brown solid, which was used in the next step without further purification. To a suspension of ethyl 3',5'-bis(trifluoromethyl)-[1,1'-biphenyl]-4-carbimidate hydrochloride (316 mg, 0.794 mmol) and Et3N (0.60 mL, 4.30 mmol) in THF (4 mL) was added quinoxaline- 6-carbonyl chloride (322 mg, 1.67 mmol) in a single portion. The reaction mixture was heated in a microwave at 100 °C for 15 min then cooled to RT. Methyl 3-hydrazineylbenzoate hydrochloride (307 mg, 1.51 mmol) was then added and the reaction mixture was heated in a microwave at 100 °C for a further 30 min. The reaction mixture was diluted with EtOAc (20 mL), washed with 0.1 M aq. HCl (10 mL), then dried over anhydrous Na2SO4, filtered and concentrated in vacuo onto Celite®. The crude residue was purified by flash column chromatography (0 → 40% EtOAc in Pet. Ether) then recrystallised from MeOH to afford methyl 3-(3-(3',5'-bis(trifluoromethyl)-[1,1'-biphenyl]-4-yl)-5-(quinoxalin-6-yl)-1H-1,2,4- triazol-1-yl)benzoate (49.2 mg, 10%) as an amorphous off-white solid.1H NMR (500 MHz, CDCl3) δ 8.91‒8.88 (m, 2H), 8.42 (d, J = 8.4 Hz, 2H), 8.30 (d, J = 1.9 Hz, 1H), 8.26‒8.25 (m, 1H), 8.19‒8.15 (m, 2H), 8.10 (br s, 2H), 8.06 (dd, J = 8.6, 1.9 Hz, 1H), 7.89 (br s, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.64‒7.62 (m, 1H), 7.56 (t, J = 7.9 Hz, 1H), 3.92 (s, 3H);13C NMR (125 MHz, CDCl3) δ 165.7 (C), 162.0 (C), 154.0 (C), 146.4 (CH), 146.2 (CH), 143.6 (C), 142.9 (C), 142.6 (C), 139.4 (C), 138.4 (C) 132.4 (C, q, J = 33.4), 132.3 (C), 131.1 (C), 130.7 (CH), 130.6 (CH), 130.5 (CH), 130.1 (CH), 130.0 (CH), 129.8 (CH), 129.3 (C), 127.7 (CH), 127.7 (CH), 127.3 (CH), 126.8 (CH), 123.5 (C, q, J = 272.5 Hz) 121.3 (CH, pent, J = 4.1 Hz), 52.7 (CH3); HRMS (ESI+ / TOF-Q) m / z: [M+H]+calcd for C32H20F6N5O2, 620.1515; found, 620.1512. 3',5'-Bis(trifluoromethyl)-[1,1'-biphenyl]-4-carbonitrile To a stirred suspension of 1-bromo-3,5-bis(trifluoromethyl)benzene (1.17 mL, 6.83 mmol), 4- cyanophenylboronic acid (1.05 g, 7.17 mmol) and K3PO4(2.90 g, 13.7 mmol) in a mixture of DMF-H2O (70 mL, 1:1 v / v) was added Pd(OAc)2 (17.9 mg, 0.80 mmol) in a single portion. The reaction was stirred at RT for 80 min then diluted with H2O (70 mL) and extracted with Et2O / EtOAc (2 × 100 mL, 1:1 v / v). The combined organic extracts were washed with H2O (100 mL) and brine (2 × 100 mL) then dried over anhydrous Na2SO4, filtered and concentrated in vacuo afforded 3',5'-bis(trifluoromethyl)-[1,1'-biphenyl]-4-carbonitrile (0.958 g, 45 %) as an amorphous brown solid.1H NMR (400 MHz, CDCl3) δ 8.02 (br s, 2H), 7.94 (br s, 1H), 7.83‒ 7.72 (m, 4H);13C NMR (100 MHz, CDCl3) δ 142.6 (C), 141.5 (C), 133.2 (CH), 132.8 (C, q, J = 33.5 Hz), 128.2 (CH), 127.5 (CH, q, J = 3.6 Hz), 123.2 (C, q, J = 272.9 Hz), 122.4 (CH, pent, J = 3.7 Hz), 118.4 (C), 113.0 (C); HRMS (ESI / TOF-Q) m / z: molecular ion not observed. Methyl 3-(3-(4'-(pyrrolidin-1-yl)-[1,1'-biphenyl]-4-yl)-5-(quinoxalin-6-yl)-1H-1,2,4- triazol-1-yl)benzoate To a suspension of ethyl 4'-(pyrrolidin-1-yl)-[1,1'-biphenyl]-4-carbimidate (199 mg, 0.677 mmol) and Et3N (0.56 mL, 4.0 mmol) in THF (3.4 mL) was added quinoxaline-6-carbonyl chloride (286 mg, 1.49 mmol) in a single portion. The reaction mixture was heated in a microwave at 100 °C for 15 min then cooled to RT. Methyl 3-hydrazineylbenzoate hydrochloride (266 mg, 1.31 mmol) was then added and the reaction mixture was heated in a microwave at 100 °C for a further 30 min. The reaction mixture was diluted with EtOAc (200 mL), washed with H2O (50 mL), brine (3 × 100 mL) then dried over anhydrous Na2SO4, filtered and concentrated in vacuo onto Celite®. The crude residue was purified by flash column chromatography (0 → 40% EtOAc in Pet. Ether) then recrystallised from MeOH to afford methyl 3-(3-(4'-(pyrrolidin-1-yl)-[1,1'-biphenyl]-4-yl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1- yl)benzoate (43.7 mg, 12%) as a yellow solid.1H NMR (400 MHz, CDCl3) δ 8.89‒8.86 (m, 2H), 8.29‒8.24 (m, 4H), 8.16‒8.13 (m, 2H), 8.07‒8.05 (m, 1H), 7.70 (d, J = 8.4 Hz, 2H), 7.64‒ 7.58 (m, 3H), 7.53 (t, J = 7.9 Hz, 1H), 6.66 (d, J = 8.7 Hz, 2H), 3.90 (s, 3H), 3.37‒3.34 (m, 4H), 2.05‒2.02 (m, 4H);13C NMR (100 MHz, CDCl3) δ 165.8 (C), 162.8 (C), 153.7 (C), 147.8 (C), 146.2 (CH), 146.1 (CH), 143.5 (C), 142.9 (C), 142.6 (C), 138.5 (C), 132.2 (C), 130.5 (CH), 130.43 (CH), 130.38 (CH), 130.2 (CH), 129.91 (CH), 129.85 (CH), 129.6 (C), 127.9 (CH), 127.7 (C), 127.4 (C), 127.2 (CH), 126.8 (CH), 126.3 (CH), 112.1 (CH), 52.6 (CH3), 47.8 (CH2), 25.6 (CH2); HRMS (ESI / TOF-Q) m / z: molecular ion not observed. Ethyl 4'-(pyrrolidin-1-yl)-[1,1'-biphenyl]-4-carbimidate To a stirred solution of 4'-(pyrrolidin-1-yl)-[1,1'-biphenyl]-4-carbonitrile (0.739 g, 2.34 mmol) in EtOH (4.5 mL) at 0 °C was added AcCl (3.1 mL, 43.6 mmol) dropwise. The mixture was warmed to RT and stirred for 2 d then concentrated in vacuo. The crude residue was diluted with EtOAc (25 mL) and washed with sat. aq. NaHCO3 (25 mL), then concentrated in vacuo to afford crude ethyl 4'-(pyrrolidin-1-yl)-[1,1'-biphenyl]-4-carbimidate, which was used in the next step without further purification.1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.2 Hz, 2H), 7.59 (d, J = 8.4 Hz, 2H), 7.52 (d, J = 8.8 Hz, 2H), 6.64 (d, J = 8.7 Hz, 2H), 4.34 (q, J = 7.0 Hz, 2H), 3.36‒3.32 (m, 4H), 2.06‒2.00 (m, 4H), 1.44 (t, J = 7.0 Hz, 3H); HRMS (ESI+ / TOF-Q) m / z: [M+H]+calcd for C19H23N2O, 295.1805; found, 295.1802. 4'-(Pyrrolidin-1-yl)-[1,1'-biphenyl]-4-carbonitrile A stirred solution of 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrrolidine (1.02 g, 3.74 mmol), 4-bromobenzonitrile (0.688 g, 3.78 mmol) and PdCl(dppf)·CH2Cl2 (0.137 g, 0.187 mmol) in 1,4-dioxane (37 mL) was degassed with N2for 10 min, followed by the quick addition of 2 M aq. K3PO4 (5.5 mL). The resultant mixture was heated to 50 °C and stirred for 20 h. The reaction mixture was then allowed to cool to RT, diluted with EtOAc (80 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude residue was purified by flash column chromatography (5% EtOAc in Pet. Ether) to afford 4'-(pyrrolidin-1-yl)-[1,1'- biphenyl]-4-carbonitrile (833 mg, 90%) as a brown solid.1H NMR (400 MHz, CDCl3) δ 7.66‒ 7.61 (m, 4H), 7.51 (d, J = 8.7 Hz, 2H), 6.64 (d, J = 8.8 Hz, 2H), 3.36‒3.33 (m, 4H), 2.06‒2.02 (m, 4H);13C NMR (100 MHz, CDCl3) δ 148.4 (C), 146.0 (C), 132.6 (CH), 128.1 (CH), 126.3 (CH), 125.6 (C), 119.7 (C), 112.2 (CH), 108.8 (C), 47.8 (CH2), 25.6 (CH2); HRMS (ESI+ / TOF- Q) m / z: [M+H]+calcd for C17H17N2, 249.1386; found, 249.1385. Methyl 3-(3-(4'-isopropoxy-[1,1'-biphenyl]-4-yl)-5-(pyrazin-2-yl)-1H-1,2,4-triazol-1- yl)benzoate To a suspension of ethyl 4'-isopropoxy-[1,1'-biphenyl]-4-carbimidate hydrochloride (200 mg, 0.624 mmol) and Et3N (696 µL, 4.99 mmol) in anhydrous THF (8 mL) was added pyrazine-2- carbonyl chloride (178 mg, 1.25 mmol) in a single portion. The reaction mixture was heated in a microwave at 100 °C for 15 min then cooled to RT. Methyl 3-hydrazinobenzoate hydrochloride (253 mg, 1.25 mmol) was then added and the reaction mixture was heated in a microwave at 100 °C for a further 30 min. The reaction mixture was diluted with EtOAc (100 mL), washed with H2O (3 × 30 mL) and brine (30 mL), then dried over anhydrous Na2SO4, filtered and concentrated in vacuo onto Celite®. The crude residue was purified by automated silica gel column chromatography (25 → 50% EtOAc in Pet. Ether) to afford methyl 3-(3-(4'- isopropoxy-[1,1'-biphenyl]-4-yl)-5-(pyrazin-2-yl)-1H-1,2,4-triazol-1-yl)benzoate (137 mg, 45%) as an amorphous off-white solid.1H NMR (400 MHz, CDCl3) δ 9.44 (d, J = 1.5 Hz, 1H), 8.60 (d, J = 2.5 Hz, 1H), 8.39 (dd, J = 2.5, 1.5 Hz, 1H), 8.29 (d, J = 8.6 Hz, 2H), 8.18 – 8.13 (m, 2H), 7.72 – 7.67 (m, 3H), 7.62 – 7.51 (m, 3H), 6.98 (d, J = 8.7 Hz, 2H), 4.61 (hept, J = 6.0 Hz, 1H), 3.93 (s, 3H), 1.38 (d, J = 6.0 Hz, 6H);13C NMR (101 MHz, CDCl3) δ 166.04, 162.47, 157.94, 151.07, 145.38, 143.46, 143.35, 142.34, 139.09, 132.92, 131.39, 130.36, 130.21, 129.22, 128.49, 128.28, 127.21, 126.99, 116.32, 70.13, 52.58, 22.23; HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C29H26N5O3492.2030; found 492.2029. Methyl 3-(5-(benzo[c][1,2,5]oxadiazol-5-yl)-3-(4'-isopropoxy-[1,1'-biphenyl]-4-yl)-1H- 1,2,4-triazol-1-yl)benzoate To a suspension of ethyl 4'-isopropoxy-[1,1'-biphenyl]-4-carbimidate hydrochloride (250 mg, 0.78 mmol) and Et3N (652 µL, 4.68 mmol) in anhydrous THF (5 mL) was added 2,1,3- benzoxadiazole-5-carbonyl chloride (284 mg, 1.56 mmol) in a single portion. The reaction mixture was heated in a microwave at 100 °C for 15 min then cooled to RT. Methyl 3- hydrazinobenzoate hydrochloride (372 mg, 1.56 mmol) was then added and the reaction mixture was heated in a microwave at 100 °C for a further 30 min. The reaction mixture was diluted with EtOAc (100 mL), washed with H2O (3 × 30 mL) and brine (30 mL), then dried over anhydrous Na2SO4, filtered and concentrated in vacuo onto Celite®. The crude residue was purified by automated silica gel column chromatography (10 → 30% EtOAc in Pet. Ether) followed by trituration with MeOH to afford methyl 3-(5-(benzo[c][1,2,5]oxadiazol-5-yl)-3- (4'-isopropoxy-[1,1'-biphenyl]-4-yl)-1H-1,2,4-triazol-1-yl)benzoate (90 mg, 22%) as an orange foam.1H NMR (400 MHz, CDCl3) δ 8.27 (d, J = 8.6 Hz, 2H), 8.23 – 8.18 (m, 2H), 8.00 (t, J = 1.3 Hz, 1H), 7.90 (dd, J = 9.4, 1.1 Hz, 1H), 7.77 (dd, J = 9.4, 1.4 Hz, 1H), 7.70 (d, J = 8.4 Hz, 2H), 7.68 – 7.64 (m, 1H), 7.63 – 7.56 (m, 3H), 6.99 (d, J = 8.8 Hz, 2H), 4.62 (hept, J = 6.0 Hz, 1H), 3.93 (s, 3H), 1.38 (d, J = 6.1 Hz, 6H);13C NMR (101 MHz, CDCl3) δ 165.57, 162.72, 157.99, 152.60, 148.85, 148.71, 142.49, 138.18, 132.83, 132.45, 131.97, 131.06, 130.85, 130.25, 129.71, 128.29, 127.20, 127.03, 126.71, 117.53, 117.49, 116.33, 70.15, 52.77, 22.23; HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C31H26N5O4532.1979; found 532.1977. Ethyl 3-(5-(4-chlorophenyl)-3-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)benzoate To a solution of methyl quinoxaline-6-carbimidate (130 mg) in DCM (5 mL) at 0 °C was added triethylamine (0.28 mL, 2.0 mmol), followed by a solution of 4-chlorobenzoyl chloride (175 mg, 1.0 mmol) in DCM (1 mL). The reaction mixture was then allowed to warm to RT and stirred for a further 5 h. Et3N (0.14 mL, 1.0 mmol) and ethyl 3-hydrazinobenzoate hydrochloride (216 mg, 1.0 mmol) were then added sequentially and the reaction mixture was stirred at RT overnight. The mixture was then diluted with DCM (20 mL) and washed with H2O (20 mL). The aqueous layer was further extracted with DCM (2 × 20 mL) and the combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash column chromatography (25% EtOAc in Pet. Ether) afforded ethyl 3-(5-(4-chlorophenyl)-3-(quinoxalin-6-yl)-1H-1,2,4-triazol-1-yl)benzoate (30 mg, 7% over 3 steps from quinoxaline-6-carbonitrile) as a light-yellow solid.1H NMR (400 MHz, CDCl3) δ 8.98 – 8.96 (m, 1H), 8.89 – 8.85 (m, 2H), 8.63 (dd, J = 8.8, 1.8 Hz, 1H), 8.22 – 8.13 (m, 3H), 7.61 – 7.51 (m, 4H), 7.38 (d, J = 8.7 Hz, 2H), 4.39 (q, J = 7.2 Hz, 2H), 1.39 (t, J = 7.2 Hz, 2H). Methyl quinoxaline-6-carbimidate To a solution of quinoxaline-6-carbonitrile (155 mg, 1.0 mmol) in MeOH (3 mL) at RT was carefully added portion-wise sodium methoxide (54 mg, 1.0 mmol). The mixture was stirred at RT for a further 72 hours, then diluted with DCM (20 mL) and washed with H2O. The aqueous layer was further extracted with DCM (2 × 20 mL) and the combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford methyl quinoxaline-6-carbimidate (130 mg, 70%) as a purple solid, which was used in the next step without further purification.1H NMR (400 MHz, CDCl3) δ 8.90 – 8.88 (m, 2H), 8.18 – 8.04 (m, 3H), 4.04 (s, 3H). 2,2,2-Trifluoro-1-(p-tolyl)ethyl 4-(3-(4-chlorophenyl)-5-(quinoxalin-6-yl)-1H-1,2,4- triazol-1-yl)benzenesulfonate To a solution of ethyl 4-chlorobenzimidate (100 mg, 0.54 mmol) and Et3N (627 µL, 4.35 mmol) in anhydrous THF (5 mL) was added quinoxaline-6-carbonyl chloride (208 mg, 1.08 mmol) in a single portion. The reaction mixture was heated in a microwave at 100 °C for 15 min then cooled to RT. 2,2,2-Trifluoro-1-(p-tolyl)ethyl 4-hydrazineylbenzenesulfonate (389 mg, 1.08 mmol) was then added and the reaction mixture was heated in a microwave at 100 °C for a further 30 min. The reaction mixture was diluted with EtOAc (100 mL), washed with H2O (3 × 30 mL) and brine (30 mL), then dried over anhydrous Na2SO4, filtered and concentrated in vacuo onto Celite®. The crude residue was purified by automated silica gel column chromatography (10 → 40% EtOAc in Pet. Ether) followed by trituration with MeOH to afford 2,2,2-trifluoro-1-(p-tolyl)ethyl 4-(3-(4-chlorophenyl)-5-(quinoxalin-6-yl)-1H-1,2,4-triazol-1- yl)benzenesulfonate (62 mg, 18%) as an amorphous off-white solid.1H NMR (400 MHz, CDCl3) δ 8.94 (d, J = 1.8 Hz, 1H), 8.92 (d, J = 1.8 Hz, 1H), 8.30 (d, J = 1.9 Hz, 1H), 8.24 – 8.15 (m, 3H), 7.89 (dd, J = 8.7, 2.0 Hz, 1H), 7.82 (d, J = 8.6 Hz, 2H), 7.53 (d, J = 8.6 Hz, 2H), 7.49 (d, J = 8.6 Hz, 2H), 7.25 (d, J = 8.3 Hz, 2H), 7.17 (d, J = 8.3 Hz, 2H), 5.70 (q, J = 6.3 Hz, 1H), 2.34 (s, 3H);13C NMR (101 MHz, CDCl3) δ 162.32, 154.19, 146.67, 146.41, 143.70, 142.70, 142.25, 141.13, 136.61, 136.24, 130.90, 130.80, 129.77, 129.71, 129.55, 129.21, 129.01, 128.60, 128.29, 128.16, 126.39, 125.33, 79.12, 78.78, 31.06, 21.45;19F NMR (376 MHz, CDCl3) δ -75.91; HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C31H2235ClF3N5O332S 636.1078; found 636.1073. 2,2,2-Trifluoro-1-(p-tolyl)ethyl 4-hydrazineylbenzenesulfonate To a solution of 2,2,2-trifluoro-1-(p-tolyl)ethyl 4-fluorobenzenesulfonate (0.5 g, 1.43 mmol) in DMSO (2.5 mL) under argon was added hydrazine hydrate (558 µL, 11.5 mmol). The resulting mixture was heated to 50 °C and stirred for 2 h. The reaction mixture was then added dropwise to ice-cold H2O (50 mL) resulting in the formation of a crystalline white solid. The solid was collected by vacuum filtration and washed with H2O (3 × 10 mL) to afford 2,2,2- trifluoro-1-(p-tolyl)ethyl 4-hydrazineylbenzenesulfonate (460 mg, 89%) as a crystalline white solid.1H NMR (400 MHz, DMSO-d6) δ 7.92 (s, 1H), 7.50 (d, J = 9.3 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 7.18 (d, J = 7.9 Hz, 2H), 6.74 (d, J = 8.8 Hz, 2H), 6.08 (q, J = 6.7 Hz, 1H), 4.29 (s, 2H), 2.29 (s, 3H);13C NMR (101 MHz, DMSO-d6) δ 156.62, 139.58, 129.61, 129.06, 127.79, 127.50, 124.11, 118.38, 109.72, 75.80 (q, J = 32.9 Hz), 20.78;19F NMR (376 MHz, DMSO- d6) δ -75.34; HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C15H16F3N2O3361.0828; found 361.0828. 2,2,2-Trifluoro-1-(p-tolyl)ethyl 4-fluorobenzenesulfonate To a solution of 2,2,2-trifluoro-1-(p-tolyl)-ethan-1-ol (1 g, 5.26 mmol) and Et3N (1.47 mL, 10.52 mmol) in anhydrous DCM (10 mL) at 0 °C was added 4-fluorobenzenesulfonyl chloride (1.12 g, 5.78 mmol) in a single portion. The reaction was allowed to gradually warm to RT and stirred overnight. The reaction was then heated at reflux for 2 h and allowed to cool to RT. The reaction was then quenched with sat. aq. NaHCO3 (50 mL) and the resulting mixture was extracted with Et2O (4 × 20 mL). The combined organic extracts were washed with sat. aq. NaHCO3 (3 × 20 mL), 0.1 M aq. HCl (3 × 20 ml) and brine (20 mL) then dried over anhydrous Na2SO4, filtered and concentrated in vacuo onto Celite®. The crude residue was purified by automated silica gel column chromatography (0 → 5% EtOAc in Pet. Ether) to afford 2,2,2- trifluoro-1-(p-tolyl)ethyl 4-fluorobenzenesulfonate (1.52 g, 83%) as a crystalline white solid.1H NMR (400 MHz, CDCl3) δ 7.81 – 7.73 (m, 2H), 7.21 (d, J = 8.2 Hz, 2H), 7.15 – 7.04 (m, 4H), 5.66 (q, J = 6.3 Hz, 1H), 2.34 (s, 3H);13C NMR (101 MHz, CDCl3) δ 167.17, 164.61, 140.77, 132.32, 130.84, 130.74, 129.44, 128.10, 126.39, 123.62, 120.82, 116.55, 116.33, 78.53 (q, J = 34.5 Hz), 21.27;19F NMR (376 MHz, CDCl3) δ -76.07, -102.28; HRMS (ESI+ / Q-TOF) m / z: [M+Na]+calcd for C15H12F4O332S23Na 371.0335; found 371.0334. Methyl 3-(3-(4'-isopropoxy-[1,1'-biphenyl]-4-yl)-5-(quinoxalin-2-yl)-1H-1,2,4-triazol-1- yl)benzoate To a suspension of ethyl 4'-isopropoxy-[1,1'-biphenyl]-4-carbimidate hydrochloride (250 mg, 0.78 mmol) and Et3N (652 µL, 4.68 mmol) in anhydrous THF (5 mL) was added quinoxaline- 2-carbonyl chloride (225 mg, 1.17 mmol) in a single portion. The reaction mixture was heated in a microwave at 100 °C for 15 min then cooled to RT. Methyl 3-hydrazinobenzoate hydrochloride (279 mg, 1.17 mmol) was then added and the reaction mixture was heated in a microwave at 100 °C for a further 30 min. The reaction mixture was diluted with EtOAc (100 mL), washed with H2O (3 × 30 mL) and brine (30 mL), then dried over anhydrous Na2SO4, filtered and concentrated in vacuo onto Celite®. The crude residue was purified by automated silica gel column chromatography (10 → 40% EtOAc in Pet. Ether) followed by trituration with MeOH to afford methyl 3-(3-(4'-isopropoxy-[1,1'-biphenyl]-4-yl)-5-(quinoxalin-2-yl)- 1H-1,2,4-triazol-1-yl)benzoate (24 mg, 6%) as an amorphous yellow solid.1H NMR (500 MHz, CDCl3) δ 9.75 (s, 1H), 8.37 (t, J = 1.9 Hz, 1H), 8.34 (d, J = 8.3 Hz, 2H), 8.21 (dt, J = 8.0, 1.4 Hz, 1H), 8.14 (dd, J = 8.4, 1.3 Hz, 1H), 7.83 – 7.75 (m, 2H), 7.74 – 7.69 (m, 3H), 7.66 (dd, J = 8.4, 1.6 Hz, 1H), 7.63 – 7.54 (m, 3H), 6.99 (d, J = 8.7 Hz, 2H), 4.62 (hept, J = 6.1 Hz, 1H), 3.93 (s, 3H), 1.38 (d, J = 6.0 Hz, 6H);13C NMR (126 MHz, CDCl3) δ 166.16, 162.49, 157.93, 151.34, 145.17, 142.40, 142.34, 141.89, 140.92, 139.41, 132.92, 131.30, 131.16, 131.04, 130.79, 130.30, 129.80, 129.49, 128.94, 128.53, 128.30, 127.90, 127.25, 127.01, 116.31, 70.12, 52.56, 22.23; HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C33H28N5O3 542.2187; found 542.2186. Methyl 3-(3-(4-chlorophenyl)-5-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-1H-1,2,4-triazol-1- yl)benzoate To a suspension of ethyl 4-chlorobenzimidate hydrochloride (200 mg, 0.91 mmol) and Et3N (758 µL, 5.45 mmol) in anhydrous THF (5 mL) was added 2,2-difluoro-1,3-benzodioxole-4- carbonyl chloride (299 mg, 1.36 mmol) in a single portion. The reaction mixture was heated in a microwave at 100 °C for 15 min then cooled to RT. Methyl 3-hydrazinobenzoate hydrochloride (325 mg, 1.36 mmol) was then added and the reaction mixture was heated in a microwave at 100 °C for a further 30 min. The reaction mixture was diluted with EtOAc (100 mL), washed with H2O (3 × 30 mL) and brine (30 mL), then dried over anhydrous Na2SO4, filtered and concentrated in vacuo onto Celite®. The crude residue was purified by automated silica gel column chromatography (5 → 10% EtOAc in Pet. Ether) to afford methyl 3-(3-(4- chlorophenyl)-5-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-1H-1,2,4-triazol-1-yl)benzoate (60 mg, 14%) as an amorphous white solid.1H NMR (400 MHz, CDCl3) δ 8.18 – 8.13 (m, 4H), 7.58 – 7.54 (m, 2H), 7.45 (d, J = 8.6 Hz, 2H), 7.34 (d, J = 1.7 Hz, 1H), 7.24 (dd, J = 8.3, 1.7 Hz, 1H), 7.04 (d, J = 8.3 Hz, 1H), 3.94 (s, 3H);13C NMR (101 MHz, CDCl3) δ 165.58, 161.40, 153.69, 145.04, 143.98, 138.16, 135.72, 132.09, 130.32, 129.83, 129.57, 128.96, 128.84, 127.93, 126.53, 125.13, 123.62, 110.37, 109.77, 52.60; HRMS (ESI+ / Q-TOF) m / z: [M+H]+calcd for C23H1535ClF2N3O4470.0714; found 470.0711. In vitro studies The compounds of the present invention were initially screened for activity using an in vitro fully automated incubation system for the measurement of total gas production and gas composition (methane and hydrogen). The system used is described in detail in the paper by Muetzel et al. (2014; Animal Feed Science and Technology 196, 1-11). The system in this specification is referred to as the rumen in vitro system or RIV. The RIV system provides a relatively simple tool for determining the rate and production of methane and also whether the rate and production of methane is inhibited or reduced by a particular compound or feed. Rumen in vitro assay method. Rumen in vitro assays use rumen fluid from donor animals (typically either sheep or cattle) which is typically combined with a buffer and then incubated in sealed fermentation vessels at 39 °C for either 24 or 48 h. These assays systems have been well-characterised and used by the scientific community over the last two decades (Rymer et al.2005). The system that has been used here to characterise the effects of inhibitors on methane production and gas production, and the formation of H2, was described by Muetzel et al. (2014). Rumen in vitro assay systems reflect what can occur in the rumen in vivo, but only short-term, due to their short incubation times (typically not exceeding 48 h) which is limited by its buffering capacity and the fact that it is a closed system. Stock solutions of inhibitors were re-suspended in dimethylformamide (DMF) at concentrations 1000-fold higher than the highest used for the assays. Any further dilutions were also prepared using DMF. The total amount of inhibitor solution added to the rumen fluid- buffer mixture (60 mL) was 60 µl. Incubations used 60 ml of medium containing 12 ml of filtered rumen fluid and 48 ml of buffer in serum bottles for 24-48 h, essentially as described by Muetzel et al. (2014). Two fistulated cattle were used as donor animals for rumen fluid and treatments were incubated in duplicate bottles. Sets of duplicate incubation vials that contained ryegrass (with rumen fluid-buffer mixture), and ryegrass with 30 μM bromoethanesulfonate (BES) were also incubated as negative and positive controls, respectively. One experiment consists of 2 replicates of an inhibitor at any one concentration run at the same time, and a run can contain up to 32 bottle, including positive (30 µM BES) and negative (no inhibitor added) controls. Compound 1, for example, was tested using the 60 mL rumen in vitro assay system at 50 µM, 10 µM, and 2 µM final concentrations and compared to a positive control with 30 µM BES. At 30 µM, BES inhibition levels were 70.5% inhibition at 10 hours and 55.6% inhibition at 18 hours.

[0003]

[0004] In vivo trial methods The trial for testing the effects of Compound 7 on methane emissions from sheep over a 30- day period in methane measurement chambers was approved by the Grasslands Animal Ethics Committee. Five sheep were used for the Compound 7 treatment group. The animals received a general-purpose diet (GP) at 1.5 x maintenance energy requirements throughout the trials consisting of 500 g hay, 100 g soybean meal, 290 g barley, 100 g molasses, 6 g mineral mix and 5.5 g dicalcium phosphate dihydrate. During the time in the respiration chambers the animals had free access to water, with the feed offered twice a day at approximately 9:00 and 16:00 h in equal amounts. Feed refusals were weighed. The animals were adapted to GP diet for 14 days prior to entering the methane measurement chambers. Rumen contents were sampled by stomach tubing after being released from the respiration chambers, to allow for the future examination of any effects on volatile fatty acids (VFAs). Rumen samples from stomach tubing were immediately subsampled for short chain fatty acid (SCFA) analysis (1.8 ml). The samples were centrifuged (21,000 g, 10 min, 4 °C). An aliquot of 0.9 ml of the supernatant was collected into 0.1 ml of internal standard (20 mM ethylbutyrate in 20% w / v phosphoric acid) for SCFA analysis and stored at -20 °C. SCFA samples were thawed and centrifuged (21,000 g, 10 min, 4 °C) and 0.8 ml of the supernatant was collected into a crimp cap glass vial. GC vials were stored at 4 °C until analysis. From the remaining supernatant 0.2 ml was collected into 1.5 mL tubes (Eppendorf, Hamburg, Germany) for derivatised SCFA analysis. SCFA were analysed by a Shimadzu GC-2010 Plus gas chromatograph and AOC-6000 autosampler (Shimadzu Corporation, Kyoto, Japan). After the 14-day acclimatisation period, methane emissions were measured in open circuit respiration chambers as described in Chapter 1 of the technical manual on respiration chamber design (http: / / www.globalresearchalliance.org / wp-content / uploads / 2012 / 03 / GRA- MAN-Facility-BestPract-2012-ch13.pdf ). Dry matter intake (DMI, kg / d) was recorded during methane measurements from the weight difference of feed offered and refused. The first measurement period in the chambers (48 hours; Period 1) served as a control for each animal. After a week the sheep received Compound 7 initially at 36 mg per day (Period 2), which was increased to 110 mg / day (Period 3) and finally 330 mg / day (Periods 4-6). Results Methane gas outputs in open circuit respiration chambers were determined. Background methane emissions were measured over two days (Period 1). In the following week dosing started in the treatment group on the first day of a 4-day chamber period (Period 2). This was followed by weekly measurement periods (Periods 3-6, each 2 days). Methane inhibition during the dosing periods is summarised in Table 1. Table 1 Average methane inhibition (%) (Av ± SD) resulting from dosing Compound 7 in feed to sheep, twice daily. Methane yields (g CH4 / kg DMI) were compared to those from the same animals at the start of the trial (Period 1), prior to them receiving any inhibitor. Dose (mg / day) in each period is indicated. Methane inhibition is an average from all animals in the group. The present invention and its examples have been described in detail. However, the scope of the present invention is not intended to be limited to the particular examples of the invention described in the specification. Various modifications, substitutions, and variations can be made to the disclosed material without departing from the spirit and / or essential characteristics of the present invention. Accordingly, one of ordinary skill in the art will readily appreciate from the disclosure that later modifications, substitutions, and / or variations performing substantially the same function or achieving substantially the same result as examples described herein may be utilized according to such related examples of the present invention. Thus, the following claims are intended to encompass within their scope modifications, substitutions, and variations to the examples of the invention disclosed herein.

Claims

Claims1. A compound of Formula Iwherein R may be selected from:-C(=O)-C1-C6-C(=O)-OH, -C(=O)-C1-C6-C(=O)-O-C1-C6, -C(=O)-C1-C6-C(=O)-O-C1-C6-O-(C=O)-C1-C6, or-C(=O)-C1-C6-C(=O)-NH2, -C(=O)-C1-C6-C(=O)-NH-C1-C6, -C(=O)-C1-C6-C(=O)-NH-C3-C8-cycloalkyl, -C(=O)-C1-C6-C(=O)-N(C1-C6)2,wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or-C(=O)-C1-C6-C(=O)-NH-S(O)2-C1-C6, -C(=O)-C1-C6-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-aryl, C(=O)-C1-C6-C(=O)-NH-S(O)2-C1-C6-aryl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-heteroaryl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-C1-C6-heteroaryl, or-C(=O)-C1-C6-C(=O)-NH-S(O)2-NH2, -C(=O)-C1-C6-C(=O)-NH-S(O)2-NH-C1-C6, -C(=O)- C1-C6-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-NH-aryl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-NH- heteroaryl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-NH- C1-C6-heteroaryl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-,NC1-C6-, -S- or -O-; or-C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-C1-C6, -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-C3-C8- cycloalkyl, -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-aryl, -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2- heteroaryl, or-C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-NH2, -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-NH-C1-C6, -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-NH-aryl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or-C1-C6-C(=O)-OH, -C1-C6-C(=O)-O-C1-C6, .C1-C6-C(=O)-O-C1-C6-O-(C=O)-C1-C6, -C1-C6-OH, or-C1-C6-C(=O)-NH2, -C1-C6-C(=O)-NH-C1-C6, -C1-C6-C(=O)-NH-C3-C8-cycloalkyl, -C1-C6- C(=O)-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or-C1-C6-C(=O)-NH-S(O)2-C1-C6, -C1-C6-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -C1-C6-C(=O)-NH-S(O)2-aryl, -C1-C6-C(=O)-NH-S(O)2-C1-C6-aryl, -C1-C6-C(=O)-NH-S(O)2-heteroaryl, - C1-C6-C(=O)-NH-S(O)2-C1-C6-heteroaryl, or-C1-C6-C(=O)-NH-S(O)2-NH2, -C1-C6-C(=O)-NH-S(O)2-NH-C1-C6, -C1-C6-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C1-C6-C(=O)-NH-S(O)2-NH-aryl, -C1-C6-C(=O)-NH-S(O)2- NH-C1-C6-aryl, -C1-C6-C(=O)-NH-S(O)2-NH-heteroaryl, -C1-C6-C(=O)-NH-S(O)2-NH- C1-C6-heteroaryl, -C1-C6-C(=O)-NH-S(O)2-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or-C1-C6-NH-C(=O)-NH-S(O)2-C1-C6, -C1-C6-NH-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -C1-C6-NH-C(=O)-NH-S(O)2-aryl, -C1-C6-NH-C(=O)-NH-S(O)2-heteroaryl, or-C1-C6-NH-C(=O)-NH-S(O)2-NH2, -C1-C6-NH-C(=O)-NH-S(O)2-NH-C1-C6, -C1-C6-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C1-C6-NH-C(=O)-NH-S(O)2-NH-aryl, -C1-C6-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C1-C6-NH-C(=O)-NH-S(O)2-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or or-C(=O)-aryl-C(=O)-OH, -C(=O)-aryl-C(=O)-O-C1-C6, -C(=O)-aryl-C(=O)-O-C1-C6-O-(C=O)-C1-C6, -C(=O)-aryl-OH, or-C(=O)-aryl-C(=O)-NH2, -C(=O)-aryl-C(=O)-NH-C1-C6, -C(=O)-aryl-C(=O)-NH-C3-C8- 2 cycloalkyl, -C(=O)-aryl-C(=O)-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from - NH-, -NC1-C6-, -S- or -O-; or-C(=O)-aryl-C(=O)-NH-S(O)2-C1-C6, -C(=O)-aryl-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -C(=O)-aryl-C(=O)-NH-S(O)2-aryl, -C(=O)-aryl-C(=O)-NH-S(O)2-C1-C6-aryl, -C(=O)-aryl-C(=O)-NH-S(O)2-heteroaryl, -C(=O)-aryl-C(=O)-NH-S(O)2-C1-C6-heteroaryl, or-C(=O)-aryl-C(=O)-NH-S(O)2-NH2, -C(=O)-aryl-C(=O)-NH-S(O)2-NH-C1-C6, -C(=O)-aryl- C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C(=O)-aryl-C(=O)-NH-S(O)2-NH-aryl, -C(=O)- aryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C(=O)-aryl-C(=O)-NH-S(O)2-NH-heteroaryl,C(=O)-aryl-C(=O)-NH-S(O)2-NH-C1-C6-heteroaryl, -C(=O)-aryl-C(=O)-NH-S(O)2-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or-C(=O)-aryl-NH-C(=O)-NH-S(O)2-C1-C6, -C(=O)-aryl-NH-C(=O)-NH-S(O)2-C3-C8- cycloalkyl, -C(=O)-aryl-NH-C(=O)-NH-S(O)2-aryl, -C(=O)-aryl-NH-C(=O)-NH-S(O)2- heteroaryl, or-C(=O)-aryl-NH-C(=O)-NH-S(O)2-NH2, -C(=O)-aryl-NH-C(=O)-NH-S(O)2-NH-C1-C6, -C(=O)-aryl-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C(=O)-aryl-NH-C(=O)-NH-S(O)2-NH-aryl, -C(=O)-aryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C(=O)-aryl-NH-C(=O)-NH-S(O)2-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or or-aryl-C(=O)-OH, -aryl-C(=O)-O-C1-C6, -aryl-C(=O)-O-C1-C6-O-(C=O)-C1-C6, -aryl-C1-C6-OH, -aryl-C1-C6-(C=O)OH, or-aryl-C(=O)-NH2, -aryl-C(=O)-NH-C1-C6, -aryl-C(=O)-NH-C3-C8-cycloalkyl, -aryl-C(=O)-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or-aryl-C(=O)-NH-S(O)2-C1-C6, -aryl-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -aryl-C(=O)-NH- S(O)2-aryl, -aryl-C(=O)-NH-S(O)2-C1-C6-aryl, -aryl-C(=O)-NH-S(O)2-heteroaryl, -aryl- C(=O)-NH-S(O)2-C1-C6-heteroaryl, or-aryl-C(=O)-NH-S(O)2-NH2, -aryl-C(=O)-NH-S(O)2-NH-C1-C6, -aryl-C(=O)-NH-S(O)2-NH- C3-C8-cycloalkyl, -aryl-C(=O)-NH-S(O)2-NH-aryl, -aryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, - aryl-C(=O)-NH-S(O)2-NH-heteroaryl, -aryl-C(=O)-NH-S(O)2-NH-C1-C6-heteroaryl, -aryl-C(=O)-NH-S(O)2-N(C1-C6)2wherein J is a 5 or 6membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or-aryl-NH-C(=O)-NH-S(O)2-C1-C6, -aryl-NH-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -aryl-NH-C(=O)-NH-S(O)2-aryl, -aryl-NH-C(=O)-NH-S(O)2-heteroaryl, or-aryl-NH-C(=O)-NH-S(O)2-NH2, -aryl-NH-C(=O)-NH-S(O)2-NH-C1-C6, -aryl-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -aryl-NH-C(=O)-NH-S(O)2-NH-aryl, -aryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -aryl-NH-C(=O)-NH-S(O)2-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or-aryl-S(O)2-OH, -aryl-S(O)2-NH2, -aryl-S(O)2-NH-C1-C6, -aryl-S(O)2-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or-aryl-S(O)2-NH-C3-C8-cycloalkyl, or, wherein J is a 5 membered heterocycle ring containing up to 4 heteroatoms selected from _-N= - NH-, or -O-;-C(=O)-heteroaryl-C(=O)-OH, -C(=O)-heteroaryl-C(=O)-O-C1-C6, -C(=O)-heteroaryl-C(=O)-O-C1-C6-O-(C=O)-C1-C6, -C(=O)-aryl-OH, or-C(=O)-heteroaryl-C(=O)-NH2, -C(=O)-heteroaryl-C(=O)-NH-C1-C6, -C(=O)-heteroaryl-C(=O)-NH-C3-C8-cycloalkyl, -C(=O)-heteroaryl-C(=O)-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or-C(=O)-heteroaryl-C(=O)-NH-S(O)2-C1-C6, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-C3-C8- cycloalkyl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-aryl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2- C1-C6-aryl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-heteroaryl, -C(=O)-heteroaryl-C(=O)-NH- S(O)2-C1-C6-heteroaryl, or-C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH2, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6, - C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C(=O)-heteroaryl-C(=O)-NH- S(O)2-NH-aryl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C(=O)-heteroaryl- C(=O)-NH-S(O)2-NH-heteroaryl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH- C1-C6-heteroaryl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or-O-; or-C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-C1-C6, -C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2- C3-C8-cycloalkyl, -C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-aryl, -C(=O)-heteroaryl-NH- C(=O)-NH-S(O)2-heteroaryl, or-C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-NH2, -C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-NH- C1-C6, -C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-NH-aryl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl,C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or or-heteroaryl-C(=O)-OH, -heteroaryl-C(=O)-O-C1-C6, -heteroaryl-C(=O)-O-C1-C6-O-(C=O)- C1-C6, -heteroaryl-C1-C6-OH, -heteroaryl-C1-C6-(C=O)OH, or-heteroaryl-C(=O)-NH2, -heteroaryl-C(=O)-NH-C1-C6, -heteroaryl-C(=O)-NH-C3-C8- cycloalkyl, -heteroaryl-C(=O)-N(C1-C6)2,, wherein J is a5 or 6 membered heterocycle ring optionally including a second heteroatom selected from - NH-, -NC1-C6-, -S- or -O-; or-heteroaryl-C(=O)-NH-S(O)2-C1-C6, -heteroaryl-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, heteroaryl-C(=O)-NH-S(O)2-aryl, -heteroaryl-C(=O)-NH-S(O)2-C1-C6-aryl, -heteroaryl -C(=O)-NH-S(O)2-heteroaryl, -heteroaryl-C(=O)-NH-S(O)2-C1-C6-heteroaryl, or-heteroaryl-C(=O)-NH-S(O)2-NH2, -heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6, -heteroaryl-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -heteroaryl-C(=O)-NH-S(O)2-NH-aryl, -heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -heteroaryl-C(=O)-NH-S(O)2-NH-heteroaryl, -heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-heteroaryl, -heteroaryl-C(=O)-NH-S(O)2-N(C1-C6)2,wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or-heteroaryl-NH-C(=O)-NH-S(O)2-C1-C6, -heteroaryl-NH-C(=O)-NH-S(O)2-C3-C8-cycloalkyl,-heteroaryl-NH-C(=O)-NH-S(O)2-aryl, -heteroaryl-NH-C(=O)-NH-S(O)2-heteroaryl, or-heteroaryl-NH-C(=O)-NH-S(O)2-NH2, -heteroaryl-NH-C(=O)-NH-S(O)2-NH-C1-C6, heteroaryl-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -heteroaryl-NH-C(=O)-NH-S(O)2- NH-aryl, -heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -heteroaryl-NH-C(=O)-NH-S(O)2-N(C1-C6)2,wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or-C1-C6-aryl-C(=O)-OH, -C1-C6-aryl-C(=O)-O-C1-C6, -C1-C6-aryl-C(=O)-O-C1-C6-O-(C=O)- C1-C6, -C1-C6-aryl-C1-C6-OH, or-C1-C6-aryl-C(=O)-NH2, -C1-C6-aryl-C(=O)-NH-C1-C6, -C1-C6-aryl-C(=O)-NH-C3-C8- cycloalkyl, -C1-C6-aryl-C(=O)-N(C1-C6)2,, wherein J is a5 or 6 membered heterocycle ring optionally including a second heteroatom selected from - NH-, -NC1-C6-, -S- or -O-; or-C1-C6-aryl-C(=O)-NH-S(O)2-C1-C6, -C1-C6-aryl-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -C1-C6- aryl-C(=O)-NH-S(O)2-aryl, -C1-C6-aryl-C(=O)-NH-S(O)2-C1-C6-aryl, -C1-C6-aryl-C(=O)- NH-S(O)2-heteroaryl, -C1-C6-aryl-C(=O)-NH-S(O)2-C1-C6-heteroaryl, or-C1-C6-aryl-C(=O)-NH-S(O)2-NH2, -C1-C6-aryl-C(=O)-NH-S(O)2-NH-C1-C6, -C1-C6-aryl-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C1-C6-aryl-C(=O)-NH-S(O)2-NH-aryl, -C1-C6-aryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C1-C6-aryl-C(=O)-NH-S(O)2-NH-heteroaryl, -C1-C6-aryl-C(=O)-NH-S(O)2-NH-C1-C6-heteroaryl, -C1-C6-aryl-C(=O)-NH-S(O)2-N(C1-C6)2, -C1-C62, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or-C1-C6-aryl-NH-C(=O)-NH-S(O)2-C1-C6, -C1-C6-aryl-NH-C(=O)-NH-S(O)2-C3-C8- cycloalkyl, -C1-C6-aryl-NH-C(=O)-NH-S(O)2-aryl, -C1-C6-aryl-NH-C(=O)-NH-S(O)2- heteroaryl, or-C1-C6-aryl-NH-C(=O)-NH-S(O)2-NH2, -C1-C6-aryl-NH-C(=O)-NH-S(O)2-NH-C1-C6, -C1-C6-aryl-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C1-C6-aryl-NH-C(=O)-NH-S(O)2-NH- aryl, -C1-C6-aryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C1-C6-aryl-NH-C(=O)-NH-S(O)2-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or-C1-C6-aryl-S(O)2-OH, -C1-C6-aryl-S(O)2-NH2, -C1-C6-aryl-S(O)2-NH-C1-C6, -C1-C6-aryl-S(O)2-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or-C1-C6-aryl-S(O)2-NH-C3-C8-cycloalkyl, or-C1-C6-heteroaryl-C(=O)-OH, -C1-C6-heteroaryl-C(=O)-O-C1-C6, -C1-C6-heteroaryl-C(=O)-O-C1-C6-O-(C=O)-C1-C6, -C1-C6-heteroaryl-C1-C6-OH, or-C1-C6-heteroaryl-C(=O)-NH2, -C1-C6-heteroaryl-C(=O)-NH-C1-C6, -C1-C6-heteroaryl-C(=O)-NH-C3-C8-cycloalkyl, -C1-C6-heteroaryl-C(=O)-N(C1-C6)2, 2, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or-C1-C6-heteroaryl-C(=O)-NH-S(O)2-C1-C6, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-C3-C8- cycloalkyl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-aryl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-C1-C6-aryl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-heteroaryl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2- C1-C6-heteroaryl, or-C1-C6-heteroaryl-C(=O)-NH-S(O)2-NH2, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6, - C1-C6heteroaryl-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C1-C6-heteroaryl-C(=O)-NH- S(O)2-NH-aryl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C1-C6-heteroaryl- C(=O)-NH-S(O)2-NH-heteroaryl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-heteroaryl, - C1-C6-heteroaryl-C(=O)-NH-S(O)2-N(C1-C6)2,wherein J is a 5 or 6 memberedheterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or-C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-C1-C6, -C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-C3-Cg-cycloalkyl, -C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-aryl, -C1-C6-heteroaryl-NH-C(=O)- NH-S(O)2-heteroaryl, or-C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-NH2, -C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-NH- C1-C6, -C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-NH-aryl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C1-C6- heteroaryl-NH-C(=O)-NH-S(O)2-N(C1-C6)2,wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; wherein P may be a 5 to 10 membered aryl ring or rings optionally containing one or more heteroatoms, and wherein P may be further substituted with one or more halo, -C1-C6-alkyl, - C1-C6-alkyl substituted with one or more halo or hydroxy; -C3-C8-cycloalkyl, -CN, hydroxy, - O-C1-C6-alkyl, -O-C1-C6-alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, - S-C1-C6-alkyl, -S-C1-C6-alkyl substituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1--C6-alkyl, -N(C1-C6-alkyl)2,, wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O- or C2-Cs cycloheteroalkyl including one or more heteroatoms selected from -NH-, -NC1-C6-, -S- or -O-; or aryl, aryl substituted with one or more, halo, -C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo or hydroxy, -C3-C8-cycloalkyl, -CN, hydroxy, -O-C1-C6-alkyl, -O-C1-C6-alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, -S-C1-C6-alkyl, -S-C1-C6-alkylsubstituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1-C6-alkyl, -N(C1-C6-alkyl)2,, wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or C1-C6-aryl; C1-C6-aryl substituted with one or more halo, -C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo or hydroxy, -C3-C8-cycloalkyl, -CN, hydroxy, -O-C1-C6-alkyl, -O-C1-C6-alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, -S-C1-C6-alkyl, -S-C1-C6-alkyl substituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1-C6-alkyl, -N(C1-C6- alkyl)2, , wherein M is a 5 or 6 membered heterocycle ring optionally includinga second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or heteroaryl; heteroaryl substituted with one or more halo, -C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo or hydroxy, -C3-C8-cycloalkyl, -CN, hydroxy, -O-C1-C6-alkyl, -O-C1-C6-alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, -S-C1-C6-alkyl, -S-C1-C6-alkyl substituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1-C6-alkyl, -N(C1-C6- alkyl), wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or C1-C6-heteroaryl; C1-C6-heteroaryl substituted with one or more halo, -C1-C6-alkyl, -C1-C6- alkyl substituted with one or more halo or hydroxy, -C3-C8-cycloalkyl, -CN, hydroxy, -O-C1-C6-alkyl, -O-C1-C6-alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, -S-C1-C6-alkyl, -S-C1-C6-alkyl substituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1-C6-alkyl,-N(C1-C6-alkyl)2,, wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or-O-aryl; -O-aryl substituted with one or more halo, -C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo or hydroxy, -C3-C8-cycloalkyl, -CN, hydroxy, -O-C1-C6-alkyl, -O-C1-C6- alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, -S-C1-C6-alkyl, -S-C1-C6- alkyl substituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1-C6-alkyl, -N(C1-C6-alkyl)2,, wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or-O-C1-C6-aryl; -O-C1-C6-aryl substituted with one or more halo, -C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo or hydroxy, -C3-C8-cycloalkyl, -CN, hydroxy, -O-C1-C6- alkyl, -O-C1-C6-alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, -S-C1-C6- alkyl, -S-C1-C6-alkyl substituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1-C6-alkyl, -N(C1-C6-alkyl)2,, wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or wherein Q may be selected from or oror or or or20and wherein R3, R4, or Re are independently selected from -H, halo, -C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo, -CN, hydroxy, -O-C1-C6-alkyl, -O-C1-C6-alkyl substituted with one or more halo; and or a salt thereof and with the proviso that the compoundis excluded and with the further proviso that the compoundexcluded and with the further proviso that the compound is excluded.

2. The compound as claimed in claim 1, wherein R is selected from-C(=O)-C1-C6-C(=O)-OH, -C(=O)-C1-C6-C(=O)-O-C1-C6, -C(=O)-C1-C6-C(=O)-O-C1-C6-O-(C=O)-C1-C6, or-C(=O)-C1-C6-C(=O)-NH2, -C(=O)-C1-C6-C(=O)-NH-C1-C6, -C(=O)-C1-C6-C(=O)-N(C c6)2,-C(=O)-C1-C6-C(=O)-NH-S(O)2-C1-C6, -C(=O)-C1-C6-C(=O)-NH-S(O)2-aryl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-N(C1-C6)2,, wherein J is a5 or 6 membered heterocycle ring optionally including a second heteroatom selected from - NH-, NC1-C6-, -S- or -O-; or-C1-C6-C(=O)-OH, or-aryl-C(=O)-OH, or-aryl-C(=O)-NH-S(O)2-C1-C6, or-C(=O)-C1-C6-C(=O)-NH-S(O)2-aryl, or-C1-C6-C(=O)-NH-S(O)2-C1-C6, or-C1-C6-C(=O)-NH-S(O)2-aryl, or-C1-C6-C(=O)-NH-S(O)2-N(C1-C6)2, or-aryl-C(=O)-NH-S(O)2-C1-C6,-aryl-C(=O)-NH-S(O)2-aryl, or-aryl-C(=O)-NH-S(O)2-N(C1-C6)2, heteroaryl-C(=O)-OH, or-heteroaryl-C(=O)-NH-S(O)2-C1-C6, or-heteroaryl-C(=O)-NH-S(O)2-aryl, or-heteroaryl-C(=O)-NH-S(O)2-N(C1-C6)2.

3. The compound as claimed in claim 1 or claim 2, wherein R is selected from -C(=O)-C1- C6-C(=O)-OH, -C(=O)-C 1-C6-C(=O)-NH-S(O)2-C 1-C6, -C(=O)-C 1-C6-C(=O)-NH-S(O)2- N(C1-C6)2, -C1-C6-C(=O)-OH, -aryl-C(=O)-OH, -C(=O)-C1-C6-C(=O)-NH-S(O)2-aryl, - C1-C6-C(=O)-NH-S(O)2-C1-C6, -C1-C6-C(=O)-NH-S(O)2-aryl, -C1-C6-C(=O)-NH-S(O)2- N(C1-C6)2, -aryl-C(=O)-NH-S(O)2-C1-C6, -aryl-C(=O)-NH-S(O)2-aryl, -aryl-C(=O)-NH- S(O)2-N(C1-C6)2, heteroaryl-C(=O)-OH, -heteroaryl-C(=O)-NH-S(O)2-C1-C6, -heteroaryl- C(=O)-NH-S(O)2-aryl, -heteroaryl-C(=O)-NH-S(O)2-N(C1-C6)2.

4. The compound as claimed in any one of claims 1 to 3, wherein R is C(=O)-C1-C6- C(=O)-OH.

5. The compound as claimed in any one of claims 1 to 3, wherein R is -C(=O)-C1-C6- C(=O)-NH-S(O)2-C1-C6.

6. The compound as claimed in any one of claims 1 to 3, wherein R is -C(=O)-C1-C6- C(=O)-NH-S(O)2-aryl.

7. The compound as claimed in any one of claims 1 to 3, wherein R is -C(=O)-C1-C6- C(=)-NH-S(O)2-N(C1-C6)2.

8. The compound as claimed in any one of claims 1 to 3, wherein R is -C1-C6-C(=O)-OH.

9. The compound as claimed in any one of claims 1 to 3, wherein R is -C1-C6-C(=O)- NH-S(O)2-C1-C6.

10. The compound as claimed in any one of claims 1 to 3, wherein R is -C1-C6-C(=O)- NH-S(O)2-aryl.

11. The compound as claimed in any one of claims 1 to 3, wherein R is -C1-C6-C(=O)- NH-S(O)2-N(C1-C6)2.

12. The compound as claimed in any one of claims 1 to 3, wherein R is aryl-C(=O)-OH.

13. The compound as claimed in any one of claims 1 to 3, wherein R is -aryl-C(=O)-NH- S(O)2-C1-C6.

14. The compound as claimed in any one of claims 1 to 3, wherein R is -aryl-C(=O)-NH- S(O)2-aryl.

15. The compound as claimed in any one of claims 1 to 3, wherein R is -aryl-C(=O)-NH- S(O)2-N(C1-C6)2.

16. The compound as claimed in any one of claims 1 to 3, wherein R is -heteroaryl- C(=O)-OH.

17. The compound as claimed in any one of claims 1 to 3, wherein R is -heteroaryl- C(=O)-NH-S(O)2-C1-C6.

18. The compound as claimed in any one of claims 1 to 3, wherein R is -heteroaryl- C(=O)-NH-S(O)2-aryl.

19. The compound as claimed in any one of claims 1 to 3, wherein R is -heteroaryl- C(=O)-NH-S(O)2-N(C1-C6)2.

20. The compound as claimed in any one of claims 1 to 3, wherein R is -C3-C(=O)-OH.

21. The compound as claimed in any one of claims 1 to 3, wherein R is -C(=O)-CH2- CH2-C(=O)-OH.

22. The compound as claimed in any one of claims 1 to 3, wherein R is -C(=O)-CH2- CH2-C(=O)-NH-S(O)2-Me.

23. The compound as claimed in any one of claims 1 to 3, wherein R is -C(=O)-CH2- CH2-C(=O)-NH-S(O)2-iPr.

24. The compound as claimed in any one of claims 1 to 3, wherein R is -C(=O)-CH2- CH2-C(=O)-NH-S(O)2-Ph.

25. The compound as claimed in any one of claims 1 to 3, wherein R is -C(=O)-CH2- CH2-C(=O)-NH-S(O)2-NMe2.

26. The compound as claimed in any one of claims 1 to 3, wherein R is -CH2-CH2-CH2- C(=O)-OH.

27. The compound as claimed in any one of claims 1 to 3, wherein R is -CH2-CH2-CH2- C(=O)-NH-S(O)2-Me.

28. The compound as claimed in any one of claims 1 to 3, wherein R is -CH2-CH2-CH2- C(=O)-NH-S(O)2-iPr.

29. The compound as claimed in any one of claims 1 to 3, wherein R is -CH2-CH2-CH2- C(=O)-NH-S(O)2-Ph.

30. The compound as claimed in any one of claims 1 to 3, wherein R is -CH2-CH2-CH2- C(=O)-NH-S(O)2-NMe2.

31. The compound as claimed in any one of claims 1 to 3, wherein R is -phenyl-C(=O)-OH.

32. The compound as claimed in any one of claims 1 to 3, wherein R is -phenyl-C(=O)- NH-S(O)2-Me.

33. The compound as claimed in any one of claims 1 to 3, wherein R is -phenyl-C(=O)- NH-S(O)2-iPr.

34. The compound as claimed in any one of claims 1 to 3, wherein R is -phenyl-C(=O)- NH-S(O)2-Ph.

35. The compound as claimed in any one of claims 1 to 3, wherein R is -phenyl-C(=O)- NH-S(O)2-NMe2.

36. The compound as claimed in any one of claims 1 to 3, wherein R is -pyridyl-C(=O)-OH.

37. The compound as claimed in any one of claims 1 to 3, wherein R is -pyridyl-C(=O)- NH-S(O)2-Me.

38. The compound as claimed in any one of claims 1 to 3, wherein R is -pyridyl-C(=O)- NH-S(O)2-iPr.

39. The compound as claimed in any one of claims 1 to 3, wherein R is -pyridyl-C(=O)- NH-S(O)2-Ph.

40. The compound as claimed in any one of claims 1 to 3, wherein R is -pyridyl-C(=O)- NH-S(O)2-NMe2.

41. The compound as claimed in claim 1 wherein R is wherein J is a 5membered heterocycle ring containing up to 4 heteroatoms selected from -N=, -NH-, or -O-.

42. The compound as claimed in claim 41 wherein R is -phenyl -tetrazole.

43. The compound as claimed in claim 41 wherein R is -phenyl-oxadiazolone.

44. The compound as claimed in any one of claims 1 to 43 wherein P is selected from aryl or an aryl substituted with one or more halo, -CN, -C1-C6-alkyl, -O-C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo, or -O-C1-C6-alkyl substituted with one or more halo.

45. The compound as claimed in claim 44 wherein P is selected from phenyl or a phenyl substituted with one or more halo, -CN, -C1-C6-alkyl, -O-C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo, or -O-C1-C6-alkyl substituted with one or more halo.

46. The compound as claimed in claim 45 wherein P is phenyl substituted with halo.

47. The compound as claimed in claim 46 wherein P is phenyl substituted with -Cl.

48. The compound as claimed in any one of claims 1 to 43 wherein P is selected from aryl substituted with aryl or an aryl substituted with halo, -CN, -C1-C6-alkyl, -O-C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo, or -O-C1-C6-alkyl substituted with one or more halo.

49. The compound as claimed in claim 48 wherein P is selected from phenyl substituted with phenyl or a phenyl substituted with halo, -CN, -C1-C6-alkyl, -O-C1-C6-alkyl, -C1-C6- alkyl substituted with one or more halo, or -O-C1-C6-alkyl substituted with one or more halo.

50. The compound as claimed in claim 49 wherein P is phenyl substituted with a phenyl.

51. The compound as claimed in claim 49 wherein P is phenyl substituted with a phenyl substituted with one or more halo.

52. The compound as claimed in claim 51 wherein P is phenyl substituted with a phenyl substituted with -Cl.

53. The compound as claimed in claim 49 wherein P is phenyl substituted with a phenyl substituted with -O-C1-C6-alkyl.

54. The compound as claimed in claim 53 wherein P is phenyl substituted with a phenyl substituted with -O-C3-alkyl.

55. The compound as claimed in claim 54 wherein P is phenyl substituted with a phenyl substituted with -O'Pr.

56. The compound as claimed in claim 54 wherein P is phenyl substituted with a phenyl substituted with -OnPr.

57. The compound as claimed in claim 49 wherein P is phenyl substituted with a phenyl substituted with -O-C1-C6-alkyl substituted with one or more halo.

58. The compound as claimed in claim 57, wherein P is phenyl substituted with a phenyl substituted with -OCF3 or -OCH2CF3.

59. The compound as claimed in claim 49, wherein P is phenyl substituted with a phenyl substituted with a -C1-C6-alkyl substituted with one or more halo.

60. The compound as claimed in claim 59, wherein P is phenyl substituted with a phenyl substituted with one or more -CF3.

61. The compound as claimed in claim 59, wherein P is phenyl substituted with a phenyl substituted with -CH2CF3.

62. The compound as claimed in claim 49, wherein P is phenyl substituted with a phenyl substituted with a halo and a O-C1-C6-alkyl.

63. The compound as claimed in claim 62, wherein P is phenyl substituted with a phenyl substituted with -F and a O-C1-C6-alkyl.

64. The compound as claimed in claim 49, wherein P is phenyl substituted with a phenyl substituted with a -C1-C6-alkyl and a -O-C1-C6-alkyl.

65. The compound as claimed in claim 64, wherein P is phenyl substituted with a phenyl substituted with a -C1-C3-alkyl and a O-C1-C6-alkyl.

66. The compound as claimed in claim 49, wherein P is phenyl substituted with a phenyl substituted with -CN and -O-C1-C6-alkyl.

67. The compound as claimed in any one of claims 1 to 43, wherein P is -aryl -heteroaryl and wherein the heteroaryl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O- C1-C6-alkyl and -O-C1-C6-alkyl optionally substituted with one or more halo.

68. The compound as claimed in claim 67, wherein P is -phenyl -heteroaryl and wherein the heteroaryl is optionally substituted with one or more substituents selected from -halo, - CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O-C1-C6-alkyl optionally substituted with one or more halo.

69. The compound as claimed in claim 68, wherein P is -phenyl -heteroaryl and wherein the heteroaryl is substituted with -O-C1-C6-alkyl.

70. The compound as claimed in claim 69, wherein P is -phenyl -heteroaryl and wherein the heteroaryl is substituted with -O-C3-alkyl.

71. The compound as claimed in claim 70, wherein P is -phenyl -heteroaryl and wherein the heteroaryl is substituted with -O'Pr.

72. The compound as claimed in claim 70, wherein P is -phenyl -heteroaryl and wherein the heteroaryl is substituted with -OnPr.

73. The compound as claimed in claim 68, wherein P is -phenyl -heteroaryl and wherein the heteroaryl is substituted with -O-C1-C6-alkyl substituted with one or more halo.

74. The compound as claimed in claim 73, wherein P is -phenyl -heteroaryl and wherein the heteroaryl is substituted with -OCF3.

75. The compound as claimed in claim 73, wherein P is -phenyl -heteroaryl and wherein the heteroaryl is substituted with -OCH2CF3.

76. The compound as claimed in claim 67, wherein P is -aryl-pyridyl and wherein the pyridyl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O- C1-C6-alkyl optionally substituted with one or more halo.

77. The compound as claimed in claim 76, wherein P is -phenyl-pyridyl and wherein the pyridyl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O- C1-C6-alkyl optionally substituted with one or more halo.

78. The compound as claimed in claim 77, wherein P is -phenyl-pyridyl and wherein the pyridyl is optionally substituted with -O-C1-C6-alkyl.

79. The compound as claimed in claim 78, wherein P is -phenyl-pyridyl and wherein the pyridyl is optionally substituted with -O'Pr.

80. The compound as claimed in claim 76, wherein P is -phenyl-pyridyl and wherein the pyridyl is substituted with -O-C1-C6-alkyl substituted with one or more halo.

81. The compound as claimed in claim 80, wherein P is -phenyl-pyridyl and wherein the pyridyl is substituted with -OCH2CF3.

82. The compound as claimed in any one of claims 1 to 43, wherein P is -heteroaryl-aryl and wherein the aryl is optionally substituted with one or more substituents selected from - halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6- alkyl and -O-C1-C6-alkyl optionally substituted with one or more halo.

83. The compound as claimed in claim 82 wherein P is -heteroaryl -phenyl and wherein the phenyl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and - O-C1-C6-alkyl optionally substituted with one or more halo.

84. The compound as claimed in claim 83, wherein P is a heteroaryl -phenyl and wherein the phenyl is substituted with -O-C1-C6-alkyl.

85. The compound as claimed in claim 84, wherein P is a heteroaryl -phenyl and wherein the phenyl is substituted with -O-C3-alkyl.

86. The compound as claimed in claim 85, wherein P is a heteroaryl -phenyl and wherein the phenyl is substituted with -O'Pr.

87. The compound as claimed in claim 85, wherein P is a heteroaryl -phenyl and wherein the phenyl is substituted with -OnPr.

88. The compound as claimed in claim 83, wherein P is a heteroaryl -phenyl and wherein the phenyl is substituted with -O-C1-C6-alkyl substituted with one or more halo.

89. The compound as claimed in claim 88, wherein P is a heteroaryl -phenyl and wherein the phenyl is substituted with -OCF3.

90. The compound as claimed in claim 88, wherein P is a heteroaryl -phenyl and wherein the phenyl is substituted with -OCH2CF3.

91. The compound as claimed in claim 82, wherein P is -pyridyl-aryl and wherein the aryl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O-C1-C6-alkyl optionally substituted with one or more halo.

92. The compound as claimed in claim 91, wherein P is -pyridyl -phenyl and wherein the phenyl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O- C1-C6-alkyl optionally substituted with one or more halo.

93. The compound as claimed in claim 92, wherein P is a -pyridyl-phenyl and wherein the phenyl is substituted with -O-C1-C6-alkyl.

94. The compound as claimed in claim 93, wherein P is a -pyridyl-phenyl and wherein the phenyl is substituted with -O-C3-alkyl.

95. The compound as claimed in claim 94, wherein P is a -pyridyl-phenyl and wherein the phenyl is substituted with -O'Pr.

96. The compound as claimed in claim 94, wherein P is a -pyridyl-phenyl and wherein the phenyl is substituted with -OnPr.

97. The compound as claimed in claim 92, wherein P is a -pyridyl-phenyl and wherein the phenyl is substituted with -O-C1-C6-alkyl substituted with one or more halo.

98. The compound as claimed in claim 97, wherein P is a -pyridyl-phenyl and wherein the phenyl is substituted with -OCF3.

99. The compound as claimed in claim 97, wherein P is a -pyridyl-phenyl and wherein the phenyl is substituted with -OCH2CF3.

100. The compound as claimed in any one of claims 1 to 43, wherein P is -phenyl-phenyl- substituted with a heterocycle.

101. The compound as claimed in claim 100, wherein P is -phenyl -phenyl- substituted with a pyrrolidine.

102. The compound as claimed in any one of claims 1 to 101, wherein Q is selected from:Nor or oror103. The compound as claimed in any one of claims 1 to 102, wherein Q is selected from:orIn one example Q. is selected from: or o104. The compound as claimed in any one of claims 1 to 103 wherein Q is105. The compound as claimed in claim 1, wherein the compound or salt of Formula I is selected from one or more of the following:

106. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

107. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

108. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

109. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

110. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

111. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

112. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

113. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

114. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

115. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

116. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

117. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

118. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

119. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

120. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

121. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

122. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

123. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

124. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

125. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

126. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

127. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

128. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

129. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

130. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

131. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

132. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

133. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

134. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

135. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

136. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

137. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

138. The compound as claimed in claim 1, wherein the compound of Formula I is:or a salt thereof.

139. The compound as claimed in claim 1, wherein the compound of Formula I is: or a sait thereof.

140. A compound of Formula IIFormula II wherein R may be selected from:-C(=O)-C1-C6-C(=O)-OH, -C(=O)-C1-C6-C(=O)-O-C1-C6, -C(=O)-C1-C6-C(=O)-O-C1-C6-O-(C=O)-C1-C6, or-C(=O)-C1-C6-C(=O)-NH2, -C(=O)-C1-C6-C(=O)-NH-C1-C6, -C(=O)-C1-C6-C(=O)-NH-C3-C8-cycloalkyl, -C(=O)-C1-C6-C(=O)-N(C1-C6)2,wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or-C(=O)-C1-C6-C(=O)-NH-S(O)2-C1-C6, -C(=O)-C1-C6-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-aryl, C(=O)-C1-C6-C(=O)-NH-S(O)2-C1-C6-aryl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-heteroaryl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-C1-C6-heteroaryl, or-C(=O)-C1-C6-C(=O)-NH-S(O)2-NH2, -C(=O)-C1-C6-C(=O)-NH-S(O)2-NH-C1-C6, -C(=O)- C1-C6-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-NH-aryl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-NH- heteroaryl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-NH- C1-C6-heteroaryl, -C(=O)-C1-C6-C(=O)-NH-wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-,NC1-C6-, -S- or -O-; or-C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-C1-C6, -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-C3-C8- cycloalkyl, -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-aryl, -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2- heteroaryl, or-C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-NH2, -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-NH-C1-C6, -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-NH-aryl, -C(=O)-C1-C6-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C(=O)-C1-C6-NH-C(=O)-NH-S(O)2-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or-C1-C6-C(=O)-OH, -C1-C6-C(=O)-O-C1-C6, .C1-C6-C(=O)-O-C1-C6-O-(C=O)-C1-C6, -C1-C6-OH, or-C1-C6-C(=O)-NH2, -C1-C6-C(=O)-NH-C1-C6, -C1-C6-C(=O)-NH-C3-C8-cycloalkyl, -C1-C6-, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or-C1-C6-C(=O)-NH-S(O)2-C1-C6, -C1-C6-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -C1-C6-C(=O)-NH-S(O)2-aryl, -C1-C6-C(=O)-NH-S(O)2-C1-C6-aryl, -C1-C6-C(=O)-NH-S(O)2-heteroaryl, - C1-C6-C(=O)-NH-S(O)2-C1-C6-heteroaryl, or-C1-C6-C(=O)-NH-S(O)2-NH2, -C1-C6-C(=O)-NH-S(O)2-NH-C1-C6, -C1-C6-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C1-C6-C(=O)-NH-S(O)2-NH-aryl, -C1-C6-C(=O)-NH-S(O)2- NH-C1-C6-aryl, -C1-C6-C(=O)-NH-S(O)2-NH-heteroaryl, -C1-C6-C(=O)-NH-S(O)2-NH- Ci-C6-heteroaryl, -, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or-C1-C6-NH-C(=O)-NH-S(O)2-C1-C6, -C1-C6-NH-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -C1-C6-NH-C(=O)-NH-S(O)2-aryl, -C1-C6-NH-C(=O)-NH-S(O)2-heteroaryl, or-C1-C6-NH-C(=O)-NH-S(O)2-NH2, -C1-C6-NH-C(=O)-NH-S(O)2-NH-C1-C6, -C1-C6-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C1-C6-NH-C(=O)-NH-S(O)2-NH-aryl, -C1-C6-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C1-C6-NH-C(=O)-NH-S(O)2-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or or-C(=O)-aryl-C(=O)-OH, -C(=O)-aryl-C(=O)-O-C1-C6, -C(=O)-aryl-C(=O)-O-C1-C6-O-(C=O)-C1-C6, -C(=O)-aryl-OH, or-C(=O)-aryl-C(=O)-NH2, -C(=O)-aryl-C(=O)-NH-C1-C6, -C(=O)-aryl-C(=O)-NH-C3-C8- cycloalkyl, -C(=O)-aryl-C(=O)-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from - NH-, -NC1-C6-, -S- or -O-; or-C(=O)-aryl-C(=O)-NH-S(O)2-C1-C6, -C(=O)-aryl-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -C(=O)-aryl-C(=O)-NH-S(O)2-aryl, -C(=O)-aryl-C(=O)-NH-S(O)2-C1-C6-aryl, -C(=O)-aryl-C(=O)-NH-S(O)2-heteroaryl, -C(=O)-aryl-C(=O)-NH-S(O)2-C1-C6-heteroaryl, or-C(=O)-aryl-C(=O)-NH-S(O)2-NH2, -C(=O)-aryl-C(=O)-NH-S(O)2-NH-C1-C6, -C(=O)-aryl-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C(=O)-aryl-C(=O)-NH-S(O)2-NH-aryl, -C(=O)- aryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C(=O)-aryl-C(=O)-NH-S(O)2-NH-heteroaryl,C(=O)-aryl-C(=O)-NH-S(O)2-NH-C1-C6-heteroaryl, -C(=O)-aryl-C(=O)-NH-S(O)2-N(Ci-C6)2,wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or-O-; or-C(=O)-aryl-NH-C(=O)-NH-S(O)2-C1-C6, -C(=O)-aryl-NH-C(=O)-NH-S(O)2-C3-C8- cycloalkyl, -C(=O)-aryl-NH-C(=O)-NH-S(O)2-aryl, -C(=O)-aryl-NH-C(=O)-NH-S(O)2- heteroaryl, or-C(=O)-aryl-NH-C(=O)-NH-S(O)2-NH2, -C(=O)-aryl-NH-C(=O)-NH-S(O)2-NH-C1-C6, -C(=O)-aryl-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C(=O)-aryl-NH-C(=O)-NH-S(O)2-NH-aryl, -C(=O)-aryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C(=O)-aryl-NH-C(=O)-NH-S(O)2-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or or-aryl-C(=O)-OH, -aryl-C(=O)-O-C1-C6, -aryl-C(=O)-O-C1-C6-O-(C=O)-C1-C6, -aryl-C1-C6-OH, -aryl-C1-C6-(C=O)OH, or-aryl-C(=O)-NH2, -aryl-C(=O)-NH-C1-C6, -aryl-C(=O)-NH-C3-C8-cycloalkyl, -aryl-C(=O)-N(C1-C6)2,wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or-aryl-C(=O)-NH-S(O)2-C1-C6, -aryl-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -aryl-C(=O)-NH- S(O)2-aryl, -aryl-C(=O)-NH-S(O)2-C1-C6-aryl, -aryl-C(=O)-NH-S(O)2-heteroaryl, -aryl- C(=O)-NH-S(O)2-C1-C6-heteroaryl, or-aryl-C(=O)-NH-S(O)2-NH2, -aryl-C(=O)-NH-S(O)2-NH-C1-C6, -aryl-C(=O)-NH-S(O)2-NH- C3-C8-cycloalkyl, -aryl-C(=O)-NH-S(O)2-NH-aryl, -aryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, - aryl-C(=O)-NH-S(O)2-NH-heteroaryl, -aryl-C(=O)-NH-S(O)2-NH-C1-C6-heteroaryl, -aryl- C(=O)-NH-S(O)2-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-,NC1-C6-, -S- or -O-; or-aryl-NH-C(=O)-NH-S(O)2-C1-C6, -aryl-NH-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -aryl-NH-C(=O)-NH-S(O)2-aryl, -aryl-NH-C(=O)-NH-S(O)2-heteroaryl, or-aryl-NH-C(=O)-NH-S(O)2-NH2, -aryl-NH-C(=O)-NH-S(O)2-NH-C1-C6, -aryl-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -aryl-NH-C(=O)-NH-S(O)2-NH-aryl, -aryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -aryl-NH-C(=O)-NH-S(O)2-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or-aryl-S(O)2-OH, -aryl-S(O)2-NH2, -aryl-S(O)2-NH-C1-C6, -aryl-S(O)2-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or-aryl-S(O)2-NH-C3-C8-cycloalkyl, or-C(=O)-heteroaryl-C(=O)-OH, -C(=O)-heteroaryl-C(=O)-O-C1-C6, -C(=O)-heteroaryl-C(=O)-O-C1-C6-O-(C=O)-C1-C6, -C(=O)-aryl-OH, or-C(=O)-heteroaryl-C(=O)-NH2, -C(=O)-heteroaryl-C(=O)-NH-C1-C6, -C(=O)-heteroaryl-C(=O)-NH-C3-C8-cycloalkyl, -C(=O)-heteroaryl-C(=O)-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or-C(=O)-heteroaryl-C(=O)-NH-S(O)2-C1-C6, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-C3-C8- cycloalkyl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-aryl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2- C1-C6-aryl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-heteroaryl, -C(=O)-heteroaryl-C(=O)-NH- S(O)2-C1-C6-heteroaryl, or-C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH2, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH-aryl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C(=O)-heteroaryl- C(=O)-NH-S(O)2-NH-heteroaryl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH- C1-C6-heteroaryl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or-C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-C1-C6, -C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2- C3-C8-cycloalkyl, -C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-aryl, -C(=O)-heteroaryl-NH- C(=O)-NH-S(O)2-heteroaryl, or-C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-NH2, -C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-NH- C1-C6, -C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C(=O)-heteroaryl- NH-C(=O)-NH-S(O)2-NH-aryl, -C(=O)-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, C(=O)-heteroaryl-NH-C(=O)-NH-S(O)2-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or or-heteroaryl-C(=O)-OH, -heteroaryl-C(=O)-O-C1-C6, -heteroaryl-C(=O)-O-C1-C6-O-(C=O)- C1-C6, -heteroaryl-C1-C6-OH, -heteroaryl-C1-C6-(C=O)OH, or-heteroaryl-C(=O)-NH2, -heteroaryl-C(=O)-NH-C1-C6, -heteroaryl-C(=O)-NH-C3-C8- cycloalkyl, -heteroaryl-C(=O)-N(C1-C6)2,, wherein J is a5 or 6 membered heterocycle ring optionally including a second heteroatom selected from - NH-, -NC1-C6-, -S- or -O-; or-heteroaryl-C(=O)-NH-S(O)2-C1-C6, -heteroaryl-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, heteroaryl-C(=O)-NH-S(O)2-aryl, -heteroaryl-C(=O)-NH-S(O)2-C1-C6-aryl, -heteroaryl -C(=O)-NH-S(O)2-heteroaryl, -heteroaryl-C(=O)-NH-S(O)2-C1-C6-heteroaryl, or-heteroaryl-C(=O)-NH-S(O)2-NH2, -heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6, -heteroaryl-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -heteroaryl-C(=O)-NH-S(O)2-NH-aryl, -heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -heteroaryl-C(=O)-NH-S(O)2-NH-heteroaryl, -heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-heteroaryl, -heteroaryl-C(=O)-NH-S(O)2-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or-heteroaryl-NH-C(=O)-NH-S(O)2-C1-C6, -heteroaryl-NH-C(=O)-NH-S(O)2-C3-C8-cycloalkyl,-heteroaryl-NH-C(=O)-NH-S(O)2-aryl, -heteroaryl-NH-C(=O)-NH-S(O)2-heteroaryl, or-heteroaryl-NH-C(=O)-NH-S(O)2-NH2, -heteroaryl-NH-C(=O)-NH-S(O)2-NH-C1-C6, heteroaryl-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -heteroaryl-NH-C(=O)-NH-S(O)2-NH-aryl, -heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -heteroaryl-NH-C(=O)-NH-S(O)2-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or-C1-C6-aryl-C(=O)-OH, -C1-C6-aryl-C(=O)-O-C1-C6, -C1-C6-aryl-C(=O)-O-C1-C6-O-(C=O)- C1-C6, -C1-C6-aryl-C1-C6-OH, or-C1-C6-aryl-C(=O)-NH2, -C1-C6-aryl-C(=O)-NH-C1-C6, -C1-C6-aryl-C(=O)-NH-C3-C8- cycloalkyl, -C1-C6-aryl-C(=O)-N(C1-C6)2,wherein J is a5 or 6 membered heterocycle ring optionally including a second heteroatom selected from - NH-, -NC1-C6-, -S- or -O-; or-C1-C6-aryl-C(=O)-NH-S(O)2-C1-C6, -C1-C6-aryl-C(=O)-NH-S(O)2-C3-C8-cycloalkyl, -C1-C6- aryl-C(=O)-NH-S(O)2-aryl, -C1-C6-aryl-C(=O)-NH-S(O)2-C1-C6-aryl, -C1-C6-aryl-C(=O)- NH-S(O)2-heteroaryl, -C1-C6-aryl-C(=O)-NH-S(O)2-C1-C6-heteroaryl, or-C1-C6-aryl-C(=O)-NH-S(O)2-NH2, -C1-C6-aryl-C(=O)-NH-S(O)2-NH-C1-C6, -C1-C6-aryl-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C1-C6-aryl-C(=O)-NH-S(O)2-NH-aryl, -C1-C6-aryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C1-C6-aryl-C(=O)-NH-S(O)2-NH-heteroaryl, -C1-C6-aryl-C(=O)-NH-S(O)2-NH-C1-C6-heteroaryl, -C1-C6-aryl-C(=O)-NH-S(O)2-N(C1-C6)2, -C1-C6wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or-C1-C6-aryl-NH-C(=O)-NH-S(O)2-C1-C6, -C1-C6-aryl-NH-C(=O)-NH-S(O)2-C3-C8- cycloalkyl, -C1-C6-aryl-NH-C(=O)-NH-S(O)2-aryl, -C1-C6-aryl-NH-C(=O)-NH-S(O)2- heteroaryl, or-C1-C6-aryl-NH-C(=O)-NH-S(O)2-NH2, -C1-C6-aryl-NH-C(=O)-NH-S(O)2-NH-C1-C6, -C1-C6-aryl-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C1-C6-aryl-NH-C(=O)-NH-S(O)2-NH- aryl, -C1-C6-aryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C1-C6-aryl-NH-C(=O)-NH-S(O)2-N(Ci-Ce)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or-C1-C6-aryl-S(O)2-OH, -C1-C6-aryl-S(O)2-NH2, -C1-C6-aryl-S(O)2-NH-C1-C6, -C1-C6-aryl-S(O)2-N(C1-C6)2,wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or-C1-C6-aryl-S(O)2-NH-C3-C8-cycloalkyl, or-C1-C6-heteroaryl-C(=O)-OH, -C1-C6-heteroaryl-C(=O)-O-C1-C6, -C1-C6-heteroaryl-C(=O)-O-C1-C6-O-(C=O)-C1-C6, -C1-C6-heteroaryl-C1-C6-OH, or-C1-C6-heteroaryl-C(=O)-NH2, -C1-C6-heteroaryl-C(=O)-NH-C1-C6, -C1-C6-heteroaryl-C(=O)-NH-C3-C8-cycloalkyl, -C1-C6-heteroaryl-C(=O)-N(C1-C6)2, 2, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or-C1-C6-heteroaryl-C(=O)-NH-S(O)2-C1-C6, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-C3-C8- cycloalkyl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-aryl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-C1-C6-aryl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-heteroaryl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2- C1-C6-heteroaryl, or-C1-C6-heteroaryl-C(=O)-NH-S(O)2-NH2, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6, - C1-C6heteroaryl-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C1-C6-heteroaryl-C(=O)-NH- S(O)2-NH-aryl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C1-C6-heteroaryl- C(=O)-NH-S(O)2-NH-heteroaryl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-heteroaryl, - C1-C6-heteroaryl-C(=O)-NH-S(O)2-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; or-C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-C1-C6, -C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-C3-C9-cycloalkyl, -C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-aryl, -C1-C6-heteroaryl-NH-C(=O)- NH-S(O)2-heteroaryl, or-C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-NH2, -C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-NH- C1-C6, -C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-NH-C3-C8-cycloalkyl, -C1-C6-heteroaryl-NH-C(=O)-NH-S(O)2-NH-aryl, -C1-C6-heteroaryl-C(=O)-NH-S(O)2-NH-C1-C6-aryl, -C1-C6- heteroaryl-NH-C(=O)-NH-S(O)2-N(C1-C6)2,, wherein J is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, NC1-C6-, -S- or -O-; wherein P may be a 5 to 10 membered aryl ring or rings optionally containing one or more heteroatoms, and wherein P may be further substituted with one or more halo, -C1-C6-alkyl, - C1-C6-alkyl substituted with one or more halo or hydroxy; -C3-C8-cycloalkyl, -CN, hydroxy, - O-C1-C6-alkyl, -O-C1-C6-alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, - S-C1-C6-alkyl, -S-C1-C6-alkyl substituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1-C6-alkyl, -N(C1-C6-alkyl), wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O- or C2-C8 cycloheteroalkyl including one or more heteroatoms selected from -NH-, -NC1-C6-, -S- or -O-; or aryl, aryl substituted with one or more, halo, -C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo or hydroxy, -C3-C8-cycloalkyl, -CN, hydroxy, -O-C1-C6-alkyl, -O-C1-C6-alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, -S-C1-C6-alkyl, -S-C1-C6-alkyl substituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1-C6-alkyl, -N(C1-C6-alkyl)2,, wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or C1-C6-aryl; C1-C6-aryl substituted with one or more halo, -C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo or hydroxy, -C3-C8-cycloalkyl, -CN, hydroxy, -O-C1-C6-alkyl, -O-C1-C6-alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, -S-C1-C6-alkyl, -S-C1-C6-alkyl substituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1-C6-alkyl, -N(C1-C6- alkyl), wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or heteroaryl; heteroaryl substituted with one or more halo, -C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo or hydroxy, -C3-C8-cycloalkyl, -CN, hydroxy, -O-C1-C6-alkyl, -O-C1-C6-alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, -S-C1-C6-alkyl, -S-C1-C6-alkyl substituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1-C6-alkyl, -N(C1-C6- alkyl), wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or C1-C6-heteroaryl; C1-C6-heteroaryl substituted with one or more halo, -C1-C6-alkyl, -C1-C6- alkyl substituted with one or more halo or hydroxy, -C3-C8-cycloalkyl, -CN, hydroxy, -O-C1-C6-alkyl, -O-C1-C6-alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, -S-C1-C6-alkyl, -S-C1-C6-alkyl substituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1-C6-alkyl,-N(C1-C6-alkyl)2,, wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or-O-aryl; -O-aryl substituted with one or more halo, -C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo or hydroxy, -C3-C8-cycloalkyl, -CN, hydroxy, -O-C1-C6-alkyl, -O-C1-C6- alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, -S-C1-C6-alkyl, -S-C1-C6- alkyl substituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1-C6-alkyl, -N(C1-C6-alkyl)2,, wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or-O-C1-C6-aryl; -O-C1-C6-aryl substituted with one or more halo, -C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo or hydroxy, -C3-C8-cycloalkyl, -CN, hydroxy, -O-C1-C6- alkyl, -O-C1-C6-alkyl substituted with one or more halo, -O-C3-C8-cycloalkyl, -SH, -S-C1-C6- alkyl, -S-C1-C6-alkyl substituted with one or more halo, -SF6, -NO2, -NH2, -NH-C1-C6-alkyl, -N(C1-C6-alkyl)2,, wherein M is a 5 or 6 membered heterocycle ring optionally including a second heteroatom selected from -NH-, -NC1-C6-, -S- or -O-; or wherein Q may be selected fromandwherein R3, R4, or R6 are independently selected from -H, halo, -C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo, -CN, hydroxy, -O-C1-C6-alkyl, -O-C1-C6-alkyl substituted with one or more halo; and or a salt thereof.

141. The compound as claimed in claim 140, wherein R is selected from-C(=O)-C1-C6-C(=O)-OH, -C(=O)-C1-C6-C(=O)-O-C1-C6, -C(=O)-C1-C6-C(=O)-O-C1-C6-O-(C=O)-C1-C6, or-C(=O)-C1-C6-C(=O)-NH2, -C(=O)-C1-C6-C(=O)-NH-C1-C6, -C(=O)-C1-C6-C(=O)-N(C c6)2,-C(=O)-C1-C6-C(=O)-NH-S(O)2-C1-C6, -C(=O)-C1-C6-C(=O)-NH-S(O)2-aryl, -C(=O)-C1-C6- ( ) ( ) ( ), wherein J is a5 or 6 membered heterocycle ring optionally including a second heteroatom selected from - NH-, NC1-C6-, -S- or -O-; or-C1-C6-C(=O)-OH, or-aryl-C(=O)-OH, or-aryl-C(=O)-NH-S(O)2-C1-C6, or-C(=O)-C1-C6-C(=O)-NH-S(O)2-aryl, or-C1-C6-C(=O)-NH-S(O)2-C1-C6, or-C1-C6-C(=O)-NH-S(O)2-aryl, or-C1-C6-C(=O)-NH-S(O)2-N(C1-C6)2, or-aryl-C(=O)-NH-S(O)2-C1-C6, or-aryl-C(=O)-NH-S(O)2-aryl, or-aryl-C(=O)-NH-S(O)2-N(C1-C6)2, or heteroaryl-C(=O)-OH, or-heteroaryl-C(=O)-NH-S(O)2-C1-C6, or-heteroaryl-C(=O)-NH-S(O)2-aryl, or-heteroaryl-C(=O)-NH-S(O)2-N(C1-C6)2.

142. The compound as claimed in claim 140 or claim 141, wherein R is selected from - C(=O)-C1-C6-C(=O)-OH, -C(=O)-C1-C6-C(=O)-NH-S(O)2-C1-C6, -C(=O)-C1-C6-C(=O)-NH- S(O)2-N(C1-C6)2, -C1-C6-C(=O)-OH, -aryl-C(=O)-OH, -C(=O)-C1-C6-C(=O)-NH-S(O)2-aryl, -C1-C6-C(=O)-NH-S(O)2-C1-C6, -C1-C6-C(=O)-NH-S(O)2-aryl, -C1-C6-C(=O)-NH-S(O)2- N(C1-C6)2, -aryl-C(=O)-NH-S(O)2-C1-C6, -aryl-C(=O)-NH-S(O)2-aryl, -aryl-C(=O)-NH- S(O)2-N(C1-C6)2, heteroaryl-C(=O)-OH, -heteroaryl-C(=O)-NH-S(O)2-C1-C6, -heteroaryl- C(=O)-NH-S(O)2-aryl, -heteroaryl-C(=O)-NH-S(O)2-N(C1-C6)2.

143. The compound as claimed in any one of claims 140 to 142, wherein R is C(=O)-C C6-C(=O)-OH.

144. The compound as claimed in any one of claims 140 to 143, wherein R is -C(=O)-C C6-C(=O)-NH-S(O)2-C1-C6.

145. The compound as claimed in any one of claims 140 to 142, wherein R is -C(=O)-C C6-C(=O)-NH-S(O)2-aryl.

146. The compound as claimed in any one of claims 140 to 142, wherein R is -C(=O)-C C6-C(=)-NH-S(O)2-N(C1-C6)2.

147. The compound as claimed in any one of claims 140 to 142, wherein R is -C1-C6- C(=O)-OH.

148. The compound as claimed in any one of claims 140 to 142, wherein R is -C1-C6- C(=O)-NH-S(O)2-C1-C6.

149. The compound as claimed in any one of claims 140 to 142, wherein R is -C1-C6- C(=O)-NH-S(O)2-aryl.

150. The compound as claimed in any one of claims 140 to 142, wherein R is -C1-C6- C(=O)-NH-S(O)2-N(C1-C6)2.

151. The compound as claimed in any one of claims 140 to 142, wherein R is selected from aryl-C(=O)-OH.

152. The compound as claimed in any one of claims 140 to 142, wherein R is -aryl-C(=O)- NH-S(O)2-C1-C6.

153. The compound as claimed in any one of claims 140 to 142, wherein R is -aryl-C(=O)- NH-S(O)2-aryl.

154. The compound as claimed in any one of claims 140 to 142, wherein R is -aryl-C(=O)- NH-S(O)2-N(C1-C6)2.

155. The compound as claimed in any one of claims 140 to 142, wherein R is -heteroaryl- C(=O)-OH.

156. The compound as claimed in any one of claims 140 to 142, wherein R is -heteroaryl- C(=O)-NH-S(O)2-C1-C6.

157. The compound as claimed in any one of claims 140 to 142, wherein R is -heteroaryl- C(=O)-NH-S(O)2-aryl.

158. The compound as claimed in any one of claims 140 to 142, wherein R is -heteroaryl- C(=O)-NH-S(O)2-N(C1-C6)2.

159. The compound as claimed in any one of claims 140 to 142, wherein R is -C3-C(=O)-OH.

160. The compound as claimed in any one of claims 140 to 142, wherein R is -C(=O)-CH2- CH2-C(=O)-OH.

161. The compound as claimed in any one of claims 140 to 142, wherein R is -C(=O)-CH2- CH2-C(=O)-NH-S(O)2-Me.

162. The compound as claimed in any one of claims 140 to 142, wherein R is -C(=O)-CH2- CH2-C(=O)-NH-S(O)2-iPr.

163. The compound as claimed in any one of claims 140 to 142, wherein R is -C(=O)-CH2- CH2-C(=O)-NH-S(O)2-Ph.

164. The compound as claimed in any one of claims 140 to 142, wherein R is -C(=O)-CH2- CH2-C(=O)-NH-S(O)2-NMe2.

165. The compound as claimed in any one of claims 140 to 142, wherein R is -CH2-CH2- CH2-C(=O)-OH.

166. The compound as claimed in any one of claims 140 to 142, wherein R is -CH2-CH2- CH2-C(=O)-NH-S(O)2-Me.

167. The compound as claimed in any one of claims 140 to 142, wherein R is -CH2-CH2- CH2-C(=O)-NH-S(O)2-iPr.

168. The compound as claimed in any one of claims 140 to 142, wherein R is -CH2-CH2- CH2-C(=O)-NH-S(O)2-Ph.

169. The compound as claimed in any one of claims 140 to 142, wherein R is -CH2-CH2- CH2-C(=O)-NH-S(O)2-NMe2.

170. The compound as claimed in any one of claims 140 to 142, wherein R is -phenyl- C(=O)-OH.

171. The compound as claimed in any one of claims 140 to 142, wherein R is -phenyl- C(=O)-NH-S(O)2-Me.

172. The compound as claimed in any one of claims 140 to 142, wherein R is -phenyl- C(=O)-NH-S(O)2-iPr.

173. The compound as claimed in any one of claims 140 to 142, wherein R is -phenyl- C(=O)-NH-S(O)2-Ph.

174. The compound as claimed in any one of claims 140 to 142, wherein R is -phenyl- C(=O)-NH-S(O)2-NMe2.

175. The compound as claimed in any one of claims 140 to 142, wherein R is -pyridyl- C(=O)-OH.

176. The compound as claimed in any one of claims 140 to 142, wherein R is -pyridyl- C(=O)-NH-S(O)2-Me.

177. The compound as claimed in any one of claims 140 to 142, wherein R is -pyridyl- C(=O)-NH-S(O)2-iPr.

178. The compound as claimed in any one of claims 140 to 142, wherein R is -pyridyl- C(=O)-NH-S(O)2-Ph.

179. The compound as claimed in any one of claims 140 to 142, wherein R is -pyridyl- C(=O)-NH-S(O)2-NMe2.

180. The compound as claimed in claim 140 wherein R iwherein J is a 5 membered heterocycle ring containing up to 4 heteroatoms selected from -N=, -NH-, or -O-.

181. The compound as claimed in claim 140 wherein R is -phenyl -tetrazole.

182. The compound as claimed in claim 140 wherein R is -phenyl-oxadiazolone.

183. The compound as claimed in any one of claims 140 to 179 wherein P is selected from aryl or an aryl substituted with one or more halo, - CN, -C1-C6-alkyl, -O-C1-C6-alkyl, -C1-C6- alkyl substituted with one or more halo, or -O-C1-C6-alkyl substituted with one or more halo.

184. The compound as claimed in claim 183 wherein P is selected from phenyl or a phenyl substituted with one or more halo, -CN, -C1-C6-alkyl, -O-C1-C6-alkyl, -C1-C6-alkyl substituted with one or more halo, or -O-C1-C6-alkyl substituted with one or more halo.

185. The compound as claimed in claim 184 wherein P is phenyl substituted with halo.

186. The compound as claimed in claim 185 wherein P is phenyl substituted with -Cl.

187. The compound as claimed in any one of claims 140 to 179 wherein P is selected from aryl substituted with aryl or an aryl substituted with halo,-CN, -C1-C6-alkyl, -O-C1-C6-alkyl, - C1-C6-alkyl substituted with one or more halo, or -O-C1-C6-alkyl substituted with one or more halo.

188. The compound as claimed in claim 187 wherein P is selected from phenyl substituted with phenyl or a phenyl substituted with halo, -CN, -C1-C6-alkyl, -O-C1-C6-alkyl, -C1-C6- alkyl substituted with one or more halo, or -O-C1-C6-alkyl substituted with one or more halo.

189. The compound as claimed in claim 188 wherein P is phenyl substituted with a phenyl.

190. The compound as claimed in claim 188 wherein P is phenyl substituted with a phenyl substituted with one or more halo.

191. The compound as claimed in claim 191 wherein P is phenyl substituted with a phenyl substituted with -Cl.

192. The compound as claimed in claim 188, wherein P is phenyl substituted with a phenyl substituted with -O-C1-C6-alkyl.

193. The compound as claimed in claim 192 wherein P is phenyl substituted with a phenyl substituted with -O-C3-alkyl.

194. The compound as claimed in claim 193, wherein P is phenyl substituted with a phenyl substituted with -O'Pr.

195. The compound as claimed in claim 193, wherein P is phenyl substituted with a phenyl substituted with -OnPr.

196. The compound as claimed in claim 188, wherein P is phenyl substituted with a phenyl substituted with -O-C1-C6-alkyl substituted with one or more halo.

197. The compound as claimed in claim 196, wherein P is phenyl substituted with a phenyl substituted with - OCF3 or -OCH2CF3.

198. The compound as claimed in claim 188, wherein P is phenyl substituted with a phenyl substituted with a -C1-C6-alkyl substituted with one or more halo.

199. The compound as claimed in claim 198, wherein P is phenyl substituted with a phenyl substituted with one or more -CF3.

200. The compound as claimed in claim 198, wherein P is phenyl substituted with a phenyl substituted with -CH2CF3.

201. The compound as claimed in claim 188, wherein P is phenyl substituted with a phenyl substituted with a halo and a O-C1-C6-alkyl.

202. The compound as claimed in claim 201, wherein P is phenyl substituted with a phenyl substituted with -F and a O-C1-C6-alkyl.

203. The compound as claimed in claim 188, wherein P is phenyl substituted with a phenyl substituted with a -C1-C6-alkyl and a -O-C1-C6-alkyl.

204. The compound as claimed in claim 203, wherein P is phenyl substituted with a phenyl substituted with a -C1-C3-alkyl and a - O-C1-C6-alkyl.

205. The compound as claimed in claim 188, wherein P is phenyl substituted with a phenyl substituted with -CN and -O-C1-C6-alkyl.

206. The compound as claimed in any one of claims 140 tol79, wherein P is -arylheteroaryl and wherein the heteroaryl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O-C1-C6-alkyl optionally substituted with one or more halo.

207. The compound as claimed in claim 206, wherein P is -phenyl -heteroaryl and wherein the heteroaryl is optionally substituted with one or more substituents selected from -halo, - CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O-C1-C6-alkyl optionally substituted with one or more halo.

208. The compound as claimed in claim 207, wherein P is -phenyl -heteroaryl and wherein the heteroaryl is substituted with -O-C1-C6-alkyl.

209. The compound as claimed in claim 207, wherein P is -phenyl -heteroaryl and wherein the heteroaryl is substituted with -O-C3-alkyl.

210. The compound as claimed in claim 209, wherein P is -phenyl -heteroaryl and wherein the heteroaryl is substituted with -O'Pr.

211. The compound as claimed in claim 209, wherein P is -phenyl -heteroaryl and wherein the heteroaryl is substituted with -OnPr.

212. The compound as claimed in claim 207, wherein P is -phenyl -heteroaryl and wherein the heteroaryl is substituted with -O-C1-C6-alkyl substituted with one or more halo.

213. The compound as claimed in claim 212, wherein P is -phenyl -heteroaryl and wherein the heteroaryl is substituted with -OCF3.

214. The compound as claimed in claim 212, wherein P is -phenyl -heteroaryl and wherein the heteroaryl is substituted with -OCH2CF3.

215. The compound as claimed in claim 206, wherein P is -aryl-pyridyl and wherein the pyridyl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O- C1-C6-alkyl optionally substituted with one or more halo.

216. The compound as claimed in claim 215, wherein P is -phenyl-pyridyl and wherein the pyridyl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O- C1-C6-alkyl optionally substituted with one or more halo.

217. The compound as claimed in claim 216, wherein P is -phenyl-pyridyl and wherein the pyridyl is optionally substituted with -O-C1-C6-alkyl.

218. The compound as claimed in claim 217, wherein P is -phenyl-pyridyl and wherein the pyridyl is optionally substituted with -O'Pr.

219. The compound as claimed in claim 216, wherein P is -phenyl-pyridyl and wherein the pyridyl is substituted with -O-C1-C6-alkyl substituted with one or more halo.

220. The compound as claimed in claim 219, wherein P is -phenyl-pyridyl and wherein the pyridyl is substituted with -OCF3 or -OCH2CF3.

221. The compound as claimed in any one of claims 140 to 179, wherein P is -heteroarylaryl and wherein the aryl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O-C1-C6-alkyl optionally substituted with one or more halo.

222. The compound as claimed in claim 221 wherein P is -heteroaryl-phenyl and wherein the phenyl is optionally substituted with one or more substituents selected from -halo, -CN, - C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and - O-C1-C6-alkyl optionally substituted with one or more halo.

223. The compound as claimed in claim 222, wherein P is a heteroaryl-phenyl and wherein the phenyl is substituted with -O-C1-C6-alkyl.

224. The compound as claimed in claim 223, wherein P is a heteroaryl-phenyl and wherein the phenyl is substituted with -O-C3-alkyl.

225. The compound as claimed in claim 224, wherein P is a heteroaryl-phenyl and wherein the phenyl is substituted with -O'Pr.

226. The compound as claimed in claim 224, wherein P is a heteroaryl-phenyl and wherein the phenyl is substituted with -OnPr.

227. The compound as claimed in claim 222, wherein P is a heteroaryl-phenyl and wherein the phenyl is substituted with -O-C1-C6-alkyl substituted with one or more halo.

228. The compound as claimed in claim 227, wherein P is a heteroaryl-phenyl and wherein the phenyl is substituted with -OCF3.

229. The compound as claimed in claim 227, wherein P is a heteroaryl-phenyl and wherein the phenyl is substituted with -OCH2CF3.

230. The compound as claimed in any one of claims 140 to 179, wherein P is -pyridyl-aryl and wherein the aryl is optionally substituted with one or more substituents selected from - halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6- alkyl and -O-C1-C6-alkyl optionally substituted with one or more halo.

231. The compound as claimed in claim 230, wherein P is -pyridyl-phenyl and wherein the phenyl is optionally substituted with one or more substituents selected from -halo, -CN, -C1-C6-alkyl, -C1-C6-alkyl optionally substituted with one or more halo, -O-C1-C6-alkyl and -O- C1-C6-alkyl optionally substituted with one or more halo.

232. The compound as claimed in claim 231, wherein P is a -pyridyl-phenyl and wherein the phenyl is substituted with -O-C1-C6-alkyl.

233. The compound as claimed in claim 232, wherein P is a -pyridyl-phenyl and wherein the phenyl is substituted with -O-C3-alkyl.

234. The compound as claimed in claim 233, wherein P is a -pyridyl-phenyl and wherein the phenyl is substituted with -O'Pr.

235. The compound as claimed in claim 233, wherein P is a -pyridyl-phenyl and wherein the phenyl is substituted with -OnPr.

236. The compound as claimed in claim 231, wherein P is a -pyridyl-phenyl and wherein the phenyl is substituted with -O-C1-C6-alkyl substituted with one or more halo.

237. The compound as claimed in claim 236, wherein P is a -pyridyl-phenyl and wherein the phenyl is substituted with -OCF3.

238. The compound as claimed in claim 236, wherein P is a -pyridyl-phenyl and wherein the phenyl is substituted with -OCH2CF3.

239. The compound as claimed in any one of claims 140 to 179, wherein P is -phenylphenyl- substituted with a heterocycle.

240. The compound as claimed in claim 240, wherein P is -phenyl -phenyl- substituted with a pyrrolidine.

241. The compound as claimed in any one of claims 140 to 240, wherein Q is selected from: or or oror or or10or242. The compound as claimed in any one of claims 140 to241, wherein Q is selected from: or or oror243. The compound as claimed in any one of claims 140 to 242 wherein Q isor244. The compound as claimed in claim 140 wherein the compound or salt of Formula II is selected from one or more of the following:

245. The compound as claimed in claim 140, wherein the compound of Formula II is:or a salt thereof.

246. The compound as claimed in claim 140, wherein the compound of Formula II is:or a salt thereof.

247. The compound as claimed in claim 140, wherein the compound of Formula II is:or a salt thereof.

248. The compound as claimed in claim 140, wherein the compound of Formula II is:or a salt thereof.

249. The compound as claimed in claim 140, wherein the compound of Formula II is:or a salt thereof.

250. The compound as claimed in claim 140, wherein the compound of Formula II is:or a salt thereof.

251. The compound as claimed in claim 140, wherein the compound of Formula II is:or a salt thereof.

252. The compound as claimed in claim 140, wherein the compound of Formula II is:or a salt thereof.

253. The compound as claimed in claim 140, wherein the compound of Formula II is:or a salt thereof.

254. The compound as claimed in claim 140, wherein the compound of Formula II is:or a salt thereof.

255. The compound as claimed in claim 140, wherein the compound of Formula II is:or a salt thereof.

256. The compound as claimed in claim 140, wherein the compound of Formula II is:or a salt thereof.

257. The compound as claimed in claim 140, wherein the compound of Formula II is:or a salt thereof.

258. The compound as claimed in claim 140, wherein the compound of Formula II is:or a salt thereof.

259. The compound as claimed in claim 140, wherein the compound of Formula II is:or a salt thereof.

260. The compound as claimed in claim 140, wherein the compound of Formula II is:or a salt thereof.

261. The compound as claimed in claim 140, wherein the compound of Formula II is:or a salt thereof.

262. The compound as claimed in claim 140, wherein the compound of Formula II is:or a salt thereof.

263. The compound as claimed in claim 140, wherein the compound of Formula II is:or a salt thereof.

264. The compound as claimed in claim 140, wherein the compound of Formula II is:or a salt thereof.

265. The compound of Formula I or II as claimed in any one of claims 1 to 264 for reducing the formation of methane from the digestive actions of ruminants and / or for improving ruminant performance.

266. The compound of Formula I or II as claimed in any one of claims 1 to 264 for reducing the formation of methane from the digestive actions of ruminants.

267. The compound of Formula I or II as claimed in any one of claims 1 to 264 for reducing the formation of methane from the digestive actions of ruminants by at least 10%.

268. The compound of Formula I or II as claimed in any one of claims 1 to 264 for reducing the formation of methane from the digestive actions of ruminants by at least 15%.

269. The compound of Formula I or II as claimed in any one of claims 1 to 264 for reducing the formation of methane from the digestive actions of ruminants by at least 20%.

270. A method for reducing the production of methane emanating from a ruminant and / or for improving ruminant animal performance, comprising administering orally to the ruminant an effective amount of at least one compound of Formula I or II or a salt thereof, as claimed in any one of claims 1 to 264.

271. The method as claimed in claim 270, wherein the effective amount of at least one compound of Formula I or II or a salt thereof is administered at least once-daily to the ruminant.

272. The method as claimed in claim 270 or claim 271, wherein the effective amount of at least one compound of Formula I or II or a salt thereof reduces the production of methane emanating from the ruminant by at least 10% per day.

273. The method as claimed in any one of claims 270 to 272, wherein the effective amount of at least one compound of Formula I or II or a salt thereof reduces the production of methane emanating from the ruminant by at least 15% per day.

274. The method as claimed in any one of claims 270 to 273, wherein the effective amount of at least one compound of Formula I or II or a salt thereof reduces the production of methane emanating from the ruminant by at least 20% per day.

275. A composition for oral administration comprising at least one compound of Formula I or II or a salt thereof as claimed in any one of claims 1 to 270 for reducing the production of methane emanating from a ruminant, and the composition further including at least one agriculturally and orally acceptable excipient.

276. The composition as claimed in claim 275, being adapted for use as a feed additive.

277. The composition as claimed in claim 275, being adapted for use as a water additive.

278. The composition as claimed in claim 275, adapted for use as a ruminant lick.

279. The composition as claimed in claim 275, adapted for use as an oral drench.

280. The composition as claimed in claim 275, adapted for use as a rumen bolus or capsule.

281. The composition as claimed in any one of claims 275 to 280, being adapted to reduce the production of methane emanating from the ruminant by at least 10% per day.

282. The composition as claimed in any one of claims 275 to 281, being adapted to reduce the production of methane emanating from the ruminant by at least 15% per day.

283. The composition as claimed in any one of claims 275 to 282, being adapted to reduce the production of methane emanating from the ruminant by at least 20% per day.

284. The composition as claimed in any one of claims 275 to 283, wherein the excipient may include one or more minerals and / or one or more vitamins.

285. The composition as claimed in any one of claims 275 to 284, wherein the excipient may include one or more vitamins selected from vitamin A, vitamin D3, vitamin E, and vitamin K, e.g. vitamin K3, vitamin B 12, biotin and choline, vitamin Bl, vitamin B2, vitamin B6, niacin, folic acid or the like.

286. The composition as claimed in any one of claims 275 to 285, wherein the excipient may include one or more minerals selected from calcium, phosphorus, sodium, manganese, zinc, iron, copper, chlorine, sulphur, magnesium, iodine, selenium, and cobalt or the like.

287. The composition as claimed in any one of claims 275 to 286 further including sunflower oil, electrolytes such as ammonium chloride, calcium carbonates, starch, proteins or the like.

Images