Pteridine dione monocarboxylate transporter inhibitors

A MCT-inhibitory compound of formula A or of formula B

• wherein
• R1 and R2 are each independently selected from the group consisting of hydrogen, (C1-C6)alkyl, (C3-C6)branched alkyl, (C3-C7)cycloalkyl, (C1-C6)fluoroalkyl, a (C6-C10)aryl ring system, a 5- to 9-membered heteroaryl ring system, a (C1-C6)alkyl-(C6-C10)aryl ring system, and a (C1-C6)alkyl-(5- to 9-membered)heteroaryl ring system;
• provided that when R2 comprises an aryl or heteroaryl ring system, the ring system bears 0-2 independently selected substituents from the group consisting of fluoro, chloro, trifluoromethyl, (C1-C6)alkoxy, and (C1-C6)fluoroalkoxy;
• E is CH2, CH(C1-C6)alkyl, or CH(C3-C7)cycloalkyl;
• J is O, S, S(O), S(O)2, NH, N(C1-C6)alkyl, or NC(═O)(C1-C6)alkyl;
• R3 is a monocyclic or bicyclic (C6-C10)aryl or a monocyclic or bicyclic (5- to 10-membered) heteroaryl group wherein the aryl or heteroaryl can be substituted or unsubstituted;
• R4 is hydrogen, (C1-C6)alkyl, (C3-C6)branched alkyl, (C1-C6)fluoroalkyl, (C3-C7)cycloalkyl, a (4- to 7-membered)heteroaryl, or a monocyclic or bicyclic (C6-C10)aryl or a monocyclic or bicyclic (5- to 10-membered) heteroaryl group wherein the aryl or heteroaryl can be substituted or unsubstituted;
• Z is a bond, or is —O—, —CH2—, —CH(Me)-, —S—, —NH—, or —N(C1-C6)alkyl;
• n=1, 2, 3, or 4;
• the cyclic group indicated as “ring” is an aryl or heteroaryl group of any one of the following formulas:
• wherein wavy lines indicate points of bonding, and wherein each M is an independently selected CH or N, provided that M group is a nitrogen atom in one or two instances;
• G is S, O, NH, NMe, or NCF3;
• T is independently at each occurrence CH or N;
• wherein R5 is optionally present, R5 being one to four instances of independently selected F, Cl, Br, CF3, (C1-C6)alkyl, OCF3, O(C1-C6)alkyl, or CO—(C1-C6)alkyl;
• or,
• the cyclic group indicated as “ring” is a (C3-C7)cycloalkyl or a saturated (3- to 7-membered)heterocyclyl comprising 1-2 heteroatoms selected from the group consisting of O, NH, N(C1-C6)alkyl, and N(C1-C6)fluoroalkyl;
• wherein the points of bonding may be cis or trans;
• or a pharmaceutically acceptable salt thereof.