Heterocyclic inhibitors of monocarboxylate transporter

A method of inhibiting monocarboxylate transporter MCT1, monocarboxylate transporter MCT4, or both, comprising contacting the monocarboxylate transporter with an effective amount or concentration of a compound of formula A

• wherein:
• R1 is selected from the group consisting of hydrogen, (C1-C6)alkyl, (C3-C6)branched alkyl, (C3-C7)cycloalkyl, and (C1-C6)fluoroalkyl;
• R2 is 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;
• 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, (C3-C7)cycloalkyl, (C6-C10)aryl, (5- to 7-membered)heteroaryl, or (4- to 7-membered) saturated heterocyclyl with 1-2 instances of heteroatoms selected from the group consisting of NH, NMe, O, and S;
• Z is CH2, CH((C1-C6)alkyl), CH((C3-C7)cycloalkyl), O, N, S, S(O), or SO2;
• n=1, 2, or 3;
• the cyclic group indicated as “ring” is an aryl or heteroaryl group of any one of the following:
• wherein wavy lines indicate points of bonding, and wherein M is independently selected CH or N, provided that M group can be a nitrogen atom in 0, 1, or 2, instances;
• L is S, O, NH, N(C1-C6)alkyl, or NCF3,
• each Q is independently CH or N;
• wherein R5 is optionally present, when present, R5 is 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;
• wherein R5 is optionally present, when present, R5 is 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 a pharmaceutically acceptable salt thereof.