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US 10,851,113 B2Granted
Heterocyclic inhibitors of monocarboxylate transporters
AssigneeThe Scripps Research Institute
InventorsThomas D. Bannister, William R. Roush, Jun Yong Choi, Reji Nair, Andy S. Tsai, Jitendra K. Mishra, John L. Cleveland
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Abstract
The invention provides heterocyclic compounds of formula A, B, and C as described herein that inhibit monocarboxylate transporters, such as MCT1 and MCT4. Compounds of the invention can be used for treatment of a condition in a patient, wherein the condition is characterized by the heightened activity or by the high prevalence of MCT1 and/or MCT4, such as cancer or type II diabetes.
Claims18
A compound of formula B
- wherein:
- R1 is selected from the group consisting of hydrogen and C1-C6)alkyl;
- R2 is selected from the group consisting of hydrogen and (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, CF3, (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), or O;
- 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 a pharmaceutically acceptable salt thereof.
10 more elements
Dependencies are inferred from the claim text.