| abstract |
The present invention provides selective proton coupled folate transporter and folate receptor, and glycinamide ribonucleotide formyltransferase enzyme and/or other folate metabolizing enzyme inhibitors having a fused cyclic pyrimidine compound, including tautomers thereof, and pharmaceutically acceptable salts, prodrugs, solvates and hydrates thereof. These compounds are useful in methods for treating cancer, selectively targeting cancerous cells via the proton coupled folate transporter, folate receptor alpha, and/or folate receptor beta pathways, inhibiting GARFTase and/or other folate metabolizing enzymes in cancerous cells, and selectively targeting activated macrophages in a patient having an autoimmune disease, such as rheumatoid arthritis. |