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Urea - Inosine monophosphate dehydrogenese (IMPDH), a key enzyme that is involved in the de novo synthesis of purine nucleotides, is an attractive target for immunosuppressive, anticancer, and antiviral therapies (18). Compound 15 (VX-497) is an orally active inhibitor of IMPDH (19) recently discovered using a structure-based design approach. Using a bioisosteric replacement of the amide portion of the urea moiety with an oxazole, a novel series of potent inhibitors such as 16 with low nanomolar potency against the enzyme were developed. Compound 16 also showed excellent In vivo activity in the inhibition of antibody production in mice and in the adjuvant induced arthritis model in rats (20). Replacing the urea linkage in 15 with an oxalamic diamide linkage also led to a series of potent IMPDH inhibitors as exemplified by 17 (21).
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Thank you for deciding to learn more about the disorder, Osteoarthritis. Inside these pages, you will learn what it is, who is most at risk for developing it, what causes it, and some treatment plans to help those that do have it feel better. While there is no definitive “cure” for Osteoarthritis, there are ways in which individuals can improve their quality of life and change the discomfort level to one that can be tolerated on a daily basis.