Quinazolinones 8 and pyrido[3,4-d]pyrimidin-4-ones 9 as orally active and specific matrix metalloproteinase-13 inhibitors were discovered for the treatment of osteoarthritis. Starting from a high-through-put screening (HTS) hit thizolopyrimidin-dione 7, we obtained two chemotypes, 8 and 9, using computer-aided drug design (CADD) and methodical structure-activity relationship (SAR) studies. They occupy the unique S 1'-specificity pocket and do not bind to the Zn(2+) ion. Some pyrido[3,4-d]pyrimidin-4-ones, such as 10a, possess favorable absorption, distribution, metabolism, and elimination (ADME) and safety profiles. 10a effectively prevents cartilage damage in rabbit animal models of osteoarthritis without inducing musculoskeletal side effects when given at extremely high doses to rats.

2-Aminophenyl-1H-pyrazole was discovered as a removable bidentate directing group for copper-mediated aerobic oxidative C(sp(2)-H) bond amidation and sulfonamidation. When Cu(OAc)2 was employed as the copper source and 1,1,3,3-tetramethylguanidine as an organic base, the reaction, optimally carried out overnight in DMSO at 80 °C in open air, produced a variety of amides and sulfonamides in moderate to excellent yields. This directing group has proven to be particularly efficient in C-H sulfonamidation.

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