abstract |
The present disclosure provides compounds having Bcl inhibitory activity. Phosphonoamidate compounds usually contain a P-phenylphosphonoamidate moiety substituted with an N-aryl or N-heteroaryl group. The P-phenylphosphonoamidate moiety may be substituted in phosphorus with thio (= S) instead of oxo (= O) and / or with a tioxy group or a second amino group instead of an oxy group. .. One of the phosphorus-bonded heteroatoms may be cyclically bonded to the phosphorus-bonded N-substituted nitrogen atom to provide a heterocycle. By incorporating such a cyclic constraint between the two phosphorus substituents at the core binding moiety, favorable binding conformations can be promoted in the compound. Since the selected compounds promote apoptosis in senescent cells, they can be developed to treat aging-related conditions such as osteoarthritis, eye disease, lung disease, and atherosclerosis. The selected compound promotes apoptosis in cancer cells and can be developed as a chemotherapeutic agent. |