The use of a P53 inhibitor for the treatment of cancer, hyperthermia, hypoxia, a burn, trauma to the central nervous system, a seizure, acute inflammation, tissue ageing, preservation of organs for transplant and preparation of a host for bone marrow transplant

摘要

A temporary p53 inhibitor of formula (I), (II) (III) or (IV) or a mixture or pharmaceutically acceptable salts and hydrates thereof is used to treat a disease or condition wherein inhibition of p53 activity provides a benefit such as a p53-deficient cancerous tumor, hyperthermia, hypoxia, a burn, a trauma to the central nervous system, a seizure, an acute inflammation or senescence of fibroblasts. In formulae (I) to (IV): X is O, S, or NH, m is 0 or 1, n is 1 to 4, R1 and R2 independently are hydrogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, alkaryl, haloalkyl, haloaryl, a heterocyclic, heteroaryl, heteroaralkyl, alkoxy, aryloxy, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, halo, (alkylthio)alkyl, (arylthio)alkyl, or (aralkylthio)alkyl or together form an aliphatic or aromatic, 5-to 8-membered carbocyclic or heterocyclic ring; R3 is hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, aryl, aralkyl, haloaryl, heteroaralkyl, a heterocycle, alkoxy, aryloxy, halo, NR4R5, NHSO2NR4R5, NHSO2R4, or SO2NR4R5; and R4 and R5 independently are hydrogen, alkyl, aryl, heteroaryl, or a heterocycle or together form an aliphatic or aromatic, 5-to 8-membered carbocyclic or heterocyclic ring.