Synthesis And Studies On PTP1B Inhibitory Activity Of Quinazolinone Derivatives

This thesis was mainly forcused on synthesis of quinazolinone derivatives for small molecular Protein Tyrosine Phosphatase1B (PTP1B) inhibitiors.1. The parent structure of quinazolinone was constructed by the cyclization reaction of2-amiho-5-iodobenzoic acid or2-aminobenzoic acid with2-methoxy-phenylisocy-anate, and which reacted with variety of halides by nucleophilic substitution to afford46quinazolinone derivatives. All the compounds were characterized by1H NMR,13C NMR, and HRMS spectroscopy.2. All the quinazolinone derivatives’bioactivity on PTP1B inhibition were tested for the first time, and the prelimilary results showed that most of the compounds displayed comparative PTP1B inhibitory activity with maslinic acid (2alpha,3beta)--2,3-Dihydroxy-olean-12-en-28-oic acid). Among them, compound45gave the best result (IC50=2.08±0.61uM). The quinazolinon derivatives with iodo group at C-6position showed better inhibitory activity which is2-3folds higher than that of the non-substituted compounds. Although the different substitution at S atom didn’t obviously influence the bioactiovity, phenyl or unsaturated group substitution gave nicer inhibitory activity than that of N-alkyl amides. Moreover, the inhibitory activity on PTP1B was not affected by the electron-donating group or electron-withdrawing group.These novel small molecular PTP1B inhibitors provide new lead compounds for anti-obesity and diabetes drugs.