ABSTRACT
@#Conformational restriction has become one of the important strategies for modification and optimization of lead compounds in structure-based drug design. In this review, we select some recent practical examples from literature to present applications of conformational restriction in structure-based drug design. By introducing fused rings, macrocycles, spiral rings, cyclopropyl groups, bridging rings, methyl groups into molecules, we can find that the conformational restriction strategy is widely used in improving pharmacokinetic properties, enhancing the activity and selectivity, and increasing the novelty of compounds. By using these conformational restriction strategies, the drug-like properties of lead compounds can be significantly improved. This paper can help to provide theoretical guidance and practical experience for innovation in drug design and development.
ABSTRACT
OBJECTIVE:To investigate the characteristics of cecum and colon-specific drug delivery system of 4-aminosalicyl-ic acid-maltoside (4-ASA-Mal) in vitro. METHODS:With the cumulative release rate of 4-ASA as the index,HPLC was em-ployed to observe the delivery of 4-ASA-Mal (equivalent to 250 μg/ml 4-ASA) in the buffer solutions of different pH (1.2,6.8 and 7.4)and in the aqueous contents in different parts(stomach,small intestine,cecum and colon)of normal rats and the rat mod-els of ulcerative colitis. RESULTS:4-ASA-Mal was hardly released in the buffer solutions of different pH. 12 h cumulative release rates were less than 8% in the aqueous contents in the stomachs and small intestines of normal rats and rat models,and were 55%and 81% in the aqueous contents in the cecum and colons of normal rats,and 55% and 74% in the aqueous contents in the cecum and colons of model rats with ulcerative colitis. CONCLUSIONS:4-ASA-Mal can release a lot of 4-ASA in aqueous contents in ce-cum and colon,targeting cecum and colon in vitro.