Novel PF74-like small molecules targeting the HIV-1 capsid protein: Balance of potency and metabolic stability

Of all known small molecules targeting human immunodeficiency virus (HIV) capsid protein (CA), PF74 represents by far the best characterized chemotype, due to its ability to confer antiviral phenotypes in both early and late phases of viral replication. However, the prohibitively low metabolic stability renders PF74 a poor antiviral lead. We report herein our medicinal chemistry efforts toward identifying novel and metabolically stable small molecules targeting the PF74 binding site. Specifically, we replaced the inter-domain-interacting, electron-rich indole ring of PF74 with less electron-rich isosteres, including imidazolidine-2,4-dione, pyrimidine-2,4-dione, and benzamide, and identified four potent antiviral compounds (

Application of multimedia technology in disease management on patients with chronic obstructive pulmonary disease / 中国基层医药

Objective To investigate the effect of multimedia technology on disease management capability in patients with chronic obstructive pulmonary disease (COPD).Methods 77 patients with COPD were randomly divided into control group ( 38 cases ) and observation group ( 39 cases ) .The control group was educated and managed on the basis of authorization education .While the observation group was cooperated with multimedia technology for COPD education and management , on the basis of authorization education .The intervention time lasted for 3 months.And the self -management capacity and quality of life of patients in the two groups were evaluated by utilizing self-management scale and St .George Respiratory Questionnaire ( SGRQ) respectively before intervention and 3 months after intervention .Results There were no statistically significant differences in self -management capacity and SGRQ score in all subjects before intervention (all P>0.05).After 3 months of intervention,the scores of self-management capacity on symptom management , daily life management , emotional management , information management and self -efficacy of the observation group were (30.71 ±6.79)points,(42.10 ±5.92)points,(39.51 ± 5.64) points,(30.92 ±6.08) points and (31.58 ±5.43) points,respectively,which were significantly higher than those in the control group [(27.76 ±4.12) points,(39.31 ±5.11) points,(36.28 ±6.38) points,(28.39 ± 4.70)points and (29.21 ±3.3)points],and the differences were statistically significant (t=-2.299,-2.207,-2.348,-2.037,-2.299,all P<0.05).The SGRQ scores of respiratory symptoms,disease effects and motion limitation of the observation group were (40.87 ±7.27) points,(41.17 ±7.15) points and (40.48 ±5.91) points, respectively,which were significantly lower than those in the control group [( 44.7 ±8.13 ) points, ( 45.21 ± 7.60)points,(43.60 ±5.87)points],and the differences were statistically significant (t=2.199,2.395,2.321,all P<0.05).Conclusion Application of advanced digital equipment and demonstration equipment to the disease education and management of patients with COPD based on patients 'needs provides effective ways and models to patients'health education ,which promotes the establishment of patients'healthy behaviors and the management of their own diseases ,and significantly improves the patients'self-management capacity and quality of life .