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A series of new 5-oxo-1,2,4-oxadiazole derivatives with 1, 4-disubsituted or 1, 5-disubsituted indole group was designed, synthesized, and pharmacologically evaluated. These derivatives displayed high affinities to the AT1 receptor at the same order of magnitude to losartan. The methyl ester with 1, 4-disubsituted indole group, 1 (5.01 ± 1.67 nM) showed high antihypertension activity on spontaneously hypertensive rats (SHRs). Its maximal response lowered 30 mmHg of mean blood pressure (MBP) at 10 mg/kg after oral administration, which was better than irbesartan, and the antihypertensive effect lasted beyond 24 h. These results made 1 deserve further investigation.

Background Turnover of medical staff is a vital issue in the global healthcare system. Previous evidence has confirmed the critical effect of distributive justice on turnover intention, but few studies have focused on the mediating mechanism behind this relationship or the medical staff. This study aimed to examine the mediating roles of organizational commitment and work engagement in the relationship between distributive justice and turnover intention of medical staff, and explore potential occupational differences. Methods Stratified random sampling was adopted to select qualified medical staff from each clinical department of a large general hospital in Shenzhen, China, at a physician-to-nurse ratio of 1:1.5. The medical staff were surveyed using the Distributive Justice Scale, the Organizational Commitment Scale, the Work Engagement Scale, and the Turnover Intention Scale from May to July 2020. Of the 500 medical staff sampled, 480 responded (response rate: 96.00%), and 457 were finally included for analysis (effective response rate: 95.21%). A mediation analysis was performed using Model 6 of the SPSS macro PROCESS program. Results There were significant positive correlations among distributive justice, organizational commitment, and work engagement and significant negative correlations among distributive justice, organizational commitment, work engagement, and turnover intention. Distributive justice directly and negatively affected the turnover intention of physicians and nurses, but there were occupational differences in the underlying mechanism between distributive justice and turnover intention. Distributive justice indirectly affected turnover intention among physicians mainly through the mediating effect of organizational commitment, and indirectly among nurses through three different pathways: the mediating effect of organizational commitment, the mediating effect of work engagement, and the chain mediating effect of organizational commitment and work engagement. Conclusion The relationship between distributive justice and turnover intention was found to be mediated by organizational commitment and work engagement among medical staff in Shenzhen, with variations between physicians and nurses. Thus, appropriately targeted interventions are needed for physicians and nurses to reduce turnover intention.

A series of novel angiotensin II receptor 1 antagonists (1a-f, 2a-f) were designed, synthesized and evaluated. Radioligand binding assays showed that all these prepared compounds displayed nanomolar affinity for angiotensin II type 1 receptor, among which compound 1f was more affinitive than telmisartan at the same order of magnitude with an IC 50 value of 1.13 AE 1.68 nM. The antihypertensive effects showed that all these compounds could decrease blood pressure in a dose dependent manner on spontaneously hypertensive rats. And compound 2-(4- (1f), showed efficient and long-lasting effects in reducing blood pressure, with a maximal response lowered 55.98 AE 4.74 mmHg at 10 mg kg À1 and 35.82 AE 6.20 mmHg at 5 mg kg À1 , the antihypertensive effect of it lasted beyond 24 h which was better than telmisartan. In the single-dose pharmacokinetic experiments, compound 1f was absorbed efficiently and metabolized smoothly in Wistar rats. The values of C max , T max , AUC 0-72 , MRT 0-72 and T 1/2 were 17.92 AE 10.85 ng mL À1 , 2.60 AE 3.05 h, 252.85 AE 144.59 ng mL À1 h, 18.75 AE 0.43 h and 17.16 AE 4.24 h respectively. Compound 1f was distributed into tissues rapidly and extensively after oral administration and the level of it was the highest in the liver, followed by in the kidney, and the lowest in brain. The acute toxicity assays in ICR rats of 1f showed that it had low acute toxicity with an LD 50 value of 1459.89 mg kg À1 . These encouraging results make 1f an efficient, long-acting and safe antihypertensive drug candidate and deserving of further investigation.