Allenes are molecules based on three carbons connected by two cumulated carbon-carbon double bonds. Given their axially chiral nature and unique reactivity, substituted allenes have a variety of applications in organic chemistry as key synthetic intermediates and directly as part of biologically active compounds. Although the demands for these motivated many endeavours to make axially chiral, substituted allenes by exercising asymmetric catalysis, the catalytic asymmetric synthesis of fully substituted ones (tetrasubstituted allenes) remained largely an unsolved issue. The fundamental obstacle to solving this conundrum is the lack of a simple synthetic transformation that provides tetrasubstituted allenes in the action of catalysis. We report herein a strategy to overcome this issue by the use of a phase-transfer-catalysed asymmetric functionalization of 1-alkylallene-1,3-dicarboxylates with N-arylsulfonyl imines and benzylic and allylic bromides.
Abstract-N-Type calcium channel antagonists may suppress sympathetic activity. The purpose of this study was to assess the effects of amlodipine and cilnidipine on the cardiac sympathetic nervous system and the neurohormonal status of essential hypertension. 123 I-metaiodobenzylguanidine (MIBG) cardiac imaging was performed and blood samples were taken to determine plasma renin activity and plasma norepinephrine concentration before and 3 months after drug administration in 47 patients with mild essential hypertension. Twenty-four of the patients were treated with 5 to 10 mg/d of amlodipine; the other 23 were treated with 10 to 20 mg/d of cilnidipine. For comparison, 12 normotensive subjects were also studied. No significant differences were found in the basal characteristics between the 2 hypertensive groups. In both hypertensive groups, both the systolic and diastolic blood pressures were significantly reduced to similar levels 3 months after drug treatment. Before the drug treatment, the 2 hypertensive groups had a significantly higher washout rate and lower heart-to-mediastinum (H/M) ratio compared with the normotensive subjects. The H/M ratio significantly increased (PϽ0.05) in combination with a decreased washout rate (PϽ0.02) after drug treatment in the cilnidipine group. In the amlodipine group, a significant decrease in washout rate (PϽ0.04) was noted, without an increase in the H/M ratio. However, no significant changes were found in plasma renin activity and plasma norepinephrine concentration in either group. Thus, in patients with essential hypertension, cilnidipine suppressed cardiac sympathetic overactivity and amlodipine had a little suppressive effect. Cilnidipine may provide a new strategy for treatment of cardiovascular diseases with sympathetic overactivity. (Hypertension. 1999;33:1447-1452.) Key Words: calcium channels Ⅲ amlodipine Ⅲ cilnidipine Ⅲ sympathetic nervous system Ⅲ plasma Ⅲ renin Ⅲ imaging C alcium antagonists are now widely used for the treatment of various types of hypertension. Despite their ability to lower the high blood pressure effectively, calcium antagonists do not always protect against cardiovascular complications because the use of short-acting calcium antagonists is associated with increased risk of acute myocardial infarction and mortality 1 and does not reduce the incidence of cardiac events. 2 Doubt about the use of calcium antagonists has arisen from their effects on neurohormonal status of patients, because neurohormonal activation is considered to be an important variable in the unexpected results obtained with short-acting calcium channel blockers. 3 Sympathetic overactivity plays a major role in the pathophysiology of hypertension. 4 -7 To lessen or avoid the further neurohormonal activation caused by short-acting calcium channel blockers, third-generation dihydropyridine-based calcium antagonists have been developed that have potential clinical benefits: gradual onset of action and a long duration of effects. However, a recent report on an increase in cardio...
Intestinal aganglionosis produced by serosal application of 0.1% benzalkonium solution to the colon of the rat was studied electronmicroscopically, and it was concluded that a higher susceptibility to the agent and a lower recovering ability of the nerve elements might be responsible for the phenomenon.
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