PubMed · 14940202
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E G McQUEEN. 1952-06-07. Hexamethonium bromide and kidney function.. https://doi.org/10.5694/j.1326-5377.1952.tb84157.x
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Lubeluzole [(S)-9] has been synthesized by a convergent synthesis, alkylation of N-methyl-N-piperidin-4-yl-1,3-benzothiazol-2-amine (4) with (+)-(R)-1-chloro-3-(3,4-difluorophenoxy)propan-2-ol [(+)-(R)-8] being the key step. Alcohol (+)-(R)-8 was obtained from commercially available (R)-epichlorohydrin [(R)-6], while the thiazole derivative 4 was easily obtained starting from N-protected piperidin-4-one (1) in a three-step procedure. The same method was used in order to obtain both the (R)-stereoisomer of lubeluzole [(R)-9] and its racemate [(RS)-9]. Overall yields ranged from 20% to 35%. The enantiomeric excess values for (S)-9 and (R)-9 were 97% and 94% respectively, as analyzed by chiral HPLC.
Stent-based drug delivery system is a revolutionary approach to mitigate the negative affects of balloon angioplasty, improve immune responsiveness and prevent hyperplastic growth of smooth muscle in the restenotic state. Its success is therefore empirically associated with effective delivery of potent therapeutics to the target site at a therapeutic concentration, for a sufficient time, and in a biologically active form. However, local delivery with drug-eluting stents imparts large dynamic concentration gradients across tissues that can be difficult to identify, characterize and control. This review explores the factors such as physiological transport forces, drug physicochemical properties, local biological tissue properties and stent design that governs the local pharmacokinetics within the arterial wall by drug-eluting stent. Rational design and optimization of drug-eluting stents for local delivery thus requires a careful consideration of all these factors.
Diastolic heart failure occurs when signs and symptoms of heart failure are present but left ventricular systolic function is preserved (i.e., ejection fraction greater than 45 percent). The incidence of diastolic heart failure increases with age; therefore, 50 percent of older patients with heart failure may have isolated diastolic dysfunction. With early diagnosis and proper management the prognosis of diastolic dysfunction is more favorable than that of systolic dysfunction. Distinguishing diastolic from systolic heart failure is essential because the optimal therapy for one may aggravate the other. Although diastolic heart failure is clinically and radiographically indistinguishable from systolic heart failure, normal ejection fraction and abnormal diastolic function in the presence of symptoms and signs of heart failure confirm diastolic heart failure. The pharmacologic therapies of choice for diastolic heart failure are angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, diuretics, and beta blockers.