Synthesis and hypotensive activity of benzamidopiperidylethylindoles

Abstract

18 65 87 93 100 0.3'* Cunen X 10_,! ' M for 50% inhibition of MAO activity of scintillation fluid and the radioactivity was measured. A blank contg boiled enzyme was carried through the entire procedure. The reported results are the averages of replicates and the average variation in the same experiment was ± ó %. The 1.0 was derived from a graph of the log conen/per cent inhibition. Chemistry.I.-The N-nitrosoamines were prepd by the method of Hartman and Roll.13 HC1 was replaced by AcOH, the reaction was carried out under N2 (HONO is lost by reaction with O»), and the mixt was heated to 60-70°after the addn of the NaN()2 soln. The compds were distd and anald, but can be used crude in the redns. The nmr spectra show split Me and CH2 peaks.

Pharmacological Options in the Treatment of Benign Prostatic Hyperplasia

“…Indoramin is the first generation of piperidine-based R 1 subtype-selective antagonists used in BPH (Figure 1). 65 A significant drawback with indoramin, however, is its interaction with other receptors, in particular 5-HT and histamine, leading to sedation as a side effect. The major challenge within this class has been to improve upon the levels of R 1 subtype selectivity seen with indoramin while removing the polypharmacology.…”

“…Piperidines. Indoramin is the first generation of piperidine-based α 1 subtype-selective antagonists used in BPH (Figure ) . A significant drawback with indoramin, however, is its interaction with other receptors, in particular 5-HT and histamine, leading to sedation as a side effect.…”

Medicinal Chemistry and Animal Pharmacology of Indoramin

“…Chemically, indoramin is the 1-(2-[3-indolyllethyl) derivative of 4-benzamidopiperidine (Figure 1). The original synthesis of indoramin involved quaternization of 4-benzamidopyridine with bromoethylindole followed by reduction (Archibald et al, 1971). Although indoramin was one of a large series of 4-aminopiperidine derivatives synthesized in the search for new and improved antihypertensive agents, it has emerged as the member of the series with the most favourable overall profile and mode of action for this indication.…”

Antihypertensives Acting by a Peripheral Mechanism

“…0 Indoramin was the product of investigation at Wyeth Labora tories of a number of compounds containing the indolylethylpiperidine group. Structure-activity relationships have been published in detail (51)(52)(53). The most remarkable findings appear to be that no advantage was gained by extensive modification of the 4-benzamidopiperidine moiety nor by replacement of the indole group by other heterocycles.…”