Psychosedative agents. N-(4-phenyl-1-piperazinylalkyl)-substituted cyclic imides

Abstract

In cold-stressed rats,11 IVa and j and V did not decrease peripheral plasma corticosterone levels at oral doses which exceeded those used to induce a natriuretic response (100 mg/kg).14 However, in rats, V caused adrenal hypertrophy, decreased male sex accessory organ weights, and decreased the rate of gain in body weight. These effects have not been observed with IVa and j.Earlier studies1•'2 had established that VI possessed a highly desirable spectrum of activity in natriuretic and adrenal corticosteroid inhibition assays. It caused marked natriuresis in Na+-depleted rats (a finding conil l) W. A. Zuccarello and G. J. Frishmuth, unpublished observations. sisteut with, but not. proof of, aldosterone inhibition) at oral doses which did not suppress peripheral plasma, corticosterone levels.1 In vitro findings supported the in vivo observations.1/2 Among (lie natriuretic agents tested in our laboratories, VI liad been the most potent of those which appeared to act by selectively inhibiting aldosterone biosynthesis.14 In the present series of compounds, both IVa. and j liad the same desirable biological selectivity as VI but were more active. In comparative studies, it was shown that VI was about two to three times as potent as VII. In turn, IVa. was about• twice as potent as XT, and IVj was about twice as potent as IVa (about four times as potent• as XT, and about eight to twelve times as potent as VII).14 The biological activity of IVj will be described in greater detail elsewhere.

8-[4-[2-(1,2,3,4-Tetrahydroisoquinolinyl)]butyl]-8-azaspiro[4.5]decane-7,9-dione: A New 5-HT1AReceptor Ligand with the Same Activity Profile as Buspirone

“…The following compounds were commercial products: 7 − 9 and 13 (Aldrich) and 12 (Lancaster Syntheses). Compound 2 was obtained according to the described procedure …”

N‐(4‐(4‐(2‐Halogenophenyl)piperazin‐1‐yl)butyl) Substituted Cinnamoyl Amide Derivatives as Dopamine D2 and D3 Receptor Ligands

“…Reduction of nitrile 1a could be achieved by treatment with lithium aluminium hydride to obtain 4-(4-(2-chlorophenyl)piperazin-1-yl)butylamine 2a. A more economic synthetic approach turned out to be the catalytic hydrogenation of the nitrile using Raney Nickel [16]. This method allowed scaling up to amounts of 20 g nitrile as educt and has been applied for synthesizing 4-(4-(2-fluorophenyl)piperazin-1-yl)butylamine 2b.…”

Buspirone free base

“…Since early studies (Wu et al, 1969(Wu et al, , 1972Wu & Rayburn, 1971, 1973 of the synthesis and biological activities of N-(4aryl-1-piperazinyl-alkyl)-substituted cyclic imides, a dependance between the alkyl chain length, the type of aryl group or imide residue and the activity has been known. These compounds show psychotropic properties.…”