111626-10-9Relevant articles and documents
Synthesis, Calcium-Channel-Blocking Activity, and Antihypertensive Activity of 4-(Diarylmethyl)-1-piperidines and Structurally Related
Shanklin, James R.,Johnson, Christopher P.,Proakis, Anthony G.,Barrett, Richard J.
, p. 3011 - 3022 (2007/10/02)
A series of 4-(diarylmethyl)-1-piperidines and structurally related compounds were synthesized as calcium-channel blockers and antihypertensive agents.Compounds were evaluated for calcium-channel-blocking activity by determineng their ability to antagonize calcium-induced contractions of isolated rabbit aortic strips.The most potent compounds were those with fluoro substituents in the 3- and/or 4-positions of both rings of the diphenylmethyl group.Bis(4-fluorophenyl)acetonitrile analogue 79 was similar in potency to bis(4-fluorophenyl)methyl compound 1.The methylene analogue of 1 (78) and derivatives of 1 that contained a hydroxyl (76), carbamoyl (80), amino (81), or acetamido (82) substituent on the methyl group were less potent.In most cases substituents on the phenoxy ring, changes in the distance between the aryloxy group and the piperidine nitrogen, and the substitution of S, N(CH3), or CH2 for the oxygen atom of the aryloxy group had only a small to moderate effect on the potency.The best compounds in this series were more potent than verapamil, diltiazem, flunarizine, and lidoflazine, but were less potent than nifedipine.Compounds were evaluated for antihypertensive activity in spontaneusly hypertensive rats (SHR) at an oral dose of 30 mg/kg.Of the 55 compounds tested, only nine produced a statistically significant (p-1-piperidinyl>propoxy>-3-methoxyphenyl>ethanone (63), which produced a 35percent reduction in blood pressure and was similar in activity to nifedipine.At lower doses, however, 4--1-piperidine (93) was one of the most effective antihypertensive agents, producing reductions in blood pressure of 17 and 11percent at oral doses of 10 and 3 mg/kg, respectively; 63 was inactive at 10 mg/kg.
Arylalkyl-heterocyclic amines, n-substituted by aryloxyalkyl groups used in a method for allergy treatment
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, (2008/06/13)
A method of treating allergy with substituted heterocyclic amines is disclosed wherein the active agents are expressed generally by the formula which includes certain known and certain novel compounds: STR1 wherein p is zero, one or two; m is one to six inclusive; A is selected from hydrogen, hydroxy or cyano; d is zero or one; Q is --CH--, --CH2 -- or STR2 n is zero or one and when Q is --CH-- and n is one, a double bond is formed with one of the adjacent carbons but not both at the same time, and when n and d are zero at the same time, a double bond is formed between the α carbon and a carbon of the central heterocyclic amine ring; Ar, D and R are selected from phenyl, substituted phenyl, pyridinyl, thienyl, furanyl or naphthyl and in addition, R may have the values benzyl, substituted benzyl, cycloalkyl or loweralkyl and D may additionally have the values: 2H-1-benzopyran-2-one, 4-oxo-4H-1-benzopyran-2-carboxylic acid loweralkyl ester, 2,3-dihydro-4H-1-benzopyran-4-one or 1,4-benzodioxan-loweralkyl-2-yl, and the pharmaceutically acceptable salts thereof.
