1-(Alkylamino)isochromans: hypotensives with peripheral and central activities

Abstract

A series of 1-[1-(3,4-dimethoxy-1H-2-benzopyran-1-yl)alkyl]-4-arylpiperazines that shows hypotensive activity in the conscious rat has been investigated. Structure-activity relationships are described. A typical example that was investigated in greater detail is 1-[2-(3,4-dihydro-6,7-dimethoxy-1H-2-benzopyran-1-yl)ethyl]-4-(4-fluorophenyl)piperazine. This compound decreases sympathetic nerve activity recorded from the external carotid and splanchnic nerves of baroreceptor-denervated cats and, therefore, has a central component to its mechanism of action. It also blocks pressor effects of norepinephrine and phenylephrine and is thus an alpha-adrenergic antagonist. Binding data characterize this as alpha 1-adrenergic receptor blockade.

A new approach to isochromanes

“…The discovered reaction can serve as a convenient tool for modification of the components of essential oils of plants such as myristicin, apiol, dillapiol, 13 and other natural allyl substituted polyphenols. 1 …”

“…Some isochromane derivatives exhibit hypotensive, 1 antitumor, 2 and growth regulating 3 activities; some others have a specific effect on the dopaminergic system. 4 The two most commonly used approaches to the for mation of the pyran ring of isochromanes are (1) cycliza tion of β phenylethanols with aldehydes in the presence of HCl 5-7 and (2) base catalyzed cyclization of various 2 allylbenzylic alcohols.…”

1-(4-Chlorophenyl)-6,7-dimethoxyisochroman

“…These are also intermediates in the synthesis of pharmaceuticals and drugs. 1-Aryl-6,7-dimethoxyisochromans are an important class of isochromans which exhibit a wide range of biological activities such as analgesic, muscle relaxant, antidepressant, anti-inflammatory, antihistaminic, anticoagulant and antihypertensive (Dobson et al, 1975;Yamato et al, 1985;McCall et al, 1982). 6,7-Dimethoxyisochromans substituted at C-1 via a one-to three-carbon chain with arylpiperazines, p-fluorophenyl, etc., are hypotensives which lower blood pressure, presumably by both peripheral and central -adrenoreceptor blockade (TenBrink et al, 1996).…”

Microwave‐accelerated Synthesis of Some (±)‐1‐Aryl‐5‐chloroisochromans

“…6,7-Dimethoxyisochromans substituted at C-1 via a one-to three-carbon chain with arylpiperazines are hypotensive with peripheral and central activities and are adrenergic antagonists. 15,16 The oxa-Pictet-Spengler reaction is a variation of the Pictet-Spengler reaction in which a phenethyl alcohol reacts with a carbonyl compound to give a 1-substituted isochroman derivative. Typically, aqueous HCl, zinc chloride HCl gas, p-toluenesulfonic acid, titanium tetrachloride or stannic chloride have been used as FriedelCrafts catalysts along with high reaction temperatures.…”