Guanadrel

Description

Guanadrel is an adrenergic neuron blocker used for essential hypertension. Its mechanism of action and side effects are similar to those of guanethidine.

Originator

Hylorel,Pennwalt,US,1983

Uses

Antihypertensive.

Uses

Guanadrel is an adrenergic neuron blocker used for essential hypertension. The mechanism of action and side effects are similar to guanethidine. It is used for treating hypertension in patients who do not respond to thiazide diuretics. It can be used as an adjuvant drug in thiazide treatment for reaching an optimal level of blood pressure.

Uses

It is used to treat hypertension in patients who do not adequately respond to thiazide diuretics. It can be used as an adjuvant in thiazide treatment for reaching an optimal level of blood pressure.

Definition

ChEBI: A spiroketal resulting from the formal condensation of the keto group of cyclohexanone with the hydroxy groups of 1-(2,3-dihydroxypropyl)guanidine. A postganglionic adrenergic blocking agent formerly used (generally as the sulfate salt) for the management f hypertension, it has been largely superseded by other drugs less likely to cause orthostatic hypotension (dizzy spells on standing up or stretching).

Manufacturing Process

A mixture of 10.5 g of 1,4-dioxaspiro[4.5]decane-2-methylamine and 8.6 g of 2-methyl-2-thiopseudourea sulfate in 40 ml of water was heated on the steam bath for 4 hours during which 2.0 g of methylmercaptan was collected in a dry ice bath connected to the reaction flask through a water cooled reflux condenser. The reaction mixture was then evaporated at 15 mm pressure to a solid residue which was then dissolved in 80 ml of 50/50 methanol-ethanol. The solution was filtered and evaporated to approximately 50 ml volume and allowed to cool and crystallize, giving a crop melting at 213.5°C to 215°C of 1,4-dioxaspiro[4.5]decan-2-ylmethyl)-guanidine sulfate.

brand name

Hylorel (Pharmacia & Upjohn).

Therapeutic Function

Antihypertensive

Synthesis

Guanadrel, (1,4-dioxaspiro[4,5]dec-2-ylmethyl)guanidine (12.3.8), is synthesized when cyclohexanone undergoes ketalization by 3-chloro-1,2-proandiol, forming 2- chloromethyl-1,4-dioxyspiro[4,5]decane (12.3.5), which is further akylated by sodium phthalimide. After alkyline hydrazinolysis, the resulting phthalimide derivative (12.3.6) is transformed into 2-aminomethyl-1,4-dioxyspiro[4,5]decane (12.3.7), which is reacted with S-methylthiourea, giving the desired guanadrel (12.3.8) [80¨C82].

Raw materials

Preparation Products