Guanfacine is a phenylacetyl-guanidine derivative hypotensive and a centrally-acting, alpha (2) - adrenergic receptor agonist used alone or in combination with other drugs for the treatment of hypertension. It was approved by FDA on Oct. 27, 1986. It was developed and marketed as TenexÒ by Promius Pharma in the US. It can also been used for the treatment of attention deficit hyperactivity disorder (ADHD) in pediatric patients. FDA approved Intuniv (the active substance is guanfacine) for the treatment of ADHD on Sep. 2, 2009. And on Jun. 10, 2015, EMA approved Intuniv to treat ADHD in children and adolescents aged 6 to 17 years when stimulant medicines are not appropriate or do not control their symptoms well enough. In the following, synthesis method for guanfacine is introduced briefly.

In the patent CN103058890A, several methods for preparing guanfacine hydrochloride were described. (a) 2, 6-dichlorophenylacetonitrile was dissolved in methanol and concentrated sulfuric acid was added. Through alcoholysis, incubation, distillation etc., 2, 6-dichlorophenylacetate was obtained. Then it was added to guanidine solution of isopropanol to give crude product. The advantage is that concentrated sulfuric acid is remained. (b) 2, 6-dichlorophenylacetic acid dissolved in toluene was added to the guanidine in toluene, heated to reflux for 12 h in 120 °C, distilled under reduced pressure to remove toluene to give crude guanfacine. Although the process is simple, more toxic toluene was used as solvent. (c) Guanidine hydrochloride and 2, 6-dichlorobenzeneacetyl chloride were as raw materials, potassium carbonate as an acid binding agent, and acetonitrile as a solvent; then preparing crude guanfacine hydrochloride via the reaction of guanfacine with hydrochloric acid. Further purification was carried out to obtain guanfacine hydrochloride. The process of this method is simple and operation steps are reduced comparing with the previous two synthesis methods.

Through the aforementioned introduction, we have some knowledge of the indication and synthesis method for guanfacine hydrochloride.

Edited by Suzhou Yacoo Science Co., Ltd.