Antiarrhythmic 2-phenyl 2-(4-piperidinyl) acetonitrile derivs. - eeeee.g. 2-(4-piperidyl) 2-(3-,4,5-trimethoxyphenyl) acetonitrile

• Main Author: PHILIPPE MICHEL JACQUES MANOURY, GERARD EUGENE ALPHONSE DEFOSSE, HENRY NAJER, DON PIERRE RENE LUCIEN GIUDICELLI, ICILIO ANGELO GIROLAMO CAVERO, FRANCOISE MARIE LEFEVRE
• Format: Patent
• Language: English; French
• Published: 01.10.1976
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

2-Phenyl-2-(4-piperidinyl)-acetonitrile derivs of formula (I): and their acid-addn. salts are new: (where R1 is H or MeO, R2 is H or 1-4C alkyl. R3 is Me, H or Ar-A-; A is 1-4C alkyl-1 ene opt. substd by OH or oxo Ar is phenyl opt. mono- or disubstd. by OH, MeO or benzyloxy). Cpds. (I) are antiarrhythmic agents, e.g. (I; R1=H, R2=i-Pr, R3 = 1-p-hydroxyphenyl-1-hydroxy-2-propyl) is more active than verapamil against aconitine-induced ventricular tachycardia and fibrillation, and has much lower toxicity (LD50 = 56 mg/kg, i.v mouse). In an example, 2-(4-piperidyl)-2-(3,4,5-trimethoxyphenyl)-acetonitrile is prepd. by reacting 2-(3,4,5-trimethoxyphenyl)acetonitrile with 1-benzyl-4-piperidone and hydrogenating the prodt. with a Pd/C catalyst. Specifically claimed is (I) where R1 = H, R2=i-Pr, and R3 = 1-p-hydroxyphenyl-1-hydroxy-2-propyl.