Spofa, Spojene Podniky Pro Zdravotnickou Vyrobu

Spofa United Pharmaceutical Works

Spofa Spojene Podniky Pro Zdravotnickou

Vyzkumny Ustav Pro Farmacii a Biochemii S.p.

Vaclav Trcka

Miroslav Rajsner

Ivan Helfert

Jaroslava Grimova

Miroslav Semonsky

Karel Rezabek

Miroslav Seda

Antonin Cerny

Oldrich Nemecek

Gabriel Butora

Sverluse Macova

Jan Koenig

Luedvik Blaha

N-arylalkylderivatives of 2-aminomethyl-2,3-dihydro-1,4-benzodioxine and

2-Isopropyl-2-(2-methylphenyl)-5-(N-methylhomoveratrylamino)-valeronitrile ('mepamil') of the Formula I: ##STR1## preferably administered in the form of water-soluble acid addition salts such as e.g. hydrochloride. The claimed compound is advantageously prepared by alkylation of 2-(2-methylphenyl)-3-methylbutyronitrile with 3,3-diethoxypropylchloride. Subsequently, the obtained 5,5-diethoxy-2-isopropyl-2-(2-Methylphenyl)-valeronitrile is mildly, acidically hydrolisized to yield the appropriate aldehye, i.e. 2-isopropyl-2-(2-methylphenyl)-5-oxovaleronitrile. This aldehyde is then reacted with N-methylhomoveratrylamine under conditions of reductive alkylation, suitably by catalytic hydrogenation over a platinum or palladium catalyst or by chemical reduction with the use of formic acid as a reducing agent. The resulting base is optionally converted by neutralization with a pharmaceutically acceptable organic or inorganic acid, i.e. hydrochloric or fumaric acid, into the corresponding acid addition salt.

2-Isopropyl-2-(2-methylphenyl)-5-(N-methyl-N-homoveratr

Substituted acylpiperazinoquinazolines of formula I ##STR1## wherein n is 0 or 1, R represents an alkyl group with 1 to 4 carbon atoms or a benzyl group, and R.sub.1 is a hydrogen atom, a methyl group or a phenyl group. Addition salts of these compounds with inorganic and organic acids are also disclosed. The compounds possess a significant antihypertensive activity. They can be prepared by the reaction of 2-halogeno quinazoline derivatives with the corresponding acylpiperazines, followed (if required) by neutralization of the respective base with a suitable acid to form its pharmaceutically convenient addition salt. The acid addition salts, especially hydrochlorides, are readily soluble in water and give stable, almost neutral aqueous solutions which can be used in parenteral (injectable) and peroral medicinal dosage forms.

Substituted acylpiperazinoquinazolines and pharmaceutical compositions

8-(.beta.-AMINOETHYL)ERGOLINES-I of the general formula ##STR1## wherein R.sup.1 is a hydrogen atom or an acyl group of the general formula R.sup.3 --CO, R.sup.3 being a hydrogen atom, an alkyl group having from 1-5 carbon atoms, a phenyl group, a phenylalkyl group or a pyridyl group or substituents thereof, and R.sup.2 is a hydrogen atom or a methyl group. Acid addition salts of the described ergolines evidence pharmacological activity in the anti-inflammation and hypotensive fields.

8-(.beta.-AMINOETHYL)ERGOLINES-I

Growing community of inventors

Praha, Czechoslovakia

Vaclav Trcka