Spofa, Spojene Podniky Pro Zdravotnickou Vyrobu

Spofa Spojene Podniky Pro Zdravotnickou

Vyzkumny Ustav Pro Farmacii a Biochemii S.p.

Spofa, Spojene Podinky Pro Zdravotnickou Vyrobu

Miroslav Rajsner

Vaclav Trcka

Ivan Helfert

Miroslav Protiva

Antonin Dlabac

Jirina Metysova

Karel Sindelar

Josef Pomykacek

Jiri Jilek

Jan Leiner

Leon Langsadl

Luedvik Blaha

Vladislava Hola

Vaclav Bartl

Frantisek Miksik

Sverluse Macova

Gabriel Butora

Jan Koenig

Iva Matunova

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

The present invention relates to imidazolyl thieno-benzothiepin derivatives of the Formula I: ##STR1## and acid addition salts thereof with pharmaceutically acceptable inorganic and organic acids, wherein R is a hydrogen or a chlorine atom. The invention also relates to processes for the preparation of these compounds. These compounds demonstrate substantial in vitro and in vivo antimycotic properties of the kind useful for the treatment of dermal and vaginal mycoses. The new compounds can be prepared by reacting 4,9-dihydrothieno(2,3-c)-2-benzothiepin-4-ol or its 6-chloro derivative with imidazole or a reactive derivative thereof, such as 1,1'-carbonyl-diimidazole or 1,1'-thionyldiimidazole; or by first converting the respective thieno-benzothiepin-4-ol into its alkane- or arenesulfonate ester, followed by reaction with imidazole.

Imidazole thieno-benzothiepins

Techniques for the preparation of 3-fluoro-10-piperazino-8-substituted 10,11-dihydrodibenzo-(b,f) thiepins and their addition salts with organic and inorganic acids are disclosed. The described compositions evidence psychotropic activity and low toxicity and are characterized as neuroliptics with a high degree of cataleptic, anti-apomorphine and central depressant action.

3 Fluoro-10-piperazino-8-substituted 10,11-dihydrodibenzo-(bf) thiepins

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Miroslav Rajsner