SACCHARIN DERIVATIVES AS ORALLY ACTIVE ELASTASE INHIBITORS, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

Saccharin derivatives (I), are new. Saccharin derivatives of formula (I) and their salts, solvates and hydrates are new. [Image] R1>methyl, ethyl or 2-morpholino-ethyl; R2>piperidino, morpholino or 4 methyl-piperazinyl; n : 2 or 3. Independent claims are included for: (a) preparation of (I); and (b) new intermediates of formula (III). [Image] ACTIVITY : Antiasthmatic; Antirheumatic; Antiarthritic; Antiinflammatory; Cytostatic; Antiulcer; Antiallergic; Hepatotropic; Virucide; Dermatological; Immunosuppressive; Nephrotropic; Antipsoriatic; Neuroprotective; Antibacterial; Cardiant; Tranquilizer; Vulnerary; Respiratory General; Antipsoriatic. Hypotensive; Gastrointestinal General; Endocrinal General. MECHANISM OF ACTION : Elastase inhibitor. A test was carried out to determine inhibition of acute lung damaging effect caused by human leukocyte elastase enzyme in mice. Test compounds were administered per os, and 1 hour later, human leukocyte elastase enzyme in physiological saline solution was administered intratracheally. After 3 hours the animals were euthanized. Bronchoalveolar lavage fluids were examined and haemorrhagic response determined. 2-(9-(2-Piperidino-ethoxy)-4 oxo-4H-pyrido(1,2-a)pyrimidin-2-yl-oxymethyl)-4-isopropyl-6 methoxy-1,2-benzisothiazol-3(2H)-one-1,1-dioxide (Ia) at 10 mg/kg showed 80 % inhibition. Jelen találmány tárgyát az (I) általános képletű -- ahol R1 jelentésemetil, etil vagy 2-morfolino-etil-csoport, R2 piperidino, morfolino -vagy 4-metil-piperazinil-csoport, n értéke 2 vagy 3, orálisan aktívvegyületek, sóik, szolvátjaik és hidrátjaik képezik. A találmánytárgya kiterjed a vegyületek előállítására és ezeket tartalmazógyógyszerkészítményekre is. Ó