| 摘要 |
<p>New hydroxyamidine or hydroxyguanidine compounds consist of N-alpha -(2,4,6-triisopropyl-phenylsulfonyl)-phenylalanine-piperazine derivatives (I) and N-substituted dipeptide (or analog) benzylamides (II), ring-substituted by a hydroxyamidine or hydroxyguanidine group in the phenylalanine or benzyl moiety respectively. Hydroxyamidine or hydroxyguanidine compounds of formulae (I) and (II) and their salts (specifically the hydrogen sulfates) are new. [Image] E : -C(NH 2)=NOR 3> or -NH-C(=NH)-NH-OR 3>; B : SO 2 or CO; X : NR 1> or CHR 1>; Z : R 4>, OR 4> or NHR 4>; Y : OR 2> or NHR 2>; R 1>H, 1-6C alkyl, 2-6C alkenyl or 2-6C alkynyl; R 2>H, OR 1>, COR 1>, CON(R 1>) 2 or COOR 1>; R 3>H, 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl, COR 6>, COOR 6> or an oligo- or polyalkylenoxy group; R 4>H, 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl or cyclic group; R 5>OR 6>, N(R 6>) 2, 1-6C alkyl, 2-6C alkenyl or 2-6C alkynyl; R 6>as for R 4>; all cyclic groups are optionally substituted by one or more of 1-3C alkyl, 1-3C alkoxy, halo, OR 6>, =O, NO 2, CN, COOR 6>, N(R 6>) 2, NR 6>COR 6>, NR 6>CON(R 6>) 2 or OCOR 6>; all alkyl, alkenyl or alkynyl groups are optionally substituted by one or more of halo, OR 6>, OCOR 6>, N(R 6>) 2, NR 6>COR 6>, NR 6>CON(R 6>) 2, COOR 6> or cyclic groups. ACTIVITY : Cytostatic; Hypotensive; Cardiant; Antiinflammatory; Antiarthritic; Osteopathic; Dermatological; Ophthalmological; Virucide; Antibacterial. In tests in rats with implanted BN472 breast cancer, oral administration of N-alpha -(2,4,6-triisopropyl-phenylsulfonyl)-3-hydroxyamidino-(L)-phenylalanine-4-ethoxycarbonyl-piperazine (Ia) at 5 mg/kg per day (starting 3 days after implantation) reduced the tumor weight on day 30 by ca. 66% relative to that in untreated controls. MECHANISM OF ACTION : Urokinase plasminogen activator (uPa) inhibitor; Urokinase inhibitor.</p> |
