New 3alpha-amino-5alpha-androstane derivatives are protein cyclin-dependent kinase 5/p25 interaction inhibitors useful to treat e.g. stroke, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and diabetes

摘要

3alpha -Amino-5alpha -androstane derivatives (I) or their salts, racemates, and/or geometrical or optical isomers are new. 3alpha -Amino-5alpha -androstane derivatives of formula (I) or their salts, racemates, and/or geometrical or optical isomers are new. R 1>-NH 2-NH-(R 3>), -N(R 3>) 2, -N +>(R 3>) 3, -NH-COR 3>, -N(R 3>)-CO-R 3>, OH, =O, tetrazolyl or -O-CO-R 3>, preferably NH 2; R 2>CO-R 3>, -CH 2-OH, -C(R3)=N-OH, -C(R 3>)-N-NH-C(=NH)-NH 2, -C-(R 3>)=N-NH 2, 1-8C-alkyl, -CH(OH)-R 3>, =CH-R 3>, -CH(R 3>)-NH-R 3>, OH, -CH-(R 3>)-NH-CO-R 3>, -CH(R 3>)-N(R 3>) 2, -CH(R 3>)-NH 2, -CH(R 3>)-N(R 3>)-CO-R 3>, -CH(R 3>)-N +>(R 3>) 3, -CH(R 3>)-NH-CO-R 3>, oxazolonyl, H-(CH 2) n-P-(C 6H 5) 3, chain type polyalkylene glycol with a terminal group, such as -NH 2(which is capable of forming a bond on activated sepharose beads), or a biotinylated group; and R 3>1-3C-alkyl or H. ACTIVITY : CNS-Gen.; Cerebroprotective; Vasotropic; Neuroprotective; Nootropic; Antiparkinsonian; Analgesic; Cytostatic; Antidiabetic; Virucide. MECHANISM OF ACTION : Protein cyclin-dependent kinase 5/p25 interaction inhibitor. The ability of (I) to inhibit protein cyclin-dependent kinase 5/p25 interaction was tested using bioluminescence resonance energy transfer technique. The results showed that (3R,5S,8S,9S,10S,13S,14S)-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-3-ylamine exhibited an IC 50value of 4 mu m.