| 摘要 |
<p>N-(Carbamoyloxyalkyl)-N-phenyl-(hetero)arylsulfonamide derivatives (I) are new. N-(Carbamoyloxyalkyl)-N-phenyl-(hetero)arylsulfonamide derivatives of formula R1>SO2-N(R2>)-CR3>R4>-CH2-O-CO-NR5>R6> (I) and their salts, solvates and solvated salts are new. R1>phenyl or heteroaryl (both optionally substituted by one or more halo, CN, CF3, OCF3, 1-6C alkyl, hydroxy-1-6C alkyl, 3-8C cycloalkyl, 1-6C alkoxy or 1-6C alkylthio); R2>phenyl (optionally substituted by one or more halo, CN, CF3, OCF3, 1-6C alkyl, hydroxy-1-6C alkyl, 3-8C cycloalkyl, 1-6C alkoxy or 1-6C alkylthio); R3>H, CN or CF3, or 1-6C alkyl or 3-8C cycloalkyl (both optionally substituted by one or more OH, 1-6C alkoxy, CN, CF3, OCF3, NO2, NH2, amino-1-6C alkyl, COOH or 2-7C alkoxycarbonyl); R4>H or 1-6C alkyl; R5>H, 1-6C alkyl or 3-8C cycloalkyl; R6>-A1-A2-(A3)d-CO-R8>; or NR5>R6>heterocycle, substituted by -A4-(A5)d-CO-R8> and optionally substituted by one or more 6-10C aryl, 1-6C alkyl, =O and OH; d : 0 or 1; A11-6C alkylene; A26-10C arylene, heteroarylene or heterocyclylene (all optionally substituted by one or more halo, CN, =O, OH, 1-6C alkyl, 1-6C alkoxy, CF3 or OCF3); A3, A41-6C alkylene (optionally having one CH2 replaced by O or NR9>); R9>H or 1-6C alkyl; R8>OR1>0> or NR1>1>R1>2>; R1>0>H, 1-6C alkyl, 3-10C cycloalkyl or heterocyclyl; R1>1>, R1>2>H, 1-6C alkyl or 3-10C cycloalkyl; or NR1>1>R1>2>heterocycle; A56-10C arylene or heteroarylene; An independent claim is also included for the preparation of (I). ACTIVITY : Nootropic; Neuroprotective; Cerebroprotective; Tranquilizer; Antiparkinsonian; Anticonvulsant; Anti-HIV; Neuroleptic. MECHANISM OF ACTION : gamma -Secretase inhibitor; beta -amyloid synthesis inhibitor. In tests for inhibition of amyloid-beta peptide release in cultures of human cells (H4, HEK293) stably expressing human amyloid precursor peptide (APP), 2-(1-((rac-2-((2,5-difluorophenyl)-((4-chlorophenyl)-sulfonyl)-amino)-propyl)-oxycarbonyl)-4-piperidyl)-acetic acid (Ia) had an IC50 value of less than 3 MicroM.</p> |
