REMEDIAL AGENT FOR VIRAL INFECTIOUS DISEASE

摘要

Benzoxacine derivatives (I) are new. Benzoxacine derivatives of formula (I) and their salts and tautomers are new. [Image] R1, R2A (optionally substituted by Cyc, halo, guanidinyl, COOH, OH, OA, S(O)qA, phenyl or Het), Cyc, Ar, Het, R7NR10COOR11, R7NR8R9, R7CONR12R13, R7NR10CONR12R13 or R7NR10COR14, or R1 + R2 or R1 + CR2Cyc; A : alkyl; Cyc : cycloalkyl; Ar : aryl; Het : heterocyclyl; q : 0-2; R3H, A, ANHA, AAr, or AHet, or R1 + R3 or R2 + R35-7 membered optionally partially unsaturated Het; n : 0 or 1; R4H, A, alkenyl, Cyc, ACyc, Ar, Het, ANHA or AHet; R5alkylene; R6H, halo, A, NR15R16, NR17CONR18R19, NR17COOR20, NR21SO2R22 or NR17COR25; R7alkylene; R8, R9, R11, R13H, A, Cyc, ACyc, ANH2, ANHA, hydroxyalkyl, AOA, AOAra, Ar, Het, Ara, or AHet; or NR8R9, NR12R135-7 membered Het; Ara : aralkyl; R10H, A or Ara; R11A, Cyc, ACyc, ANHA, AOA, AOAra, Ar, Ara, Het or AHet; R14H, A (optionally substituted by Cyc, NHA, COOH, CONH2, OH, Ara, Ar or Het), Cyc, Ar or Het; R15, R16H, A, Cyc, ACyc, Ar, Ara, Het, AHet, ANHA, ANHAra, AOA or AOAra, or NR4R5, NR15R165-7 membered Het; R17, R21H, A or Ara; R18, R19H, A (optionally substituted by halo, NH2, NHA, COOH, CONH, CONHA, OH, OA, OAra, S(O)aA, Ar or Het), Cyc or Het, or NR4R5, NR15R16, NR18R195-7 membered Het; R20A (optionally substituted by halo, NHA, COOH, CONH2, CONHA, OAra, OA, Cyc, S(O)qA, Ar or Het) Cyc, Ar or Het; R22NH2, A, NHA, ANHA or Ar; R23a group R18, aralkenyl or a group of formula (i); R24, R25a group R1; R26, R28alkylene, and R27a group R6. [Image] ACTIVITY : Virucide. MECHANISM OF ACTION : Protease inhibitor. In assays, t-butyl (5-methyl-2-{1-methyl-1-[methyl-(2-pyrid-2-ylethyl)carbamoyl]ethylamino}-4-oxo-4H-benzo[d][1,3]oxazin-6-yl)carbamylate (Ia) exhibited an IC50 value for HSV-1 protease of 0.4 mu M.