Caspase inhibitors containing isoxazoline ring

A compound of the following formula (1):

• in which
• I) R represents H, simple alkyl chain (—SAC), simple cycloalkyl chain (—SCAC), aryl group (—Ar), or simple alkyl chain substituted by aryl (—SAC—Ar),
• II) R1 represents —SAC, —SCAC, —Ar, —SAC—Ar, or a side chain residue of all the natural amino acids;
• and the compound of formula (1) may exist in a specific diastereomeric form, or mixtures thereof when the carbon to which R′ is attached becomes a stereocenter due to the R1 group;
• or the compound of formula (1) may have a protecting group in an ester form (—CO2R3 wherein R3 is —SAC) or a sulfonamide form (—CONHSO2R4 wherein R4 is —SAC), or may exist in the form of pharmaceutically acceptable salt, when R1is a side chain residue of an amino acid containing carboxyl moiety;
• or the compound of formula (1) may also exist in the form of pharmaceutically acceptable salt when R1 is a side chain residue of an amino acid containing a base moiety,
• III) R2 represents —SAC, —SCAC, —Ar, —SAC—Ar, or a side chain residue of the natural amino acids;
• and the compound of formula (1) may exist in a specific diastereomeric form, or mixtures thereof when the carbon to which R2 is attached becomes a stereocenter due to the R2 group;
• the compound of formula (1) may have a protecting group in an ester form (—CO2R5 wherein R5 is —SAC) or a sulfonamide form (—CONHSO2R6 wherein R6 is —SAC), or may exist in the form of pharmaceutically acceptable salt, when R2 is a side chain residue of an amino acid containing carboxyl moiety;
• or the compound of formula (1) may also exist in the form of pharmaceutically acceptable salt when R2 is a side chain residue of an amino acid containing a base moiety, or
• R2 further represents H;
• —(CH2)n OR7 wherein R7 is —SAC, —SCAC, —Ar, or —SAC—Ar, and n=1 or 2;
• or —(CH2)n OC(═O)R8 wherein R is —SAC, —SCAC, —Ar, or —SAC—Ar, and n=1 or 2,
• IV) A represents —(CH2)n-(n=0-4), —O—(CH2)n-(n=0-4), or —NR9—(CH2)n-(n=0-4) wherein R9 is —SAC, —SCAC, —Ar, or —SAC—Ar,
• V) Brepresents H, —SAC, —SCAC, —Ar, or —SAC—Ar, or
• VI) R and R1 may form a cycle together with the carbon atom to which they are attached, where —R—R1— is —(CH2)n—, —(CH2)n—O—(CH2)m—, or —(CH2)n—NR10O—(CH2)m— wherein n+m<9 and R10 is —SAC, —SCAC, —Ar, —SAC—Ar, —C(═O)—SAC, —C(═O)—SCAC, —C(═O)—Ar, or —C(═O)—SAC—Ar,
• VII) X represents —C(═O)CH2OR11 wherein R11 is —SAC, —SCAC, —Ar, or —SAC—Ar;
• —C(═O)CH2OC(═O)R12 wherein R12 is —SAC, —SCAC, —Ar, or —SAC—Ar;
• —CH═CH—CO2R13 wherein R13 is —SAC, —SCAC, —Ar, or —SAC—Ar;
• —CH═CH—SO2 R14 wherein R14 is —SAC, —SCAC, —Ar, or —SAC—Ar;
• —C(═O)CH═CH2;
• or —COCH2—W wherein W is —N2, —F, —Cl, —Br, —I, —NR15R16 (R15 and R16 each are —SAC, —SCAC, —Ar, or —SAC—Ar, or together may form 3- to 6-membered saturated or unsaturated cyclic group), —SR17 (R17 is —SAC, —SCAC, —Ar, or —SAC—Ar), or is the following formula:
• wherein
• Y is H, —OH, —OR18 (R18═—SAC or —SCAC), —C(═O)R19 (R19═—H, —SAC, or —SCAC), —F, —Cl, —Br, —I, —C, —NC, —N3, —CO2H, CF3, —CO2R20 (R20═—SAC or —SCAC), —C(═O)NHR21 (R21═—SAC or —SCAC), or —C(═O)NR22 R23 (R22 and R23 each are —SAC, —SCAC, —Ar, or —SAC—Ar),
• R24 is H, —SAC, —SAC—Ar, or —Ar, salt, or stereoisomer thereof.