| 摘要 |
A peptide-containing a-ketoamide inhibitor of cysteine and serine proteases or a pharmaceutically acceptable salt thereof has the formula (I) Q-(Aaa)n-[N(R3)-M(R1)(H)-C(O)]q-NH-C(H)(R2)-Z wherein: Q has the formula G-B-(CHR4)v; v is 0, 1, or 2; B is C(O), OC(O), S(O)m, CH2, a bond, NR5C(O), S(O)m-A-C(O) or C(O)-A-C(O); m is 0, 1, or 2; A and A1 are independently optionally substituted alkylene or cycloalkylene; M is a carbon atom; G is H, a blocking group, or optionally substituted alkyl, alkenyl, aryl, heterocyclyl, heterocycloalkyl, arylalkyl, heteroarylalkyl or arylheteroalkyl wherein the aryl portion can be unfused or fused with the heteroalkyl ring; each Aaa is independently an amino acid which optionally contains one or more blocking groups; n is 0, 1, 2, or 3; R1 and R2 are independently H, or optionally substituted alkyl, arylalkyl, heteroalkyl, heteroarylalkyl, alkoxyalkyl or a side chain of a naturally occurring amino acid in the R or S configuration or (CH2)pNH-L; p is 0, 1, 2, or 3; R3 is H or optionally substituted alkyl, arylalkyl, heteroalkyl, heteroarylalkyl, alkoxyalkyl or a side chain of a naturally occurring amino acid in the R or S configuration, (CH2)pNH-L, C(O)R7, S(O)2R7, a blocking group, and when combined with the carbon atom to which R1 is attached an optionally substituted alkylene group; q is 0 or 1; Z is C(O)C(O)NH-X-A1-K or 5-(C(O)C(O)-NH)-2-oxo-piperidine; X is a bond or -O- and R4, R5, R7, L and K are as defined in the specification. A pharmaceutical composition thereof is useful for inhibiting a serine protease or cysteine protease.
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