| 摘要 |
This invention relates to compounds of the formula: (see formula I) wherein: A' is absent, Asn, Gln, Ala or Abu; A is absent or a D- or L- amino acid chosen from Arg, HArg, (Me2)Arg, (Et2)Arg, Abu, Ala, Gly, His, Lys, or an .alpha.-R' substituted derivative thereof, Dtc, Tpr or Pro; B is a D- or L- amino acid chosen from Arg, HArg, NArg, (Me2)Arg, (Et2)Arg, Lys or an .alpha.-R' substituted derivative thereof; Q is absent or a D or L amino acid chosen from Tyr, (Alk)Tyr, Phe, (4'W)Phe, HPhe, Phg, Pro, Trp, His, Ser, (Alk)Ser, Thr, (Alk)Thr, (Alk)Cys, (Alk)Pen, Ala, Val, Nva, Met, Leu, Ile, Nle or Nal, or an .alpha.-R' substituted derivative thereof; M is absent or Gly or D or L Glu, Phe, Pro, Lys, Ser or, provided n is 1, B-Gly-Glu-Q; W is halogen or Alk; R' is Alk or PhCH2; Z1 is (see formula II), (see formula III), (see formula IV), ~ (see formula V) or (see formula VI); ~ Z2 is (see formula VII), (see formula VIII), (see formula IX), (see formula X) or (see formula XI), wherein Z1 and Z2 are linked via a covalent bond between L1 and L2; or Z1 and Z2 are, taken together, a covalent bond between the amino terminal residue and the carboxy terminal residue; L1 and L2 are -S- or -(CH2)p-; X is R4R5N or H;Y is H, CONR1R2 or CO2R2; R1 and R2 are H, Alk or (CH2)p Ar; R3 and R3, are H, Alk, (CH2)p Ar or taken together are -(CH2)4- or -(CH2)5-; R4 is H or Alk; R5 is R11, R11CO, R11OCO, R11OCH(R11')CO, R11NHCH(R11')CO, R11SCH(R11')CO, R11SO2 or R11SO; R6 is Alk, OAlk, halogen or X; R7 is H, Alk, OAlk, halogen or Y; R8 and R8' are H, Alk, (CH2)p Ph, (CH2)p Nph or taken together are -(CH2)4- or -(CH2)5-: R9 is H, Alk or Y; R10 is H or Alk; R11 and R11' are H, C1-5alkyl, C3-7cycloalkyl, Ar, Ar-C1-5alkyl, Ar-C3-7cycloalkyl; Ar is phenyl or phenyl substituted by one or two C1-5alkyl, trifluoromethyl, hydroxy, C1-5alkoxy or halogen groups; n is 1 or 2; q is 0 or 1; and p is 0, 1, 2 or 3; or a pharmaceutically acceptable salt thereof;. which are effective for inhibiting platelet aggregation, pharmaceutical compositions for effecting such activity, a method for inhibiting platelet aggregation and clot formation in a mammal, and a method for inhibiting reocclusion of a blood vessel following fibrinolytic therapy.
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