Combination therapy using signal transduction inhibitors with paclitaxel and other taxane analogs

  • US 5,565,478 A
  • Filed: 03/14/1994
  • Issued: 10/15/1996
  • Est. Priority Date: 03/14/1994
  • Status: Expired due to Term
First Claim
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1. A pharmaceutical composition comprising, an effective amount of a first compound having formula I:

  • 
    
    space="preserve" listing-type="equation">Y--(CH.sub.2).sub.p --Ar.sup.11 --X--Ar.sup.12 (I)wherein;

    is an integer of from 0 to 4;

    Ar11 and Ar12 are each aromatic moieties independently selected from the group consisting of phenyl, naphthyl, halo-substituted phenyl, halo-substituted naphthyl;

    X is a linking moiety selected from the group consisting of O, S, SO2, CO, CHCN, straight chain alkyl, alkoxy, and alkoxyalkyl; and

    Y is a nitrogen-containing heterocyclic moiety of formula II;

    ##STR5## wherein;

    A is a member selected from the group consisting of N and CH;

    R1 is a member selected from the group consisting of hydrogen, --CONH2, --CONHR3, --CO2H, --CO2 R3, and --SO2 NH2, R2 is a member selected from the group consisting of hydrogen, --NHCOC6 H5, --NH2, --NHR3, --NC(R3)2, --NHCOR3, and --NHCHO; and

    R3 is lower alkyl of from 1 to 6 carbon atoms, and an effective amount of a second compound selected from the group consisting of paclitaxel, motere, and modified taxane analogs in a pharmaceutically acceptable carrier.

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