Highly soluble pyrimido-dione-quinoline compounds and their use in the treatment of cancer

摘要

The present invention features pyrimido-dione-quinoline compounds having improved solubility, pharmaceutical compositions of substituted pyrimido-dione-quinoline compounds and methods of treating a patient suffering from cancer, the method comprising administering to a patient one or more pyrimido-dione-quinoline compounds of the invention.

主权项

1. A method of treating a subject suffering from colon cancer, comprising
determining that the subject has cancer cells that comprise a wild type p53 gene, and administering to the subject an effective amount of a compound according to Formula I: wherein: R1 is selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclic aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, or optionally substituted heteroalicyclic; R2 is selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, or optionally substituted heteroalicyclic; R3 is, for each occurrence, selected from the group consisting of H, amino, hydroxy, cyano, nitro, carboxylate, carboxamide, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclic aryl, optionally substituted heteroaryl, optionally substituted alkoxy, optionally substituted mono- or di-alkyl amino, optionally substituted cycloalkyl, optionally substituted heteroalicyclic, optionally substituted aminoalkyl, —ORa, —NRaRb, —S(O)qRa, —C(O)Ra,—OC(O)Ra, —NRaC(O)Ra—C(S)Ra, —OC(S)Ra, —SC(S)Ra, —NRaC(S)Ra, —C(NRa)Ra, —OC(NRa)Ra, —SC(NRa)Ra, —NRaSO2Rc, —OS(O)2Ra; Z is selected from N, O, or S(O)q; wherein Ra is absent if not allowed; Ra, for each instance is independently selected from the group consisting of H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted heterocycloalkyl, an optionally substituted aralkyl, an optionally substituted heteroaralkyl, an optionally substituted aryl, an optionally substituted heteroaryl, haloalkyl, hydroxylalkyl, alkylcarbonylalkyl, mercaptoalkyl, aminoalkyl, sulfonylalkyl, sulfonylaryl, or thioalkoxy; Rb, for each instance is independently selected from the group consisting of H, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted alkynyl, an optionally substituted cycloalkyl, an optionally substituted heterocycloalkyl, an optionally substituted araalkyl, an optionally substituted heteroaralkyl, an optionally substituted aryl, an optionally substituted heteroaryl, haloalkyl, —(CH2)nORc, —(CH2)nSRc, —(CH2)nNRcRc, hydroxylalkyl, alkylcarbonylalkyl, mercaptoalkyl, aminoalkyl, sulfonylalkyl, sulfonylaryl, or thioalkoxy; Rc, for each instance is independently selected from the group consisting of H or an optionally substituted alkyl; n is an integer from 0 to 3; q is an integer from 0 to 2; or a pharmaceutically acceptable salt thereof.