PYRROLOQUINOLINYL-PYRROLIDINE-2,5-DIONE FORMULATIONS AND METHODS FOR PREPARING AND USING SAME

摘要

The present invention provides pyrroloquinolinyl-pyrrole-2,5-dione formulations and methods of treating a cell proliferative disorder, such as a cancer, by administering to a subject in need thereof a therapeutically effective amount of the formulations containing pyrroloquinolinyl-pyrrole-2,5-dione compounds.

主权项

1. A composition comprising a compound having solubility of 0 to 10 pg/mL in water at 37° C., wherein the compound is in the form of crystalline particles and wherein 99% of the particles have a diameter of 27 nm or lower, wherein the compound is a compound of formula III, IVa, IVb, Va, or Vb: or a pharmaceutically acceptable salt thereof, wherein:
R1, R2 and R3 are independently selected from the group consisting of hydrogen, F, Cl, Br, I, —NR5R6, —(C1-C6) alkyl, —(C1-C6) substituted alkyl, —(C3-C9) cycloalkyl, —(C3-C9) substituted cycloalkyl, —O—(C1-C6) alkyl, —O—(C1-C6) substituted alkyl, —O—(C3-C9) cycloalkyl, —O—(C3-C9) substituted cycloalkyl, aryl, heteroaryl, and heterocyclyl; R4 is selected from the group consisting of hydrogen, —(C1-C6) alkyl, and —CH2R7; R5 and R6 are independently selected from the group consisting of hydrogen and —(C1-C6) alkyl; R7 is selected from the group consisting of —O—P(═O)(OH)2, —O—P(═O)(—OH)(—O—(C1-C6) alkyl), —O—P(═O)(—O—(C1-C6) alkyl)2, —O—P(═O)(—OH) (—O—(CH2)phenyl), —O—P(═O)(—O—(CH2)phenyl)2, a carboxylic acid group, an amino carboxylic acid group, and a peptide; Q is selected from the group consisting of aryl, heteroaryl, —O—aryl, —S—aryl, —O—heteroaryl, and —S—heteroaryl; X is selected from the group consisting of —(CH2)—, —(NR8)—, S, and O; R8 is selected from the group consisting of hydrogen, —(C1-C6) alkyl, —(C1-C6) substituted alkyl, —(C3-C9) cycloalkyl, —(C3-C9) substituted cycloalkyl, —O—(C1-C6) alkyl, —C(═O)—O—(C1-C6) alkyl, and —C(═O)—O—(C1-C6) substituted alkyl; Y is selected from the group consisting of —(CH2)— and a bond; and m is 1 or 2,wherein the aryl, heteroaryl, —O—aryl, —S—aryl, —O—heteroaryl, and —S—heteroaryl groups may be substituted with one or more substituents independently selected from the group consisting of F, Cl, Br, I, —NR5R6, —(C1-C6) alkyl, —(C1-C6) substituted alkyl, —(C3-C9) cycloalkyl, —(C3-C9) substituted cycloalkyl, —O—(C1-C6) alkyl, —O—(C1-C6) substituted alkyl, —O—(C3-C9) cycloalkyl, —O—(C3-C9) substituted cycloalkyl, —aryl, —aryl—(C1-C6) alkyl, —aryl—(C1-C6) alkyl, —O—aryl, —O—(C1-C4) alkyl aryl, heteroaryl, heterocyclyl, —O—(C1-C4) alkyl heterocycle, and —(S(═O)2)—(C1-C6) alkyl.