Patent NZ-708314-A (NZ)
Title: Quinazolinones for use as anticancer agents
Inventor: HANSEN C HENRIK
IPC: C07D295/088
Filed: 2010-03-16
Abstract: Disclosed is the use of a 2-phenyl-4-oxo-3,4-dihydroquinazoline derivative of Formula III, or a stereoisomer, tautomer, pharmaceutically acceptable salt, or hydrate thereof, in the preparation of a medicament for treating and/or preventing cancer characterized by altered expression of IL-6 or VCAM-1 in a subject (such as multiple myeloma, lymphoma, leukemia, solid tumors, prostate and bladder cancers, cardiac myxoma, tumor-induced cachexia, cerebral edema secondary to brain tumors, hormone-independent prostate cancer, B cell lymphoma, AIDS associated lymphoma, and metastatic renal cell carcinoma); wherein: Q is CR12; V is nitrogen; U is C=O; X is selected from oxygen, sulfur, NH, and CR6R7; Z is selected from unsubstituted alkyl and alkyl substituted with one or more groups selected from alkyl, alkoxy, cyclopropyl, hydroxyl, amino, and halogen; n is 0, 1, 2, 3, 4, or 5; G is selected from heterocycle optionally substituted by one or more groups selected from oxo, phenyl, methyl, ethyl, isopropyl, acetyl, C(O)NMe2, NHC(O)Me, N(i-Pr)C(O)Me, and NH(i-Pr), and/or optionally fused to phenyl; cycloalkyl; and aryl optionally substituted by one or more methyl; R1 is selected from hydrogen and alkyl; R6, R7, and R12 are independently selected from hydrogen, alkyl, cycloalkyl, heterocycle, alkoxy, and halogen; Rc is selected from hydrogen, alkyl, and cycloalkyl; Ra1, Ra2, and Ra3 are independently selected from hydrogen, alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, halogen, amino, amide, hydroxyl, and heterocycle, wherein Ra1 and Ra2 and/or Ra2 and Ra3 may be connected to form a cycloalkyl or a heterocycle; Rb2 and Rb6 are independently selected from hydrogen, halogen, alkyl, cycloalkyl, alkenyl, hydroxyl, and amino; and Rb3 and Rb5 are independently selected from hydrogen, halogen, alkyl, cycloalkyl, alkoxy, hydroxyl, and amino; wherein amide is -NRaC(O)(Rb) or -C(O)NRbRc, wherein Ra, Rb and Rc are each independently selected from alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen; and wherein amino is -N(Rd)Re, where Rd and Re are independently selected from alkyl, alkenyl, alkynyl, aryl, arylalkyl, cycloalkyl, haloalkyl, heteroaryl, heterocyclyl, and hydrogen; provided that at least one of Ra1, Ra2, and Ra3 is not hydrogen; wherein each aryl, heterocycle, and cycloalkyl is unsubstituted unless otherwise specified. Also disclosed are the uses of representative compounds such as 2-(3,5-dimethyl-4-(2-morpholinoethoxy)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one, 2-(3,5-dimethyl-4-(2-morpholinoethoxy)phenyl)quinazolin-4(3H)-one, 2-(3,5-dimethyl-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one, 2-(3,5-dimethyl-4-(3-(pyrrolidin-1-yl)propoxy)phenyl)-5,7-dimethoxy-3-(3-(pyrrolidin-1-yl)propyl)quinazolin-4(3H)-one, 2-(3,5-dimethyl-4-(2-(piperidin-1-yl)ethoxy)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one, 3-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-1-isopropylimidazolidine-2,4-dione, 2-(4-(2-(azepan-1-yl)ethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one, 2-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)isoindoline-1,3-dione, 2-(4-((4-isopropylpiperazin-1-yl)methyl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one and 3-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-5-phenylimidazolidine-2,4-dione.