Use of benzopyranones for treating or preventing a primary brain cancer or a brain metastasis

A method for treating or preventing a primary brain cancer or a brain metastasis in a patient, comprising administering to a patient in need thereof an effective amount of a compound of the formula:

• 80
• or a pharmaceutically acceptable salt thereof, wherein:
• n is 0, 1, 2, 3 or 4;
• p is 0;
• R1 is an unsubstituted or substituted C6-12aryl, C7-12arylalkyl, C3-12heterocycle or C4-16heterocyclealkyl;
• R2 is NRaRb wherein Ra and Rb are independently hydrogen, C1-8alkyl, C6-12aryl, or heterocycle, and wherein Ra and Rb are optionally substituted with up to three substituents independently selected from C1-6alkyl, halogen, C1-6alkoxy, hydroxy and carboxyl;
• or R2 is a heterocyclic ring of the following structure:
• 81
• wherein
• m1 and m2 are independently 0, 1 or 2, and both of m1 and m2 are not 0,
• A is CH2, O, S or NH,
• Z represents 0, 1, 2 or 3 heterocyclic ring substituents selected from halogen, C1-8alkyl, C6-12aryl, C7-12arylalky, C3-12heterocycle, or C4-16heterocyclealkyl,
• and wherein any hydrogen atom on the heterocyclic ring may, taken together with a hydrogen atom on an adjacent atom of the heterocylic ring, form a double bond;
• R3is hydrogen, R4, C(═O)R4, C(═O)OR4, CONHR4, CONR4R5, or SO2NR5R5;
• R4 and R5 are independently C1-8alkyl, C6-12aryl, C7-12aralkyl, or a five- or six-membered heterocycle containing up to two heteroatoms selected from O, NR6 and S(O)q, wherein each of the above groups are optionally substituted with one to three substituents independently selected from R7 and q is 0, 1 or 2;
• R6 is hydrogen or C1-4alkyl;
• and
• R7 is hydrogen, halogen, hydroxy, C1-6alkyl, C1-4alkoxy, C1-4acyloxy, C1-4thio, C1-4alkylsulfinyl, C1-4alkylsulfonyl, (hydroxy)C1-4alkyl, C6-12aryl, C7-12aralkyl, COOH, CN, CONHOR8, SO2NHR8, NH2, C1-4alkylamino, C1-4dialkylamino, NHSO2R8, NO2, or a five- or six-membered heterocycle, where each occurrence of R8 is independently C1-6alkyl.