Hydroquinone ansamycins for treatment of gastrointestinal stromal tumors.

Use of a hydroquinone ansamycin compound represented by formula 1: ** (See formula) ** wherein, independently for each occurrence: W is oxygen or sulfur; Q is oxygen, NR, N (acyl) or a bond; X- is a conjugate base of a pharmaceutically acceptable acid; R for each occurrence is selected independently from the group consisting of hydrogen, alkyl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroaryl and heteroarylalkyl; R1 is hydroxyl, alkoxyl, -OC (O) R8, -OC (O) OR9, -OC (O) NR10R11, -OSO2R12, -OC (O) NHSO2NR13R14, -NR13R14, or halide; and R2 is hydrogen, alkyl, or aralkyl; or R1 and R2 together with the carbon to which they are attached represent -C (= O) -, -C (C = N-OR) -, - (C = N-NHR) -, or - (C = NR) - ; R3 and R4 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroaryl, heteroarylalkyl, and - [(CR2) p] -R 16; or R3 together with R4 represent a 4-8 membered heterocyclic ring optionally substituted; R5 is selected from the group consisting of H, alkyl, aralkyl, and a group having the formula 1a: ** (See formula) ** in which R17 is independently selected from the group consisting of hydrogen, halide, hydroxyl, alkoxyl , aryloxy, acyloxy, amino, alkylamino, arylamino, acylamino, nitro, acylthio, carboxamide, carboxyl, nitrile, -COR18, -CO2R18, -N (R18) CO2R19, -OC (O) N (R18) (R19) , -N (R18) SO2R19, -N (R18) C (O) N (R18) (R19) and -CH2O-heterocyclyl; R6 and R7 are both hydrogen; or R6 and R7 together form a bond; R8 is hydrogen, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroaryl, heteroarylalkyl or - [(CR2) p] -R 16; R9 is alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaryl, heteroaralkyl, or - [(CR2) p] -R 16; R10 and R11 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaryl, heteroaralkyl, and - [(CR2) p] -R 16; or R10 and R11, together with the nitrogen to which they are attached represent a 4-8 membered heterocyclic ring optionally substituted; R12 is alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaryl, heteroaralkyl, or - [(CR2) p] -R 16; R13 and R14 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaryl, heteroaralkyl, and - [(CR2) p] -R 16; or R13 and R14 together with the nitrogen to which they are attached represent a 4-8 membered heterocyclic ring optionally substituted; R16 for each occurrence, is independently selected from the group consisting of hydrogen, hydroxyl, acylamino, -N (R18) COR19, -N (R18) C (O) OR 19, -N (R18) SO2 (R19), -CON (R18) (R19), -OC (O) N (R18) (R19), -SO2N (R18) (R19), -N (R18) (R19), -OC (O) OR 18, -COOR18, -C (O) N (OH) (R18), -OS (O) 2OR18, -S (O2) OR 18, -OP (O) (OR 18) (OR 19), -N (R18) P (O) (OR 18) ( OR 19) and -P (O) (OR 18) (OR 19); p is 1, 2, 3, 4, 5 or 6; R18 for each occurrence, is independently selected from the group consisting of hydrogen, alkyl, aryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroaryl and heteroarylalkyl; R19 is independently selected for each occurrence from the group consisting of hydrogen, alkyl, aryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroaryl and heteroarylalkyl; or R18 together with R19 represent a 5-8 membered ring optionally substituted; R20, R21, R22, R24 and R25 are for each occurrence independently alkyl; R23 is alkyl, -CH2OH, -CHO, -COOR18, or -CH (OR 18) 2; R26 and R27 for each occurrence, are independently selected from the group consisting of hydrogen, alkyl, aryl, cycloalkyl, heterocycloalkyl, arylalkyl, heteroaryl and heteroarylalkyl; and the absolute stereochemistry at a stereogenic center of formula 1 may be R or S or a mixture thereof and the stereochemistry of a double bond may be E or Z or a mixture thereof; in the manufacture of a medicament for use in the treatment of one more gastrointestinal stromal tumors in a mammal.