Method of inhibiting c-kit kinase

A method of treating a disorder related to C KIT selected from the group consisting of mast cell leukemia, sinonasal natural killer/T-cell lymphoma, seminoma, dysgerminoma, thyroid carcinoma, small-cell lung carcinoma, malignant melanoma, adenoid cystic carcinoma, angiosarcoma, endometrial carcinoma, and pediatric T-cell ALL comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition comprising a compound of Formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• A is
• phenyl or pyridyl, either of which is optionally substituted with one of chloro, fluoro, methyl, —N3, —NH2, —NH(alkyl), —N(alkyl)2, —S(alkyl), —O(alkyl), or 4-aminophenyl;
• W is
• pyrrolyl, imidazolyl, isoxazolyl, oxazolyl, 1,2,4 triazolyl, or furanyl, any of which is connected through any carbon atom, wherein the pyrrolyl, imidazolyl, isoxazolyl, oxazolyl, 1,2,4 triazolyl, or furanyl is optionally substituted by one —Cl, —CN, —NO2, —OMe, or —CF3, connected to any other carbon;
• R2 is
• cycloalkyl, thiophenyl, dihydrosulfonopyranyl, phenyl, furanyl, tetrahydropyridyl, or dihydropyranyl, any of which is optionally independently substituted with one or two chloro, fluoro, or C(1-3)alkyl, with the proviso that tetrahydropyridyl is connected to the ring A through a carbon-carbon bond;
• X is
• Z is
• CH or N;
• D1 and D2 are
• each hydrogen or taken together form a double bond to an oxygen;
• D3 and D4 are
• each hydrogen or taken together form a double bond to an oxygen;
• D5 is
• hydrogen or —CH3, wherein said —CH3 is relatively oriented syn or anti;
• Ra and Rb are each independently
• hydrogen, cycloalkyl, haloalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl;
• E is
• N, S, O, SO or SO2, with the proviso that E is not N if the following three conditions are simultaneously met:
• Qa is absent, Qb is absent, and R3 is an amino group or cyclic amino radical wherein the point of attachment to E is N;
• Qa is
• absent, —CH2—, —CH2CH2—, or C(O);
• Qb is
• absent, —NH—, —CH2—, —CH2CH2—, or C(O), with the proviso that Qb is not C(O) if Qa is C(O), and further provided that Qb is not —NH— if E is N and Qa is absent, further provided that Qb is not —NH— if R3 is an amino group or cyclic amino radical wherein the point of attachment to Qb is N;
• R3
• hydrogen, hydroxyalkylamino, (hydroxyalkyl)2-amino, alkylamino, aminoalkyl, dihydroxyalkyl, alkoxy, dialkylamino, hydroxyalkyl, —COOH, —CONH2, —CN, —SO2-alkyl-R4, —NH2, or a 5 or six membered ring which contains at least one heteroatom N and optionally contains an additional heteromoiety selected from S, SO2, N, and O, and the 5 or 6 membered ring is optionally saturated, partially unsaturated or aromatic, wherein aromatic nitrogen in the 5 or 6 membered ring is optionally present as N-oxide, and the 5 or 6 membered ring is optionally substituted with methyl, halogen, alkylamino, or alkoxy;
• or R3 is absent, with the proviso that R3 is not absent when E is nitrogen;
• R4 is
• hydrogen, —OH, alkoxy, carboxy, carboxamido, or carbamoyl.