Compositions and methods for inhibition of hepatocyte growth factor receptor c-Met signaling

A method for treating a mammal having a neoplastic disease,

• wherein the treatment delays the onset of symptoms, complications, or biochemical indicia of the disease;
• alleviates the symptoms of the disease, arrests further development of the disease;
• or inhibits further development of the disease;
• wherein the neoplastic disease is characterized by a c-Met mutation or an overexpression of c-Met, comprising administering to the mammal a therapeutically effective amount of a compound of Formula I:
• or a pharmaceutically acceptable salt thereof,
• wherein
• R1 and R2 are each independently H, —CN, S, O, N, F, —CH2—OH, —OH, C1-C4 alkyl, amine, or ethanone, and at least one of R1 and R2 is —CN, S, O, N, or F;
• R3 is H;
• C1-C4 alkyl optionally substituted with halo or sulfonate;
• phenyl, phenoxy, or phenoxyalkyl, each optionally substituted with one or two substituents selected from hydroxyl, alkoxy, alkyl, halo, acetamido, acetamido alkoxy, carboxyl, and optionally-substituted amino;
• indolyl;
• pyridinyl;
• furanyl;
• thiophenyl;
• benzo[1,3]dioxolyl;
• or morpholinoalkyl, phenylalkyl or naphthylalkyl, each optionally substituted with alkyl, halo, or haloalkyl;
• R4 and R5 are each independently H;
• —CN;
• S;
• O;
• N;
• F;
• OH;
• C1-C4 alkyl;
• amine;
• ethanone;
• phenyl optionally substituted with hydroxyl, alkyl, or halo;
• or morpholinoalkyl, and at least one of R4 and R5 is —CN, S, O, N, F, or OH;
• R6 is O or N—R7;
• and
• R7 and R8 are each independently H;
• C1-C4 alkyl;
• hydroxyalkyl;
• carboxyalkyl;
• phenyl optionally substituted with one or more substituent selected from hydroxyl, alkoxy, carboxyl, halo, and acetamide-oxy;
• phenylamido;
• phenylamido carboxyl;
• phenylalkyl;
• phenylalkenyl;
• phenylhydrazonoalkyl;
• morpholinoalkyl;
• piperidine-proprionyl optionally substituted with carboxyl;
• or chromen-5-one optionally substituted with alkyl, dialkyl, or amino;
• and
• R9, R10, and R11 are each independently H, lower alkyl, or halo.