Method for inhibiting growth of cancer cells

A method of inhibiting the growth of cancerous cells that contain an enhanced amount of one or more of phosphorylated-mTOR, phosphorylated-Akt1, phosphorylated-ERK2 and serine2152-phosphorylated filamin A that comprises contacting said cancer cells with an FLNA-binding effective amount of a compound or a pharmaceutically acceptable salt thereof that binds in a solid phase assay to the pentapeptide of FLNA of SEQ ID NO:

• 1, said compound or salt exhibits at least about 60 percent of the FITC-labeled naloxone binding amount when present at a 10 μM concentration, using unlabeled naloxone as the control inhibitor at the same concentration as said compound or salt, said pentapeptide of FLNA being biotinylated at its N-terminal valine residue and bound to a streptavidin-coated solid support, wherein said enhanced amount of phosphorylated-mTOR, phosphorylated-Akt1, phosphorylated-ERK2 and serine2152-phosphorylated filamin A being an amount that is significantly greater than the amount present in a non-cancerous cell of the same type, wherein said compound is a compound of Series C-2 that corresponds in structure to the Formula I below:
• wherein
• J and F are the same or different and are CH2, CHD or CD2 (where D is deuterium);
• Q is CHR9 or C(O), Z is CHR10 or C(O), and only one of Q and Z is C(O);
• each of m, n and p is zero or one and the sum of m+n+p is 2;
• W is selected from the group consisting of NR2, NR7, S and O, where R7 and R2 are the same or different and are H, C(H)v(D)h where each of v and h is 0, 1, 2 or 3 and v+h =3, C(H)q(D)r-aliphatic C1-C11 hydrocarbyl where each of q and r is 0, 1, or 2 and q+r =0, 1 or 2, aliphatic C1-C12 hydrocarbyl sulfonyl or aliphatic C1-C12 hydrocarboyl, and X-circle A-R1 is as defined hereinafter;
• X is SO2 or CH2;
• circle A is an aromatic or heteroaromatic ring system that contains a single ring or two fused rings;
• R1 is H or represents up to three substituents, R1a, R1b, and R1c, that can be the same or different, wherein each of those three groups, R1a-c, is separately selected from the group consisting of H, C1-C6 hydrocarbyl, C1-C6 hydrocarbyloxy, C1-C6 hydrocarbyloxycarbonyl, trifluoromethyl, trifluoromethoxy, C1-C7 hydrocarboyl, hydroxy-, trifluoromethyl- or halogen-substituted C1-C7 hydrocarboyl, C1-C6 hydrocarbylsulfonyl, C1-C6 hydrocarbyloxysulfonyl, halogen, nitro, phenyl, cyano, carboxyl, C1-C7 hydrocarbyl carboxylate, carboxamide or sulfonamide,
• wherein the amido nitrogen in either amide group has the formula NR3R4 in which R3 and R4 are the same or different and are H, C1-C4 hydrocarbyl, or R3 and R4 together with the amido nitrogen form a 5-7-membered ring that optionally contains 1 or 2 additional hetero atoms that independently are nitrogen, oxygen or sulfur,
• MAr, where M is —CH2—, —O— or —N═N— and Ar is a single-ringed aryl or heteroaryl group and NR5R6 wherein R5 and R6 are the same or different and are H, C1-C4 hydrocarbyl, C1-C4 acyl, C1-C4 hydrocarbylsulfonyl, or R5 and R6 together with the nitrogen form a 5-7-membered ring that optionally contains 1 or 2 additional hetero atoms that independently are nitrogen, oxygen or sulfur;
• and
• R8, R9, and R10 are each H, or two of R8, R9, and R10 are H and one is a C1-C8 hydrocarbyl group that is unsubstituted or is substituted with up to three atoms that are the same or different and are oxygen or nitrogen atoms.