Bisphosphonate compounds and methods with enhanced potency for multiple targets including FPPS, GGPPS, and DPPS

A compound of formula XA1:

• or salts or hydrates thereof, wherein;
• X is hydrogen, hydroxyl group, or a halogen;
• each M is independently selected from the group consisting of a negative charge, a hydrogen, an alkyl group, and a —(CH2)p—O—CO—R or —(CH2)p—O—CO—O—R group, where p is 1 to 6, and R is selected from the group consisting of hydrogen, optionally substituted alkyl and optionally substituted aryl;
• or
• —OM is a salt of form —O−A+, where A+ is a cation;
• n is 1, 2, or 3;
• each R1 and R2, independently, is selected from the group consisting of a hydrogen, a halogen, —N(R)2, —SR′, OR′, an optionally substituted alkyl, an optionally substituted alkenyl, and an optionally substituted aryl group, where each R′ is independently selected from the group consisting of H, an optionally substituted alkyl group and an optionally substituted aryl group, and one of R1 and one of R2 together optionally form a 3-10 member carbocyclic or heterocyclic ring containing one to three heteroatoms, particularly N, S, and O;
• wherein R3-R7 are independently selected from the group consisting of a hydrogen, a halogen, —CN, —OR′″, —COOR′″, —OCOOR′″, —COR′″, —CON(R′″)2, —OCON(R′″)2, —N(R′″)2, —NO2, —SR, —SO2R, —SO2N(R′″)2, —SOR′″ group, an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted alkynyl group and an optionally substituted aryl group, where each R or R′″ is independently selected from H, an optionally substituted alkyl group, an optionally substituted aryl group, and an optionally substituted acyl group;
• wherein at least one of R3-R7 is RL, where RL is selected from the group consisting of alkyl, alkoxy, alkenyl, alkynyl, alkenoxy and alkynoxy groups having 6 to 20 carbon atoms, each of which are optionally substituted;
• alkyl ether groups which are alkyl groups having 6-20 carbon atoms in which one or more non-adjacent carbon atoms are replaced with an O;
• and a 3-RM or 4-RM substituted phenyl group, where RM is selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, alkenyoxy, alkynoxy and alkyl ether groups having 3-15 carbon atoms;
• and
• wherein the other ring positions of the phenyl ring are optionally substituted with one or more halogens, or one or more optionally substituted alkyl groups having 1-3 carbon atoms.