Fused bicyclic-substituted amines as histamine-3 receptor ligands

A method of selectively modulating the effects of histamine-3 receptors in a mammal comprising administering an effective amount of a compound of the formula:

• or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof, wherein:
• X is O, S, NH, or N(alkyl);
• Y, and Y′ are each independently selected from the group consisting of CH, CF, and N;
• Z is C or N, provided that when X is O or S, Z is N;
• one of R1 and R2 is selected from the group consisting of aryl, heteroaryl, and heterocycle;
• the other of R1 and R2 is selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, cycloalkyl, halo, cyano, and thioalkoxy;
• R3 is absent when Z is N and, when present, R3 is selected from the group consisting of hydrogen, methyl, alkoxy, halo, and cyano;
• R4 and R5 are each independently selected from the group consisting of alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, and cycloalkylalkyl, or R4 and R5 taken together with the nitrogen atom to which each is attached form a non-aromatic ring of the structure (a):
• R7, R8, R9, and R10 are each independently selected from the group consisting of hydrogen, hydroxyalkyl, fluoroalkyl, and alkyl;
• or one of the pair R7 and R8 or the pair R9 and R10 is taken together to form a C3-C6 ring, wherein 0, 1, or 2 heteroatoms selected from O, N, or S replace a carbon atom in the ring;
• R11 and R12 are each independently selected from the group consisting of hydrogen, hydroxy, hydroxyalkyl, alkyl, and fluoro;
• R13 and R14 at each occurrence are independently selected from the group consisting of hydrogen, alkyl, and fluoro;
• L is —[C(R15)(R16)]n—;
• R15 and R16 at each occurrence are independently selected from the group consisting of hydrogen, alkyl, alkoxy, and fluoro;
• m is an integer from 0-3;
• and
• n is an integer from 2-3.