Carbon-linked substituted piperidines and derivatives thereof useful as histamine H3 antagonists

A compound represented by the structural formula

• or a pharmaceutically acceptable salt thereof, wherein:
• a is 0;
• b is 0;
• d is 0;
• e is 0;
• n is 2;
• p is 2;
• M1 is N;
• M2 is CH or CF;
• M3 is N;
• Y is —C(═O)—;
• Z is CH2;
• R1 is H, alkyl, alkenyl, R10-cycloalkyl, R10-aryl, R10-monoheteroaryl or R10-heterocycloalkyl,
• wherein said monocyclic heteroaryl ring has from 1 to 6 carbon atoms and 1 to 4 heteroatoms, each heteroatom independently selected from O, S and N;
• R2 is a six-membered heteroaryl
• R3 and R4 are independently selected from the group consisting of H, halo, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, hydroxyalkoxy, alkoxyalkoxy, aryl, arylalkyl, cycloalkyl, heterocycloalkyl, heteroaryl, heteroarylalkyl, —OR12, —CN, —(CH2)f—N(R12)2, —(CH2)f—N(R19)—SO2R12, —(CH2)f—N(R19)—C(O)R12, —(CH2)f—NHC(O)NHR12, —(CH2)f—NHC(O)OR12, —O—C(O)NHR12, —(CH2)f—C(O)OR12 and —O—(CH2)f—C(O)OR12, provided that when one of R3 and R4 is a heteroatom-linked substituent, the other is H, wherein f is 0, 1 or 2;
• or R3 and R4, together with the carbon to which they are attached, form —C(═C(R15)(R18))—, a 3- to 7-membered cycloalkyl ring substituted by R13, a 3- to 7-membered heterocycloalkyl ring substituted by R13, a R13-phenyl ring, or a 5 to 6-membered heteroaryl ring substituted by R13;
• each R9 is independently selected from the group consisting of H and alkyl;
• R10 is 1 to 4 substituents independently selected from the group consisting of H, halo, alkyl, —OH, alkoxy, R10′-cycloalkyl, R10′-aryl, R10′-heteroaryl, R10′-aryloxy, haloalkyl, haloalkoxy —NO2, —CO2R11, —N(R11)2, —CON(R11)2, —NHC(O)R11, —NHC(O)OR11, —NHSO2R11, —SO2N(R11)2 and —CN;
• each R10′is 1 to 4 substituents independently selected from the group consisting of H, halo, alkyl, —OH, alkoxy, aryl, heteroaryl, aryloxy, haloalkyl, haloalkoxy, —NO2, —CO2R11, —N(R11)2, —CON(R11)2, —NHC(O)R11, —NHC(O)OR11, —NHSO2R11, —SO2N(R11)2 and —CN;
• each R11 is independently selected from the group consisting of H, alkyl, haloalkyl, R18-aryl, R18-heteroaryl, R18-arylalkyl, R18-cycloalkyl and R18-heterocycloalkyl;
• each R12 is independently selected from the group consisting of H, alkyl, alkenyl, haloalkyl, R18-aryl, R18-arylalkyl, R18-heteroaryl, R18-heteroarylalkyl, R18-cycloalkyl, R18-cycloalkylalkyl and R18-heterocycloalkyl;
• R13 is 1 to 4 substituents independently selected form the group consisting of H, halo, alkyl, —OH, alkoxy, hydroxyalkyl, alkoxyalkyl, —CO2R14, —C(O)N(R14)2, haloalkyl, —CF3, and —CN;
• or two R13 substituents on the same carbon atom form ═O;
• each R14 is independently selected from the group consisting of H and alkyl;
• R15 is H, alkyl, halo, aryl or haloalkyl;
• R16 is 1 to 3 substituents independently selected from the group consisting of H, halo, alkyl, —OH, alkoxy, R10-aryl, R10-aryloxy, haloalkyl, —CF3, haloalkoxy, —NO2, —CO2R17, —N(R17)2, —CON(R17)2, —NHC(O)R17, —NHC(O)OR17, —NHSO2R17, —SO2N(R17)2 and —CN;
• each R17is independently selected from the group consisting of H, alkyl, haloalkyl, R10-aryl, R10-heteroaryl, R10-cycloalkyl and R10-heterocycloalkyl;
• R18 is H, alkyl, halo, aryl, haloalkyl, alkoxy, heteroaryl, —O—C(O)R12, —C(O)N(R12)2, —C(O)OR12, —NO2, —CN or —C(O)-heterocycloalkyl;
• R19 is H, alkyl or R10-heterocycloalkylalkyl.