Phenoxypiperidines and analogs thereof useful as histamine H3 antagonists

A compound having the formula:

• or a pharmaceutically acceptable salt or solvate thereof, wherein:
• a is 0, 1, 2, 3 or 4;
• b is 0, 1, 2 or 3;
• M is CH, n is 1 or 2, and p is 0, 1 or 2;
• or M is N, n is 2, and p is 1 or 2;
• U and W are each CH, or one of U and W is CH and the other is N;
• X is a bond, alkylene, —C(O)—, —C(N—OR5)—, —C(N—OR5)—CH(R6)—, —CH(R6)—C(N—OR5)—, —O—, —OCH2—, —CH2O—, —CH(OH)—, —S—, —S(O)— or —S(O)2—;
• Y is —O—, —CH2—, —(CH2)2—, —C(═O)—, —C(═NOR7)—, —S—, —S(O)— or —SO2—, provided that when M is N, Y is —CH2—, —(CH2)2—, —C(═O)—, —S—, —S(O)— or —SO2—,
• Z is a bond, —CH(R9)—(R10—C1-C5 alkylene), —CH(R9)—CH(R9)—O—, —CH(R9)—CH(R9)—N—, —CH(R9)—C(R9a)═C(R9a)—, —CH(R9)—C(R9a)═C(R9a)—(R10—C1-C3 alkylene) or R8-alkylene interrupted by a cycloalkylene or heterocycloalkylene group, provided that when Z is R8-alkylene interrupted by a heterocycloalkylene group bonded through a ring nitrogen, the alkylene portion of the Z group has 2-4 carbon atoms between the ring to which it is attached and said nitrogen;
• R1 is R11-alkyl, R11-cycloalkyl, R11-aryl, R11-arylalkyl, R11-(6-membered heteroaryl), R11-(6-membered heteroaryl)alkyl, R11-(5-membered heteroaryl), R11-(5-membered heteroaryl)alkyl, R11-heterocycloalkyl,
• provided that when R1 is attached to X by a nitrogen atom, X is a bond or alkylene;
• k is 0, 1, 2, 3 or 4;
• k1 is 0, 1, 2 or 3;
• k2 is 0, 1 or 2;
• Q is O or S;
• R2 is R13-alkyl, R13-alkenyl, R13-aryl, R13-arylalkyl, R13-heteroaryl, R13-heteroarylalkyl, R13-cycloalkyl or R13-heterocycloalkyl;
• each R3 is independently selected from the group consisting of H, alkyl, halo, —OH, alkoxy, —CF3, —OCF3, —OCHF2, —NO2, —CO2R14, —N(R14)2, —CON(R14)2, —NHC(O)R14,
• —NHSO2R14, —SO2N(R14)2 and —CN;
• each R4 is independently selected from the group consisting of H, halo, alkyl, haloalkyl, —OH, alkoxy, —CF3 and —CN;
• R5 is H, alkyl, haloalkyl, R15-aryl, R15-heteroaryl, R15-cycloalkyl, R15-heterocycloalkyl, R15-arylalkyl, —CF3 or —CH2CF3;
• R6 is H or alkyl;
• R7 is H, alkyl, haloalkyl, R15-aryl or R15-heteroaryl;
• R8 is 1, 2 or 3 substituents independently selected from the group consisting of H, R15-cycloalkyl, R15-heterocycloalkyl, R15-aryl, R15-heteroaryl and haloalkyl, provided that when the R8 substituent is on the carbon joined to the nitrogen atom of the M-containing ring, R8 is joined through a ring carbon atom;
• R9 is independently selected from the group consisting of H, alkyl and haloalkyl;
• R9a is independently selected from the group consisting of H, fluoro, alkyl and haloalkyl;
• R10 is 1, 2 or 3 substituents independently selected from the group consisting of H, R15-cycloalkyl, R15-heterocycloalkyl, R15-aryl, R15-heteroaryl, halo, haloalkyl, —CN, —OH, alkoxy, —OCF3, —NO2, and —N(R6)2;
• R11 is 1, 2, 3 or 4 substituents independently selected from the group consisting of H, halo, alkyl, haloalkyl, —OH, alkoxy, alkylthio, R15-cycloalkyl, R15-heterocycloalkyl, R15-aryl, R15-arylalkyl, R15-heteroaryl, R15-heteroarylalkyl, aryloxy, —OCF3, —OCHF2, —NO2, —CO2R12, —N(R12)2, —CON(R12)2, —NHC(O)R12, —NHSO2R12, —SO2N(R12)2 and —CN;
• R11a is H, alkyl, haloalkyl, alkoxy, alkylthio, R15-cycloalkyl, R15-heterocycloalkyl, R15-aryl, R15-arylalkyl, R15-cycloalkyl, R15-heterocycloalkyl, R15-heteroaryl, R15-heteroarylalkyl, R15-aryloxy, —OCF3, —OCHF2, —N(R12)2 or —SCF3;
• R12 is independently selected from the group consisting of H, alkyl, haloalkyl, R15-aryl, R15-heteroaryl, R15-arylalkyl, R15-cycloalkyl and R15-heterocycloalkyl;
• R13 is 1, 2 or 3 substituents independently selected from the group consisting of H, halo, alkyl, haloalkyl, —OH, alkoxy, R15-aryl, R15-aryloxy, —OCF3, —OCHF2, —NO2, —CO2R14, —N(R14)2, —CON(R14)2, —NHC(O)R14, —NHSO2R14, —SO2N(R14)2 and —CN;
• R14 is independently selected from the group consisting of H, alkyl, haloalkyl, R15-aryl, R15-heteroaryl, R15-cycloalkyl and R15-heterocycloalkyl;
• R15 is 1, 2 or 3 substituents independently selected from the group consisting of H, alkyl, halo, haloalkyl, alkoxy, —N(R18)2, -alkylene-N(R18)2, —CN, —OCF3 and —OCHF2;
• R16 is independently selected from the group consisting of alkyl, halogen, haloalkyl, alkenyl, OH, alkoxy, —SO0-2-alkyl and —OCF3;
• R17 is H, alkyl, hydroxyl-substituted (C2-C6)alkyl-, haloalkyl-, haloalkoxyalkyl-, alkoxyalkyl-, R15-aryl, R15-arylalkyl-, R15-heteroaryl, R15-heteroarylalkyl-, R15-cycloalkyl or R15-cycloalkylalkyl;
• and
• R18 is independently selected from the group consisting of H and alkyl.