Histamine-3 receptor ligands for diabetic conditions

A method of treating diabetic condition comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound selected from the group consisting of:

• a compound of formula (I):
• 14
• a compound of formula (III):
• 15
• and a compound of formula (IV):
• 16
• or pharmaceutically acceptable salts, esters, amides, or prodrugs thereof, wherein
• A is selected from the group consisting of carbonyl and a covalent bond;
• D is selected from the group consisting of O and S;
• L is selected from the group consisting of lower alkylene, fluoroalkylene, and hydroxyalkylene;
• P and Q taken together form a covalent bond or are both hydrogen;
• R1 and R2 are each independently selected from the group consisting of hydrogen, alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heterocycle, heterocyclealkyl, hydroxyalkyl, alkenyl, and alkynyl;
• or
• R1 and R2 taken together with the nitrogen atom to which they are attached, together form a heterocycle;
• R3 is selected from the group consisting of hydrogen, alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylcarbonyloxy, alkylsulfinyl, alkylsulfonyl, alkylthio, aryl, carboxy, carboxyalkyl, cyano, cyanoalkyl, formyl, halogen, haloalkoxy, haloalkyl, heterocycle, hydroxy, hydroxyalkyl, mercapto, nitro, —NRARB, (NRARB)alkyl, (NRARB)carbonyl, and (NRARB)sulfonyl;
• R4, R5, R6 and R7 are each independently selected from the group consisting of hydrogen, alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylcarbonyloxy, alkylsulfinyl, alkylsulfonyl, alkylthio, aryl, carboxy, carboxyalkyl, cyano, cyanoalkyl, cycloalkyl, formyl, halogen, haloalkoxy, haloalkyl, heterocycle, hydroxy, hydroxyalkyl, mercapto, nitro, —NRARB, (NRARB)alkyl, (NRARB)carbonyl, (NRARB)sulfonyl, -L2R20, and —R20L3R22, provided that at least one of R4, R5, R6, or R7 is aryl, heterocycle, cycloalkyl, -L2R20 or —R20L3R22;
• L2 is selected from the group consisting of alkylene, alkenylene, O, S, S(O), S(O)2, C(═O), C=(NOR21), and N(RA);
• L3 is selected from the group consisting of a covalent bond, alkylene, alkenylene, O, S, C(═O), N(═OR2,), and N(RA);
• R10 and R11 are each independently selected from the group consisting of hydrogen, alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heterocycle and heterocyclealkyl;
• or
• R10 and R11 taken together with the nitrogen atom to which they are attached, together form a heterocycle selected from the group consisting of azepanyl, azetidinyl, morpholinyl, piperazinyl, piperidinyl, pyrrolidinyl, 2,5-dihydro-1H-pyrrolyl, pyrrolyl, thiomorpholinyl and 1,1-dioxidothiomorpholinyl, provided that when R10 and R11 together form pyrrolidinyl and wherein said pyrrolidinyl is substituted with 1 substituent then said substituent is other than alkoxy, hydroxy or —NRARB;
• R12 and R13 are each independently selected from the group consisting of hydrogen, alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heterocycle and heterocyclealkyl;
• or
• R12 and R13 taken together with the nitrogen atom to which they are attached, together form a heterocycle selected from the group consisting of azepanyl, azetidinyl, morpholinyl, piperazinyl, piperidinyl, pyrrolidinyl, 2,5-dihydro-1H-pyrrolyl, pyrrolyl, thiomorpholinyl and 1,1-dioxidothiomorpholinyl;
• R14 and R15 are each independently selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylcarbonyloxy, alkylsulfinyl, alkylsulfonyl, alkylthio, alkynyl, carboxy, carboxyalkyl, cyano, cyanoalkyl, formyl, halogen, haloalkoxy, haloalkyl, hydroxy, hydroxyalkyl, mercapto, nitro, —NRARB, (NRARB)alkyl, (NRARB)carbonyl and (NRARB)sulfonyl;
• R20 is selected from the group consisting of aryl, heterocycle, and cycloalkyl;
• R21 is selected from the group consisting of hydrogen and alkyl;
• R22 is selected from the group consisting of aryl, heterocycle, and cycloalkyl;
• RA and RB are each independently selected from hydrogen, alkyl, alkylcarbonyl or formyl;
• Z1 is selected from the group consisting of a covalent bond and CH2;
• R31 is selected from the group consisting of OR32, NR33R34 and
• 17
• R32 is selected from the group consisting of hydrogen, alkoxycarbonyl, alkyl, alkylcarbonyl, aminocarbonyl, sulfono and phosphono;
• R33 and R34 are independently selected from the group consisting of hydrogen, alkenyl, alkenylcarbonyl, alkenyloxycarbonyl, alkenylsulfonyl, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl, alkynyl, alkynylcarbonyl, alkynyloxycarbonyl, alkynylsulfonyl, aminocarbonyl, aminosulfonyl, arylalkyl, arylalkenylcarbonyl, arylalkenylsulfonyl, arylalkylcarbonyl, arylalkylsulfonyl, arylarylcarbonyl, arylarylsulfonyl, arylcarbonyl, arylheterocylecarbonyl, arylheterocylesulfonyl, aryloxyarylcarbonyl, aryloxyarylsulfonyl, arylsulfonyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkylcarbonyl, cycloalkylalkylsulfonyl, cycloalkylcarbonyl, cycloalkylsulfonyl, formyl, heterocycle, heterocyclealkyl, heterocyclealkylcarbonyl, heterocyclealkylsulfonyl, heterocyclearylcarbonyl, heterocyclearylsulfonyl, heterocyclecarbonyl, heterocycleheterocyclecarbonyl, heterocycleheterocyclesulfonyl, heterocycleoxyalkylcarbonyl, heterocycleoxyarylcarbonyl, heterocycleoxyarylsulfonyl, heterocyclesulfonyl, and heterocyclethioalkylcarbonyl;
• R35 and R36 are independently selected from the group consisting of hydrogen and alkyl;
• R37 is selected from the group consisting of hydrogen and alkyl;
• or
• R31 and R37 together form (═O);
• R38 is selected from the group consisting of alkylcarbonyl, aryl, arylcarbonyl, arylcarbonylaryl, arylcarbonylheterocycle, cycloalkylcarbonyl, cycloalkylcarbonylaryl, cycloalkylcarbonylheterocycle, heterocycle, heterocyclecarbonyl, heterocyclecarbonylaryl, and heterocyclecarbonylheterocycle;
• R39 is selected from the group consisting of hydrogen and lower alkyl;
• and
• RA1, RB1, RC1 and RD1 are independently selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylcarbonyloxy, alkylsulfinyl, alkylsulfonyl, alkylthio, alkynyl, amino, aminoalkyl, aminocarbonyl, carboxy, carboxyalkyl, cyano, cyanoalkyl, formyl, halogen, haloalkoxy, haloalkyl, hydroxy, hydroxyalkyl, mercapto or nitro.