Substituted Phenoxypropylcycloamine Derivatives as Histamine-3 (H3) Receptor Ligands

A compound of Formula I:

• wherein:
• R1 is a 4 to 10 membered heterocycloalkyl ring containing 1 nitrogen atom and optionally a second nitrogen atom or an oxygen atom, wherein R1 is optionally substituted with one to three R20 groups;
• R2 at each occurrence is independently F, Cl, Br, I, OR21, NR23R24, NO2, CN, CF3, C1-C6 alkyl, C(═O)R25, CO2R25, or C(═O)NR23R24;
• R3 is H or C1-C6 alkyl, or R3 can combine with A to form a 5 or 6 membered heterocycloalkyl ring containing 1 or 2 nitrogen atoms, wherein said heterocycloalkyl ring is optionally substituted with one to three R20 groups;
• R4 is H or C1-C6 alkyl;
• R5 is
• wherein R5 is para or meta to Y;
• X is O or NOR10;
• Y is O;
• R10 is H, C1-C4 alkyl, cycloalkyl, or arylalkyl;
• R11 is H, C1-C6 alkyl, C(═O)R25, CO2R25;
• A is selected from pyrrolidin-1-yl;
• piperidin-1-yl;
• morpholin-4-yl;
• piperazin-1-yl;
• thiomorpholin-4-yl;
• 2,3-dihydro-indol-1-yl;
• 1,3-dihydro-isoindol-2-yl;
• 3,4-dihydro-2H-quinolin-1-yl;
• 3,4-dihydro-1H-isoquinolin-2-yl;
• 2,3,4,5-tetrahydro-benzo[b]azepin-1-yl;
• indol-1-yl;
• and benzoimidazol-1-yl;
• wherein A can be optionally substituted with one to three R20 groups;
• or A can combine with R3 to form a 5 or 6 membered heterocycloalkyl ring containing 1 or 2 nitrogen atoms, wherein said heterocycloalkyl ring is optionally substituted with one to three R20 groups;
• R20 at each occurrence is independently, F, Cl, Br, I, OR21, OR22, NR23R24, NHOH, NO2, CN, CF3, C1-C6 alkyl optionally substituted with OR21, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, 3-7 membered heterocycloalkyl, aryl, 5 or 6 membered heteroaryl, arylalkyl, (═O), C(═O)R26, CO2R28, OC(═O)R25, C(═O)NR23R24, NR27C(S)R25, NR27C(═O)OR25, OC(═O)NR27C(═S), or S(O)qR25, wherein said aryl groups are optionally substituted with one to three R30 groups;
• R21 at each occurrence is independently H, C1-C6 alkyl, aryl, or arylalkyl;
• R22 at each occurrence is independently the residue of an amino acid after the hydroxyl group of the carboxyl group is removed;
• R23 and R24 at each occurrence are each independently selected from H, C1-C6 alkyl, and aryl, or R23 and R24, together with the nitrogen atom to which they are attached, form a 3 to 7 membered heterocyclic ring optionally substituted with ═O;
• R25 at each occurrence is independently C1-C6 alkyl, aryl, or arylalkyl;
• R26 at each occurrence is independently NR23R24, CF3, C1-C6 alkyl, C3-C7 cycloalkyl, 3-7 membered heterocycloalkyl, aryl, 5-10 membered heteroaryl, or arylalkyl, wherein said alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl groups are optionally substituted with one to three R30 groups;
• R27 at each occurrence is independently H or C1-C6 alkyl;
• R28 at each occurrence is independently C1-C6 alkyl, aryl, or arylalkyl, wherein said groups are optionally substituted with one to three R30 groups;
• R30 at each occurrence is independently F, Cl, Br, I, OR21, OR22, NR23R24, NHOH, NO2, CN, CF3, C1-C6 alkyl, aryl, or arylalkyl;
• n is 0, 1, 2, 3, or 4;
• m is 3;
• q is 0, 1, or 2;
• or a stereoisomer or a pharmaceutically acceptable salt thereof.