Histamine-3 receptor antagonists

A compound of formula I

• or a pharmaceutically acceptable salt thereof, wherein:
• n=1, 2, or 3
• Xn are independently selected from H, F, Cl, Br, I, C1-C6 alkyl (optionally substituted by F), C1-C6 alkoxyl (optionally substituted by F), (C1-C6 alkyl)-S(O)p (optionally substituted by F, NO2, COOH, COOR9, CONR10R11;
• wherein R9 is hydrogen, C1-C6 alkyl (optionally substituted by F), aryl, heteroaryl, C1-C6 alkyl-aryl, C1-C6 alkyl-heteroaryl;
• R10 and R11 are chosen from the group consisting of hydrogen, C1-C6 alkyl, aryl, heteroaryl, C1-C6 alkyl-(aryl), or R10 and R11 taken together with the nitrogen to which they are attached form a ring of 4-8 atoms with up to 3 additional heteroatoms including N, O, S;
• and
• p=0, 1 or 2.
• R1 and R2 are independently selected from the group consisting of
• hydrogen;
• C1-C8 alkyl optionally substituted with 1 to 4 halogens or OH;
• C3-C7 cycloalkyl;
• 3-8-membered heterocycloalkyl optionally substituted with a C1-C4 alkyl-carbonyl group;
• C6-C10 arylsulfonyl optionally substituted with C1-C2 alkyl;
• and
• 5-10-membered heteroaryl;
• R3 is selected from the group consisting of
• C1-C8 alkyl optionally substituted with 1 to 4 halogens;
• C3-C7 cycloalkyl;
• C6-C14 aryl;
• or
• R1 and R2 together with the nitrogen of the NR1R2 group form a 4-7 member ring, wherein one of the carbons in the ring is optionally replaced by O, S, NR6, or CO, and the ring is optionally fused to a C6-C10 arylene and is optionally substituted at a ring carbon with one or two C1-C4 alkyl groups, wherein R6 is
• hydrogen;
• C1-C8 alkyl optionally substituted with 1 to 4 halogens;
• 5-10-membered heteroaryl optionally substituted with a substituent selected from the group consisting of halogen, C1-C4 alkyl, C1-C2 alkoxy, C6-C10 aryl, C1-C4 alkylaminocarbonyl, cyano;
• C6-C10 aryl optionally substituted with one or two C1-C2 alkyl;
• or
• C1-C4 alkyl-carbonyl;
• or
• R1 and R3 together with the nitrogen of the NR1R3 group form a 4-7 member ring, wherein one of the carbons in the ring is optionally replaced by O, S, NR6′, or CO, and the ring is optionally fused to a C6-C10 arylene and is optionally substituted at a ring carbon with one or two C1-C4 alkyl groups, wherein R6′ is
• hydrogen;
• C1-C8 alkyl optionally substituted with 1 to 4 halogens;
• 5-10-membered heteroaryl optionally substituted with a substituent selected from the group consisting of halogen, C1-C4 alkyl, C1-C2 alkoxy, C6-C10 aryl, C1-C4 alkylaminocarbonyl, cyano;
• C6-C10 aryl optionally substituted with one or two C1-C2 alkyl;
• or
• C1-C4 alkyl-carbonyl;
• R4 is
• hydrogen, or
• C1-C8 alkyl optionally substituted with 1 to 4 halogens;
• R5 is —CHR7′NR2″R3;
• R2″ is hydrogen, C1-C8 alkyl optionally substituted with 1 to 4 halogens, C3-C7 cycloalkyl-C0-C4 alkyl, C6-C14 aryl-C0-C4 alkyl, 5-10-membered heteroaryl-C0-C4 alkyl, or C6-C14 aryl-C0-C4 alkylene-O—C0-C4 alkyl, wherein each C0-C4 alkyl and each C0-C4 alkylene is optionally substituted with one to four C1-C4 alkyl;
• R3″ is hydrogen, C1-C8 alkyl optionally substituted with 1 to 4 halogens, C6-C14 aryl, C6-C14 arylcarbonyl-C6-C14 aryl, C6-C14 arylcarbonyl-3-8-membered heterocycloalkyl, C3-C8 cycloalkylcarbonyl-C6-C14 aryl, C3-C8 cycloalkylcarbonyl-3-8-membered heterocycloalkyl, 3-8-membered heterocycloalkyl, 3-8-membered heterocycloalkylcarbonyl-C6-C14 aryl, or 3-8-membered heterocycloalkylcarbonyl-3-8-membered heterocycloalkyl;
• or R3″ and R2″ together with the nitrogen of the CHR7′NR2″R3″ group form a second 5-, 6- or 7-membered aliphatic ring, wherein one of the carbons in the second 5-, 6-, or 7-membered aliphatic ring is optionally replaced by O, S, NR11, or C═O and the second 5-, 6-, or 7-membered aliphatic ring is optionally substituted with one or two C1-C4 alkyl, wherein R11 is hydrogen, C1-C8 alkyl optionally substituted with 1 to 4 halogens, C3-C7 cycloalkyl-C0-C4 alkyl, C6-C14 aryl-C0-C4 alkyl, 5-10-membered heteroaryl-C0-C4 alkyl, or C6-C14 aryl-C0-C4 alkylene-O—C0-C4 alkyl, wherein each C0-C4 alkyl and each C0-C4 alkylene is optionally substituted with one to four C1-C4 alkyl;
• and
• R7′ is hydrogen, C1-C8 alkyl optionally substituted with 1 to 4 halogens, C3-C7 cycloalkyl-C0-C4 alkyl, C6-C14 aryl-C0-C4 alkyl, 5-10-membered heteroaryl-C0-C4 alkyl, C6-C14 aryl-C0-C4 alkylene-O—C0-C4 alkyl, wherein each C0-C4 alkyl and each C0-C4 alkylene is optionally substituted with one to four C1-C4 alkyl, or SO2C1-C10 alkyl.