Novel compounds which interact with the histamine H3 receptor are defined. These compounds are particularly useful in the treatment of a variety of diseases or conditions in which histamine H3 interactions are beneficial. Thus, the compounds may find use, e.g., in the treatment of diseases of the central nervous system, the peripheral nervous system, the cardiovascular system, the pulmonary system, the gastrointestinal system and the endocrinological system. The novel compounds have a core consisting of a 6 membered aromatic ring containing at least one nitrogen atom and two carbon atoms in the ring and, at the remaining positions in the ring, there is either a carbon or a nitrogen atom.
1. A compound of the formula I-9:
wherein
q is 1; and
R 11 is either
(i) C 3-8 -alkyl, C 3-8 -cycloalkyl, or C 3-8 -cycloalkyl-C 1-3 -alkyl, or
(ii) C 1-6 -alkyl or C 3-8 -cycloalkyl, which both are substituted with at least one substituent selected from the group consisting of hydroxy, C 1-6 -alkoxy, C 1-6 -alkylcarbonyl, cyano, —NR 5 R 6 , —C(═O)NR 5 R 6 , arylcarbonyl, heteroarylcarbonyl, C 1-6 -alkylsulfonyl, arylsulfonyl, heterocyclylcarbonyl, C 1-6 -alkoxycarbonyl, aryl-C 1-6 -alkoxycarbonyl, heteroaryl and heterocyclyl, which heterocyclyl may optionally be substituted with C 1-6 -alkyl, and R 5 and R 6 independently are hydrogen or C 1-6 -alkyl;
A is phenyl substituted with one or more substituents selected independently from R 12 ; and
R 12 is —(CH 2 )—NR 13 R 14 ;
R 13 is C 1-6 -alkylcarbonyl; and
R 14 is hydrogen;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 wherein R 11 is C 3-8 -alkyl, C 3-8 -cycloalkyl or C 3-8 -cycloalkyl-C 1-3 -alkyl.
3. The compound of claim 1 , wherein R 11 is C 1-6 -alkyl or C 3-8 -cycloalkyl, which both are substituted with at least one substituent selected from the group consisting of hydroxy, C 1-6 -alkoxy, C 1-6 -alkylcarbonyl, cyano, —NR 5 R 6 , —C(═O)NR 5 R 6 , arylcarbonyl, heteroarylcarbonyl, C 1-6 -alkylsulfonyl, arylsulfonyl, heterocyclylcarbonyl, C 1-6 -alkoxycarbonyl, aryl-C 1-6 -alkoxycarbonyl, heteroaryl and heterocyclyl, which heterocyclyl may optionally be substituted with C 1-6 -alkyl.
4. The compound of claim 1 , wherein R 13 is acetyl.
5. A compound selected from the group consisting of:
N-{4-[2-(4-Isopropylpiperazin-1-yl)pyrimidin-5-yl]benzyl}acetamide;
N-{4-[2-(4-Isopropylpiperazin-1-yl)pyrimidin-5-yl]benzyl}isobutyramide; and
N-{4-[2-(4-Cyclopropylpiperazin-1-yl)pyrimidin-5-yl]benzyl}acetamide;
or a pharmaceutically acceptable salt thereof.
6. N-{4-[2-(4-Isopropylpiperazin-1-yl)pyrimidin-5-yl]benzyl}-acetamide, or a pharmaceutically acceptable salt thereof.
7. N-{4-[2-(4-Cyclopropylpiperazin-1-yl)pyrimidin-5-yl]benzyl}-acetamide, or a pharmaceutically acceptable salt thereof.
8. N-{4-[2-(4-Isopropylpiperazin-1-yl)pyrimidin-5-yl]benzyl}isobutyramide, or a pharmaceutically acceptable salt thereof.
9. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier or excipient.
10. A pharmaceutical composition comprising a compound of claim 5 and a pharmaceutically acceptable carrier or excipient.
11. A pharmaceutical composition comprising a compound of claim 6 and a pharmaceutically acceptable carrier or excipient.
12. A pharmaceutical composition comprising a compound of claim 7 and a pharmaceutically acceptable carrier or excipient.
13. A pharmaceutical composition comprising a compound of claim 8 and a pharmaceutically acceptable carrier or excipient.