Medicaments

• US 8,501,739 B2
• Filed: 06/30/2006
• Issued: 08/06/2013
• Est. Priority Date: 07/04/2005
• Status: Expired due to Fees

• Current Assignee: vTv Therapeutics LLC (vTv Therapeutics, Inc.)
• Original Assignee: High Point Pharmaceuticals, LLC
• Inventors: Hohlweg, Rolf, Andersen, Knud Erik, Sorensen, Jan Lindy, Lundbeck, Jane Marie
• Primary Examiner(s): Ward, Paul V.
• Application Number:
  US11/917,823
• Publication Number:
  US 20090312309A1
• Time in Patent Office: 2,594 Days
• Field of Search: 544/238, 514/252.02
• US Class Current: 514/252.02
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 213/74 Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• CPC Class Codes: C07D 213/84 Nitriles
• CPC Class Codes: C07D 213/87 in position 3
• CPC Class Codes: C07D 237/20 Nitrogen atoms nitro radicals C07D237/12
• CPC Class Codes: C07D 403/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/10 linked by a carbon chain containing aromatic rings

Abstract

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.

Claims

1. A compound of the formula I-9:

2. The compound of claim 1 wherein R¹¹ 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 R¹¹ 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, —

NR⁵R⁶, —

C(═

O)NR⁵R⁶, 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 R¹³ is acetyl.

9. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier or excipient.

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.

10. A pharmaceutical composition comprising a compound of claim 5 and a pharmaceutically acceptable carrier or excipient.

6. N-{4-[2-(4-Isopropylpiperazin-1-yl)pyrimidin-5-yl]benzyl}-acetamide, or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition comprising a compound of claim 6 and a pharmaceutically acceptable carrier or excipient.

7. N-{4-[2-(4-Cyclopropylpiperazin-1-yl)pyrimidin-5-yl]benzyl}-acetamide, or a pharmaceutically acceptable salt thereof.

12. A pharmaceutical composition comprising a compound of claim 7 and a pharmaceutically acceptable carrier or excipient.

8. N-{4-[2-(4-Isopropylpiperazin-1-yl)pyrimidin-5-yl]benzyl}isobutyramide, or a pharmaceutically acceptable salt thereof.

13. A pharmaceutical composition comprising a compound of claim 8 and a pharmaceutically acceptable carrier or excipient.