8-[3-AMINO-PIPERIDIN-1-YL]-XANTHINES, THE PREPARATION THEREOF AND THEIR USE AS PHARMACEUTICAL COMPOSITIONS

• US 20160194327A1
• Filed: 03/15/2016
• Published: 07/07/2016
• Est. Priority Date: 08/21/2002
• Status: Active Grant

• Current Assignee: Boehringer Ingelheim International GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim International GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: HIMMELSBACH, Frank, LANGKOPF, Elke, ECKHARDT, Matthias, MARK, Michael, MAIER, Roland, LOTZ, Ralf, TADAYYON, Mohammad
• Granted Patent: US 9,556,175 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C07D 473/04 two oxygen atoms
• CPC Class Codes: C07D 473/06 with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
• CPC Class Codes: C07D 473/08 with methyl radicals in positions 1 and 3, e.g. theophylline
• CPC Class Codes: C07D 519/00 Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

The present invention relates to substituted xanthines of general formula

wherein R¹ to R³ are as defined herein, the tautomers, the stereoisomers, the mixtures, the prodrugs thereof and the salts thereof which have valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).

Claims

1. A compound of formula (I)

2. The compound of claim 1, wherein

R¹ denotes a [2-(methylcarbonylamino)-phenyl]-carbonylmethyl group,

a [2-(ethylcarbonylamino)-phenyl]-carbonylmethyl group or

a [2-(isopropylcarbonylamino)-phenyl]-carbonylmethyl group,

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1, wherein

R¹ denotes a [2-(aminocarbonylmethoxy)-phenyl]-carbonylmethyl group,

[2-(methylaminocarbonylmethoxy)-phenyl]-carbonylmethyl group,

a [2-(ethylaminocarbonylmethoxy)-phenyl]-carbonylmethyl group or

a [2-(isopropylaminocarbonylmethoxy)-phenyl]-carbonylmethyl group,

or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

(14) 1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,

(15) 1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,

(16) 1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,

(17) 1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine, and

(18) 1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine.

5. A physiologically acceptable salt of a compound according to claim 1, with inorganic or organic acids or bases.

6. A pharmaceutical composition comprising a pharmaceutically acceptable amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof, optionally together with one or more inert carriers and/or diluents.