8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions

• US 9,108,964 B2
• Filed: 01/14/2014
• Issued: 08/18/2015
• Est. Priority Date: 08/21/2002
• Status: Expired due to Term

• 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, Maier, Roland
• Primary Examiner(s): Shameem, Golam M M
• Assistant Examiner(s): DANIEL, LAURA M
• Application Number:
  US14/154,885
• Publication Number:
  US 20140128604A1
• Time in Patent Office: 581 Days
• Field of Search: 544/268
• 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 (III)

2. 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine.

3. 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine.

4. A process for preparing a compound of formula (I),

5. The process according to claim 4, wherein the tert.-butyloxycarbonyl group is cleaved by treatment with an acid or by treatment with bromotrimethylsilane or iodotrimethylsilane, optionally using a solvent at temperatures between 0 and 80°

C.

6. The process according to claim 5, wherein the acid is trifluoroacetic acid or hydrochloric acid.

7. The process according to claim 5, wherein the solvent is selected from the group consisting of methylene chloride, ethyl acetate, dioxane, methanol, isopropanol and diethyl ether.

8. A process for preparing a pharmaceutical composition comprising the compound of formula (I) of claim 4, the process comprising:

preparing the compound of formula (I) according to the process of claim 4; and

combining the compound of formula (I), optionally in combination with an additional active substance, with one or more inert carriers and/or diluents into a galenic preparation selected from the group consisting of a plain or coated tablet, capsule, powder, suspension and suppository.