Substituted quinazolines, the preparation thereof and the use thereof in pharmaceutical compositions

• US 9,199,998 B2
• Filed: 12/23/2014
• Issued: 12/01/2015
• Est. Priority Date: 07/15/2011
• 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: Pfrengle, Waldemar, Frank, Markus, Klein, Thomas
• Primary Examiner(s): VAJDA, KRISTIN ANN
• Application Number:
  US14/580,650
• Publication Number:
  US 20150112062A1
• Time in Patent Office: 343 Days
• Field of Search: 544/268
• US Class Current: 1/1
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 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

Abstract

The present invention relates to substituted quinazolines of formula (I) wherein X and Y are defined as in claim 1, the tautomers, stereoisomers, mixtures and salts thereof, which have valuable pharmacological properties, particularly an inhibitory effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).

Claims

1. A method for preparing a compound of formula (II) or a salt thereof,

2. The method according to claim 1, further comprising

(a) carrying out the dissociation of the compound of formula (IA) in a suitable solvent or mixture of solvents, and

(b) isolating the obtained compound of formula (II) from the suitable solvent or mixture of solvents.

3. The method according to claim 2, wherein the solvent or solvent system comprises one or more solvents selected from the group consisting of ketones, lactones, ethers, hydrocarbons, chlorinated hydrocarbons, low-molecular-weight aliphatic alcohols, esters, amides or lactames, nitriles, sulfoxides, amines, and water;

or a mixture thereof.

4. The method according to claim 3, wherein the solvent is a polar solvent or mixture of polar solvents.

5. The method according to claim 3, wherein the solvent or solvent system comprises a low-molecular-weight aliphatic alcohol.

6. The method according to claim 3, wherein the solvent is water or an aqueous medium.

7. The method according to claim 2, wherein the compound of formula (II) or a salt thereof is obtained in crystalline, amorphous, lyophilized or dried form.

8. The method according to claim 1, which is conducted in the presence of an acid.

9. The method according to claim 8, wherein the acid is HCl.

10. The method according to claim 8, wherein the acid is aqueous hydrochloric acid.