Nova Patents
EP1532149B9

8-[3-amino-piperidin-1-yl]-xanthines, the production thereof and the use of the same as medicaments

Abstract

This record has no abstract on file.

EP1532149B9, drawing sheet 1
Sheet 1 of 18

Term

Term ended

Expired 18 August 2023, 3.1 years ago.

  1. Priority
  2. Filed
  3. Granted
  4. Expired
  5. Today

20 claims: 20 independent, 0 dependent

  1. c-en-01-0001
    Compounds of general formula I wherein R1 denotes a 4-methoxy-1-naphthylmethyl group,a 2-quinolinylmethyl, 4-quinolinylmethyl or a 6-quinolinylmethyl group,a 1-isoquinolinylmethyl, 3-methyl-1-isoquinolinylmethyl, 4-methyl-1-isoquinolinylmethyl or a 3-isoquinolinylmethyl group ora 2-quinazolinylmethyl, 4-methyl-2-quinazolinylmethyl or a 4-quinazolinylmethyl group,R2 denotes a methyl group andR3 denotes a 2-buten-1-yl or a 2-butyn-1-yl group,the tautomers, enantiomers, diastereomers, the mixtures thereof and the salts thereof.
  2. c-en-01-0002
    The following compounds of general formula I according to claim 1:1-[(4-methoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine, -->1-[(4-methoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,1-[(4-methoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine, and the tautomers, enantiomers, diastereomers, mixtures thereof and salts thereof.
  3. c-en-01-0003
    The following compounds of general formula I according to claim 1:1-[(quinolin-4-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine1-[(quinolin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine, and the tautomers, enantiomers, diastereomers, mixtures thereof and salts thereof.
  4. c-en-01-0004
    The following compounds of general formula I according to claim 1:1-[(isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine, -->1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,1-[(isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine, and the tautomers, enantiomers, diastereomers, mixtures thereof and salts thereof.
  5. c-en-01-0005
    The following compounds of general formula I according to claim 1:1-[(quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine, -->1-[(quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,1-[(quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,1-[(quinazolin-2-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,1-[(quinazolin-2-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(S)-amino-piperidin-1-yl)-xanthine,1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R) -amino-piperidin-1-yl)-xanthine, and the tautomers, enantiomers, diastereomers, the mixtures thereof and the salts thereof.
  6. c-en-01-0006
    Compound of general formula I according to claim 5:1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine and the salts thereof.
  7. c-en-01-0007
    Compound of general formula I according to claim 6:1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine.
  8. c-en-01-0008
    Physiologically acceptable salts of the compounds according to at least one of claims 1 to 7 with inorganic or organic acids or bases. -->
  9. c-en-01-0009
    Physiologically acceptable salts of the compounds according to claim 6 with inorganic or organic acids.
  10. c-en-01-0010
    Medicaments containing a compound according to at least one of claims 1 to 7 or a physiologically acceptable salt according to claim 8 or 9, optionally together with one or more inert carriers and/or diluents.
  11. c-en-01-0011
    Medicaments containing the compound according to claim 6 or a physiologically acceptable salt according to claim 9, optionally together with one or more inert carriers and/or diluents.
  12. c-en-01-0012
    Medicaments containing the compound according to claim 7, optionally together with one or more inert carriers and/or diluents.
  13. c-en-01-0013
    Use of a compound according to at least one of claims 1 to 9 for preparing a medicament which is suitable for treating type I and type II diabetes mellitus, arthritis, obesity, allograft transplantation and calcitonin-induced osteoporosis.
  14. c-en-01-0014
    Use of a compound according to at least one of claims 6, 7 and 9 for preparing a medicament which is suitable for treating type II diabetes mellitus or obesity.
  15. c-en-01-0015
    Use of the compound according to claim 7, for preparing a medicament which is suitable for treating type II diabetes mellitus.
  16. c-en-01-0016
    Process for preparing a medicament according to at least one of claims 10 to 12, characterised in that a compound according to at least one of claims 1 to 9 is incorporated in one or more inert carriers and/or diluents by a non-chemical method.
  17. c-en-01-0017
    Process for preparing a medicament according to claim 11, characterised in that a compound according to claim 6 or 9 is incorporated in one or more inert carriers and/or diluents. -->
  18. c-en-01-0018
    Process for preparing a medicament according to claim 12, characterised in that a compound according to claim 7 is incorporated in one or more inert carriers and/or diluents.
  19. c-en-01-0019
    Process for preparing the compounds of general formula I according to claims 1 to 9, characterised in thata) a compound of general formula wherein R1 to R3 are defined as in claim 1 andZ1 denotes a leaving group such as a halogen atom, a substituted hydroxy, mercapto, sulphinyl, sulphonyl or sulphonyloxy group,is reacted with 3-aminopiperidine, the enantiomers or the salts thereof, orb) a compound of general formula -->wherein R1, R2 and R3 are defined as in claim 1, is deprotected, and/orsubsequently, if desired, any protecting groups used during the reaction are cleaved and/orthe compounds of general formula I thus obtained are resolved into their enantiomers or diastereomers and/orthe compounds of formula I thus obtained are converted into the salts thereof, particularly for pharmaceutical use into the physiologically acceptable salts thereof with inorganic or organic acids or bases.
  20. c-en-01-0020
    Process for preparing the compound of general formula I according to claim 6, characterised in thata) a compound of general formula wherein R1 denotes a 4-methyl-1-quinazolinylmethyl group,R2 denotes a methyl group,R3 denotes a 2-butyn-1-yl group,andZ1 denotes a leaving group such as a halogen atom, a substituted hydroxy, mercapto, sulphinyl, sulphonyl or sulphonyloxy group, -->is reacted with (R)-3-aminopiperidine or the salts thereof, orb) a compound of general formula wherein R1 denotes a 4-methyl-2-quinazolinylmethyl group,R2 denotes a methyl group,R3 denotes a 2-butyn-1-yl group,is deprotected, and/or subsequently, if desired, any protecting groups used during the reaction are cleaved and/or the compound of formula I thus obtained is converted into the salts thereof, particularly for pharmaceutical use into the physiologically acceptable salts thereof with inorganic or organic acids.
Independent claims20