Search Images Maps Play YouTube News Gmail Drive More »
Sign in
Screen reader users: click this link for accessible mode. Accessible mode has the same essential features but works better with your reader.

Patents

  1. Advanced Patent Search
Publication numberUS20070259900 A1
Publication typeApplication
Application numberUS 11/744,700
Publication dateNov 8, 2007
Filing dateMay 4, 2007
Priority dateMay 4, 2006
Also published asCA2651089A1, CA2810295A1, CA2810522A1, CA2810839A1, CA2873524A1, CN101437823A, CN101437823B, CN102838599A, CN103951667A, CN107235980A, EP2016079A1, EP2540725A1, US9266888, US9493462, US20120296091, US20140357646, US20160122352, US20170022203, WO2007128721A1
Publication number11744700, 744700, US 2007/0259900 A1, US 2007/259900 A1, US 20070259900 A1, US 20070259900A1, US 2007259900 A1, US 2007259900A1, US-A1-20070259900, US-A1-2007259900, US2007/0259900A1, US2007/259900A1, US20070259900 A1, US20070259900A1, US2007259900 A1, US2007259900A1
InventorsPeter Sieger, Dirk Kemmer, Peter Kohlbauer, Thomas Nicola, Martin Renz
Original AssigneePeter Sieger, Dirk Kemmer, Peter Kohlbauer, Thomas Nicola, Martin Renz
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Polymorphs
US 20070259900 A1
Abstract
The invention relates to polymorphous crystal modifications of a DPP-IV inhibitor, the preparation thereof and the use thereof for preparing a medicament.
Images(7)
Previous page
Next page
Claims(12)
1. Anhydrous polymorph A of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine, characterised in that it melts at 206±3° C.
2. Polymorph A according to claim 1, characterised in that in the X-ray powder diagram it has inter alia characteristic reflexes at the following d values: 11.49 Å, 7.60 Å, 7.15 Å, 3.86 Å, 3.54 Å and 3.47.
3. Anhydrous polymorph B of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine, characterised in that at a temperature of 10-40° C. it transforms reversibly into the polymorph A of claim 1.
4. Polymorph B according to claim 3, characterised in that in the X-ray powder diagram it has inter alia characteristic reflexes at the following d values: 11.25 Å, 9.32 Å, 7.46 Å, 6.98 Å and 3.77 Å.
5. Polymorph C of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine, characterised in that it loses water at a temperature of 30-100° C. and in the DSC diagram it exhibits further thermal effects at approx. 150° C. and 175° C.
6. Polymorph C according to claim 5, characterised in that in the X-ray powder diagram it has inter alia characteristic reflexes at the following d values: 12.90 Å, 11.10 Å, 6.44 Å, 3.93 Å and 3.74 Å.
7. Anhydrous polymorph D of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine, characterised in that it melts at 150±3° C.
8. Anhydrous polymorph E of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine, characterised in that it melts at 175±3° C.
9. Method of preparing the polymorph C according to claim 5, characterised in that
(a) 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine is refluxed in methanol,
(b) the methanolic solution is cooled to a temperature of 40-60° C.,
(c) a solvent such as tert.-butylmethylether is added,
(d) the resulting suspension is cooled first of all to 15-25° C. and then to 0-5° C.,
(e) the crystals are suction filtered and
(f) dried in vacuo at a temperature of 70° C.
10. Method according to claim 9, characterised in that after step (a) the hot solution is filtered.
12. A method for the treatment of patients with type I and type II diabetes mellitus, prediabetes or reduced glucose tolerance, rheumatoid arthritis, obesity, or calcitonin-induced osteoporosis, as well as patients in whom an allograft transplant has been carried out, the method comprising the step of administering a pharmaceutical composition comprising at least one of the polymorphs A, B, and C, and one or more inert carriers, diluents, or carriers and diluents.
13. A pharmaceutical composition comprising at least one of the polymorphs A, B, and C, and one or more inert carriers, diluents, or carriers and diluents.
Description
    BACKGROUND OF THE INVENTION
  • [0001]
    This Application claims priority of EP 06 009 202, which is hereby incorporated by reference in its entirety.
  • [0002]
    1. Field of the Invention
  • [0003]
    The invention relates to polymorphous crystal modifications of a DPP-IV inhibitor, the preparation thereof and the use thereof for preparing a medicament.
  • [0004]
    2. Description of the Prior Art
  • [0005]
    The enzyme DPP-IV, also known by the name CD26, is a serine protease which promotes the cleaving of dipeptides in proteins with a proline or alanine group at the N-terminal end. DPP-IV inhibitors thereby influence the plasma level of bioactive peptides including the peptide GLP-1. Compounds of this type are useful for the prevention or treatment of illnesses or conditions which are associated with an increased DPP-IV activity or which can be prevented or alleviated by reducing the DPP-IV activity, particularly type I or type II diabetes mellitus, prediabetes, or reduced glucose tolerance.
  • [0006]
    WO 2004/018468 describes DPP-IV inhibitors with valuable pharmacological properties. One example of the inhibitors disclosed therein is 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • [0007]
    FIG. 1 shows the thermoanalysis of the anhydrous form A/B.
  • [0008]
    FIG. 2 shows a cyclic DSC diagram, in which the phase transition from −40° C. to 120° C. and vice versa has been run through a total of 3 times.
  • [0009]
    FIG. 3 shows an X-ray powder diagram of the anhydrous form A.
  • [0010]
    FIG. 4 shows an X-ray powder diagram of the anhydrous form B.
  • [0011]
    FIG. 5 shows an X-ray powder diagram of polymorph C.
  • [0012]
    FIG. 6 shows the thermoanalysis of form C.
  • DETAILED DESCRIPTION OF THE INVENTION
  • [0013]
    Within the scope of the present invention it has been found that 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine may take on various polymorphous crystal modifications and that the compound prepared in WO 2004/018468 is present at ambient temperature as a mixture of two enantiotropic polymorphs. The temperature at which the two polymorphs transform into one another is 25±15° C. (see FIGS. 1 and 2).
  • [0014]
    The pure high temperature form (polymorph A), which can be obtained by heating the mixture to temperatures >40° C., melts at 206±3° C. In the X-ray powder diagram (see FIG. 3) this form shows characteristic reflexes at the following d values: 11.49 Å, 7.60 Å, 7.15 Å, 3.86 Å, 3.54 Å and 3.47 Å (cf. also Table 1 and 2).
  • [0015]
    Anhydrous polymorph A may be prepared by
    • (a) refluxing 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in absolute ethanol and optionally filtering the mixture,
    • (b) cooling the hot solution or the hot filtrate until crystallisation sets in,
    • (c) diluting with a solvent such as tert.-butylmethylether,
    • (d) suction filtering the solvent mixture and
    • (e) drying the polymorph A at 45° C. in vacuo.
  • [0021]
    The low temperature form (polymorph B) is obtained by cooling to temperatures <10° C. In the X-ray powder diagram (see FIG. 4) this form shows characteristic reflexes at the following d values: 11.25 Å, 9.32 Å, 7.46 Å, 6.98 Å and 3.77 Å (cf. also Table 3 and 4).
  • [0022]
    Anhydrous polymorph B may be prepared by
    • (a) dissolving 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in absolute ethanol and refluxing and optionally filtering the mixture,
    • (b) cooling the hot solution or the hot filtrate for crystallisation to a temperature below 10° C.,
    • (c) diluting with a solvent such as tert.-butylmethylether,
    • (d) suction filtering the solvent mixture and
    • (e) drying the polymorph at a temperature below 10° C. in vacuo.
  • [0028]
    Another polymorph (polymorph C) shows characteristic reflexes in the X-ray powder diagram (see FIG. 5) at the following d values: 12.90 Å, 11.10 Å, 6.44 Å, 3.93 Å and 3.74 Å (cf. also Table 5).
  • [0029]
    Polymorph C is obtained if
    • (a) 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine is dissolved in methanol and refluxed and optionally filtered in the presence of activated charcoal,
    • (b) the methanolic solution is cooled to a temperature of 40-60° C.,
    • (c) a solvent such as tert.-butylmethylether or diisopropylether is added,
    • (d) the resulting suspension is first of all cooled slowly to 15-25° C. and then later to 0-5° C.,
    • (e) the crystals formed are suction filtered and washed again with tert.-butylmethylether or diisopropylether and
    • (f) the crystals thus obtained are dried at a temperature of 70° C. in the vacuum dryer.
  • [0036]
    Another polymorph (polymorph D) melts at 150±3° C. This polymorph is obtained if polymorph C is heated to a temperature of 30-100° C. or dried at this temperature.
  • [0037]
    Finally, there is also polymorph E, which melts at a temperature of 175±3° C. Anhydrous polymorph E is formed if polymorph D is melted. On further heating, polymorph E crystallises out of the melt.
  • [0038]
    The polymorphs thus obtained may be used in the same way as the mixture of the two polymorphs A and B described in WO 2004/018468 for preparing a pharmaceutical composition which is suitable for treating patients with type I and type II diabetes mellitus, prediabetes or reduced glucose tolerance, with rheumatoid arthritis, obesity, or calcitonin-induced osteoporosis, as well as patients in whom an allograft transplant has been carried out. These medicaments contain in addition to one or more inert carriers at least 0.1% to 0.5%, preferably at least 0.5% to 1.5% and particularly preferably at least 1% to 3% of one of the polymorphs A, B, or C.
  • [0039]
    The following Examples are intended to illustrate the invention in more detail.
  • EXAMPLE 1 Crystallisation of Polymorph A
  • [0040]
    Crude 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine is refluxed with 5 times as much absolute ethanol and the hot solution is filtered clear through activated charcoal. After the filtrate has been cooled to 20° C. and crystallisation has set in, the solution is diluted to double the volume with tert.-butylmethylether. Then the suspension is cooled to 2° C., stirred for 2 hours, suction filtered and dried in the vacuum dryer at 45° C.
  • [0041]
    FIG. 1 shows the thermoanalysis of the anhydrous form A/B.
  • [0042]
    Plymorph A melts at 206±3° C. In the DSC diagram another slightly endothermic signal can be seen at approx. 25° C. This is a fully reversible solid-solid phase transition between the two enantiotropic crystal modifications A and B. The form A is the thermodynamically stable modification above this transformation temperature, w| form B is the thermodynamically stable modification below this transformation temperature.
  • [0043]
    FIG. 2 shows a cyclic DSC diagram, in which the phase transition from −40° C. to 120° C. and vice versa has been run through a total of 3 times. During heating, the phase transition is observed as an endothermic signal and, correspondingly, during cooling it is observed as an exothermic signal. During the first heating cycle the phase transition may also be observed as an endothermic double signal or as a very broad signal while in all the other cycles the signal occurs as a very sharp endothermic or exothermic signal, depending on whether heating or cooling is taking place.
  • [0044]
    FIG. 3 shows an X-ray powder diagram of the anhydrous form A
  • [0000]
    TABLE 1
    Labelled X-ray reflexes up to 30° 2 Θ with intensities (standardised) for
    the anhydrous polymorph A
    2 Θ intensity dhkl labelling dexp-calc
    [°] I/Io [%] [Å] h k l [Å]
    5.56 1 15.89 1 0 0 −0.008
    7.18 32 12.31 0 1 1 0.005
    7.62 100 11.59 1 1 0 0.007
    8.49 20 10.41 −1 1 1 0.002
    9.91 24 8.92 0 0 2 0.003
    10.41 18 8.49 0 2 0 0.024
    11.18 24 7.91 2 0 0 0.038
    11.63 41 7.60 −1 1 2 0.003
    12.37 59 7.15 −1 2 1 −0.003
    13.19 6 6.71 1 2 1 −0.014
    13.45 3 6.58 −2 0 2 0.007
    14.05 6 6.30 2 1 1 0.011
    14.38 6 6.16 0 2 2 0.003
    14.71 10 6.02 −1 2 2 −0.008
    15.26 13 5.80 2 2 0 0.001
    15.76 10 5.62 −1 1 3 0.008
    16.09 1 5.51 1 2 2 −0.010
    16.32 1 5.43 2 0 2 0.035
    16.69 4 5.31 2 2 1 −0.007
    17.03 3 5.20 −1 3 1 0.026
    17.63 6 5.03 1 3 1 0.006
    18.17 5 4.88 −1 2 3 −0.004
    18.78 7 4.72 −1 3 2 −0.014
    19.30 1 4.60 −2 3 1 −0.019
    19.61 2 4.52 −3 2 1 0.036
    19.86 20 4.47 −2 2 3 0.040
    20.29 10 4.37 2 0 3 0.019
    20.57 4 4.31 0 1 4 0.006
    21.12 1 4.20 3 0 2 0.048
    21.57 12 4.12 −2 1 4 0.028
    22.46 10 3.96 1 4 1 0.035
    23.03 35 3.86 4 1 0 0.022
    23.39 21 3.80 −1 4 2 0.019
    24.08 2 3.69 −3 1 4 −0.006
    24.51 1 3.63 −4 0 3 0.036
    24.91 10 3.57 −2 4 2 0.003
    25.14 39 3.54 3 1 3 0.043
    25.69 36 3.47 −3 3 3 0.041
    26.68 3 3.34 0 5 1 0.035
    26.90 2 3.31 3 4 0 0.027
    27.10 2 3.29 0 2 5 0.030
    27.42 3 3.25 4 3 0 0.006
    28.19 2 3.16 −1 5 2 −0.035
    28.54 2 3.12 3 0 4 0.047
    28.94 11 3.08 0 4 4 −0.036
    29.18 5 3.06 −4 3 3 0.017
    29.50 4 3.03 −1 0 6 0.041
    30.18 7 2.96 −1 5 3 −0.042
  • [0000]
    TABLE 2
    Lattice metrics of the anhydrous form A
    Symmetry: monocline
    spatial group: P
    a: 16.16(2) Å
    b: 17.02(1) Å
    c: 18.18(2) Å
    β: 100.95(6)°
    cell volume: 4907(11) Å3
  • EXAMPLE 2 Crystallisation of Polymorph B
  • [0045]
    Polymorph B is obtained by cooling form A from Example 1 to temperatures <10° C.
  • [0046]
    FIG. 4 shows an X-ray powder diagram of the anhydrous form B
  • [0000]
    TABLE 3
    Labelled X-ray reflexes up to 30° 2 Θ with intensities (standardised) for
    the anhydrous form B
    2 Θ intensity dhkl labelling dexp-calc
    [°] I/Io [%] [Å] h k l [Å]
    5.82 3 15.17 1 0 0 −0.007
    7.04 33 12.55 0 1 1 0.001
    7.82 100 11.3 1 1 0 −0.004
    8.84 11 10 −1 1 1 0.001
    9.44 40 9.36 1 1 1 0.011
    10.62 14 8.32 −1 0 2 0.013
    10.79 24 8.19 0 1 2 −0.005
    11.82 39 7.48 −1 1 2 −0.003
    12.64 53 7 −1 2 1 −0.009
    13.07 11 6.77 1 2 1 −0.006
    13.24 6 6.68 −2 1 1 0.004
    14.04 16 6.3 2 1 1 0.003
    15.23 17 5.81 −2 1 2 0.003
    15.70 22 5.64 2 2 0 0.016
    16.38 2 5.41 0 3 1 −0.010
    16.73 6 5.3 2 2 1 0.008
    17.67 8 5.02 0 2 3 0.014
    18.16 3 4.88 −1 2 3 0.005
    18.33 9 4.84 3 1 0 0.016
    18.48 10 4.8 −3 1 1 −0.003
    18.97 15 4.68 0 0 4 −0.001
    19.56 6 4.54 1 3 2 0.013
    20.00 17 4.44 2 1 3 0.000
    20.42 9 4.35 1 0 4 0.009
    20.76 4 4.27 3 0 2 −0.014
    20.97 4 4.23 0 4 0 0.010
    21.07 5 4.21 1 1 4 −0.009
    21.22 12 4.18 0 3 3 0.001
    21.40 7 4.15 3 2 1 0.004
    21.66 4 4.1 −1 3 3 0.018
    21.98 7 4.04 2 2 3 −0.003
    22.16 10 4.01 −3 1 3 0.008
    22.97 3 3.87 1 2 4 −0.006
    23.58 43 3.77 −2 3 3 −0.003
    23.78 15 3.74 −2 2 4 −0.004
    24.05 6 3.7 4 1 0 −0.002
    24.29 8 3.66 −2 4 1 −0.008
    24.46 5 3.64 3 3 1 0.018
    24.71 7 3.6 0 3 4 0.001
    24.96 23 3.56 2 3 3 −0.001
    25.45 12 3.5 −2 4 2 −0.010
    25.75 35 3.46 4 2 0 0.011
    25.99 4 3.43 3 2 3 0.014
    26.15 6 3.41 3 3 2 0.010
    26.57 12 3.35 −2 3 4 −0.001
    26.82 4 3.32 −3 2 4 0.011
    27.20 6 3.28 1 2 5 −0.010
    27.43 4 3.25 −2 4 3 −0.003
    27.60 3 3.23 −2 2 5 −0.005
    28.19 4 3.16 3 4 1 0.010
    28.40 15 3.14 0 4 4 −0.013
    28.64 12 3.11 0 0 6 0.016
    29.18 6 3.06 −4 3 2 0.004
    29.42 2 3.03 1 4 4 0.002
    29.99 10 2.98 0 5 3 −0.008
    30.77 3 2.9 −4 3 3 0.018
  • [0000]
    TABLE 4
    Lattice metrics of the anhydrous form B
    Symmetry: monocline
    spatial group: P21/c (# 14)
    a: 15.23(1) Å
    b: 16.94(1) Å
    c: 18.79(1) Å
    β: 95.6(2)°
    cell volume: 4823(3) Å3
  • EXAMPLE 3 Crystallisation of Polymorph C
  • [0047]
    Crude 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine (26 kg) is refluxed with 157 l methanol, combined with 1.3 kg of activated charcoal and after 30 minutes' stirring the mixture is filtered and rinsed with 26 l methanol. 122 l of methanol are distilled off from the filtrate, then the residue is cooled to 45-55° C. 52 l of tert.-butylmethylether are added to the residue over 30 minutes. Then the mixture is stirred for another 60 minutes at 45-55° C. Crystallisation takes place within this time. A further 78 l tert. butylmethylether are added to the suspension over 30 minutes and then it is stirred again for a further 60 minutes at 45-55° C. It is diluted to four times the volume. The suspension is slowly cooled to 15-25° C. and stirred overnight at this temperature. After the suspension has been cooled to 0-5° C. the crystals are suction filtered, washed with 2 batches tert.-butylmethylether and dried at 70° C. in the vacuum dryer.
  • [0048]
    FIG. 5 shows an X-ray powder diagram of polymorph C
  • [0000]
    TABLE 5
    X-ray reflexes up to 30° 2 Θ with intensities (standardised)
    for the anhydrous form C
    2 Θ dhkl intensity
    [°] [Å] I/Io [%]
    3.38 26.16 4
    6.85 12.90 100
    7.18 12.31 11
    7.52 11.74 14
    7.96 11.10 36
    9.80 9.02 3
    11.11 7.96 2
    11.58 7.64 3
    12.30 7.19 5
    13.30 6.65 16
    13.75 6.44 26
    14.38 6.16 17
    14.74 6.01 11
    14.95 5.92 10
    15.63 5.66 6
    16.28 5.44 5
    17.81 4.98 10
    18.33 4.83 6
    18.75 4.73 15
    20.51 4.33 8
    20.77 4.27 8
    21.47 4.14 3
    21.96 4.05 4
    22.59 3.93 26
    23.76 3.74 29
    24.68 3.60 6
    25.01 3.56 7
    25.57 3.48 4
    25.96 3.43 4
    26.93 3.31 18
    27.22 3.27 13
    27.92 3.19 10
  • EXAMPLE 4 Crystallisation of Polymorph D
  • [0049]
    Polymorph D is obtained if polymorph C from Example 3 is heated to a temperature of 30-100° C. or dried at this temperature.
  • EXAMPLE 5 Crystallisation of Polymorph E
  • [0050]
    Anhydrous polymorph E is obtained if polymorph D is melted. On further heating, polymorph E crystallises out of the melt.
  • [0051]
    FIG. 6 shows a thermoanalysis of form C
  • [0052]
    In the DSC diagram of form C a whole range of signals can be observed. The strongest signal is the melting point of the anhydrous form A at approx. 206° C., which is produced in the DSC experiment. Before the melting point a number of other endothermic and exothermic signals can be observed. Thus, for example, a very broad and weak endothermic signal can be seen between 30 and 100° C., which correlates with the main loss of weight in thermogravimetry (TR). A TG/IR coupling experiment provides the information that only water escapes from the sample in this temperature range.
  • [0053]
    An X-ray powder diagram taken of a sample maintained at a temperature of 100° C. shows different X-ray reflexes from the starting material, suggesting that form C is a hydrate phase with stoichiometry somewhere in the region of a hemihydrate or monohydrate. The temperature-controlled sample is another anhydrous modification D, which only stable under anhydrous conditions. The D form melts at approx. 150° C. Another anhydrous crystal modification E crystallises from the melt, and when heated further melts at approx. 175° C. Finally, form A crystallises from the melt of form E. Form E is also a metastable crystal modification which occurs only at high temperatures.
Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US2056046 *May 11, 1934Sep 29, 1936Rhone Poulenc SaManufacture of bases derived from benz-dioxane
US2375138 *May 1, 1942May 1, 1945American Cyanamid CoAlkamine esters of aryloxymethyl benzoic acid
US2629736 *Feb 24, 1951Feb 24, 1953Searle & CoBasically substituted n-alkyl derivatives of alpha, beta, beta-triarylpropionamides
US2730544 *Jul 23, 1952Jan 10, 1956Sahyun LabAlkylaminoalkyl esters of hydroxycyclohexylbenzoic acid
US2750387 *Nov 25, 1953Jun 12, 1956Searle & CoBasically substituted derivatives of diarylaminobenzamides
US2928833 *Mar 3, 1959Mar 15, 1960S E Massengill CompanyTheophylline derivatives
US3174901 *Jan 31, 1963Mar 23, 1965Jan Marcel Didier Aron SamuelProcess for the oral treatment of diabetes
US3236891 *Apr 12, 1961Feb 22, 1966OrealNitrophenylenediamine derivatives
US3454635 *Jul 13, 1966Jul 8, 1969Hoechst AgBenzenesulfonyl-ureas and process for their manufacture
US3673241 *Mar 25, 1969Jun 27, 1972Ciba Geigy CorpSubstituted benzaldehyde guanylhydrazones
US3925357 *Jun 19, 1973Dec 9, 1975Takeda Chemical Industries Ltd' -sulfobenzylpenicillin salt
US4005208 *May 16, 1975Jan 25, 1977Smithkline CorporationN-Heterocyclic-9-xanthenylamines
US4599338 *Jan 16, 1985Jul 8, 1986Adir, S.A.R.L.Antimigraine 8-[3-(4-aminocarbonyl piperazino and piperidino) propyl[xanthines
US4687777 *Jan 17, 1986Aug 18, 1987Takeda Chemical Industries, Ltd.Thiazolidinedione derivatives, useful as antidiabetic agents
US4873330 *Feb 8, 1988Oct 10, 1989Orion-Yhtyma OyA process for the preparation of anhydrous, stable, crystalline delta-form of prazosin hydrochloride
US5041448 *Mar 9, 1989Aug 20, 1991Janssen Pharmaceutica N.V.(4-piperidinylmethyl and -hetero) purines
US5051517 *May 7, 1990Sep 24, 1991Bayer AktiengesellschaftProcess for the preparation of herbicidally active 3-amino-5-aminocarbonyl-1,2,4-triazoles
US5084460 *Dec 24, 1990Jan 28, 1992A. H. Robins Company, IncorporatedMethods of therapeutic treatment with N-(3-ouinuclidinyl)-2-hydroxybenzamides and thiobenzamides
US5223499 *May 11, 1992Jun 29, 1993Merck & Co., Inc.6-amino substituted imidazo[4,5-bipyridines as angiotensin II antagonists
US5234897 *Sep 18, 1991Aug 10, 1993Bayer AktiengesellschaftHerbicidal 3-amino-5-aminocarbonyl-1,2,4-triazoles
US5258380 *Jun 21, 1991Nov 2, 1993Janssen Pharmaceutica N.V.(4-piperidinylmethyl and -hetero)purines
US5266555 *Jul 10, 1992Nov 30, 1993Bayer AktiengesellschaftSubstituted triazoles
US5300298 *May 6, 1992Apr 5, 1994The Pennsylvania Research CorporationMethods of treating obesity with purine related compounds
US5329025 *Apr 2, 1992Jul 12, 1994G. D. Searle & Co.3-azido compound
US5332744 *May 4, 1990Jul 26, 1994Merck & Co., Inc.Substituted imidazo-fused 6-membered heterocycles as angiotensin II antagonists
US5389642 *Dec 16, 1993Feb 14, 1995Merck Patent Gesellschaft Mit Beschrankter HaftungImidazopyridines
US5399578 *Dec 29, 1992Mar 21, 1995Ciba-Geigy CorpAcyl compounds
US5407929 *Jul 27, 1993Apr 18, 1995Shionogi & Co., Ltd.Triazolylthiomethylthio cephalosporin hydrochhloride, its crystalline hydrate and the production of the same
US5470059 *Jan 18, 1995Nov 28, 1995Largent; Gerald A.Soft spherical playing ball and method of making same
US5719279 *Jun 11, 1996Feb 17, 1998Boehringer Ingelheim KgAsymmetrically substituted xanthines
US5728849 *Dec 20, 1996Mar 17, 1998Rhone-Poulenc Rorer S.A.Taxoids their preparation and pharmaceutical compositions containing them
US5753635 *Aug 16, 1996May 19, 1998Berlex Laboratories, Inc.Purine derivatives and their use as anti-coagulants
US5958951 *Jun 10, 1997Sep 28, 1999Novo NordiskialsModified form of the R(-)-N-(4,4-di(3-methylthien-2-yl)but-3-enyl)-nipecotic acid hydrochloride
US5965555 *May 30, 1997Oct 12, 1999Hoechst AktiengesellschaftXanthine compounds having terminally animated alkynol side chains
US5965592 *Jul 29, 1998Oct 12, 1999Novartis CorporationAcyl compounds
US6107302 *Jan 19, 1996Aug 22, 2000Glaxo Wellcome Inc.Guanine derivative
US6303661 *Apr 24, 1997Oct 16, 2001ProbiodrugUse of dipeptidyl peptidase IV effectors for lowering the blood glucose level in mammals
US6342601 *Jan 12, 1999Jan 29, 2002Astrazeneca AbCompounds
US6372940 *Mar 16, 2000Apr 16, 2002Sigma-Tau Industrie Farmaceutiche Riunite S.P.AProcess for the preparation of non-hygroscopic salts of L(−)-carnitine
US6548481 *Nov 28, 2000Apr 15, 2003Probiodrug AgEffectors of dipeptidyl peptidase IV
US6579868 *Dec 24, 1998Jun 17, 2003Eisai Co., Ltd.Purine derivatives and adenosine A2 receptor antagonists serving as preventives/remedies for diabetes
US6784195 *Oct 5, 2001Aug 31, 2004Vertex Pharmaceuticals IncorporatedPyrazole compositions useful as inhibitors of ERK
US6821978 *Aug 28, 2001Nov 23, 2004Schering CorporationXanthine phosphodiesterase V inhibitors
US6869947 *Jun 28, 2002Mar 22, 2005Novo Nordisk A/SHeterocyclic compounds that are inhibitors of the enzyme DPP-IV
US7060722 *Jun 2, 2005Jun 13, 2006Mitsubishi Pharma CorporationProline derivatives and use thereof as drugs
US7074794 *Aug 10, 2001Jul 11, 2006Mitsubishi Pharma CorporationProline derivatives and the use thereof as drugs
US7074798 *Feb 24, 2003Jul 11, 2006Eisai Co., LtdXanthine derivative and DPPIV inhibitor
US7074923 *May 30, 2003Jul 11, 2006Schering CorporationProcess for preparing xanthine phosphodiesterase V inhibitors and precursors thereof
US7109192 *Dec 2, 2003Sep 19, 2006Boehringer Ingelheim Pharma Gmbh & Co KgSubstituted imidazo-pyridinones and imidazo-pyridazinones, the preparation thereof and their use as pharmaceutical compositions
US7179809 *Apr 8, 2005Feb 20, 2007Boehringer Ingelheim International Gmbh2-Amino-imidazo[4,5-d]pyridazin-4-ones, their preparation and their use as pharmaceutical compositions
US7183280 *Dec 21, 2004Feb 27, 2007Boehringer Ingelheim International GmbhBicyclic imidazole derivatives, the preparation thereof and their use as pharmaceutical compositions
US7192952 *Mar 2, 2005Mar 20, 2007Novo Nordisk, A/SHeterocyclic compounds that are inhibitors of the enzyme DPP-IV
US7217711 *Dec 17, 2004May 15, 2007Boehringer Ingelheim International GmbhPiperazin-1-yl and 2-([1,4]diazepan-1-yl)-imidazo[4,5-d]-pyridazin-4-ones, the preparation thereof and their use as pharmaceutical compositions
US7235538 *Jul 17, 2003Jun 26, 2007Novo Nordisk A/SHeterocyclic compounds, which are inhibitors of the enzyme DPP-IV
US20020161001 *Aug 22, 2001Oct 31, 2002Kanstrup Anders BendtzHeterocyclic compounds, which are inhibitors of the enzyme DPP-IV
US20020169174 *Aug 28, 2001Nov 14, 2002Samuel ChackalamannilXanthine phosphodiesterase V inhibitors
US20020198205 *Feb 22, 2002Dec 26, 2002Frank HimmelsbachXanthine derivatives, the preparation thereof and their use as pharmaceutical compositions
US20030105077 *Jun 28, 2002Jun 5, 2003Kanstrup Anders BendtzHeterocyclic compounds that are inhibitors of the enzyme DPP-IV
US20030199528 *Jan 28, 2003Oct 23, 2003Kanstrup Anders B.Hetrocyclic compounds that are inhibitors of the enzyme DPP-IV
US20030232987 *May 30, 2003Dec 18, 2003Schering CorporationProcess for preparing xanthine phosphodiesterase V inhibitors and precursors thereof
US20030236272 *Apr 23, 2003Dec 25, 2003Carr Richard DavidMethod and composition for treatment of diabetes, hypertension, chronic heart failure and fluid retentive states
US20040034014 *Jul 17, 2003Feb 19, 2004Kanstrup Anders BendtzHeterocyclic compounds, which are inhibitors of the enzyme DPP-IV
US20040077645 *Feb 21, 2002Apr 22, 2004Frank HimmelsbachXanthine derivatives,production and use thereof as medicament
US20040082570 *Feb 24, 2003Apr 29, 2004Eisai Co., Ltd.Xanthine derivative and DPPIV inhibitor
US20040087587 *Oct 24, 2003May 6, 2004Boehringer Ingelheim Pharma Gmbh & Co. KgXanthine derivatives, the preparation thereof and their use as pharmaceutical compositions
US20040097510 *Aug 12, 2003May 20, 2004Boehringer Ingelheim Pharma Gmbh & Co. Kg8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
US20040116328 *Jun 6, 2003Jun 17, 2004Eisai Co., Ltd.Condensed imidazole derivatives
US20040122228 *Aug 4, 2003Jun 24, 2004Boehringer Ingelheim Pharma Gmbh & Co. KgNew purine derivatives, the preparation thereof and their use as pharmaceutical compositions
US20040138214 *Oct 28, 2003Jul 15, 2004Boehringer Ingelheim Pharma Gmbh & Co. KgXanthine derivatives, the preparation thereof and their use as pharmaceutical compositions
US20040138215 *Nov 18, 2003Jul 15, 2004Boehringer Ingelheim Pharma Gmbh & Co. KgXanthine derivatives, the preparation thereof and their use as pharmaceutical compositions
US20040166125 *Aug 7, 2003Aug 26, 2004Boehringer Ingelheim Pharma Gmbh & Co. KgXanthine derivatives, their preparation and their use in pharmaceutical compositions
US20050020574 *Dec 2, 2003Jan 27, 2005Boehringer Ingelheim Pharma Gmbh Co. KgNew substituted imidazo-pyridinones and imidazo-pyridazinones, the preparation thereof and their use as pharmaceutical compositions
US20050026921 *Jun 10, 2004Feb 3, 2005Boehringer Ingelheim International GmbhNew imidazopyridazinone and imidazopyridone derivatives, the preparation thereof and their use as pharmaceutical compositions
US20050130985 *Nov 2, 2004Jun 16, 2005Boehringer Ingelheim International Gmbh8-(piperazin-1yl)- and 8-([1,4]diazepan-1yl)-xanthines, the preparation thereof and their use as pharmaceutical composition
US20050171093 *Dec 17, 2004Aug 4, 2005Boehringer Ingelheim International GmbhNew piperazin-1-yl and 2-([1,4]diazepan-1-yl)-imidazo[4,5-d]-pyridazin-4-ones, the preparation thereof and their use as pharmaceutial compositions
US20050187227 *Feb 22, 2005Aug 25, 2005Boehringer Ingelheim Pharma Gmbh & Co. Kg8-[3-Amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical composition
US20050203095 *Mar 9, 2005Sep 15, 2005Boehringer Ingelheim International GmbhImidazopyridazinediones, their preparation and their use as pharmaceutical compositions
US20050234108 *Feb 17, 2005Oct 20, 2005Boehringer Ingelheim International Gmbh8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions
US20050261352 *May 9, 2005Nov 24, 2005Boehringer Ingelheim International GmbhImidazole derivatives, their preparation and their use as intermediates for the preparation of pharmaceutical compositions and pesticides
US20060004074 *Jun 24, 2005Jan 5, 2006Boehringer Ingelheim International GmbhNew imidazoles and triazoles, their preparation, and their use as pharmaceutical compositions
US20060058323 *Sep 1, 2005Mar 16, 2006Boehringer Ingelheim International GmbhNew 8-(3-amino-piperidin-1-yl)-7-(but-2-ynyl)-xanthines, the preparation thereof and their use as pharmaceutical compositions
US20060063787 *Aug 26, 2005Mar 23, 2006Eisai Co., Ltd.Condensed imidazole derivatives
US20060079541 *Sep 1, 2005Apr 13, 2006Boehringer Ingelheim International Gmbh3-methyl-7-butinyl-xanthines, the preparation thereof and their use as pharmaceutical compositions
US20060094722 *Sep 22, 2003May 4, 2006Eisai Co., Ltd.Combination drug
US20060100199 *Jun 3, 2003May 11, 2006Seiji YoshikawaNovel condensed imidazole derivatives
US20060142310 *Nov 4, 2005Jun 29, 2006Boehringer Ingelheim International GmbhProcess for the preparation of chiral 8-(-3-aminopiperidin-1-yl) xanthines
US20060173056 *Feb 10, 2006Aug 3, 2006Hiroshi KitajimaProline derivatives and use thereof as drugs
US20060205711 *May 22, 2006Sep 14, 2006Boehringer Ingelheim Pharma Gmbh & Co. KgXanthine derivatives, the preparation thereof and their use as pharmaceutical compositions
US20060247226 *Jul 12, 2006Nov 2, 2006Frank HimmelsbachXanthine derivatives, the preparation thereof and their use as pharmaceutical compositions
US20070027168 *Jul 30, 2006Feb 1, 2007Waldemar Pfrengle8-(3-amino-piperidin-1-yl)-xanthines, their preparation, and their use as pharmaceuticals
US20070088038 *Dec 12, 2006Apr 19, 2007Matthias Eckhardt2-amino-imidazo[4,5-d]pyridazin-4-ones, their preparation and their use as pharmaceutical compositions
US20070093659 *Dec 20, 2004Apr 26, 2007Jean-Francois BonfantiPiperdine-amino-benzimidazole derivatives as inhibitors of respiratory syncytial virus replication
US20070142383 *Feb 16, 2007Jun 21, 2007Matthias EckhardtImidazopyridazinediones, Their Preparation And Their Use As Pharmaceutical Compositions
US20070185091 *Apr 12, 2007Aug 9, 2007Boehringer Ingelheim Pharma Gmbh & Co. KgBicyclic Heterocycles, Pharmaceutical Compositions Containing These Compounds, Their Use and Processes for Preparing Them
US20070219178 *Oct 7, 2004Sep 20, 2007Eisai Co., Ltd.Preventive or therapeutic agents for multiple sclerosis
US20070281940 *May 4, 2007Dec 6, 2007Klaus DugiUses of dpp-iv inhibitors
US20080107731 *May 4, 2007May 8, 2008Anja KohlrauschDpp iv inhibitor formulations
US20080249089 *Jun 20, 2008Oct 9, 2008Boehringer Ingelheim Pharma Kg8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
US20080255159 *Jun 20, 2008Oct 16, 2008Boehringer Ingelheim Pharma Kg8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US7470716Jun 24, 2005Dec 30, 2008Boehringer Ingelheim International GmbhImidazoles and triazoles, their preparation, and their use as pharmaceutical compositions
US7495002Sep 1, 2005Feb 24, 2009Boehringer Ingelheim International Gmbh3-methyl-7-butinyl-xanthines, the preparation thereof and their use as pharmaceutical compositions
US7495003 *Sep 1, 2005Feb 24, 2009Boehringer Ingelheim International Gmbh8-(3-amino-piperidin-1-yl)-7-(but-2-ynyl)-xanthines, the preparation thereof and their use as pharmaceutical compositions
US7495005Aug 7, 2003Feb 24, 2009Boehringer Ingelheim Pharma Gmbh & Co. KgXanthine derivatives, their preparation and their use in pharmaceutical compositions
US7560450Nov 18, 2003Jul 14, 2009Boehringer Ingelheim Pharma Gmbh & Co., KgXanthine derivatives, the preparation thereof and their use as pharmaceutical compositions
US7645763Feb 22, 2005Jan 12, 2010Boehringer Ingelheim Pharma Gmbh & Co. Kg8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical composition
US7667035Sep 10, 2008Feb 23, 2010Boehringer Ingelheim International GmbhImidazole derivatives, their preparation and their use as intermediates for the preparation of pharmaceutical compositions and pesticides
US7696212Dec 10, 2008Apr 13, 2010Boehringer Ingelheim Pharma Gmbh And Co. KgXanthine derivatives, the preparation thereof and their use as pharmaceutical compositions
US7820815Nov 4, 2005Oct 26, 2010Boehringer Ingelheim International GmbhProcess for the preparation of chiral 8-(-3-aminopiperidin-1-yl) xanthines
US7838529Jan 16, 2009Nov 23, 2010Boehringer Ingelheim International GmbhXanthine derivates, their preparation and their use in pharmaceutical compositions
US7906539Aug 15, 2008Mar 15, 2011Boehringer Ingelheim International GmbhImidazoles and triazoles, their preparation, and their use as pharmaceutical compositions
US8071583Aug 7, 2007Dec 6, 2011Boehringer Ingelheim International GmbhPyrrolo[3,2-D] pyrimidines as DPP-IV inhibitors for the treatment of diabetes mellitus
US8106060Jul 30, 2006Jan 31, 2012Boehringer Ingelheim International Gmbh8-(3-amino-piperidin-1-yl)-xanthines, their preparation, and their use as pharmaceuticals
US8119648Jun 20, 2008Feb 21, 2012Boehringer Ingelheim Pharma Gmbh & Co. Kg8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
US8178541Jun 20, 2008May 15, 2012Boehringer Ingelheim Pharma Gmbh & Co. Kg8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
US8232281May 4, 2007Jul 31, 2012Boehringer Ingelheim International GmbhUses of DPP-IV inhibitors
US8513264Sep 8, 2009Aug 20, 2013Boehringer Ingelheim International GmbhCombination therapy for the treatment of diabetes and related conditions
US8541450Mar 30, 2009Sep 24, 2013Boehringer Ingelheim International GmbhProcess for the preparation of chiral 8-(3-aminopiperidin-1yl)-xanthines
US8551957Aug 15, 2008Oct 8, 2013Boehringer Ingelheim International GmbhPharmaceutical composition comprising a glucopyranosyl-substituted benzene derivate
US8637530Jan 9, 2012Jan 28, 2014Boehringer Ingelheim International Gmbh8-(3-amino-piperidin-1-yl)-xanthines, their preparation, and their use as pharmaceuticals
US8664232Apr 17, 2012Mar 4, 2014Boehringer Ingelheim Pharma Gmbh & Co. Kg8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
US8673927Nov 15, 2010Mar 18, 2014Boehringer Ingelheim International GmbhUses of DPP-IV inhibitors
US8697868Jan 27, 2009Apr 15, 2014Boehringer Ingelheim International Gmbh8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions
US8846695Jan 7, 2010Sep 30, 2014Boehringer Ingelheim International GmbhTreatment for diabetes in patients with inadequate glycemic control despite metformin therapy comprising a DPP-IV inhibitor
US8853156Aug 5, 2009Oct 7, 2014Boehringer Ingelheim International GmbhTreatment for diabetes in patients inappropriate for metformin therapy
US8865729Dec 22, 2009Oct 21, 2014Boehringer Ingelheim International GmbhSalt forms of a xanthine compound
US8883800Jul 13, 2012Nov 11, 2014Boehringer Ingelheim International GmbhSubstituted quinazolines, the preparation thereof and the use thereof in pharmaceutical compositions
US8883805Mar 1, 2013Nov 11, 2014Boehringer Ingelheim International GmbhProcess for the preparation of chiral 8-(3-aminopiperidin-1-yl)-xanthines
US8962636Jul 13, 2012Feb 24, 2015Boehringer Ingelheim International GmbhSubstituted quinazolines, the preparation thereof and the use thereof in pharmaceutical compositions
US9034883Nov 14, 2011May 19, 2015Boehringer Ingelheim International GmbhVasoprotective and cardioprotective antidiabetic therapy
US9108964Jan 14, 2014Aug 18, 2015Boehringer Ingelheim International Gmbh8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
US9149478Jun 23, 2011Oct 6, 2015Boehringer Ingelheim International GmbhDiabetes therapy
US9155705Apr 2, 2009Oct 13, 2015Boehringer Ingelheim International GmbhDPP-IV inhibitor combined with a further antidiabetic agent, tablets comprising such formulations, their use and process for their preparation
US9173859Jan 22, 2014Nov 3, 2015Boehringer Ingelheim International GmbhUses of DPP IV inhibitors
US9186392May 5, 2011Nov 17, 2015Boehringer Ingelheim International GmbhCombination therapy
US9199998Dec 23, 2014Dec 1, 2015Boehringer Ingelheim Internatioal GmbhSubstituted quinazolines, the preparation thereof and the use thereof in pharmaceutical compositions
US9212183May 9, 2014Dec 15, 2015Boehringer Ingelheim International GmbhSalt forms of 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine
US9266888Aug 19, 2014Feb 23, 2016Boehringer Ingelheim International GmbhPolymorphs
US9321791Jun 24, 2015Apr 26, 2016Boehringer Ingelheim International Gmbh8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
US9415016Aug 27, 2015Aug 16, 2016Boehringer Ingelheim International GmbhDPP-IV inhibitor combined with a further antidiabetic agent, tablets comprising such formulations, their use and process for their preparation
US9457029Nov 26, 2010Oct 4, 2016Boehringer Ingelheim International GmbhTreatment of genotyped diabetic patients with DPP-IV inhibitors such as linagliptin
US9486526Jun 3, 2014Nov 8, 2016Boehringer Ingelheim International GmbhTreatment for diabetes in patients inappropriate for metformin therapy
US9493462Jan 13, 2016Nov 15, 2016Boehringer Ingelheim International GmbhPolymorphs
US9499546Oct 6, 2014Nov 22, 2016Boehringer Ingelheim International GmbhProcess for the preparation of chiral 8-(3-aminopiperidin-1-yl)-xanthines
US9526728Feb 27, 2015Dec 27, 2016Boehringer Ingelheim International GmbhMedical use of a DPP-4 inhibitor
US9526730Oct 30, 2015Dec 27, 2016Boehringer Ingelheim International GmbhUse of a DPP-4 inhibitor in podocytes related disorders and/or nephrotic syndrome
US9555001Mar 5, 2013Jan 31, 2017Boehringer Ingelheim International GmbhPharmaceutical composition and uses thereof
US9556175Mar 15, 2016Jan 31, 2017Boehringer Ingelheim International Gmbh8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and thier use as pharmaceutical compositions
US9603851Oct 2, 2015Mar 28, 2017Boehringer Ingelheim International GmbhCombination therapy
US9713618May 21, 2013Jul 25, 2017Boehringer Ingelheim International GmbhMethod for modifying food intake and regulating food preference with a DPP-4 inhibitor
US9751855Jan 25, 2017Sep 5, 2017Boehringer Ingelheim International GmbhProcess for the preparation of chiral 8-(3-aminopiperidin-1-yl)-xanthines
US9815837Oct 5, 2016Nov 14, 2017Boehringer Ingelheim International GmbhPolymorphs
US20060058323 *Sep 1, 2005Mar 16, 2006Boehringer Ingelheim International GmbhNew 8-(3-amino-piperidin-1-yl)-7-(but-2-ynyl)-xanthines, the preparation thereof and their use as pharmaceutical compositions
US20060142310 *Nov 4, 2005Jun 29, 2006Boehringer Ingelheim International GmbhProcess for the preparation of chiral 8-(-3-aminopiperidin-1-yl) xanthines
US20080249089 *Jun 20, 2008Oct 9, 2008Boehringer Ingelheim Pharma Kg8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
US20080255159 *Jun 20, 2008Oct 16, 2008Boehringer Ingelheim Pharma Kg8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
US20080312243 *Aug 15, 2008Dec 18, 2008Matthias EckhardtImidazoles and triazoles, their preparation, and their use as pharmaceutical compositions
US20090088569 *Dec 5, 2008Apr 2, 2009Matthias Eckhardt2-amino-imidazo[4,5-d]pyridazin-4-ones, their preparation, and their use as pharmaceutical compositions
US20090137801 *Jan 27, 2009May 28, 2009Boehringer Ingelheim International Gmbh8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions
US20090192314 *Mar 30, 2009Jul 30, 2009Boehringer Ingelheim International GmbhProcess for the preparation of chiral 8-(3-aminopiperidin-1yl)-xanthines
US20100144703 *Feb 17, 2010Jun 10, 2010Boehringer Ingelheim Pharma Gmbh & Co. KgXanthine derivatives, the preparation thereof and their use as pharmaceutical compositions
US20110178134 *Aug 6, 2010Jul 21, 2011Sanofi-AventisNovel phenyl-substituted imidazolidines, process for preparation thereof, medicaments comprising said compounds and use thereof
US20110195917 *Aug 15, 2008Aug 11, 2011Boehringer Ingelheim International GmbhPharmaceutical composition comprising a glucopyranosyl-substituted benzene derivate
WO2009021740A2Aug 14, 2008Feb 19, 2009Sanofis-AventisSubstituted tetrahydronaphthalenes, process for the preparation thereof and the use thereof as medicaments
WO2010086411A1 *Jan 29, 2010Aug 5, 2010Boehringer Ingelheim International GmbhDpp-iv inhibitors for treatment of diabetes in paediatric patients
WO2011107494A1Mar 2, 2011Sep 9, 2011SanofiNovel aromatic glycoside derivatives, medicaments containing said compounds, and the use thereof
WO2011113947A1 *Mar 18, 2011Sep 22, 2011Boehringer Ingelheim International GmbhCombination of a gpr119 agonist and the dpp-iv inhibitor linagliptin for use in the treatment of diabetes and related conditions
WO2011157827A1Jun 17, 2011Dec 22, 2011SanofiAzolopyridin-3-one derivatives as inhibitors of lipases and phospholipases
WO2011161030A1Jun 20, 2011Dec 29, 2011SanofiHeterocyclic substituted methoxyphenyl derivatives having an oxo group, method for producing same, and use thereof as gpr40 receptor modulators
WO2012004269A1Jul 5, 2011Jan 12, 2012Sanofi(2-aryloxy-acetylamino)-phenyl-propionic acid derivatives, method for producing same and use thereof as pharmaceuticals
WO2012004270A1Jul 5, 2011Jan 12, 2012SanofiSpirocyclically substituted 1,3-propane dioxide derivatives, methods for the production thereof and use of the same as medicament
WO2012010413A1Jul 5, 2011Jan 26, 2012SanofiAryloxy-alkylene substituted hydroxyphenyl hexynoic acids, methods for the production thereof and use of the same as medicament
WO2012120052A1Mar 7, 2012Sep 13, 2012SanofiOxathiazine derivatives substituted with carbocycles or heterocycles, method for producing same, drugs containing said compounds, and use thereof
WO2012120053A1Mar 7, 2012Sep 13, 2012SanofiBranched oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof
WO2012120054A1Mar 7, 2012Sep 13, 2012SanofiDi- and tri-substituted oxathiazine derivates, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof
WO2012120055A1Mar 7, 2012Sep 13, 2012SanofiDi- and tri-substituted oxathiazine derivates, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof
WO2012120056A1Mar 7, 2012Sep 13, 2012SanofiTetrasubstituted oxathiazine derivatives, method for producing them, their use as medicine and drug containing said derivatives and the use thereof
WO2013037390A1Sep 12, 2011Mar 21, 2013Sanofi6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors
WO2013045413A1Sep 25, 2012Apr 4, 2013Sanofi6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors
WO2014064215A1Oct 24, 2013May 1, 2014INSERM (Institut National de la Santé et de la Recherche Médicale)TPL2 KINASE INHIBITORS FOR PREVENTING OR TREATING DIABETES AND FOR PROMOTING β-CELL SURVIVAL
WO2016151018A1Mar 23, 2016Sep 29, 2016INSERM (Institut National de la Santé et de la Recherche Médicale)Method and pharmaceutical composition for use in the treatment of diabetes
Classifications
U.S. Classification514/266.2, 544/284
International ClassificationA61K31/517, C07D405/14
Cooperative ClassificationC07D473/06, C07D473/04, C07B2200/13
European ClassificationC07D473/04
Legal Events
DateCodeEventDescription
Jul 13, 2010ASAssignment
Owner name: BOEHRINGER INGELHEIM INTERNATIONAL GMBH, GERMANY
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:SIEGER, PETER;KEMMER, DIRK;KOHLBAUER, PETER;AND OTHERS;SIGNING DATES FROM 20070606 TO 20070618;REEL/FRAME:024670/0697