Substituted pyridines as dnmt1 inhibitors
AssigneeGlaxoSmithKline Intellectual Property Development Limited
InventorsAndrew B. BENOWITZ, David T. FOSBENNER, Bryan Wayne KING, Stuart Paul ROMERIL
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Abstract
The invention relates to substituted pyridine derivatives that are inhibitors of the activity of DNA methyltransferase 1 (DNMT1). The invention also relates to pharmaceutical compositions comprising such compounds and methods of using such compounds in the treatment of cancer, pre-cancerous syndromes, beta haemoglobinopathy disorders, and other diseases associated with inappropriate DNMT1 activity.
Claims6
An anhydrous crystalline glycine salt having a formula of
- which provides an XRPD pattern substantially as set out in Table I:
- TABLE I
- XRPD Summay of Diffraction Angles and d-Spacing
- Peak #
- Diff. Angle [°2θ]
- d-spacing [Å]
- 1
- 5.42
- 16.3027
- 2
- 5.78
- 15.2672
- 3
- 7.44
- 11.8749
- 4
- 9.59
- 9.2110
- 5
- 10.56
- 8.3679
- 6
- 10.81
- 8.1745
- 7
- 11.55
- 7.6557
- 8
- 13.04
- 6.7854
- 9
- 14.46
- 6.1218
- 10
- 14.84
- 5.9641
- 11
- 15.56
- 5.6903
- 12
- 16.25
- 5.4518
- 13
- 17.01
- 5.2072
- 14
- 18.32
- 4.8394
- 15
- 18.82
- 4.7116
- 16
- 19.00
- 4.6665
- 17
- 19.20
- 4.6182
- 18
- 19.60
- 4.5246
- 19
- 20.49
- 4.3310
- 20
- 20.99
- 4.2287
- 21
- 21.18
- 4.1924
- 22
- 21.54
- 4.1216
- 23
- 21.69
- 4.0934
- 24
- 22.34
- 3.9755
- 25
- 22.65
- 3.9233
- 26
- 23.20
- 3.8313
- 27
- 23.95
- 3.7127
- 28
- 24.42
- 3.6426
- 29
- 24.99
- 3.5610
- 30
- 25.17
- 3.5354
- 31
- 26.22
- 3.3958
- 32
- 26.54
- 3.3559
An anhydrous crystalline glycine salt having a formula of
- which provides an XRPD pattern substantially in accordance with FIG. 1.
An anhydrous crystalline glycine salt having a formula of
- which provides an XRPD pattern that has representative diffraction peaks at 10.56, 14.46, 16.25, 20.99, 21.18, 21.54, 21.69, and 26.22.
A crystalline monohydrate glycine salt having a formula of
- which provides an XRPD pattern substantially as set out in Table II:
- TABLE II
- Example 1 Mono-Hydrate Glycinate Salt Summay
- of XRPD Diffraction Angles and d-Spacing
- Peak #
- Diff. Angle [°2θ]
- d-spacing [Å]
- 1
- 5.13
- 17.2011
- 2
- 5.75
- 15.3532
- 3
- 7.27
- 12.1458
- 4
- 9.28
- 9.5245
- 5
- 10.26
- 8.6117
- 6
- 10.61
- 8.3277
- 7
- 11.52
- 7.6772
- 8
- 12.87
- 6.8726
- 9
- 13.86
- 6.3858
- 10
- 14.56
- 6.0794
- 11
- 15.43
- 5.7389
- 12
- 16.31
- 5.4293
- 13
- 17.32
- 5.1171
- 14
- 18.52
- 4.7872
- 15
- 19.15
- 4.6299
- 16
- 19.89
- 4.4604
- 17
- 20.84
- 4.2586
- 18
- 21.23
- 4.1824
- 19
- 22.11
- 4.0168
- 20
- 22.55
- 3.9404
- 21
- 23.13
- 3.8421
- 22
- 23.83
- 3.7305
- 23
- 24.13
- 3.6847
- 24
- 25.47
- 3.4942
- 25
- 26.06
- 3.4171
- 26
- 27.91
- 3.1941
- 27
- 28.65
- 3.1137
- 28
- 29.05
- 3.0716
- 29
- 29.90
- 2.9860
- 30
- 30.42
- 2.9363
- 31
- 30.82
- 2.8990
- 32
- 31.34
- 2.8522
- 33
- 32.91
- 2.7196
- 34
- 33.38
- 2.6825
- 35
- 36.72
- 2.4456
A crystalline monohydrate glycine salt having a formula of
- which provides an XRPD pattern substantially in accordance with FIG. 4.
A crystalline monohydrate glycine salt having a formula of
- which provides an XRPD pattern that has representative diffraction peaks at 7.27, 10.26, 11.52, 13.86, 15.43, 20.84, 21.23, 22.11, and 26.06.
Dependencies are inferred from the claim text.