NZ752990B2 - Crystal of pyrido[3, 4-d]pyrimidine derivative or solvate thereof - Google Patents
Crystal of pyrido[3, 4-d]pyrimidine derivative or solvate thereofInfo
- Publication number
- NZ752990B2 NZ752990B2 NZ752990A NZ75299017A NZ752990B2 NZ 752990 B2 NZ752990 B2 NZ 752990B2 NZ 752990 A NZ752990 A NZ 752990A NZ 75299017 A NZ75299017 A NZ 75299017A NZ 752990 B2 NZ752990 B2 NZ 752990B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- exhibits
- crystal according
- peaks
- compound
- radiation
- Prior art date
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Abstract
Provided is a crystal of a novel pyrido[3, 4-d]pyrimidine derivative having excellent CDK 4/6 inhibitory activity. A crystal of a compound represented by formula (I). In the formula, R1represents a hydrogen atom or a C1-3alkyl group; R2represents a hydrogen atom or an oxo group; L represents a single bond or a C1-3alkylene group; and X represents CH or N.
Claims (39)
1. [Claim 1] A crystal of a compound represented by formula (I): 5 wherein R represents a hydrogen atom or a C alkyl group, R represents a hydrogen atom or an oxo group, L represents a single bond or a C alkylene group, and X represents CH or N; or a solvate thereof, wherein the compound represented by formula (I) is selected from the group 10 consisting of: (a) 1-(6-((6-((1R)hydroxyethyl)(isopropylamino)pyrido[3,4-d]pyrimidineyl)amino) pyridyl)piperazineone (hereinafter “Compound (a)”) or its solvate; (b) 1-(6-((6-((1R)methoxyethyl)(isopropylamino)pyrido[3,4-d]pyrimidineyl)amino)- 3-pyridazyl)piperazine (hereinafter “Compound (b)”); and 15 (c) (R)-N8-isopropyl(1-methoxyethyl)-N2-(5-(piperazineylmethyl)pyridin yl)pyrido[3,4-d]pyrimidine-2,8-diamine (hereinafter “Compound (c)”); wherein the crystal has a crystalline form selected from: (1) Crystalline form D of Compound (a), which exhibits peaks at diffraction angles 2? = 6.3°, 6.6°, 11.6°, 16.9°, and 20.0°, on a powder X-ray diffraction spectrum measured with Cu·Ka 20 radiation, (2) Crystalline form A of Compound (a), which exhibits peaks at diffraction angles 2? = 5.3°, 7.3°, 10.3°, 15.1°, and 17.4°, on a powder X-ray diffraction spectrum measured with Cu·Ka radiation, (3) Crystalline form B of Compound (a), which exhibits peaks at diffraction angles 2? = 5.3°, 25 6.0°, 6.7°, 10.4°, and 20.8°, on a powder X-ray diffraction spectrum measured with Cu·Ka radiation, (4) Crystalline form C of Compound (a) or its solvate with dimethyl sulfoxide, which exhibits peaks at diffraction angles 2? = 6.0 °, 10.0°, 13.7°, 20.3°, and 23.0°, on a powder X-ray diffraction spectrum measured with Cu·Ka radiation, (5) Crystalline form I of Compound (a), which exhibits peaks at diffraction angles 2? = 5.2°, 7.2°, 9.5°, 14.5°, 16.5°, 20.9°, 25.0°, and 27.9°, on a powder X-ray diffraction spectrum measured with Cu·Ka radiation, 5 (6) Crystalline form A of Compound (b), which exhibits peaks at diffraction angles 2? = 5.2°, 7.6°, 8.4°, 10.5°, 15.2°, 16.9°, 20.1°, 21.0°, 23.3°, and 26.6°, on a powder X-ray diffraction spectrum measured with Cu·Ka radiation, (7) Crystalline form B of Compound (b), which exhibits peaks at diffraction angles 2? = 5.2°, 6.6°, 8.1°, 15.2°, 15.9°, 16.2°, 18.8°, 20.5°, 20.8°, and 21.7°, on a powder X-ray diffraction 10 spectrum measured with Cu·Ka radiation, (8) Crystalline form C of Compound (b), which exhibits peaks at diffraction angles 2? = 5.2°, 7.6°, 8.4°, 10.0°, 10.5°, 11.9°, 15.2°, 17.0°, 20.9°, and 21.2°, on a powder X-ray diffraction spectrum measured with Cu·Ka radiation, and (9) Crystalline form A of Compound (c), which exhibits peaks at diffraction angles 2? = 15 4.8°, 7.6°, 8.2°, 9.7°, 15.3°, 16.6°, 19.1°, 19.8°, 22.4° and 26.2°, on a powder X-ray diffraction spectrum measured with Cu·Ka radiation.
2. [Claim 2] The crystal according to claim 1, wherein the compound is Compound (a).
3. [Claim 3] The crystal according to claim 2, which exhibits peaks at diffraction angles 2 ? = 6.3 °, 6.6 °, 11.6 °, 16.9 ° and 20.0 ° on a powder X-ray diffraction spectrum measured with Cu·Ka radiation.
4. [Claim 4] The crystal according to claim 3, which exhibits an extrapolated onset temperature for an endothermic peak of 277 °C according to differential scanning calorimetry. 30 [
5. Claim 5] The crystal according to claim 3, which exhibits distinctive absorption peaks with wave -1 -1 -1 numbers of 703 cm , 896 cm and 3418 cm on an infrared absorption spectrum (KBr method).
6. [Claim 6] The crystal according to claim 3, which exhibits distinctive peaks at 136.0ppm,
7. 2ppm, 105.1ppm, 101.8ppm, 52.7ppm, 49.6ppm, 42.9ppm, 23.8ppm and 18.5ppm on a solid NMR spectrum ( C). 5 [Claim 7] The crystal according to claim 3, which exhibits distinctive peaks at 248.6ppm,
8. 7ppm, 229.2ppm, 214.5ppm, 174.3ppm, 86.5ppm, 54.7ppm and -12.4ppm on a solid NMR spectrum ( N). 10 [Claim 8] The crystal according to claim 2, which exhibits peaks at diffraction angles 2 ? = 5.3 °,
9. 3 °, 10.3 °, 15.1 ° and 17.4 ° on a powder X-ray diffraction spectrum measured with Cu·Ka radiation. 15 [Claim 9] The crystal according to claim 8, which exhibits an extrapolated onset temperature for an endothermic peak of 277 °C according to differential scanning calorimetry.
10. [Claim 10] 20 The crystal according to claim 8, which exhibits distinctive absorption peaks with wave -1 -1 -1 numbers of 874 cm , 1330 cm and 3314 cm on an infrared absorption spectrum (KBr method).
11. [Claim 11] 25 The crystal according to claim 8, which exhibits distinctive peaks at 154.7ppm, 138.8ppm, 133.6ppm, 113.2ppm, 101.6ppm, 100.4ppm, 67.4ppm, 51.8ppm, 26.6ppm and 23.3ppm on a solid NMR spectrum ( C).
12. [Claim 12] 30 The crystal according to claim 8, which exhibits distinctive peaks at 243.6ppm, 86.7ppm, 56.7ppm and -12.4 ppm on a solid NMR spectrum ( N).
13. [Claim 13] The crystal according to claim 2, which exhibits peaks at diffraction angles 2 ? = 5.3 °, 35 6.0 °, 6.7 °, 10.4 ° and 20.8 ° on a powder X-ray diffraction spectrum measured with Cu·Ka radiation.
14. [Claim 14] The crystal according to claim 13, which exhibits an extrapolated onset temperature for an endothermic peak of 271 °C according to differential scanning calorimetry.
15. [Claim 15] The crystal according to claim 2, which exhibits peaks at diffraction angles 2 ? = 6.0 °, 10.0 °, 13.7 °, 20.3 ° and 23.0 °on a powder X-ray diffraction spectrum measured with Cu·Ka radiation.
16. [Claim 16] The crystal according to claim 15, which exhibits an extrapolated onset temperature for an endothermic peak of 100 °C and 278 °C according to differential scanning calorimetry. 15 [
17. Claim 17] The crystal according to claim 15, which exhibits distinctive absorption peaks with wave -1 -1 -1 -1 -1 numbers of 840 cm , 904 cm , 955 cm , 1490 cm and 3281 cm on an infrared absorption spectrum (KBr method). 20 [
18. Claim 18] The crystal according to claim 2, which exhibits peaks at diffraction angles 2 ? = 5.2 °, 7.2 °, 9.5 °, 14.5 °, 16.5 °, 20.9 °, 25.0 ° and 27.9 °on a powder X-ray diffraction spectrum measured with Cu·Ka radiation. 25 [
19. Claim 19] The crystal according to claim 18, which exhibits an extrapolated onset temperature for an endothermic peak of 272 °C according to differential scanning calorimetry.
20. [Claim 20] 30 The crystal according to claim 18, which exhibits distinctive absorption peaks with wave -1 -1 numbers of 1081 cm and 1260 cm on an infrared absorption spectrum (KBr method).
21. [Claim 21] The crystal according to claim 1, wherein the compound is Compound (b).
22. [Claim 22] The crystal according to claim 21, which exhibits peaks at diffraction angles 2 ? = 5.2 °,
23. 6 °, 8.4 °, 10.5 °, 15.2 °, 16.9 °, 20.1 °, 21.0 °, 23.3 ° and 26.6 °on a powder X-ray diffraction spectrum measured with Cu·Ka radiation. 5 [Claim 23] The crystal according to claim 22, which exhibits an extrapolated onset temperature for an endothermic peak of 225 °C according to differential scanning calorimetry.
24. [Claim 24] 10 The crystal according to claim 22, which exhibits distinctive absorption peaks with wave -1 -1 -1 -1 -1 numbers of 1369 cm , 1424 cm , 1508 cm , 1545 cm and 1566 cm on an infrared absorption spectrum (KBr method).
25. [Claim 25] 15 The crystal according to claim 22, which exhibits distinctive peaks at 163.4ppm, 157.6ppm, 155.5ppm, 117.8ppm, 82.2ppm, 56.1ppm and 42.3ppm on a solid NMR spectrum ( C).
26. [Claim 26] 20 The crystal according to claim 22, which exhibits distinctive peaks at 311.7ppm, 232.4ppm, 168.5ppm, 79.5ppm, 53.3ppm, 32.9ppm and -4.3ppm on a solid NMR spectrum ( N).
27. [Claim 27] 25 The crystal according to claim 21, which exhibits peaks at diffraction angles 2 ? = 5.2 °, 6.6 °, 8.1 °, 15.2 °, 15.9 °, 16.2 °, 18.8 °, 20.5 °, 20.8 ° and 21.7 °, on a powder X-ray diffraction spectrum measured with Cu·Ka radiation.
28. [Claim 28] 30 The crystal according to claim 27, which exhibits an extrapolated onset temperature for an endothermic peak of 221 °C according to differential scanning calorimetry.
29. [Claim 29] The crystal according to claim 21, which exhibits peaks at diffraction angles 2 ? =5.2 °, 35 7.6 °, 8.4 °, 10.0 °, 10.5 °, 11.9 °, 15.2 °, 17.0 °, 20.9 °and 21.2 °, on a powder X-ray diffraction spectrum measured with Cu·Ka radiation.
30. [Claim 30] The crystal according to claim 29, which exhibits an extrapolated onset temperature for an endothermic peak of 223 °C according to differential scanning calorimetry.
31. [Claim 31] The crystal according to claim 29, which exhibits distinctive absorption peaks with wave -1 -1 -1 -1 -1 numbers of 1369 cm , 1424 cm , 1507cm , 1546cm and 1566 cm on an infrared absorption spectrum (KBr method).
32. [Claim 32] The crystal according to claim 1, wherein the compound is Compound (c).
33. [Claim 33] 15 The crystal according to claim 32, which exhibits peaks at diffraction angles 2 ? = 4.8 °, 7.6 °, 8.2 °, 9.7 °, 15.3 °, 16.6 °, 19.1 °, 19.8 °, 22.4 °and 26.2 ° on a powder X-ray diffraction spectrum measured with Cu·Ka radiation.
34. [Claim 34] 20 The crystal according to claim 33 which exhibits an extrapolated onset temperature for an endothermic peak of 182 °C according to differential scanning calorimetry.
35. [Claim 35] The crystal according to claim 33, which exhibits distinctive absorption peaks with wave -1 -1 -1 -1 -1 25 numbers of 1115 cm ,1446 cm ,1508 cm , 1560 cm and 1601 cm on an infrared absorption spectrum (KBr method).
36. [Claim 36] The crystal according to claim 33, which exhibits distinctive peaks at 161.3ppm, 30 150.8ppm, 138.9ppm, 128.1ppm, 109.8ppm, 82.7ppm, 47.6ppm, 42.5ppm, 41.5ppm, 24.5ppm and 21.7ppm on a solid NMR spectrum ( C).
37. [Claim 37] The crystal according to claim 33, which exhibits distinctive peaks at 242.8ppm, 35 233.8ppm, 219.0ppm, 171.7ppm, 86.9ppm, 54.9ppm, 11.3ppm and -5.5ppm on a solid NMR spectrum ( N).
38. [Claim 38] A pharmaceutical composition comprising a crystal according to any one of claims 1 to 37 and a pharmaceutically acceptable carrier.
39. [Claim 39] A pharmaceutical composition having a CDK
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2016229973 | 2016-11-28 | ||
| PCT/JP2017/042437 WO2018097295A1 (en) | 2016-11-28 | 2017-11-27 | Crystal of pyrido[3, 4-d]pyrimidine derivative or solvate thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ752990A NZ752990A (en) | 2025-08-29 |
| NZ752990B2 true NZ752990B2 (en) | 2025-12-02 |
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