# US 9,573,951 B2 · Crystalline forms of a purine derivative

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- Number: US 9,573,951 B2
- Document ID: US9573951B2
- Status: Granted
- Kind: B2
- Application number: 14/524,686
- Filed: 2014-10-27
- Published: 2015-05-28
- Granted: 2017-02-21
- Earliest claimed: 2010-01-22
- Assignees: Cyclacel Limited
- Applicants: Cyclacel Limited
- Inventors: Benjamin Mark Skead; Christopher Peter Worrall; Jonathan Charles Christian Atherton; Julian Scott Northen; Philippe Fernandes
- Web page: https://patentgrep.com/patent/US9573951B2

## CPC

- C07D 473/16: two nitrogen atoms
- A61K 31/52: Purines, e.g. adenine
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 5/14: of the thyroid hormones, e.g. T3, T4
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 13/12: of the kidneys
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/06: Antipsoriatics
- A61P 17/14: for baldness or alopecia
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 21/04: for myasthenia gravis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 27/02: Ophthalmic agents
- A61P 27/06: Antiglaucoma agents or miotics
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- A61P 31/20: for DNA viruses
- A61P 31/22: for herpes viruses
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- C07C 51/412: {by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part}
- C07C 57/145: Maleic acid
- C07C 57/15: Fumaric acid
- C07C 59/245: containing hydroxy or O-metal groups
- C07C 59/255: Tartaric acid
- C07C 59/265: Citric acid
- C07C 65/05: o-Hydroxy carboxylic acids
- C07C 303/32: of salts of sulfonic acids
- C07C 309/04: containing only one sulfo group
- C07C 309/29: of non-condensed six-membered aromatic rings
- G01F 1/115: with magnetic or electromagnetic coupling to the indicating device
- G01P 3/4802: {by using electronic circuits in general}
- G01P 5/07: with electrical coupling to the indicating device
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- G01F: MEASURING VOLUME, VOLUME FLOW, MASS FLOW OR LIQUID LEVEL; METERING BY VOLUME
- G01P: MEASURING LINEAR OR ANGULAR SPEED, ACCELERATION, DECELERATION, OR SHOCK; INDICATING PRESENCE, ABSENCE, OR DIRECTION, OF MOVEMENT (measuring or recording blood flow A61B5/02, A61B8/06; monitoring speed or deceleration of electrically-propelled vehicles B60L3/00; vehicle lighting systems adapted to indicate speed B60Q1/54; determining position or course in navigation, measuring ground distance in geodesy or surveying G01C; combined measuring devices for measuring two or more variables of movement G01C23/00; measuring velocity of sound G01H; measuring velocity of light G01J7/00; measuring direction or velocity of solid objects by reception or emission of radiowaves or other waves and based on propagation effects, e.g. Doppler effect, propagation time, direction of propagation, G01S; measuring speed of nuclear radiation G01T; measuring acceleration of gravity G01V; {measuring or recording the speed of trains B61L23/00; speed indicators incorporated in motor vehicles B60K35/00; measuring frequency or phase G01R; traffic control G08G})
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

The present invention relates to new crystalline forms of a purine derivative which exhibits excellent anti-tumor activity. The invention also relates to a pharmaceutical composition containing said crystalline forms as an active ingredient, and use thereof in the prevention or treatment of disease. The invention further relates to a process for preparing the crystalline forms.

## Claims

### Claim 1

A crystalline form of compound (I),
wherein said compound is in the form of the free base and which is characterized by an x-ray powder diffraction pattern having two or more diffraction peaks at 2[theta] values selected from 7.53±0.2, 9.60±0.2, 10.22±0.2, 11.29±0.2, 11.66±0.2, 12.26±0.2, 12.62±0.2, 13.17±0.2, 14.06±0.2, 14.85±0.2, 15.15±0.2, 15.57±0.2, 16.99±0.2, 17.68±0.2, 18.30±0.2, 18.39±0.2, 18.63±0.2, 18.97±0.2, 19.32±0.2 and 20.20±0.2.

### Claim 2 (depends on 1)

The crystalline form of claim 1, which is further characterized by a differential scanning calorimetry trace recorded at a heating rate of 20° C. per minute which shows a maximum endothermic peak at a temperature between about 130° C. and about 140° C., or a differential scanning calorimetry trace substantially in accordance with that shown in FIG. 6.

### Claim 3 (depends on 1)

A pharmaceutical composition comprising the crystalline form of claim 1 and a pharmaceutically acceptable carrier, diluent or excipient.

### Claim 4 (depends on 1)

A method for the treatment of a proliferative disorder, wherein the proliferative disorder is cancer, said method comprising administering a pharmacologically effective amount of a crystalline form according to claim 1 to a subject in need of thereof.

### Claim 5

A process for preparing crystalline free base of compound (I),
wherein said compound is in the form of the free base and which is characterized by an x-ray powder diffraction pattern having two or more diffraction peaks at 2[theta] values selected from 7.53±0.2, 9.60±0.2, 10.22±0.2, 11.29±0.2, 11.66±0.2, 12.26±0.2, 12.62±0.2, 13.17±0.2, 14.06±0.2, 14.85±0.2, 15.15±0.2, 15.57±0.2, 16.99±0.2, 17.68±0.2, 18.30±0.2, 18.39±0.2, 18.63±0.2, 18.97±0.2, 19.32±0.2 and 20.20±0.2,
wherein said method comprises the steps of crystallising compound (I) in free base form from methyl t-butyl ether (MTBE).