Benzoimidazol-2-yl pyrimidine modulators of the histamine h4 receptor

• US 8,859,575 B2
• Filed: 03/06/2014
• Issued: 10/14/2014
• Est. Priority Date: 03/06/2013
• Status: Active Grant

• Current Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Inventors: Conza, Matteo, Hickey, Magali B., Horns, Stefan, Lochner, Susanne
• Primary Examiner(s): VAJDA, KRISTIN ANN
• Application Number:
  US14/199,634
• Publication Number:
  US 20140256942A1
• Time in Patent Office: 222 Days
• Field of Search: 544/331, 514/275
• US Class Current: 514/275
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/22 : for herpes viruses
• CPC Class Codes: A61P 33/00 : Antiparasitic agents
• CPC Class Codes: A61P 33/14 : Ectoparasiticides, e.g. scabicides
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 5/16 : for decreasing, blocking or antagonising the activity of the thyroid hormones
• CPC Class Codes: A61P 5/38 : of the suprarenal hormones
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/12 : Antidiuretics, e.g. drugs for diabetes insipidus ADH A61P5/10
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07B 2200/13 : Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07C 51/43 : by change of the physical state, e.g. crystallisation
• CPC Class Codes: C07D 401/14 : containing three or more hetero rings
• CPC Class Codes: C30B 29/54 : Organic compounds
• CPC Class Codes: C30B 7/08 : by cooling of the solution

Abstract

Benzoimidazol-2-yl pyrimidines, purification methods for the same, and pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by H₄ receptor activity, including allergy, asthma, autoimmune diseases, and pruritus.

Claims

1. A hemitartrate tetrahydrate of [5-(4,6-Dimethyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine of formula:

2. A hemitartrate tetrahydrate according to claim 1, wherein the X-ray diffraction profile of said hemitartrate tetrahydrate comprises the following peaks:

3. A hemitartrate tetrahydrate according to claim 1, wherein the X-ray diffraction profile of said hemitartrate tetrahydrate comprises the following peaks:

4. A hemitartrate tetrahydrate according to claim 1, wherein the X-ray diffraction profile of said hemitartrate tetrahydrate comprises the following peaks:

5. A hemitartrate tetrahydrate according to claim 1, wherein the X-ray diffraction profile of said hemitartrate tetrahydrate comprises the following peaks:

6. A hemitartrate tetrahydrate according to claim 1, wherein the X-ray diffraction profile of said hemitartrate tetrahydrate comprises the following peaks:

7. A pharmaceutical composition for therapeutically treating a disease, disorder, or medical condition mediated by histamine H₄ receptor activity, comprising an effective amount of at least a compound as claimed in claim 1.

8. A hemitartrate tetrahydrate of [5-(4,6-Dimethyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine of formula:

9. A hemitartrate tetrahydrate of [5-(4,6-Dimethyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine according to claim 8, wherein said hemitartrate tetrahydrate is further substantially free of at least impurity I5 of formula:

10. A hemitartrate tetrahydrate of [5-(4,6-Dimethyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine according to claim 9, wherein said hemitartrate tetrahydrate does not contain more than about 0.2% of impurity I7 of formula:

11. A hemitartrate tetrahydrate of [5-(4,6-Dimethyl-1H-benzoimidazol-2-yl)-4-methyl-pyrimidin-2-yl]-[3-(1-methyl-piperidin-4-yl)-propyl]-amine according to claim 10, wherein said hemitartrate tetrahydrate does not contain more than about 0.06% of impurity I7 of formula:

12. A pharmaceutical composition for therapeutically treating a disease, disorder, or medical condition mediated by histamine H₄ receptor activity, comprising an effective amount of at least a compound as claimed in claim 8.

13. A pharmaceutical composition for therapeutically treating a disease, disorder, or medical condition mediated by histamine H₄ receptor activity, comprising an effective amount of at least a compound as claimed in claim 9.

14. A pharmaceutical composition for therapeutically treating a disease, disorder, or medical condition mediated by histamine H₄ receptor activity, comprising an effective amount of at least a compound as claimed in claim 10.

15. A pharmaceutical composition for therapeutically treating a disease, disorder, or medical condition mediated by histamine H₄ receptor activity, comprising an effective amount of at least a compound as claimed in claim 11.