2,4-Pyrimidinediamine compounds and their uses

• US 7,435,814 B2
• Filed: 12/08/2005
• Issued: 10/14/2008
• Est. Priority Date: 02/01/2002
• Status: Expired due to Term

• Current Assignee: Rigel Pharmaceuticals, Inc.
• Original Assignee: Rigel Pharmaceuticals, Inc.
• Inventors: Clough, Jeffrey, Keim, Holger, Argade, Ankush, Sylvain, Catherine, Bhamidipati, Somasekhar, Li, Hui, Singh, Rajinder, Holland, Sacha J., Payan, Donald, Molineaux, Susan, Rossi, Alexander B.
• Primary Examiner(s): Eyler; Yvonne (Bonnie)
• Assistant Examiner(s): NWAONICHA, CHUKWUMA O
• Application Number:
  US11/299,207
• Publication Number:
  US 20060135543A1
• Time in Patent Office: 1,041 Days
• Field of Search: 544/295, 544/324, 544/105, 544/48
• US Class Current: 544/295
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 31/538 ortho- or peri-condensed with carbocyclic ring systems
• CPC Class Codes: A61K 31/5383 ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/5395 having two or more nitrogen atoms in the same ring, e.g. oxadiazines
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive 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 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics
• CPC Class Codes: A61P 27/16 Otologicals
• 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 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• 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 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• 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: C07D 239/48 : Two nitrogen atoms
• CPC Class Codes: C07D 265/36 : condensed with one six-membered ring
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 : containing three or more hetero rings
• CPC Class Codes: C07D 403/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/14 : containing three or more hetero rings
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/14 : containing three or more hetero rings
• CPC Class Codes: C07D 407/14 : containing three or more hetero rings
• CPC Class Codes: C07D 409/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/14 : containing three or more hetero rings
• CPC Class Codes: C07D 413/10 : linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 413/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/14 : containing three or more hetero rings
• CPC Class Codes: C07D 417/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/14 : containing three or more hetero rings
• CPC Class Codes: C07D 495/04 : Ortho-condensed systems
• CPC Class Codes: C07D 498/04 : Ortho-condensed systems
• CPC Class Codes: C07D 498/14 : Ortho-condensed systems
• CPC Class Codes: C07F 5/027 : Organoboranes and organoborohydrides

Abstract

The present invention provides 2,4-pyrimidinediamine compounds that inhibit the IgE and/or IgG receptor signaling cascades that lead to the release of chemical mediators, intermediates and methods of synthesizing the compounds and methods of using the compounds in a variety of contexts, including in the treatment and prevention of diseases characterized by, caused by or associated with the release of chemical mediators via degranulation and other processes effected by activation of the IgE and/or IgG receptor signaling cascades.

Claims

1. A 4-pyrimidineamine compound according to structural formula (II):

2. The compound of claim 1 in which LG is chloro.

3. The compound of claim 2 in which R⁵ is fluoro.

4. The compound of claim 3 in which R⁶ is hydrogen.

5. The compound of claim 1 in which Y and Z are each, independently of one another, selected from the group consisting of O and NH.

6. The compound of claim 5 in which Y and Z are each O.

7. The compound of claim 6 in which each R³⁵ is hydrogen.

8. The compound of claim 5 which Y is O and Z is NH.

9. The compound of claim 8 in which two R³⁵ bonded to the same carbon atom are taken together to form an oxo group.

10. The compound of claim 9 in which the other two R³⁵ are each hydrogen, methyl or fluoro.

11. The compound of claim 1 which is selected from the group consisting of compounds (IIa)-(IIe) and (IIi)-(IIn):