Pyrrolopyrimidine compounds and their uses

• US 8,324,225 B2
• Filed: 05/24/2007
• Issued: 12/04/2012
• Est. Priority Date: 05/26/2006
• Status: Active Grant

• Current Assignee: Novartis Pharmaceuticals Corporation (Novartis Ag), Astex Therapeutics Limited (Otsuka Holdings Company Limited)
• Original Assignee: Novartis Ag, Astex Therapeutics Limited (Otsuka Holdings Company Limited)
• Inventors: Brain, Christopher Thomas, Sung, Moo Je, Thoma, Gebhard
• Primary Examiner(s): MURRAY, JEFFREY H
• Application Number:
  US12/302,223
• Publication Number:
  US 20090318441A1
• Time in Patent Office: 2,021 Days
• Field of Search: None
• US Class Current: 514/265.1
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• 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 11/06 Antiasthmatics
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/06 Antiabortive agents; Labour repressants
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: 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
• 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 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• 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 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07D 487/04 : Ortho-condensed systems

Abstract

The present application describes organic compounds that are useful for the treatment, prevention and/or amelioration of diseases, particularly pyrrolopyrimidine compounds and derivatives are described which inhibit protein kinases. The organic compounds are useful in treating proliferative disease.

Claims

1. A compound of Formula I:

2. The compound of claim 1, wherein R⁴ is C(H)(CH₂CH₃)₂, C(H)(CH₂CH₃)Ph, CH₂CH₃, cyclopropyl, cyclopentyl or cyclohexyl.

3. The compound of claim 1, wherein R³ is an aryl group, which is further independently substituted one or more times by halogen, C₁-C₄-alkoxy, R¹⁵-amine, R¹⁵-heterocycle, or R¹⁵-heteroaryl, wherein R¹⁵ is a bond, C(O), N(H)C(O), N(H)SO₂, OC(O) or (CH₂)_1-4, wherein the (CH₂)_1-4 group may be interrupted by O, N(CH₃) or N(H).

4. The compound of claim 3, wherein the aryl group is phenyl.

5. The compound of claim 1, wherein the phenyl group is R³ is phenyl which is further independently substituted one or more times with fluoro, methoxy, diethylamine, R¹⁵-piperazinyl, R¹⁵-morpholinyl, R¹⁵-piperidinyl, R¹⁵-triazolyl, R¹⁵-phenyl, R¹⁵-pyridinyl, R¹⁵-piperazinyl, R¹⁵-indazolyl, R¹⁵-pyrrolidinyl or R¹⁵-imidazolyl, wherein the piperazinyl, morpholinyl, piperidinyl, triazolyl, phenyl, pyridinyl, piperazinyl, indazolyl, pyrrolidinyl or imidazolyl groups may be further substituted with C₁-C₄-alkyl, C(O)C₁-C₄-alkyl, S(O)₂C₁-C₄-alkyl, OH, C(O)(CH₂)_1-3CN or N(H)C(O)C₁-C₄-alkyl and wherein R¹⁵ is a bond, C(O), N(H)C(O), N(H)SO₂, OC(O) or (CH₂)_1-4, wherein the (CH₂)_1-4 group may be interrupted by O, N(CH₃) or N(H).

6. The compound of claim 1, wherein R³ is phenyl which is further substituted by N(H)C(O)aryl, C(O)N(H)C₁-C₄-alkyl, C(O)N(C₁-C₄-alkyl)₂ or C(O)N(H)C₃-C₆-cycloalkyl.

7. The compound of claim 1, wherein the compound is selected from the group consisting of

9. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or excipient.

8. A compound of Formula I: