Quinazolinones as inhibitors of human phosphatidylinositol 3-kinase delta

• US 8,207,153 B2
• Filed: 03/25/2010
• Issued: 06/26/2012
• Est. Priority Date: 05/13/2004
• Status: Active Grant

• Current Assignee: ICOS Corporation (Eli Lilly and Company)
• Original Assignee: ICOS Corporation (Eli Lilly and Company)
• Inventors: Fowler, Kerry W., Huang, Danwen, Kesicki, Edward A., Ooi, Hua Chee, Oliver, Amy, Ruan, Fuqiang, Treiberg, Jennifer
• Primary Examiner(s): Fetterolf, Brandon
• Assistant Examiner(s): Pagonakis, Anna
• Application Number:
  US12/732,128
• Publication Number:
  US 20100256168A1
• Time in Patent Office: 824 Days
• Field of Search: None
• US Class Current: 514/183
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine
• 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 11/08 Bronchodilators
• CPC Class Codes: A61P 11/16 Central respiratory analeptics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/04 Antipruritics
• 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 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• 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 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 35/04 : specific for metastasis
• 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 39/06 : Free radical scavengers or antioxidants
• 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 5/48 : of the pancreatic hormones
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/06 : Antianaemics
• 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 239/91 : with aryl or aralkyl radicals attached in position 2 or 3
• CPC Class Codes: C07D 473/16 : two nitrogen atoms
• CPC Class Codes: C07D 473/34 : attached in position 6, e.g. adenine
• CPC Class Codes: C07D 487/04 : Ortho-condensed systems

Abstract

Compounds that inhibit P13Kδ activity, including compounds that selectively inhibit P13Kδ activity, are disclosed. Methods of inhibiting phosphatidylinositol 3-kinase delta isoform (P13Kδ) activity, and methods of treating diseases, such as disorders of immunity and inflammation in which P13Kδ plays a role in leukocyte function, using the compounds also are disclosed.

Claims

1. A method of inhibiting a growth or a proliferation of cancer cells of hematopoietic origin comprising contacting the cancer cells with an effective amount of a compound, wherein said compound is

2. The method of claim 1, wherein the cancer of hematopoietic origin is lymphoma, leukemia, or multiple myeloma.

3. The method of claim 2, wherein the compound or the pharmaceutically acceptable salt thereof is the S-enantiomer.

4. A method of treating a condition in a subject, wherein the condition is lymphoma, leukemia or multiple myeloma, comprising administering to the subject an effective amount of a compound, wherein the compound is 5-fluoro-3-phenyl-2-[1-(9H-purin-6 -ylamino)-propyl]-3H-quinazolin-4-one or a pharmaceutically acceptable salt thereof.

5. The method of claim 4, wherein the condition is selected from the group consisting of Burkitt'"'"'s lymphoma, Hodgkins'"'"' lymphoma, non-Hodgkins lymphoma, lymphocytic lymphoma, lymphocytic leukemia, multiple myeloma and chronic myeloid leukemia.

6. The method of claim 4, wherein the compound or the pharmaceutically acceptable salt thereof is the S-enantiomer.