PDE4B inhibitors and uses therefor

• US 7,585,859 B2
• Filed: 05/06/2005
• Issued: 09/08/2009
• Est. Priority Date: 05/06/2004
• Status: Active Grant

• Current Assignee: Plexxikon Inc (Daiichi Sankyo Company Limited)
• Original Assignee: Plexxikon Inc (Daiichi Sankyo Company Limited)
• Inventors: Gillette, Sam, Artis, Dean R., Zhang, Chao, Ibrahim, Prabha N., Cho, Hanna, Zuckerman, Rebecca, England, Bruce
• Primary Examiner(s): Saeed; Kamal A
• Assistant Examiner(s): BIANCHI, KRISTIN A
• Application Number:
  US11/123,893
• Publication Number:
  US 20060041006A1
• Time in Patent Office: 1,586 Days
• Field of Search: 514/444, 514/445, 514/447, 514/448, 514/473, 514/471, 514/422, 514/423, 514/236.8, 514/326, 514/378, 549/59, 549/60, 549/63, 549/64, 549/473, 549/480, 548/530, 548/517, 548/248, 544/137, 546/209
• US Class Current: 514/236.8
• 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 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 15/06 Antiabortive agents; Labour repressants
• 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 19/08 for bone diseases, e.g. rachitism, Paget's disease
• 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 25/16 Anti-Parkinson drugs
• 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 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• 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 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: C07C 311/48 : having nitrogen atoms of sulfonamide groups further bound to another hetero atom
• CPC Class Codes: C07D 215/36 : Sulfur atoms C07D215/24 takes precedence
• CPC Class Codes: C07D 215/40 : attached in position 8
• CPC Class Codes: C07D 231/12 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 239/18 : with hetero atoms attached to said nitrogen atoms, except nitro radicals, e.g. hydrazine radicals
• CPC Class Codes: C07D 239/46 : Two or more oxygen, sulphur or nitrogen atoms
• CPC Class Codes: C07D 275/04 : condensed with carbocyclic rings or ring systems
• CPC Class Codes: C07D 277/42 : Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• CPC Class Codes: C07D 277/62 : Benzothiazoles
• CPC Class Codes: C07D 333/36 : Nitrogen atoms
• CPC Class Codes: C07D 333/38 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 333/40 : Thiophene-2-carboxylic acid
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 405/14 : containing three or more hetero rings
• CPC Class Codes: C07D 409/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 409/06 : linked by a carbon chain containing only aliphatic carbon atoms
• 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 413/06 : linked by a carbon chain containing only aliphatic carbon atoms
• 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 417/06 : linked by a carbon chain containing only aliphatic carbon atoms
• 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 471/04 : Ortho-condensed systems
• CPC Class Codes: C07D 487/04 : Ortho-condensed systems
• CPC Class Codes: C07D 495/04 : Ortho-condensed systems

Abstract

Compounds active on phosphodiesterase PDE4B are provided. Also provided herewith are compositions useful for treatment of PDE4B-mediated diseases or conditions, and methods for the use thereof.

Claims

1. A compound having the chemical structure

2. The compound of claim 1

wherein:

X is S, and

Y is O.

3. The compound of claim 2

wherein:

R¹ is selected from the group consisting of optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, acyl, optionally substituted cycloalkyl, optionally substituted heterocycle, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, and optionally substituted heteroaralkyl; and

R², R⁴ and R⁵ are hydrogen.

4. The compound of claim 1 wherein:

R⁶ is selected from the group consisting of

5. The compound of claim 4

wherein:

R⁶ is selected from the group consisting of

6. The compound of claim 1 wherein at least one of R¹ and R² is selected from the group consisting of optionally substituted cycloalkyl, optionally substituted heterocycle, and optionally substituted heterocycloalkyl.

7. The compound of claim 1 having structure

8. A composition comprising

a compound according to claim 1 and

a pharmaceutically acceptable carrier.

9. A method for treating a human patient suffering from or at risk of a disease or condition for which PDE4B modulation provides a therapeutic benefit, said method comprising administering to said patient an effective amount of a compound according to claim 1,

wherein said disease or condition is selected from the group consisting of asthma, chronic obstructive pulmonary disease (COPD), Alzheimer'"'"'s disease, diffuse large-cell B cell lymphoma, and chronic lymphocytic leukemia.