Heterocyclic compounds and uses thereof

• US 20040242673A1
• Filed: 05/17/2004
• Published: 12/02/2004
• Est. Priority Date: 05/16/2003
• Status: Abandoned Application

• Current Assignee: Ambit Biosciences Corporation (Daiichi Sankyo Company Limited)
• Original Assignee: Ambit Biosciences Corporation (Daiichi Sankyo Company Limited)
• Inventors: Patel, Hitesh K., Lockhart, David J., Lai, Andiliy G., Milanov, Zdravko V., Grotzfeld, Robert M., Mehta, Shamal Anil
• Application Number:
  US10/847,897
• Publication Number:
  US 20040242673A1
• Time in Patent Office: Days
• US Class Current: 514/448
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/381 having five-membered rings
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• 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 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/12 of the kidneys
• 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 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/18 Antioxidants, e.g. antiradicals preparations for protection against sunlight A61Q17/00
• 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 19/10 for osteoporosis
• 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 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/08 : Antiepileptics; Anticonvulsants
• 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 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 27/06 : Antiglaucoma agents or miotics
• 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 29/02 : without antiinflammatory effect
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 3/14 : for calcium homeostasis vitamin D A61P3/02; parathyroid hormones A61P5/18; calcitonin A61P5/22; osteoporosis A61P19/10; bone metastasis A61P35/04
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 33/02 : Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 33/06 : Antimalarials
• 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 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/04 : Immunostimulants
• 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 5/24 : of the sex hormones
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/06 : Antiarrhythmics
• CPC Class Codes: A61P 9/08 : Vasodilators for multiple indications
• 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: A61P 9/12 : Antihypertensives
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention provides compounds having the thiophene or furan skeleton and uses thereof. The invention provides methods of using the compounds and/or compositions in the treatment of a variety of diseases and unwanted conditions in subjects. Kits comprising the compounds of the invention are also provided. The compounds and compositions disclosed herein are preferably used in the treatment of neurodegenerative diseases, cardiovascular diseases, proliferative diseases, and visual disorders. In particular, methods and compositions for the treatment of stroke are disclosed herein.

Claims

1. A method of treating a disease comprising administering to a subject in need thereof an effective amount of a compound of formula I

2. The method of claim 1 wherein the compound is at least one of a compound selected from the compounds 781118, 781222, 781196, 781300, 781326, 781352, 781378, 781560, 779974, 781456, 781534, 781482, 781586, 781612, 781794, 781716, 781898, 781924, 783042, and 783120.

4. The method of claim 1 wherein the compound is at least one of a compound selected from the compounds 781372 and 783146.

6. The method of claim 1 wherein the compound is at least one of a compound selected from the compounds 781508, 781768, 781742, 781872, 782002, 781040, 781092, 781248, 781170, 781144, 781274, 781638, 781664, 781690, 781820, 781846, 781404, 781950, and 781976.

7. The method of claim 1, 3, or 5 wherein said disease is a PDE6-related condition.

8. The method of claim 1, 3, or 5 wherein said disease is a condition wherein a beneficial effect is obtained by modulating PDE6 or any of its subunits.

9. The method of claim 1, 3, or 5 wherein said disease is a condition wherein a beneficial effect is obtained by modulating PDE6D.

10. The method of claim 1, 3, or 5 wherein said disease is related to an aberrant or undesired phosphodiesterase activity.

11. The method of claim 1 wherein said disease is stroke.

12. The method of claim 11 wherein said PDE6 modulating compound is acutely administered to a subject following a stroke.

13. The method of claim 11 wherein said PDE6 modulating compound is prophylactically administered to a subject to prevent a stroke.

14. The method of claim 1, 3, or 5 wherein said disease is at least one of a disease selected from cancer, impaired vision, an oxidative stress disorder, inflammation, and multiple sclerosis.

15. The method of claim 1, 3, or 5 wherein said disease is at least one of a disease selected from cerebrovascular accident, neurodegenerative disease, and cardiovascular disease

16. The method of claim 15 wherein said cerebrovascular accident is a stroke.

17. The method of claim 15 wherein treatment of said cardiovascular disease decreases the frequency and/or the severity of damage of myocardial infarction

18. The method of claim 15 wherein said neurodegenerative disease is at least one of an ischemic stroke, Alzheimer'"'"'s disease, diabetic peripheral neuropathy, multiple sclerosis, amyotrophic lateral sclerosis, Huntington'"'"'s disease and Parkinson'"'"'s disease.

19. The method of claim 1, 3, or 5 wherein said compound stimulates blood vessel growth, bone growth, or immune system.

3. A method of treating a disease comprising administering to a subject in need thereof an effective amount of a compound of formula II

5. A method of treating a disease comprising administering to a subject in need thereof an effective amount of a compound of formula III

20. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula I

21. The pharmaceutical composition of claim 20 wherein the compound is at least one of a compound selected from the compounds 781118, 781222, 781196, 781300, 781326, 781352, 781378, 781560, 779974, 781456, 781534, 781482, 781586, 781612, 781794, 781716, 781898, 781924, 783042, and 783120.

22. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula II

23. The pharmaceutical composition of claim 22 wherein the compound is at least one of a compound selected from the compounds 781372 and 783146.

24. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula III

25. The pharmaceutical composition of claim 24 wherein the compound is at least one of a compound selected from the compounds 781508, 781768, 781742, 781872, 782002, 781040, 781092, 781248, 781170, 781144, 781274, 781638, 781664, 781690, 781820, 781846, 781404, 781950, and 781976.