Thiophene and benzothiophene hydroxamic acid derivatives

• US 7,935,724 B2
• Filed: 10/08/2004
• Issued: 05/03/2011
• Est. Priority Date: 10/09/2003
• Status: Active Grant

• Current Assignee: Merck HDAC Research LLC (Merck & Co., Inc.)
• Original Assignee: Merck HDAC Research LLC (Merck & Co., Inc.)
• Inventors: Belvedere, Sandro, Miller, Thomas A., Witter, David J.
• Primary Examiner(s): DENTZ, BERNARD I
• Application Number:
  US10/574,992
• Publication Number:
  US 20070213392A1
• Time in Patent Office: 2,398 Days
• Field of Search: 549/57, 549/55, 514/443
• US Class Current: 514/443
• 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 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 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 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• 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 19/10 for osteoporosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• 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 25/04 Centrally acting analgesics, e.g. opioids
• 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 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 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/18 : for HIV
• 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 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 39/00 : General protective or antinoxious agents
• CPC Class Codes: A61P 41/00 : Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• 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: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• 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 259/08 : having carbon atoms of hydroxamic groups bound to carbon atoms of rings other than six-membered aromatic rings
• CPC Class Codes: C07C 2602/08 : the other ring being five-membered, e.g. indane
• 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 333/66 : Nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 333/70 : attached in position 2
• 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 413/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 : linked by a chain containing hetero atoms as chain links

Abstract

The present invention relates to a novel class of hydroxamic acid derivatives having a benzothiophene or thiophene backbone. The hydroxamic acid compounds can be used to treat cancer. The hydroxamic acid compounds can also inhibit historic deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention are also useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases, The present invention further provides pharmaceutical compositions comprising the hydroxamic acid derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the hydroxamic acid derivatives in vivo.

Claims

1. A compound represented by the following structural Formula:

2. The compound of claim 1 of the Formula I:

3. The compound of claim 1, wherein A is selected from:

4. The compound of claim 1, wherein A is

5. The compound of claim 4, wherein at least one of R₁ and R₂ is phenyl, naphthyl, biphenyl, benzyl, —

CH₂CH₂Ph, —

CH₂CH₂CH₂Ph, —

CH═

CHPh, cyclohexyl, quinolinyl, isoquinolinyl, —

CH₂-cyclohexyl, —

CH₂-quinolinyl, —

CH₂—

isoquinolinyl, pyridyl, —

CH(Ph)₂, methyl, ethyl, propyl, isopropyl, butyl, isobutyl sec-butyl or tert-butyl.

6. The compound of claim 1, wherein A is

7. The compound of claim 6, wherein R₅ is phenyl, naphthyl, biphenyl, benzyl, —

CH₂CH₂Ph, —

CH═

CHPh, cyclohexyl, quinolinyl, isoquinolinyl, —

CH₂-cyclohexyl, —

CH₂-quinolinyl, —

CH₂-isoquinolinyl, pyridyl, —

CH(Ph)₂, methyl, ethyl, propyl, isopropyl, butyl, isobutyl sec-butyl or tert-butyl.

8. The compound of claim 1, wherein A is

9. The compound of claim 8, wherein at least one of R₆ and R₇ is phenyl, naphthyl, biphenyl, benzyl, —

CH₂CH₂Ph, —

CH═

CHPh, cyclohexyl, quinolinyl, isoquinolinyl, —

CH₂-cyclohexyl, —

CH₂-quinolinyl, —

CH₂-isoquinolinyl, pyridyl, —

CH(Ph)₂, methyl, ethyl, propyl, isopropyl, butyl, isobutyl sec-butyl or tert-butyl.

10. The compound of claim 1, wherein A is

11. The compound of claim 10, wherein R₈ is phenyl, naphthyl, biphenyl, benzyl, —

CH₂CH₂Ph, —

CH═

CHPh, cyclohexyl, quinolinyl, isoquinolinyl, —

CH₂-cyclohexyl, —

CH₂-quinolinyl, —

CH₂-isoquinolinyl, pyridyl, —

CH(Ph)₂, methyl, ethyl, propyl, isopropyl, butyl, isobutyl sec-butyl or tert-butyl.

12. The compound of claim 1, wherein A is

13. The compound of claim 12, wherein R₉ is phenyl, 1-naphthyl, 2-naphthyl, biphenyl, benzyl, —

CH₂CH₂Ph, —

CH═

CHPh, cyclohexyl, quinolinyl, isoquinolinyl, thiophenyl, —

CH₂-cyclohexyl, —

CH₂-quinolinyl, —

CH₂-isoquinolinyl, pyridyl, —

CH(Ph)₂, methyl, ethyl, propyl, isopropyl, butyl, isobutyl sec-butyl or tert-butyl.

14. The compound of claim 1, wherein A is

15. The compound of claim 14, wherein at least one of R₁₁ and R₁₂ is phenyl, naphthyl, biphenyl, benzyl, —

CH₂CH₂Ph, —

CH═

CHPh, cyclohexyl, quinolinyl, isoquinolinyl, —

CH₂-cyclohexyl, —

CH₂-quinolinyl, —

CH₂-isoquinolinyl, pyridyl, —

CH(Ph)₂, methyl, ethyl, propyl, isopropyl, butyl, isobutyl sec-butyl or tert-butyl.

17. A pharmaceutical composition comprising a pharmaceutically effective amount of the compound of any of claims 1-15 and 16, and a pharmaceutically acceptable carrier.

16. A compound selected from:

6-Phenylacetylamino-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-Benzoylamino-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[(Biphenyl-4-carbonyl)-amino]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-(3-Phenyl-propionylamino)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[(Naphthalene-2-carbonyl)-amino]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-Isobutyrylamino-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

Quinoline-2-carboxylic acid (2-hydroxycarbamoyl-benzo[b]thiophen-6-yl)-amide;

N-(2-Hydroxycarbamoyl-benzo [b]thiophen-6-yl)-nicotinamide;

6-Diphenylacetylamino-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[(Naphthalene- 1 -carbonyl)-amino]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-(3,4-Dimethoxy-benzoylamino)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[2-(3,4-Dimethoxy-phenyl)-acetylamino]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[2-(4-Fluoro-phenyl)-acetylamino]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[2-(2,5-Dimethoxy-phenyl)-acetylamino]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[2-(3-Methoxy-phenyl)-acetylamino]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[2-(4-Chloro-phenyl)-acetylamino]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[2-(4-Methoxy-phenyl)-acetylamino]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-(2-Phenyl-butyrylamino)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-(Methyl-phenylacetyl-amino)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-(2-Pyridin-2-yl-acetylamino)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-(2-Pyridin-3-yl-acetylamino)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-(2-Phenyl-propionylamino)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-{[1-(4-Chloro-phenyl)-cyclopropanecarbonyl]-amino}-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[(1-Phenyl-cyclopropanecarbonyl)-amino]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-{[1-(4-Chloro-phenyl)-cyclobutanecarbonyl]-amino}-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[2-(4-Chloro-phenyl)-2-methyl-propionylamino]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-(2S-Phenyl-butyrylamino)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-(2R-Phenyl-butyrylamino)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-(Benzoylamino-methyl)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-(Phenylacetylamino-methyl)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-{[(Naphthalene-1-carbonyl)-amino]-methyl}-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[(2-Methyl-benzoylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-[(4-Methyl-benzoylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-[(3-Methoxy-benzoylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-[(4-Methoxy-benzoylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-[(3,4-Dimethoxy-benzoylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

N-(2-Hydroxycarbamoyl-benzo[b]thiophen-6-ylmethyl)-nicotinamide;

6-(Isobutyrylamino-methyl)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[(2-Methoxy-benzoylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-[(4-Chloro-benzoylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-Phenylmethanesulfonylamino-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-Benzenesulfonylamino-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-(Biphenyl-4-sulfonylamino)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-(Naphthalene-1-sulfonylamino)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-(Naphthalene-2-sulfonylamino)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-(Toluene-4-sulfonylamino)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-(Benzenesulfonylamino-methyl)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-(Phenylmethanesulfonylamino-methyl)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[(Naphthalene-1-sulfonylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-[(Naphthalene-2-sulfonylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-[(Toluene-4-sulfonylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-[(2,4,6-Trimethyl-benzenesulfonylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-[(4-tert-Butyl-benzenesulfonylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-[(4-Fluoro-benzenesulfonylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-[(4-Chloro-benzenesulfonylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-[(3-Chloro-benzenesulfonylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-[(4-Bromo-benzenesulfonylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-[(3-Bromo-benzenesulfonylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-[(3-Methoxy-benzenesulfonylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-[(4-Nitro-benzenesulfonylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-[(4-Methoxy-benzenesulfonylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-[(Thiophene-2-sulfonylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-{[3-(4-Methoxy-phenoxy)-propane-1-sulfonylamino]-methyl}-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-(3-Benzyl-ureido)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

(2-Hydroxycarbamoyl-benzo[b]thiophen-6-yl)-carbamic acid ethyl ester;

(2-Hydroxycarbamoyl-benzo[b]thiophen-6-yl)-carbamic acid benzyl ester;

6-(3-Phenethyl-ureido)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-(3-Benzyl-ureidomethyl)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

(2-Hydroxycarbamoyl-benzo[b]thiophen-6-ylmethyl)-carbamic acid benzyl ester;

6-[3-(4-Isopropyl-phenyl)-ureidomethyl]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[3-(4-tert-Butyl-phenyl)-ureidomethyl]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[3-(3,5-Bis-trifluoromethyl-phenyl)-ureidomethyl]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[3 -(3-Phenoxy-phenyl)-ureidomethyl]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-Benzoylamino-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-Phenylacetylamino-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-(3-Phenyl-propionylamino)-benzo [b] thiophene-2-carboxylic acid hydroxyamide;

5-(3-Phenyl-acryloylamino)-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

5-[(Naphthalene-1-carbonyl)-amino]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

5-[(Naphthalene-2-carbonyl)-amino]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

Quinoline-2-carboxylic acid (2-hydroxycarbamoyl-benzo[b]thiophen-5-yl)-amide;

N-(2-Hydroxycarbamoyl-benzo[b]thiophen-5-yl)-nicotinamide;

5-[(Biphenyl-4-carbonyl)-amino]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-Diphenylacetylamino-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-Isobutyrylamino-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-[2-(4-Fluoro-phenyl)-acetylamino]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-[2-(3-Methoxy-phenyl)-acetylamino]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-[2-(3,4-Dimethoxy-phenyl)-acetylamino]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-[2-(2,5-Dimethoxy-phenyl)-acetylamino]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-(2-Phenyl-butyrylamino)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-[2-(4-Chloro-phenyl)-acetylamino]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-[2-(4-Methoxy-phenyl)-acetylamino]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-{[1-(4-Chloro-phenyl)-cyclopentanecarbonyl]-amino}-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-(Naphthalene-2-sulfonylamino)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-(Toluene-4-sulfonylamino)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-Benzenesulfonylamino-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-Phenylmethanesulfonylamino-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-(Naphthalene-1-sulfonylamino)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-(Biphenyl-4-sulfonylamino)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

(2-Hydroxycarbamoyl-benzo[b]thiophen-5-yl)-carbamic acid benzyl ester;

(2-Hydroxycarbamoyl-benzo[b]thiophen-5-yl)-carbamic acid ethyl ester;

5-(3-Benzyl-ureido)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-Dibenzylamino-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-Dibenzylamino-benzo[b]thiophene-2-carboxylic acid methyl ester;

6-Dibenzylamino-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-(Bis-phenylcarbamoylmethyl-amino)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-(Bis-phenylcarbamoylmethyl-amino)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[2-(4-Phenyl-piperazin-1-yl)-acetylamino]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-(2-3,4-Dihydro-1H-isoquinolin-2-yl-acetylamino)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[2-(4-Benzyl-piperidin-1-yl)-acetylamino]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

4-[(2-Hydroxycarbamoyl-benzo[b]thiophen-6-ylcarbamoyl)-methyl]-piperazine-1-carboxylic acid benzyl ester;

6-(2-Dibenzylamino-acetylamino)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-{2-[4(3 -Methoxy-phenyl)-piperazin-1-yl]-acetylamino}-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-[2-(4-Pyrimidin-2-yl-piperazin-1-yl)-acetylamino]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-{2-[4-(2-(2-Methoxy-phenyl)-piperazin- 1 -yl]-acetylamino}-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[2-(4-Pyridin-2-yl-piperazin-1-yl)-acetylamino]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[2-(4-Acetyl-piperazin-1-yl)-acetylamino]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-(2-Piperidin-1-yl-acetylamino)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-(2-Morpholin-4-yl-acetylamino)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[2-(Benzyl-phenethyl-amino)-acetylamino]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

{tert-Butoxycarbonylmethyl-[(2-hydroxycarbamoyl-benzo[b]thiophen-6-ylcarbamoyl)-methyl]-amino}-acetic acid tert-butyl ester;

6-{2-[4-(2-Chloro-phenyl)-piperazin-1-yl]-acetylamino}-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-{2-[4-(3-Chloro-phenyl)-piperazin-1-yl]-acetylamino}-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

4-[(2-Hydroxycarbamoyl-benzo[b]thiophen-6-ylcarbamoyl)-methyl]-[1,4]diazepane-1-carboxylic acid benzyl ester;

4-[(2-Hydroxycarbamoyl-benzo[b]thiophen-6-ylcarbamoyl)-methyl]-piperazine-1-carboxylic acid ethyl ester;

6-{2-[4(4-Methoxy-phenyl)-piperazin-1-yl]-acetylamino}-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

Benzo[b]thiophene-2,6-dicarboxylic acid 2-hydroxyamide 6-{[2-(1H-indol-2-yl)-ethyl]-amide};

Benzo[b]thiophene-2,6-dicarboxylic acid 6-benzylamide 2-hydroxyamide;

Benzo[b]thiophene-2,6-dicarboxylic acid 2-hydroxyamide 6-[(pyridin-2-ylmethyl)-amide];

Benzo[b]thiophene-2,6-dicarboxylic acid 6-[(1-benzyl-piperidin-4-yl)-amide]2-hydroxyamide;

Benzo[b]thiophene-2,6-dicarboxylic acid 6-[(2,2-diphenyl-ethyl)-amide]2-hydroxyamide;

Benzo[b]thiophene-2,6-dicarboxylic acid 6-[(1,2-diphenyl-ethyl)-amide]2-hydroxyamide;

Benzo[b]thiophene-2,6-dicarboxylic acid 6-benzhydryl-amide 2-hydroxyamide;

Benzo[b]thiophene-2,6-dicarboxylic acid 6-[(1H-benzoimidazol-2-ylmethyl)-amide]2-hydroxyamide;

Benzo[b]thiophene-2,6-dicarboxylic acid 2-hydroxyamide 6-[(2-pyridin-2-yl-ethyl)-amide];

Benzo[b]thiophene-2,6-dicarboxylic acid 2-hydroxyamide 6-[(1,2,3,4-tetrahydro-naphthalen-1-yl)-amide];

6-(Piperidine-1-carbonyl)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

Benzo[b]thiophene-2,6-dicarboxylic acid 2-hydroxyamide 6-phenylamide;

Benzo[b]thiophene-2,6-dicarboxylic acid 2-hydroxyamide 6-indan-1-ylamide;

6-(4-Phenyl-piperazine- 1-carbonyl)-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-[4-(4-Chloro-phenyl)-piperazine-1-carbonyl]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

Benzo[b]thiophene-2,6-dicarboxylic acid 2-hydroxyamide 6-[(3-phenyl-propyl)-amide];

Benzo[b]thiophene-2,6-dicarboxylic acid 2-hydroxyamide 6-(phenethyl-amide);

6-(4-Benzyl-piperidine- 1-carbonyl)-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-(4-Benzyl-piperazine- 1-carbonyl)-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

Benzo[b]thiophene-2,6-dicarboxylic acid 2-hydroxyamide 6-quinolin-8-ylamide;

Benzo[b]thiophene-2,6-dicarboxylic acid 2-hydroxyamide 6-[(4-phenyl-thiazol-2-yl)-amide];

Benzo[b]thiophene-2,5-dicarboxylic acid 2-hydroxyamide 5-(2-methoxy-benzylamide);

Benzo[b]thiophene-2,5-dicarboxylic acid 2-hydroxyamide 5-(3-methoxy-benzylamide);

Benzo[b]thiophene-2,5-dicarboxylic acid 2-hydroxyamide 5-(4-methoxy-benzylamide);

Benzo [b]thiophene-2,5-dicarboxylic acid 5-(2-chloro-benzylamide) 2-hydroxyamide;

Benzo [b]thiophene-2,5-dicarboxylic acid 5-(3-chloro-benzylamide) 2-hydroxyamide;

Benzo [b]thiophene-2,5-dicarboxylic acid 5-(4-chloro-benzylamide) 2-hydroxyamide;

Benzo [b]thiophene-2,5-dicarboxylic acid 2-hydroxyamide 5-indan-1-ylamide;

Benzo [b]thiophene-2,5-dicarboxylic acid 2-hydroxyamide 5-{[2-(1H-indol-3-yl)-ethyl]-amide};

Benzo [b]thiophene-2,5-dicarboxylic acid 5-[(3,3-diphenyl-propyl)-amide]2-hydroxyamide;

Benzo [b]thiophene-2,5-dicarboxylic acid 2-hydroxyamide 5-[(4-phenyl-butyl)-amide];

Benzo [b]thiophene-2,5-dicarboxylic acid 2-hydroxyamide 5-phenylamide;

Benzo [b]thiophene-2,5-dicarboxylic acid 2-hydroxyamide 5-(phenethyl-amide);

Benzo [b]thiophene-2,5-dicarboxylic acid 5-benzylamide 2-hydroxyamide;

Benzo [b]thiophene-2,5-dicarboxylic acid 2-hydroxyamide 5-[(3-phenyl-propyl)-amide];

Benzo [b]thiophene-2,5-dicarboxylic acid 5-(bis-phenylcarbamoylmethyl-amide) 2-hydroxyamide;

5-[(3-Methoxy-benzylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

5-(Benzylamino-methyl)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-Phenylaminomethyl-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-[(3-Benzyloxy-phenylamino)-methyl]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-[(4-Methoxy-benzylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

5-[(2-Chloro-benzylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

5-[(4-Chloro-benzylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

5-[(Benzhydryl-amino)-methyl]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-(Phenethylamino-methyl)-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

5-[(2,2-Diphenyl-ethylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

5-{[2-(3,4-Bis-benzyloxy-phenyl)-ethylamino]-methyl}-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-[(3-Phenyl-propylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

5-[(3,3-Diphenyl-propylamino)-methyl]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-[(4-Phenyl-butylamino)-methyl]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-[(2-Morpholin-4-yl-ethylamino)-methyl]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-[(Cyclohexylmethyl-amino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

5-[(2-Methoxy-benzylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

5-[(3-Chloro-benzylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

5-{[(1H-Benzoimidazol-2-ylmethyl)-amino]-methyl}-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-{[(Pyridin-2-ylmethyl)-amino]-methyl}-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-{[2-(3,4-Dimethoxy-phenyl)-ethylamino]-methyl}-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-{[2-(1H-Indol-3-yl)-ethylamino]-methyl}-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

5-[(1-Benzyl-piperidin-4-ylamino)-methyl]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-(Benzylamino-methyl)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[(2-Methoxy-benzylamino)-methyl]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[(3-Methoxy-benzylamino)-methyl]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-Phenylaminomethyl-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-(Phenethylamino-methyl)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[(3-Phenyl-propylamino)-methyl]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[(2-Chloro-benzylamino)-methyl]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[(3-Chloro-benzylamino)-methyl]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[(4-Chloro-benzylamino)-methyl]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-{[(Benzo[1,3]dioxol-5-ylmethyl)-amino]-methyl}-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-(Indan-1-ylaminomethyl)-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[(9H-Fluoren-9-ylamino)-methyl]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[(1,2-Diphenyl-ethylamino)-methyl]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[(Cyclohexylmethyl-amino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-[(1,2,3,4-Tetrahydro-naphthalen-1-ylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-{[2-(2-Methyl-1H-indol-3-yl)-ethylamino]-methyl}-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-{[(Pyridin-2-ylmethyl)-amino]-methyl}-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[(1-Benzyl-piperidin-4-ylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-[(4-Methoxy-benzylamino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-{[2-(1H-Indol-3-yl)-ethylamino]-methyl}-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[(4-Methoxy-benzylamino)-methyl]-benzo[b]thiophene-2-carboxylic acid ethyl ester;

6-{[Cyclohexyl-(4-methoxy-benzyl)-amino]-methyl}-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-{[(4-Methoxy-b enzyl)-(tetrahydro-pyran-4-yl)-amino]-methyl}-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-{[(2-Hydroxy-ethyl)-(4-methoxy-benzyl)-amino]-methyl}-benzo [b]thiophene-2-carboxylic acid hydroxyamide;

6-{[Isopropyl-(4-methoxy-benzyl)-amino]-methyl}-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-{[(4-Methoxy-benzyl)-methyl-amino]-methyl}-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[(Acetyl-benzyl-amino)-methyl]-benzo[b]thiophene-2-carboxylic acid hydroxyamide;

6-[(Benzyl-methanesulfonyl-amino)-methyl]-benzo [b]thiophene-2-carboxylic acid hydroxyamide; and

N-Hydroxy-N′

-(2-hydroxycarbamoyl-benzo [b]thiophen-6-yl)-oxalamide;

or a stereoisomer, enantiomer, racemate, pharmaceutically acceptable salt, solvate, hydrate or polymorph thereof.