Use of compound binding to mSin3B that specifically binds to neuron restrictive silencer factor (NRSF)

• US 9,206,125 B2
• Filed: 02/09/2011
• Issued: 12/08/2015
• Est. Priority Date: 02/10/2010
• Status: Expired due to Fees

• Current Assignee: Nagasaki University, Public University Corporation Nagoya City University, Public University Corporation Yokohama City University
• Original Assignee: Nagasaki University, Public University Corporation Nagoya City University, Public University Corporation Yokohama City University
• Inventors: Miyata, Naoki, Suzuki, Takayoshi, Ueda, Hiroshi, Nishimura, Yoshifumi, Nagadoi, Aritaka, Hirao, Yuuka, Goshima, Yoshio, Yamashita, Naoya, Hiraishi, Ryuta
• Primary Examiner(s): McCormick, Melenie
• Assistant Examiner(s): MATOS NEGRON, TAINA DEL MAR
• Application Number:
  US13/578,230
• Publication Number:
  US 20130203738A1
• Time in Patent Office: 1,763 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• 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 25/14 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07C 233/65 having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
• CPC Class Codes: C07C 233/66 having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07D 207/06 with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
• CPC Class Codes: C07D 211/10 with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
• CPC Class Codes: C07D 211/14 with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
• CPC Class Codes: C07D 211/16 with acylated ring nitrogen atom
• CPC Class Codes: C07D 211/96 Sulfur atom
• CPC Class Codes: C07D 223/04 : with only hydrogen atoms, halogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 225/02 : not condensed with other rings
• CPC Class Codes: C07D 265/30 : not condensed with other rings
• CPC Class Codes: C07D 295/192 : from aromatic carboxylic acids

Abstract

The present invention identifies a compound which binds to the PAH1 domain of mSin3B that specifically binds to neural restrictive silencer factor NRSF, and uses the compound as a prophylactic and/or a therapeutic for diseases associated with abnormal expression of neural restrictive silencer factor NRSF/REST or abnormal expression of genes targeted by NRSF/REST, such as Huntington'"'"'s disease, medulloblastoma and neuropathic pain.

The present invention provides a pharmaceutical composition comprising a substance capable of binding to the PAH1 domain of mSin3B, e.g., a compound represented by the following formula (1), a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof:

wherein n represents 0 or 1; R¹, R², R³, R⁴ and R⁵ each independently represent a hydrogen atom, a hydrocarbon group or a functional group; Y represents a single bond, a carbonyl group, —CONH—, —NHCO— or a sulfonyl group; and Z represents a nitrogen-containing heterocyclic group which may have a substituent, an amino group which may have a hydrocarbon group or an aromatic hydrocarbon group, or a nitrogen and oxygen-containing heterocyclic group which may have a substituent.

Claims

1. A method of treating a disease associated with abnormal expression of neural restrictive silencer factor NRSF/REST or abnormal expression of genes targeted by NRSF/REST, comprising administering to a subject a pharmacologically effective amount of a substance capable of binding to the PAH1 domain of mSin3B, wherein the disease is neuropathic pain and the substance is a compound represented by A28 or 155 or a pharmacological acceptable salt or ester thereof, where A28 and 155 are:

2. A method of preparing and administering a substance capable of binding to the PAH1 domain of mSin3B, comprising:

preparing a prophylactic and/or a therapeutic substance that binds to the PAH1 domain of mSin3B for a disease associated with abnormal expression of neural restrictive silencer factor NRSF/REST or abnormal expression of genes targeted by NRSF/REST; and

administering to a subject the substance that binds to the PAH1 domain of mSin3B,

wherein the disease is neuropathic pain and the substance is a compound represented by A28 or 155 or a pharmacological acceptable salt or ester thereof, where A28 and 155 are;

3. A method of treatment with a substance capable of binding to the PAH1 domain of mSin3B, comprising:

administering to a subject a substance capable of binding to the PAH1 domain of mSin3B to treat a disease associated with abnormal expression of neural restrictive silencer factor NRSF/REST or abnormal expression of genes targeted by NRSF/REST,

wherein the disease is neuropathic pain and the substance is a compound represented by A28 or 155 or a pharmacological acceptable salt or ester thereof, where A28 and 155 are;