Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
  • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
  • A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
  • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system

Definitions

• the invention relates to the novel use of 3-cyclopropylmethoxy-4-difluoromethoxy-N-(3,5-dichloropyrid- 4-yl)benzamide, a pharmacologically acceptable salt thereof or its N-oxide in the treatment of multiple sclerosis.
• PDE4 inhibitors - in particular rolipram - are proposed on their own or in combination with anti-inflammatory active compounds or immunomodulators for the treatment of multiple sclerosis.
• tumor necrosis factor inhibitors - in particular pentoxyfylline - are proposed for the treatment of disorders of the central nervous system.
• Multiple sclerosis is a degenerative disorder of the central nervous system, which is characterized by a localized disintegration of the myelin sheaths.
• the disorder proceeds chronically in episodes which are often far apart from one another in terms of time, often with regressions of the clinical symptomatology, but can also have a slow continuous progressive course.
• the symptoms are varied, depending on the failure of the part of the nervous system affected in each case; for example, double images due to ophthalmoplegia, trembling, attacks of giddiness, myasthenia, incontinence, perception and speech disorders and psychological changes can occur.
• multiple sclerosis is the most frequent neurological disorder.
• the disorder can only be treated symptomatically by the high-dose administration of glucocorticoids on occurrence of acute episodes with neurological symptoms, which leads to a reduction in the duration of the episode.
• numerous and severe side effects of corticoids however, it is not possible to carry out a preventive continuous therapy using these.
• Some patients also receive immunosuppressants; although these lower the episode rate they are often poorly tolerable.
• the administration of genetically engineered beta- interferons is relatively new and on regular injection they can lower the episode rate by approximately one third. The injection of beta-interferons, however, is difficult to handle for the patient and very cost- intensive.
• the object on which the invention is based is surprisingly achieved by the use of 3-cyclopropyl- methoxy-4-difluoromethoxy-N-(3,5-dichloropyrid-4-yl)benzamide, a pharmacologically tolerable salt thereof or its N-oxide in the treatment of the episodic or continuously progressive form of multiple sclerosis.
• the invention thus relates in a first aspect to the use of 3-cyclopropylmethoxy-4-difluoromethoxy-N- (3,5-dichloropyrid-4-yl)benzamide, a pharmacologically tolerable salt thereof or its N-oxide in the production of medicaments for the treatment of multiple sclerosis, in particular of the episodically proceeding form of multiple sclerosis.
• the invention further relates to the use of 3-cyclopropylmethoxy-4-difluoromethoxy-N-(3,5-dichloro- pyrid-4-yl)benzamide, a pharmacologically tolerable salt thereof or its N-oxide in the treatment of multiple sclerosis, in particular of the episodically proceeding form of multiple sclerosis.
• 3-cyclopropylmethoxy-4-difluoromethoxy-N-(3,5-dichloropyrid- 4-yl)benzamide, a pharmacologically tolerable salt thereof or its N-oxide for the production of the abovementioned medicaments, 3-cyclopropylmethoxy-4-difluoromethoxy-N-(3,5-dichloropyrid-4- yl)benzamide, a pharmacologically tolerable salt thereof or its N-oxide are processed with suitable pharmaceutical excipients or vehicles to give tablets, coated tablets, capsules, suppositories, patches (e.g.
• TTS transdermal therapeutic system
• emulsions emulsions, suspensions or solutions
• the active compound content is advantageously between 0.1 and 95%
• a pharmaceutical administration form exactly tailored to the active compound and/or to the desired onset of action e.g. a sustained-release form or an enteric form
• excipients and vehicles which are suitable for the desired pharmaceutical formulations.
• solvents for example, antioxidants, dispersants, emulsifiers, antifoams, flavor corrigents, preservatives, solubilizers, colorants or, in particular, permeation promoters and complexing agents (e.g. cyclodex- trins).
• the active compound can be administered orally, rectally, parenterally or percutaneously.
• the active compound in the case of oral administration in a daily dose of approximately 0.05 to approximately 2 mg, in particular 0.1 to 1 mg, if appropriate in the form of a number, preferably 1 to 3, individual doses to achieve the desired result, where a gradually increasing and reducing dose can be advantageous.
• a gradually increasing and reducing dose can be advantageous.
• par- enteral treatment it is possible to use similar or (in particular in the case of the intravenous administration of the active compound) as a rule lower doses.
• an active compound can vary as a function of the body weight, the age and the general condition of the patient, and his/her response behavior to the active compound.
• the pharmaceutical preparations can also contain one or more pharmacologically active constituents of other pharmaceutical groups.
• Possible other pharmaceutical groups which may be mentioned are, for example, antiinflammatory active compounds, e.g.
• glucocorticosteroids such as methylprednisolone and prednisolone, ACTH, leukotriene antagonists, iipoxygenase inhibitors, immunosuppressants such as azothioprine, mixorib- ine, cyclosporin, gusperimus, tacrolimus, leflunomide, cyclophosphamide, methotrexate or mitoxan- trone, immunomodulators such as type 1 interferons ⁇ 1 a and 1 b or 2a, linomide, aldesleukin, filgrastin, penicillamine, vinpocetine, pidotimod or imiquimod; furthermore cAMP-increasing substances, such as beta-mimetics, PGE2, PGI2, adenylate cyclase inhibitors, inhibitors of PDE1 , PDE2, PDE3, PDE 4 and PDE7 and in particular inhibitors of the lymphocyte-specific PDE7
• a further subject of the invention is a commercially available product, consisting of a customary secondary pack, a primary pack containing the medicament (for example an ampoule or a blister pack) and, if desired, a pack insert, the medicament leading to the attenuation of the symptoms of multiple sclerosis, the suitability of the medicament for the treatment of multiple sclerosis being indicated on the secondary pack and/or on the pack insert of the commercially available product, and the medicament containing 3-cyclopropylmethoxy-4-difluoromethoxy-N-(3,5-dichloropyrid-4-yl)benzamide, a pharmacologically tolerable salt therof or its N-oxide.
• the secondary pack, the primary pack containing the medicament and the pack insert otherwise correspond to what would be regarded as standard to the person skilled in the art for medicaments of this type.
• EAE Experimental autoimmune encephalomyelitis
• NAGELKERKEN et al, International Immunology, Vol. 9, No. 9, 1243-1251 , 1997) in female SJL mice by administration of a proteolipid protein.
• the immunization is carried out with P P 139 . 151 in Freund's complete adjuvant, which contains 1 mg of Mycobacterium tuberculosis H37Ra in one ml. 3 days later, 10 10 heat-inactivated Bor- detella pertussis organisms are administered intravenously.

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• Health & Medical Sciences (AREA)
• Pharmacology & Pharmacy (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Life Sciences & Earth Sciences (AREA)
• Epidemiology (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Neurology (AREA)
• Neurosurgery (AREA)
• General Chemical & Material Sciences (AREA)
• Engineering & Computer Science (AREA)
• Organic Chemistry (AREA)
• Biomedical Technology (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Pyridine Compounds (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Medicinal Preparation (AREA)

Priority Applications (10)

Applications Claiming Priority (2)

Publications (2)

Family

ID=8237737

Family Applications (1)

Country Status (12)

Cited By (7)

Families Citing this family (3)

Family Cites Families (3)

• 2000
  • 2000-03-01 ES ES00910736T patent/ES2231162T3/es not_active Expired - Lifetime
  • 2000-03-01 AT AT00910736T patent/ATE279924T1/de active
  • 2000-03-01 CA CA002364258A patent/CA2364258C/en not_active Expired - Fee Related
  • 2000-03-01 PT PT00910736T patent/PT1161239E/pt unknown
  • 2000-03-01 EP EP00910736A patent/EP1161239B1/en not_active Expired - Lifetime
  • 2000-03-01 DE DE60015098T patent/DE60015098T2/de not_active Expired - Lifetime
  • 2000-03-01 SI SI200030586T patent/SI1161239T1/xx unknown
  • 2000-03-01 DK DK00910736T patent/DK1161239T3/da active
  • 2000-03-01 WO PCT/EP2000/001703 patent/WO2000053182A2/en not_active Ceased
  • 2000-03-01 US US09/914,763 patent/US6531493B1/en not_active Expired - Lifetime
  • 2000-03-01 JP JP2000603671A patent/JP2002538207A/ja active Pending
  • 2000-03-01 AU AU32840/00A patent/AU3284000A/en not_active Abandoned

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