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WO1998017214A1 - Procede de traitement d'une demence provoquee par le syndrome d'immunodeficit acquis - Google Patents

Procede de traitement d'une demence provoquee par le syndrome d'immunodeficit acquis Download PDF

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Publication number
WO1998017214A1
WO1998017214A1 PCT/US1997/019184 US9719184W WO9817214A1 WO 1998017214 A1 WO1998017214 A1 WO 1998017214A1 US 9719184 W US9719184 W US 9719184W WO 9817214 A1 WO9817214 A1 WO 9817214A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
dementia due
effective amount
hiv disease
treating
Prior art date
Application number
PCT/US1997/019184
Other languages
English (en)
Inventor
Franklin P. Bymaster
Harlan E. Shannon
Original Assignee
Eli Lilly And Company
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Eli Lilly And Company filed Critical Eli Lilly And Company
Priority to CA002269506A priority Critical patent/CA2269506A1/fr
Priority to JP10519635A priority patent/JP2001502696A/ja
Priority to AU49957/97A priority patent/AU4995797A/en
Priority to EP97912879A priority patent/EP0934040A1/fr
Publication of WO1998017214A1 publication Critical patent/WO1998017214A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms

Definitions

  • This invention provides a method for treating or alleviating the symptoms of dementia due to AIDS, comprising administering an effective amount of 3- (4-hexyloxy-l, 2, 5- thiadiazol-3-yl) -1,2,5, 6-tetrahydro-l-methylpyridine .
  • HIV disease Human immunodeficiency virus (HIV) disease may often result in the patient being further incapacitated due to the serious psychological disorder, Dementia Due to HIV Disease (characterized in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (American Psychiatric Association, 1994) DSM-IV as catagory 294.9). Such Dementia can result in hospitalization of the patient, stress for caretakers, and increased medical expense.
  • HIV Human immunodeficiency virus
  • the present invention relates to a method of treating Dementia Due to HIV Disease. More specifically, the invention provides a method of treating Dementia Due to HIV Disease in humans using 3- (4-hexyloxy-l, 2, 5-thiadiazol-3-yl) -1, 2, 5, 6- tetrahydro-1-methylpyridine .
  • the compounds employed in the method of the present invention are known. Methods of preparing the compounds, as well as pharmaceutical formulations containing the compounds, are taught by Sauerberg in U.S. Pat. No. 5,043,345 herein incorporated by reference .
  • the present invention provides a method for treating Dementia Due to HIV Disease in humans comprising administering to a human in need thereof, an effective amount of a compound of Formula I:
  • the term "effective amount”, as used herein, represents an amount of compound necessary to prevent or treat a human susceptible to or suffering from Dementia due to HIV Disease following administration to such human.
  • the active compound is effective over a wide dosage range. For example, dosages per day will normally fall within the range of about 0.005 to about 500 mg/kg of body weight. In the treatment of adult humans, the range of about 0.05 to about 100 mg/kg, in single or divided doses, is preferred.
  • the amount of the compound actually administered will be determined by a physician, in the light of the relevant circumstances including the condition to be treated, the choice of compound to be administered, the age, weight, and response of the individual patient, the severity of the patient's symptoms, and the chosen route of administration, and therefore the above dosage ranges are not intended to limit the scope of the invention in any way.
  • the present compound may be administered orally to humans susceptible to or suffering from Dementia Due to HIV Disease, the compound is particularly well suited to be administered transdermally. When the compound is delivered transdermally, it is preferred that the effective amount is from about 50mg to about lOOmg per day delivery of base compound. It is especially preferred that such patch delivers an effective amount for about three to seven days.
  • the compound may further be delivered by a variety of other pharmaceutically accepted routes including, but in no way limited to parenterally, subcutaneous, intranasal, intramuscular and intravenous routes.
  • Such formulations may be designed to provide delayed or controlled release using formulation techniques which are known in the art.
  • treating includes prophylaxis of a physical and/or mental condition or amelioration or elimination of the developed physical and/or mental condition once it has been established or alleviation of the characteristic symptoms of such condition.
  • the term "Dementia Due to HIV Disease” refers to a disorder that upon neuropathological examination may commonly involve diffuse multifocal destruction of the white matter and subcortical structures.
  • the spinal fluid may show normal or slightly elevated protein and a mild lymphocytosis, and HIV can usually be isolated directly from the cerebrospinal fluid.
  • Dementia associated with HIV is typically characterized by slowness, poor concentration, difficulties with problem solving, and forgetfulness .
  • Behavioral manifestations most commonly include apathy and social withdrawal, and occasionally these may be accompanied by delirium, delusions, or hallucinations .
  • Tremor, impaired rapid repetitive movements, imbalance, ataxia, hypertonia, generalized hyperreflexia, positive frontal release signs, and impaired pursuit and saccadic eye movements may be presented on physical examination.
  • DSM-IV-R Diagnostic and Statistical Manual of Mental Disorders, Revised, 4th Ed. (1994) .
  • the DSM-IV-R was prepared by the Task Force on Nomenclature and Statistics of the American Psychiatric Association, and provides clear descriptions of diagnostic catagories. The skilled artisan will recognize that there are alternative nomenclatures, nosologies, and classification systems for pathologic psychological conditions and that these systems evolve with medical scientific progress.
  • the compounds employed in the invention are not believed to act via the GABA/benzodiazepine, 5HT1A, or Dl receptor systems in humans. Rather, the activity of the present compound as a treatment for Dementia Due to HIV Disease is believed to be based upon modulation of muscarinic cholinergic receptors. However, the mechanism by which the present compounds function is not necessarily the mechanism stated supra . , and the present invention is not limited by any mode of operation. The following Examples are studies to establish the usefulness of the named compounds for treating Dementia Due to HIV Disease.
  • Treatment groups are compared with respect to the number and percent of patients who ever had the symptom during the double-blind portion of the study (visits 5 through 33) , at a severity that was worse than during the baseline visits (1 through 4) .

Landscapes

  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Virology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • AIDS & HIV (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Molecular Biology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne un procédé de traitement d'une démence provoquée par le syndrome d'immunodéficit acquis (HIV) faisant appel à un composé de la formule (I).
PCT/US1997/019184 1996-10-23 1997-10-23 Procede de traitement d'une demence provoquee par le syndrome d'immunodeficit acquis WO1998017214A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
CA002269506A CA2269506A1 (fr) 1996-10-23 1997-10-23 Procede de traitement d'une demence provoquee par le syndrome d'immunodeficit acquis
JP10519635A JP2001502696A (ja) 1996-10-23 1997-10-23 エイズによる痴呆を処置する方法
AU49957/97A AU4995797A (en) 1996-10-23 1997-10-23 Method for treating dementia due to aids
EP97912879A EP0934040A1 (fr) 1996-10-23 1997-10-23 Procede de traitement d'une demence provoquee par le syndrome d'immunodeficit acquis

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US2973696P 1996-10-23 1996-10-23
US60/029,736 1996-10-23

Publications (1)

Publication Number Publication Date
WO1998017214A1 true WO1998017214A1 (fr) 1998-04-30

Family

ID=21850604

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1997/019184 WO1998017214A1 (fr) 1996-10-23 1997-10-23 Procede de traitement d'une demence provoquee par le syndrome d'immunodeficit acquis

Country Status (5)

Country Link
EP (1) EP0934040A1 (fr)
JP (1) JP2001502696A (fr)
AU (1) AU4995797A (fr)
CA (1) CA2269506A1 (fr)
WO (1) WO1998017214A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000032185A1 (fr) * 1998-11-27 2000-06-08 Sanochemia Pharmazeutika Aktiengesellschaft Utilisation d'effecteurs du systeme nerveux cholinergique central pour le traitement du delirium

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4826843A (en) * 1985-07-08 1989-05-02 Bristol-Myers Cerebral function enhancing diazinylpiperidine derivatives
US5043345A (en) * 1989-02-22 1991-08-27 Novo Nordisk A/S Piperidine compounds and their preparation and use
US5232929A (en) * 1990-11-28 1993-08-03 Pfizer Inc. 3-aminopiperidine derivatives and related nitrogen containing heterocycles and pharmaceutical compositions and use

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4826843A (en) * 1985-07-08 1989-05-02 Bristol-Myers Cerebral function enhancing diazinylpiperidine derivatives
US5043345A (en) * 1989-02-22 1991-08-27 Novo Nordisk A/S Piperidine compounds and their preparation and use
US5232929A (en) * 1990-11-28 1993-08-03 Pfizer Inc. 3-aminopiperidine derivatives and related nitrogen containing heterocycles and pharmaceutical compositions and use

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000032185A1 (fr) * 1998-11-27 2000-06-08 Sanochemia Pharmazeutika Aktiengesellschaft Utilisation d'effecteurs du systeme nerveux cholinergique central pour le traitement du delirium

Also Published As

Publication number Publication date
JP2001502696A (ja) 2001-02-27
EP0934040A1 (fr) 1999-08-11
CA2269506A1 (fr) 1998-04-30
AU4995797A (en) 1998-05-15

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