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
  • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
  • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
  • A61K31/404—Indoles, e.g. pindolol
  • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• • 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
  • A61K31/445—Non condensed piperidines, e.g. piperocaine
• • 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
  • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• • 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
  • A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
• • 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
• • 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
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P37/00—Drugs for immunological or allergic disorders
  • A61P37/02—Immunomodulators
  • A61P37/04—Immunostimulants

Definitions

• This invention relates to a method of preventing or delaying the occurrence of acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus (HIV) seropositive humans which comprises administering to such human an effective therefore amount of a substituted azaspirane.
• AIDS acquired immunodeficiency syndrome
• HIV human immunodeficiency virus
• immunosuppressive/immunomodulatory agents has been shown to suppress viral replication.
• CD8 lymphocytes have been shown to suppress replication of HIV in peripheral blood mononuclear cells (Waler et al. Science, 2-21:1563-6 (1986)) and activated CD8+ T cells have been shown to inhibit the replication of HIV in cultures of CD4+ cells from asymptomatic HIV seropositive individuals (Brinch ann et al. CD8+ T cells J. Immunol. 144 2961-2966 (1990)).
• the immunosuppressive compound cyclosporin A (CsA) has demonstrated a protective effect in several animal models of viral infection.
• Badger I discloses compounds of Formula I as a novel class of compounds which induce an immunomodulatory effect which is characterized by the stimulation of suppressor cell activity.
• R 1 and R 2 are the same or different and are selected from hydrogen or straight or branched chain alkyl, provided that the total number of carbon atoms contained by R 1 and R 2 when taken together is 5-10; or
• R 1 and R 2 together form a cyclic alkyl group having 3-7 carbon atoms
• R3 and R 4 are the same or different and are selected from hydrogen or straight chain alkyl having 1-3 carbon atoms; or R ⁇ and R 4 are joined together with the nitrogen atom to form a heterocyclic group having
• a preferred compound used in the novel method is the dihydrochloride salt of a compound of Formula (I) where R 1 and R 2 are propyl, R3 and R 4 are methyl, is 1 and n is 3 which is N,N-dimethyl-8,8-dipropyl-2- azaspiro[4,5]decane-2-propanamine dihydrochloride.
• a preferred compound used in the novel method is a compound of Formula (I) where R 1 and R 2 are propyl, R ⁇ and R 4 are ethyl, m is 1 and n is 3 which is N,N- diethyl-8,8-dipropyl-2-azaspiro[4,5]decane-2- propanamine and salts thereof.
• This invention discloses compounds of Formula (I) and pharmaceutically acceptable salts or hydrates or solvates thereof as being useful for preventing or delaying the occurrence of AIDS in HIV seropositive humans.
• This invention relates to a method of delaying or preventing the occurrence of AIDS which comprises administering to an HIV seropositive human an effective therefor amount of a compound of Formula (I) or a pharmaceutically acceptable salt or hydrate or solvate thereof.
• a compound of Formula (I) or a pharmaceutically acceptable salt or hydrate or solvate thereof can be administered to such human in a conventional dosage form prepared by combining a compound of Formula (I) or a pharmaceutically acceptable salt or hydrate or solvate thereof, with a conventional pharmaceutically acceptable carrier or diluent according to known techniques, such as those described in Badger (I), U.S. Patent No. 4,963,557.
• a compound of Formula (I) or a pharmaceutically acceptable salt or hydrate or solvate thereof is administered to an HIV seropositive human in an amount sufficient to prevent or delay the occurrence of AIDS.
• the route of administration of the Formula (I) compound is not critical but is usually oral or parenteral, preferably oral.
• parenteral as used herein includes intravenous, intramuscular, subcutaneous, intranasal, intrarectal, transdermal, intravaginal or intraperitoneal administration.
• the subcutaneous and intramuscular forms of parenteral administration are generally preferred.
• the daily parenteral dosage regimen will preferably be from about 0.01 mg/kg to about 10 mg/kg of total body weight, most preferably from about 0.1 mg/kg to about 1 mg/kg.
• each parenteral dosage unit will contain the active ingredient in an amount of from about 0.1 mg to about 100 mg.
• the compounds of Formula (I) which are active when given orally can be formulated as liquids, for example syrups, suspensions or emulsions, tablets, capsules and lozenges.
• a liquid formulation will generally consist of a suspension or solution of the compound or pharmaceutically acceptable salt in a suitable liquid carrier(s) for example, ethanol, glycerine, non-aqueous solvent, for example polyethylene glycol, oils, or water with a suspending agent, preservative, flavoring or coloring agent.
• a suitable liquid carrier(s) for example, ethanol, glycerine, non-aqueous solvent, for example polyethylene glycol, oils, or water with a suspending agent, preservative, flavoring or coloring agent.
• a composition in the form of a tablet can be prepared using any suitable pharmaceutical carrier(s) routinely used or preparing solid formulations.
• suitable pharmaceutical carrier(s) include magnesium stearate, starch, lactose, sucrose and cellulose.
• a composition in the form of a capsule can be prepared using routine encapsulation procedures.
• pellets containing the active ingredient can be prepared using standard carriers and then filled into a hard gelatin capsule; alternatively, a dispersion or suspension can be prepared using any suitable pharmaceutical carrier(s) , for example aqueous gums, celluloses, silicates or oils and the dispersion or suspension then filled into a soft gelatin capsule.
• the daily oral dosage regimen will preferably be from about 0.01 mg/kg to about 10 mg/kg of total body weight.
• each oral dosage unit will contain the active ingredient in an amount of from about 0.1 mg to about 100 mg.
• an active ingredient While it is possible for an active ingredient to be administered alone, it is preferable to present it as a pharmaceutical formulation.
• the optimal quantity and spacing of individual dosages of a compound of formula (I) or a pharmaceutically acceptable salt or hydrate or solvate thereof will be determined by the nature and extent of the condition being treated, the form, route and site of administration, and the particular patient being treated, and that such optimums can be determined by conventional techniques. It will also be appreciated by one of skill in the art that the optimal course of treatment, i.e., the number of doses of a compound of Formula (I) or a pharmaceutically acceptable salt or hydrate or solvate thereof given per day and duration of therapy, can be ascertained by those skilled in the art using conventional course of treatment determination tests.
• the compounds of the present invention can be co-administered with further active ingredients, such as other compounds known to prevent or delay the occurrence of AIDS in HIV seropositive humans such as retrovir (the brand name for zidovudine, formerly called azidothymidine (AZT) ) .
• retrovir the brand name for zidovudine, formerly called azidothymidine (AZT) .
• An oral dosage form for administering Formula (I) compounds is produced by filing a standard two piece hard gelatin capsule with the ingredients in the proportions shown in Table I, below.
• EXAMPLE 2 - TN ECTABLE PARENTERAL COMPOSITION An injectable form for administering Formula (I) compounds is produced by stirring 1.5% by weight of N,N-dimeth l-8,8-dipropyl-2-azaspiro[4,5]decane-2- propanamine dihydrochloride in 10% by volume propylene glycol in water.
• sucrose, calcium sulfate dihydrate and Formula (I) compound shown in Table II below are mixed and granulated in the proportions shown with a 10% gelatin solution.
• the wet granules are screened, dried, mixed with the starch, talc and stearic acid, screened and compressed into a tablet.

Landscapes

• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Pharmacology & Pharmacy (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• Chemical & Material Sciences (AREA)
• General Health & Medical Sciences (AREA)
• Medicinal Chemistry (AREA)
• Animal Behavior & Ethology (AREA)
• Epidemiology (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Immunology (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• General Chemical & Material Sciences (AREA)
• Virology (AREA)
• Organic Chemistry (AREA)
• Oncology (AREA)
• Communicable Diseases (AREA)
• Tropical Medicine & Parasitology (AREA)
• Molecular Biology (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• AIDS & HIV (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
• Nitrogen Condensed Heterocyclic Rings (AREA)

Applications Claiming Priority (3)

Publications (2)

Family

ID=10709398

Family Applications (1)

Country Status (7)

Families Citing this family (4)

Citations (2)

Family Cites Families (2)

• 1992
  • 1992-01-28 GB GB929201803A patent/GB9201803D0/en active Pending
• 1993
  • 1993-01-27 KR KR1019940702596A patent/KR950700068A/ko not_active Application Discontinuation
  • 1993-01-27 AU AU35951/93A patent/AU666175B2/en not_active Ceased
  • 1993-01-27 WO PCT/US1993/000730 patent/WO1993014760A2/en not_active Application Discontinuation
  • 1993-01-27 JP JP5513407A patent/JPH07503252A/ja active Pending
  • 1993-01-27 CA CA002128535A patent/CA2128535A1/en not_active Abandoned
  • 1993-01-27 EP EP93904671A patent/EP0624089A4/en not_active Withdrawn

Patent Citations (2)

Non-Patent Citations (4)

Also Published As

Similar Documents

Legal Events