WO1995003041A1 - Method of inhibiting the production of human immunodeficiency viruses with substituted azaspiranes - Google Patents
Method of inhibiting the production of human immunodeficiency viruses with substituted azaspiranes Download PDFInfo
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- WO1995003041A1 WO1995003041A1 PCT/US1994/008275 US9408275W WO9503041A1 WO 1995003041 A1 WO1995003041 A1 WO 1995003041A1 US 9408275 W US9408275 W US 9408275W WO 9503041 A1 WO9503041 A1 WO 9503041A1
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- compound
- hiv
- inhibiting
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- production
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- 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
-
- 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
Definitions
- This invention relates to a method of inhibiting the production of infectious human immunodeficiency viruses (HIV) in HIV seropositive humans which comprises administering to such human an effective amount of a substituted azaspirane.
- HIV infectious human immunodeficiency viruses
- CD8+ T cells have been shown to inhibit the replication of HIV in cultures of CD4+ cells from asymptomatic HTV seropositive individuals (Brinchmann et al. CD8+ T cells J Immunol. 1442961-2966 (1990)).
- the immunosuppressive compound cyclosporin A (CsA) has demonstrated a protective effect in several animal models of viral infection. Particularly, chronic treatment with CsA before and after infection with LP-BM5 murine leukemia virus has proven effective against the development of immunodeficiency disease (Cemy, A. et al. Eur. J. Immunol. 21: 1747-50 (1991)).
- Badger, et al., U.S. Patent No.4,963,557 discloses compounds of the formula (I) wherein: n is 3-7; m is 1 or 2; R and R ⁇ 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* and R ⁇ when taken together is 5-10; or R* and R2 together form a cyclic alkyl group having 3-7 carbon atoms; R ⁇ and R ⁇ are the same or different and are selected from hydrogen or straight chain alkyl having 1- 3 carbon atoms; or R ⁇ and R ⁇ are joined together with the nitrogen atom to form a heterocyclic group having 5-8 atoms; or a pharmaceutically acceptable salt or hydrate or solvate thereof.
- Badger I discloses compounds of Formula I as a class of novel compounds which induce an immunomodulatory effect which is characterized by the stimulation of suppressor cell activity.
- Rl and R ⁇ 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 Rl and R ⁇ when taken together is 5-10; or R 1 and R ⁇ together form a cyclic alkyl group having 3-7 carbon atoms;
- R3 and R ⁇ are the same or different and are selected from hydrogen or straight chain alkyl having 1-3 carbon atoms; or R3 and R ⁇ are joined together with the nitrogen atom to form a heterocyclic group having 5-8 atoms; or a pharmaceutically acceptable salt or hydrate or solvate thereof.
- a preferred compound used in the novel method is the dihydrochloride salt of a compound of Formula (I) where R* and R ⁇ are propyl, R ⁇ and R 4 are methyl, m is 1 and n is 3 which is N,N-dimethyl-8,8-dipropyl-2-azaspiro[4.5]decane-2- propanamine dihydrochloride.
- a particularly preferred compound used in the novel method is the dihydrochloride salt of a compound of Formula (I) where Rl and R ⁇ are propyl, R3 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 dihydrochloride.
- a particularly preferred compound used in the novel method is the dihydrochloride salt of a compound of Formula (I) where R* and R ⁇ are propyl, R3 and R 4 are joined together with the nitrogen to form a piperidine ring, m is 1 and n is 3 which is 8,8-dipropyl-2-azaspiro[4.5]decane-2-piperidinopropyl dihydrochloride.
- This invention discloses compounds of Formula (I) and pharmaceutically acceptable salts or hydrates or solvates thereof as being useful for inhibiting the production of infectious HTV in HIV seropositive humans.
- the compounds of Formula I are tested for their ability to inhibit the production of infectious HIV in the assay described in Sperber, et al., AIDS Research and Human Retroviruses. 9 No.l. 91-98.
- This invention relates to a method of inhibiting the production of infectious HIV which comprises administering to an HIV seropositive human an effective 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 inhibit the production of infectious HIV
- the route of administration of the Formula (I) ("active ingredient”) 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 for preparing solid formulations. Examples of such earners 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 method of this invention of inhibiting the production of infectious HIV in HIV seropositive humans comprises administering to a subject in need of such inhibition an effective infectious HIV inhibiting amount of a pharmaceutically active compound of the present invention.
- the invention also provides for the use of a compound of Formula (I) in the manufacture of a medicament for use in the inhibition of infectious HIV in HIV seropositive humans.
- the invention also provides for a pharmaceutical composition for use in the inhibition of the production of infectious HIV in HIV seropositive humans which comprises a compound of Formula I and a pharmaceutically acceptable carrier.
- the invention also provides for a process for preparing a pharmaceutical composition containing a pharmaceutically acceptable carrier or diluent and a compound of Formula I which comprises bringing the compound of Formula I into association with the pharmaceutically acceptable carrier or diluent.
- the compounds of the present invention can be co-administered with further active ingredients, such as 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)).
- further active ingredients such as 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)).
- An injectable form for administering Formula (I) compounds is produced by stirring 1.5% by weight of N,N-diethyl-8,8-dipropyl-2-azaspiro[4,5]decane-2- propanamine dihydrochloride in 10% by volume propylene glycol in water.
- Example 3 Tablet Composition
- sucrose, calcium sulfate dihydrate and Formula (I) compound shown in Table ⁇ 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.
Abstract
Invented is a method of inhibiting the production of infectious human immunodeficiency viruses (HIV) in HIV seropositive humans which comprises administering to such human an effective amount of a substituted azaspirane.
Description
METHOD OF INHIBITING THE PRODUCTION OF HUMAN IMMUNODEFICIENCY VIRUSES WITH SUBSTITUTED AZASPIRANES
This invention relates to a method of inhibiting the production of infectious human immunodeficiency viruses (HIV) in HIV seropositive humans which comprises administering to such human an effective amount of a substituted azaspirane.
Background of the Invention
Numerous agents are presently available that inhibit the replication of human immunodeficiency viruses in T cells and monocytes (Yarchoan et al., anCfit (1986); 1:575-580 and Broder et al., anCfil (1985); 2:627-630). These compounds are limited in their usefulness due to significant toxicities and viral resistance associated with their long-term use Volberding, et al., N. Engl J. Med 1990; 322:941-949. Additionally, certain selected immunosuppressive/immunomodulatory agents have demonstrated an ability to suppress viral replication. Specifically, immunomodulating CD8 lymphocytes have been shown to suppress replication of HIV in peripheral blood mononuclear cells (Walker et al. Science.224:1563-6 (1986)) and activated CD8+ T cells have been shown to inhibit the replication of HIV in cultures of CD4+ cells from asymptomatic HTV seropositive individuals (Brinchmann et al. CD8+ T cells J Immunol. 1442961-2966 (1990)). Further, the immunosuppressive compound cyclosporin A (CsA) has demonstrated a protective effect in several animal models of viral infection. Particularly, chronic treatment with CsA before and after infection with LP-BM5 murine leukemia virus has proven effective against the development of immunodeficiency disease (Cemy, A. et al. Eur. J. Immunol. 21: 1747-50 (1991)). Evidence that treatment of AIDS and HIV-seropositive non- AIDS patients with CsA increases T4 cells and inhibits lymphadenopathy has also been reported. (Andrieu et al. Clin. Immunol, and Immumopathol. 46:181-198 (1988)). However, none of the above references suggest that immunosuppressiveΛmmunomodulatoiy agents in general will have utility in inhibiting the production of infectious HTV in HIV seropositive humans. Further, none of the above references teaches or suggest a means for predicting whether a particular immunosuppressive/immunomodulatory agent will have utility in inhibiting the production of infectious HIV in HIV seropositive humans.
Badger, et al., U.S. Patent No.4,963,557 (Badger I) discloses compounds of the formula
(I) wherein: n is 3-7; m is 1 or 2; R and R^ 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* and R^ when taken together is 5-10; or R* and R2 together form a cyclic alkyl group having 3-7 carbon atoms; R^ and R^ are the same or different and are selected from hydrogen or straight chain alkyl having 1- 3 carbon atoms; or R^ and R^ are joined together with the nitrogen atom to form a heterocyclic group having 5-8 atoms; or a pharmaceutically acceptable salt or hydrate or solvate thereof. Badger I discloses compounds of Formula I as a class of novel compounds which induce an immunomodulatory effect which is characterized by the stimulation of suppressor cell activity.
Badger I does not disclose the compounds of Formula I as agents for inhibiting the production of infectious HIV in HTV seropositive humans.
Summary of the Invention This invention relates to a method of inhibiting the production of infectious HIV in HIV seropositive humans which comprises administering to such human an effective amount of a compound of the formula
Rl and R^ 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 Rl and R^ when taken together is 5-10; or R1 and R^ together form a cyclic alkyl group having 3-7 carbon atoms;
R3 and R^ are the same or different and are selected from hydrogen or straight chain alkyl having 1-3 carbon atoms; or R3 and R^ are joined together with the nitrogen atom to form a heterocyclic group having 5-8 atoms;
or a pharmaceutically acceptable salt or hydrate or solvate thereof.
Detailed Description of the Invention The preparation of all compounds of Formula (I) and pharmaceutically acceptable salts, hydrates and solvates and formulations thereof is disclosed in U.S. Patent No. 4,963,557, the entire disclosure of which is hereby incorporated by reference.
A preferred compound used in the novel method is the dihydrochloride salt of a compound of Formula (I) where R* and R^ are propyl, R^ and R4 are methyl, m is 1 and n is 3 which is N,N-dimethyl-8,8-dipropyl-2-azaspiro[4.5]decane-2- propanamine dihydrochloride.
A particularly preferred compound used in the novel method is the dihydrochloride salt of a compound of Formula (I) where Rl and R^ are propyl, R3 and R4 are ethyl, m is 1 and n is 3 which is N,N-diethyl-8,8-dipropyl-2- azaspiro[4.5]decane-2-propanamine dihydrochloride.
A particularly preferred compound used in the novel method is the dihydrochloride salt of a compound of Formula (I) where R* and R^ are propyl, R3 and R4 are joined together with the nitrogen to form a piperidine ring, m is 1 and n is 3 which is 8,8-dipropyl-2-azaspiro[4.5]decane-2-piperidinopropyl dihydrochloride.
This invention discloses compounds of Formula (I) and pharmaceutically acceptable salts or hydrates or solvates thereof as being useful for inhibiting the production of infectious HTV in HIV seropositive humans.
The compounds of Formula I are tested for their ability to inhibit the production of infectious HIV in the assay described in Sperber, et al., AIDS Research and Human Retroviruses. 9 No.l. 91-98.
This invention relates to a method of inhibiting the production of infectious HIV which comprises administering to an HIV seropositive human an effective 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.
It will be recognized by one of skill in the an that the form and character of the pharmaceutically acceptable carrier or diluent is dictated by the amount of active ingredient with which it is to be combined, the route of administration and other well-known variables. 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 inhibit the production of infectious HIV
The route of administration of the Formula (I) ("active ingredient") compound is not critical but is usually oral or parenteral, preferably oral. The term 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. Preferably, 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 composition in the form of a tablet can be prepared using any suitable pharmaceutical carrier(s) routinely used for preparing solid formulations. Examples of such earners include magnesium stearate, starch, lactose, sucrose and cellulose.
A composition in the form of a capsule can be prepared using routine encapsulation procedures. For example, 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. Preferably each oral dosage unit will contain the active ingredient in an amount of from about 0.1 mg to about 100 mg.
- A -
While it is possible for an active ingredient to be administered alone, it is preferable to present it as a pharmaceutical formulation.
It will be recognized by one of skill in the art that 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 method of this invention of inhibiting the production of infectious HIV in HIV seropositive humans comprises administering to a subject in need of such inhibition an effective infectious HIV inhibiting amount of a pharmaceutically active compound of the present invention.
The invention also provides for the use of a compound of Formula (I) in the manufacture of a medicament for use in the inhibition of infectious HIV in HIV seropositive humans.
The invention also provides for a pharmaceutical composition for use in the inhibition of the production of infectious HIV in HIV seropositive humans which comprises a compound of Formula I and a pharmaceutically acceptable carrier. The invention also provides for a process for preparing a pharmaceutical composition containing a pharmaceutically acceptable carrier or diluent and a compound of Formula I which comprises bringing the compound of Formula I into association with the pharmaceutically acceptable carrier or diluent.
No unacceptable toxicological effects are expected when compounds of the invention are administered in accordance with the present invention. In addition, the compounds of the present invention can be co-administered with further active ingredients, such as 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)).
Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The following examples are, therefore, to be construed as merely illustrative and not a limitation of the scope of the present invention in any way.
EXAMPLE 1 - CAPSULE COMPOSITION 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.
Table I
INGREDIENTS AMOUNTS
N,N-diethyl-8,8-dipropyl-2-azaspiro[4,5]decane-2- 25 mg propanamine dihydrochloride
Lactose 55 mg
Talc 16 mg
Magnesium Stearate 4 mg
EXAMPLE 2 - INJECTABLE PARENTERAL COMPOSITION
An injectable form for administering Formula (I) compounds is produced by stirring 1.5% by weight of N,N-diethyl-8,8-dipropyl-2-azaspiro[4,5]decane-2- propanamine dihydrochloride in 10% by volume propylene glycol in water.
Example 3 - Tablet Composition The sucrose, calcium sulfate dihydrate and Formula (I) compound shown in Table π 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.
Table II
Ingredients Amounts
N,N-diethyl-8,8-dipropyl-2-azaspiro[4,5]decane- 20 mg
2-propanamine dihydrochloride calcium sulfate dihydrate 30 mg sucrose 4 mg starch 2 mg talc l mg stearic acid 0.5 mg
While the above descriptions and examples fully describe the invention and the preferred embodiments thereof, it is understood that the invention is not limited to the particular disclosed embodiments coming within the scope of the following claims.
Claims
1. Use of a compound of the formula
R and R^ 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 and R^ when taken together is 5-10; or R and R^ together form a cyclic alkyl group having 3-7 carbon atoms;
R3 and R4 are the same or different and are selected from hydrogen or straight chain alkyl having 1-3 carbon atoms; or R^ and R are joined together with the nitrogen to form a heterocyclic group having 5-8 atoms; or a pharmaceutically acceptable salt or hydrate or solvate thereof; in the manufacture of a medicament for inhibiting the production of infectious human immunodeficiency viruses (HIV) in HIV seropositive humans.
2. The use according to claim 1 wherein the compound is N,N- diethyl-8,8-dipropyl-2-azaspiro[4.5]decane-2-propanamine; or a pharmaceutically acceptable salt, hydrate or solvate thereof.
3. The use according to claim 1 wherein the compound is administered orally.
4. The use according to claim 3 wherein from about 0.01 mg/kg to about 10 mg/kg of compound is administered per day.
5. The use according to claim 1 wherein the compound is administered parenterally.
6. The use according to claim 5 wherein from about 0.01 mg/kg to about 10 mg/kg of compound is administered per day.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP94922684A EP0713391A4 (en) | 1993-07-23 | 1994-07-22 | Method of inhibiting the production of human immunodeficiency viruses with substituted azaspiranes |
| NZ269990A NZ269990A (en) | 1993-07-23 | 1994-07-22 | Inhibiting hiv viruses; use of azaspirane compounds in preparation of medicaments |
| AU73708/94A AU7370894A (en) | 1993-07-23 | 1994-07-22 | Method of inhibiting the production of human immunodeficiency viruses with substituted azaspiranes |
| JP7505331A JPH09500647A (en) | 1993-07-23 | 1994-07-22 | A method for inhibiting human immunodeficiency virus production by substituted azaspirans. |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9315306.2 | 1993-07-23 | ||
| GB939315306A GB9315306D0 (en) | 1993-07-23 | 1993-07-23 | Methods |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1995003041A1 true WO1995003041A1 (en) | 1995-02-02 |
Family
ID=10739328
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1994/008275 WO1995003041A1 (en) | 1993-07-23 | 1994-07-22 | Method of inhibiting the production of human immunodeficiency viruses with substituted azaspiranes |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP0713391A4 (en) |
| CN (1) | CN1130870A (en) |
| AU (1) | AU7370894A (en) |
| CA (1) | CA2167841A1 (en) |
| GB (1) | GB9315306D0 (en) |
| NZ (1) | NZ269990A (en) |
| WO (1) | WO1995003041A1 (en) |
| ZA (1) | ZA945416B (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0711160A1 (en) * | 1993-07-23 | 1996-05-15 | Smithkline Beecham Corporation | Method of inhibiting the replication of human immunodeficiency viruses with substituted azaspiranes |
| EP0717622A1 (en) * | 1993-07-23 | 1996-06-26 | Smithkline Beecham Corporation | Methods of treating hiv with azaspiranes |
| US5744495A (en) * | 1995-07-13 | 1998-04-28 | Smithkline Beecham Corporation | N, N-diethyl-8, 8-dipropyl-2-azaspiro 4.5! decane-2-propanamine |
| US6025364A (en) * | 1996-05-17 | 2000-02-15 | Anormed, Inc. | Method of treating asthma |
| US7211261B1 (en) | 1998-09-11 | 2007-05-01 | Solstice Neurosciences, Inc. | Stable liquid formulations of botulinum toxin |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4963557A (en) * | 1987-09-28 | 1990-10-16 | Smithkline Beecham Corporation | Immunomodulatory azaspiranes |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA921120B (en) * | 1991-02-19 | 1993-01-27 | Smithkline Beecham Corp | Cytokine inhibitors |
| GB9201803D0 (en) * | 1992-01-28 | 1992-03-11 | Smithkline Beecham Corp | Methods |
| GB9201804D0 (en) * | 1992-01-28 | 1992-03-11 | Smithkline Beecham Corp | Methods |
| GB9315271D0 (en) * | 1993-07-23 | 1993-09-08 | Smithkline Beecham Corp | Methods |
| GB9315340D0 (en) * | 1993-07-23 | 1993-09-08 | Smithkline Beecham Corp | Methods |
| GB9315351D0 (en) * | 1993-07-23 | 1993-09-08 | Smithkline Beecham Corp | Methods |
-
1993
- 1993-07-23 GB GB939315306A patent/GB9315306D0/en active Pending
-
1994
- 1994-07-22 ZA ZA945416A patent/ZA945416B/en unknown
- 1994-07-22 NZ NZ269990A patent/NZ269990A/en unknown
- 1994-07-22 AU AU73708/94A patent/AU7370894A/en not_active Abandoned
- 1994-07-22 WO PCT/US1994/008275 patent/WO1995003041A1/en not_active Application Discontinuation
- 1994-07-22 CN CN94193372A patent/CN1130870A/en active Pending
- 1994-07-22 CA CA002167841A patent/CA2167841A1/en not_active Abandoned
- 1994-07-22 EP EP94922684A patent/EP0713391A4/en not_active Withdrawn
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4963557A (en) * | 1987-09-28 | 1990-10-16 | Smithkline Beecham Corporation | Immunomodulatory azaspiranes |
Non-Patent Citations (3)
| Title |
|---|
| CHEMICAL ABSTRACTS, Volume 117, No. 23, issued 07 December 1992, BADGER et al.: "Azaspirana Derivatives as Cytokine Inhibitors", see pages 83, column 2, abstract no. 226312z; & WO,A,9214462. * |
| CHEMICAL ABSTRACTS, Volume 119, No. 17, issued 25 October 1993, BADGER, "Preventing or Delaying Occurence of Acquired Immunodefiency Syndrome with Azaspiranes", see page 90, column 1, abstract no. 174173z; & WO,A,9314760. * |
| See also references of EP0713391A4 * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0711160A1 (en) * | 1993-07-23 | 1996-05-15 | Smithkline Beecham Corporation | Method of inhibiting the replication of human immunodeficiency viruses with substituted azaspiranes |
| EP0717622A1 (en) * | 1993-07-23 | 1996-06-26 | Smithkline Beecham Corporation | Methods of treating hiv with azaspiranes |
| EP0717622A4 (en) * | 1993-07-23 | 1998-09-09 | Smithkline Beecham Corp | Methods of treating hiv with azaspiranes |
| EP0711160A4 (en) * | 1993-07-23 | 1998-09-09 | Smithkline Beecham Corp | Method of inhibiting the replication of human immunodeficiency viruses with substituted azaspiranes |
| US5744495A (en) * | 1995-07-13 | 1998-04-28 | Smithkline Beecham Corporation | N, N-diethyl-8, 8-dipropyl-2-azaspiro 4.5! decane-2-propanamine |
| US6025364A (en) * | 1996-05-17 | 2000-02-15 | Anormed, Inc. | Method of treating asthma |
| US7211261B1 (en) | 1998-09-11 | 2007-05-01 | Solstice Neurosciences, Inc. | Stable liquid formulations of botulinum toxin |
| US8173138B2 (en) | 1998-09-11 | 2012-05-08 | Solstice Neurosciences, Llc | Stable liquid formulations of botulinum toxin |
Also Published As
| Publication number | Publication date |
|---|---|
| AU7370894A (en) | 1995-02-20 |
| CA2167841A1 (en) | 1995-02-02 |
| CN1130870A (en) | 1996-09-11 |
| ZA945416B (en) | 1995-05-10 |
| EP0713391A1 (en) | 1996-05-29 |
| EP0713391A4 (en) | 1998-09-09 |
| NZ269990A (en) | 1999-07-29 |
| GB9315306D0 (en) | 1993-09-08 |
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