EP0550595A1 - Methods - Google Patents
MethodsInfo
- Publication number
- EP0550595A1 EP0550595A1 EP91917436A EP91917436A EP0550595A1 EP 0550595 A1 EP0550595 A1 EP 0550595A1 EP 91917436 A EP91917436 A EP 91917436A EP 91917436 A EP91917436 A EP 91917436A EP 0550595 A1 EP0550595 A1 EP 0550595A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- compound
- pharmaceutically acceptable
- azaspiro
- decane
- acceptable salt
- Prior art date
- Legal status (The legal status 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 status listed.)
- Ceased
Links
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
-
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Definitions
- This invention relates to a method of treating a disease state which is exacerbated or caused by excessive glucose levels, in a mammal, including a human, in need thereof which comprises administering to such mammal an effective therefore amount of a substituted azaspirane.
- This invention relates to a method of treating, prophylactically or therapeutically, a disease state which is exacerbated or caused by excessive glucose levels, in a mammal, including a human, in need thereof which comprises administering to such mammal an effective therefore amount of a compound of the formula
- R 1 and R 2 are the same or different and are selected from hydrogen or straight chain, branched chain or cyclic 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 are joined together to 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 5-8 atoms; or a pharmaceutically acceptable salt or hydrate or solvate thereof.
- compound A refers to the dihydrochloride salt of a compound of Formula (I) where R 1 and R 2 are propyl, R ⁇ and R 4 are joined together with the nitrogen atom to form a saturated heterocyclic group having 5 carbon atoms, m is 1 and n is 3 which is 2-((l- piperidinyl)propyl)-8,8-dipropyl-2-azaspiro[4,5]decane dihydrochloride.
- compounds of Formula (I) and pharmaceutically acceptable salts or hydrates or solvates thereof are useful in treating, prophylactically or therapeutically, a disease state which is exacerbated or caused by excessive glucose levels, in a mammal, including a human. in need thereof.
- the disease state is autoimmune diabetes mellitus.
- Compound A was tested for its in vivo potency in inhibiting autoimmune diabetes mellitus in rats.
- BB/Wor Biobreeding/Worcester
- highly inbred >30 generations sib-mated, and virus antibody free
- diabetes-prone diabetes-prone
- 27 male and 48 female Universality of Massachusetts, Worcester, NIH Contract Colony
- the rats were maintained on tap water and standard laboratory chow which were available .ad. libitum.
- the 75 rats were set up in 6 groups as follows:
- Compound A and the vehicle (0.5% gum tragacanth) were administered orally by gavage begining at age 25 days and continuing until the age of 120 days or until the onset of diabetes.
- the rats were monitored daily for urine glucose.
- Diabetes as used herein, is defined as glucosuria (>.4+ by Testape) (Eli Lilly Canada Inc., Toronto) and a blood glucose .>200mg/dl (tail vein) . Blood glucose levels were determined on a Glucose Analyzer II Beckman Instruments, Fullerton California.
- the rats treated with compound A realized a significant decrease in the incidence of diabetes.
- the administration of a compound-of Formula I results in a therapeutic inhibition of autoimmune diabetes mellitus.
- This invention relates to a method of treating a disease state which is exacerbated or caused by excessive glucose levels, in a mammal, including a human, in need thereof which comprises administering an effective therefore 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 mammal, including a 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, U.S. Patent No. 4,963,557.
- 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.
- An effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt or hydrate or solvate thereof is administered to a mammal, including a human, in need of the prevention or inhibition of excessive glucose levels in an amount sufficient to prevent or inhibit said excessive glucose levels.
- the route of administration of the Formula (I) compound may be oral or parenteral.
- parenteral as used herein includes intravenous, transdermal, intramuscular, subcutaneous, intranasal, intrarectal, 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 100 mg/kg of total body weight, most preferably from about 0.1 mg/kg to about 20 mg/kg.
- the daily oral dosage regimen will preferably be from about 0.5 mg to about 2000 mg.
- each parenteral dosage unit will contain the active ingredient in an amount of from about 0.1 mg to about 100 mg.
- each oral dosage unit will contain the active ingredient in an amount of from about 0.5 mg to about 70 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 for a defined number of days, can be ascertained by those skilled in the art using conventional course of treatment determination tests.
- 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 II, below.
- An injectable form for administering Formula (I) compounds is produced by stirring 1.5% by weight of 2-((l- piperidinyl)propyl)-8,8-dipropyl-2-azaspiro[4,5]decane dihydrochloride in 10% by volume propylene glycol in water.
- Example 3 Composition for Administration by Inhalation
- An aerosol form for administering Formula (I) compounds is produced by dissolving 10 mg of 2-((l- piperidinyl)propyl)-8, 8-dipropyl-2-azas ⁇ iro[4,5]decane dihydrochloride in ethanol (6-8 ml) and 0.1 -0.2% of a lubricating agent, such as polysorbate 85 or oleic acid, in an aerosol container and dispersing such mixture in a propellant, such as freon, preferably in a combination of (1,2 dichlorotetrafluoroethane) and difluorochloro methane.
- a propellant such as freon
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Méthode de traitement d'un état pathologique qui est exacerbé ou causé par des niveaux excessifs de glucose chez un mammifère, y compris chez l'homme. Le traitement consiste à administrer au mammifère souffrant de cet état pathologique une dose efficace d'un azaspirane substitué.A method of treating a medical condition which is exacerbated or caused by excessive levels of glucose in a mammal, including a human. The treatment consists in administering to the mammal suffering from this pathological condition an effective dose of a substituted azaspirane.
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US58732290A | 1990-09-24 | 1990-09-24 | |
US587322 | 1990-09-24 |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0550595A1 true EP0550595A1 (en) | 1993-07-14 |
EP0550595A4 EP0550595A4 (en) | 1993-09-08 |
Family
ID=24349331
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP19910917436 Ceased EP0550595A4 (en) | 1990-09-24 | 1991-09-18 | Methods |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP0550595A4 (en) |
JP (1) | JPH06501468A (en) |
AU (1) | AU652583B2 (en) |
CA (1) | CA2092177A1 (en) |
WO (1) | WO1992004899A1 (en) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9201803D0 (en) * | 1992-01-28 | 1992-03-11 | Smithkline Beecham Corp | Methods |
GB9217116D0 (en) * | 1992-08-13 | 1992-09-23 | Smithkline Beecham Corp | Methods |
CZ367598A3 (en) * | 1996-05-17 | 1999-05-12 | Anormed Inc. | Use of substituted azaspiran |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4963557A (en) * | 1987-09-28 | 1990-10-16 | Smithkline Beecham Corporation | Immunomodulatory azaspiranes |
-
1991
- 1991-09-18 WO PCT/US1991/006778 patent/WO1992004899A1/en not_active Application Discontinuation
- 1991-09-18 JP JP3516064A patent/JPH06501468A/en active Pending
- 1991-09-18 EP EP19910917436 patent/EP0550595A4/en not_active Ceased
- 1991-09-18 CA CA002092177A patent/CA2092177A1/en not_active Abandoned
- 1991-09-18 AU AU86310/91A patent/AU652583B2/en not_active Ceased
Non-Patent Citations (4)
Title |
---|
INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY vol. 11, no. 7, 1989, pages 839 - 846 BADGER, A.M. ET AL 'INHIBITION OF ANIMAL MODELS OF AUTOIMMUNE DISEASE AND THE INDUCTION OF NON-SPECIFIC SUPPRESSOR CELLS BY SK&F 105685 AND RELATED AZASPIRANES' * |
JOURNAL OF AUTOIMMUNITY vol. 6, no. 1, February 1993, pages 39 - 49 RABINOVITCH, A. ET AL 'PREVENTION OF DIABETES AND INDUCTION OF NON-SPECIFIC SUPPRESSOR CELL ACTIVITY IN THE BB RAT BY AN IMMUNOMODULATORY AZASPIRANE, SK&F 106610' * |
JOURNAL OF MEDICINAL CHEMISTRY vol. 33, no. 11, November 1990, pages 2963 - 2970 BADGER, A.M. ET AL 'ANTIARTHRITIC AND SUPPRESSOR CELL INDUCING ACTIVITY OF AZASPIRANES: STRUCTURE-FUNCTION RELATIONSHIPS OF A NOVEL CLASS OF IMMUNOMODULATORY AGENTS' * |
See also references of WO9204899A1 * |
Also Published As
Publication number | Publication date |
---|---|
WO1992004899A1 (en) | 1992-04-02 |
EP0550595A4 (en) | 1993-09-08 |
CA2092177A1 (en) | 1992-03-25 |
JPH06501468A (en) | 1994-02-17 |
AU652583B2 (en) | 1994-09-01 |
AU8631091A (en) | 1992-04-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP3348230B2 (en) | Use of dextormethorphan or dextororphan for the treatment of urinary incontinence | |
EP0236684B1 (en) | Galanthamine or analogues thereof for treating alzheimer's disease | |
Chanarin | Cobalamins and nitrous oxide: a review. | |
US4775660A (en) | Treatment of breast cancer by combination therapy | |
JP2001502659A (en) | Combination therapy for the treatment of erectile dysfunction | |
EP1655037B1 (en) | Serum cholesterol lowering agent or preventive or therapeutic agent for the treatment of atherosclerosis | |
AU618997B2 (en) | Pharmaceutical compositions with anti-cancer activity and method for the treatment of cancer | |
GB2170707A (en) | An immuno-regulator | |
CA2060474C (en) | Pharmaceutical use | |
AU652583B2 (en) | Methods | |
KR930007252B1 (en) | Pharmaceutical composition for treatment of depression | |
CA1120400A (en) | Method of treating hypertension and medicaments therefor | |
JPH04500670A (en) | Methods and compositions for treating viral infections | |
EP0650723A2 (en) | Novel pharmaceutical use of forskolin derivatives | |
AU701129B2 (en) | Progesterone analogs to reverse multidrug resistance | |
JPH05320049A (en) | Antiaromatase agent containing azole derivative | |
JP2545321B2 (en) | Smooth muscle contraction inhibitor | |
CA2167841A1 (en) | Method of inhibiting the production of human immunodeficiency viruses with substituted azaspiranes | |
CA2167842A1 (en) | Method of inhibiting the replication of human immunodeficiency viruses with substituted azaspiranes | |
EP0624089A1 (en) | Methods | |
CA2167843A1 (en) | Method of treating hiv with azaspiranes | |
AU5010193A (en) | Methods of treating psoriasis employing substituted azaspiranes | |
Tfelt-Hansen | Ergotamine headache | |
KR20000010933A (en) | Use of substituted azaspirane in the treatment of asthma | |
JPS6223725B2 (en) |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 19930325 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IT LI LU NL SE |
|
A4 | Supplementary search report drawn up and despatched |
Effective date: 19930720 |
|
AK | Designated contracting states |
Kind code of ref document: A4 Designated state(s): AT BE CH DE DK ES FR GB GR IT LI LU NL SE |
|
17Q | First examination report despatched |
Effective date: 19950911 |
|
RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: ANORMED INC |
|
GRAG | Despatch of communication of intention to grant |
Free format text: ORIGINAL CODE: EPIDOS AGRA |
|
RTI1 | Title (correction) |
Free format text: USE OF AZASPIRANES FOR THE MANUFACTURE OF A MEDIAMENT FOR THE TREATMENT OF DISEASES CAUSED BY EXCESSIVE GLUCOSE LEVELS |
|
RTI1 | Title (correction) |
Free format text: USE OF AZASPIRANES FOR THE MANUFACTURE OF A MEDIAMENT FOR THE TREATMENT OF DISEASES CAUSED BY EXCESSIVE GLUCOSE LEVELS |
|
RTI1 | Title (correction) |
Free format text: USE OF AZASPIRANES FOR THE MANUFACTURE OF A MEDIAMENT FOR THE TREATMENT OF DISEASES CAUSED BY EXCESSIVE GLUCOSE LEVELS |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION HAS BEEN REFUSED |
|
18R | Application refused |
Effective date: 20000101 |
|
REG | Reference to a national code |
Ref country code: HK Ref legal event code: WD Ref document number: 1012271 Country of ref document: HK |