WO1991006298A1 - New use of condensed quinoline compound - Google Patents
New use of condensed quinoline compound Download PDFInfo
- Publication number
- WO1991006298A1 WO1991006298A1 PCT/SE1990/000673 SE9000673W WO9106298A1 WO 1991006298 A1 WO1991006298 A1 WO 1991006298A1 SE 9000673 W SE9000673 W SE 9000673W WO 9106298 A1 WO9106298 A1 WO 9106298A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- compound
- treatment
- inflammatory
- dihydro
- phenyl
- Prior art date
Links
- DKSKDQANBXDJPK-UHFFFAOYSA-N CCc1cccc(N(CC2)N=C2N)c1 Chemical compound CCc1cccc(N(CC2)N=C2N)c1 DKSKDQANBXDJPK-UHFFFAOYSA-N 0.000 description 1
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
- A61K31/47—Quinolines; Isoquinolines
Definitions
- the present invention relates to a new method for the treat- ment of inflammatory and allergic diseases.
- Compound P is included in a group of 2-ary1-pyrazolo(4,3-c)-
- Compound P is an unexpected ⁇ ly active anti-inflammatory agent with a new and interesting type of pharmacological profile.
- Compound P has a novel usefulness which could not be anticipated from what was previously known about its biolo ⁇ gical properties. Accordingly the present invention provides a new method for the treatment of diseases such as
- Compound P may be admi ⁇ nistered orally, parenterally transdermally or topically in compositions, suitable for the desired way of administration and which are prepared by using conventional methods.
- Compound P or a pharmaceutically ac ⁇ ceptable alkali metal or acid addition salt thereof may be determined in accordance with the nature and severity of the condition and the weight of the subject- requiring treatment. It is believed that an amount of from 20 to 0,01 mg/kg and more preferably 0,1 mg to 5 mg/kg per day should be suffi ⁇ cient for effective treatment.
- Dexamethasone is a well-known adrenocortical steroid with an ⁇ ti-inflammatory activity which has the following structural formula:
- BW 755 C (4,5-dihydro-l-(3-(trifluoromethyl)-phenyl)-lH-pyra- zol-3-amine) is an experimental reference compound with anti-inflammatory activity. It has the following structural formula:
- BW 755 C The properties of BW 755 C are discussed by J.A. Salmon in Adv. in Drug Research 15 (1986) 112. The development of BW 755 C has been discontinued because of animal toxicity.
- mice Male CF/1 mice weighing approximately 25 g at the start of the experiment were used. On day 1 the abdomen of the mice was shaved. On day 1 and 2 the mice were sensitized by app ⁇ lying 25 ml of a 0,5 % solution of the allergenic compound 2,4-dinitro-fluorobenzene (DNFB) in a 4:1 acetone:olive oil mixture on the shaved area. The challenge response was produced on day 7 by applying 10 ml of the DNFB solution used above on the left ear.
- DNFB 2,4-dinitro-fluorobenzene
- the thickness of the ears was measured immediately before and 24 h after the challenge.
- the test compounds were suspended in a methocel solution.
- the methocel solution was prepared by dissolving 30 g of methocel 4000-HG, 45 g of sodium chloride and 25 g of kremo- for EL in 5 litres of water and the obtained solution was sterilized.
- the methocel solutions including the test com ⁇ pounds were administered 26 and 2 h before and 22 h after the challenge.
- the control group was treated with the metho ⁇ cel solution.
- the thickness of the ears is an expression of the inflamma ⁇ tory response.
- the inhibitory effect of the test compounds is expressed in per cent after comparison with the control groups. The resultas are found in Table 1.
- test compounds were administered suspended in a methocel solution (see Example 1).
- the animals in the control group were treated with the methocel solution.
- the thickness of the ears was measured immediately before and three hours after the application of the croton oil solution.
- a cream containing Compound P as the active ingredient is produced in the following way:
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- Health & Medical Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
Abstract
The invention concerns the use of 2,5-dihydro-2-phenyl-3H-pyrazolo(4,3-c)quinolin-3-one or its pharmaceutically acceptable alkali metal or acid addition salts for treating inflammatory and allergic diseases.
Description
New use of condensed quinoline compound
The present invention relates to a new method for the treat- ment of inflammatory and allergic diseases.
US patent No 4,312,870 discloses in Example 19 a method for the preparation of 2,5-dihydro-2-phenyl-3H-pyrazolo(4,3-c) quinolin-3-one, which is named Compound P hereinafter, and which has the structural formula I
Compound P is included in a group of 2-ary1-pyrazolo(4,3-c)-
-quinolin-3-ones which are disclosed in the above mentioned patent as psychoactive agents useful in the treatment of an¬ xiety or depression.
The pharmacological and related properties of Compound P are reviewed in Drugs of the Future 13 (2) (1988) 175 where the substance is classified as a benzodiazepine antagonist.
It has now been discovered that Compound P is an unexpected¬ ly active anti-inflammatory agent with a new and interesting type of pharmacological profile.
Thus Compound P has a novel usefulness which could not be anticipated from what was previously known about its biolo¬ gical properties.
Accordingly the present invention provides a new method for the treatment of diseases such as
- psoriasis - rheumatoid arthritis
- inflammatory bowel disease
- allergic skin diseases
and other active and chronic inflammatory and allergic conditions.
According to the present invention Compound P may be admi¬ nistered orally, parenterally transdermally or topically in compositions, suitable for the desired way of administration and which are prepared by using conventional methods.
An effective amount of Compound P or a pharmaceutically ac¬ ceptable alkali metal or acid addition salt thereof may be determined in accordance with the nature and severity of the condition and the weight of the subject- requiring treatment. It is believed that an amount of from 20 to 0,01 mg/kg and more preferably 0,1 mg to 5 mg/kg per day should be suffi¬ cient for effective treatment.
In the following Examples the anti-inflammatory properties of compound P are compared with dexamethasone and BW 755 C. Dexamethasone is a well-known adrenocortical steroid with an¬ ti-inflammatory activity which has the following structural formula:
Its properties are described in A. Goodman Gilman et. al. "Goodman and Gilman's The Pharmacological Basis of Therapeutics, 7th Ed., acmillans Publishing Company, New York 1985, p.1463". Chronic use of dexamethasone is often accompanied by unacceptable side-effects.
BW 755 C (4,5-dihydro-l-(3-(trifluoromethyl)-phenyl)-lH-pyra- zol-3-amine) is an experimental reference compound with anti-inflammatory activity. It has the following structural formula:
The properties of BW 755 C are discussed by J.A. Salmon in Adv. in Drug Research 15 (1986) 112. The development of BW 755 C has been discontinued because of animal toxicity.
Example 1
The effects of Compound P and of the known anti-inflammatory agents BW755C and dexamethasone were determined and compared using the following sensitization model.
Male CF/1 mice weighing approximately 25 g at the start of the experiment were used. On day 1 the abdomen of the mice was shaved. On day 1 and 2 the mice were sensitized by app¬ lying 25 ml of a 0,5 % solution of the allergenic compound 2,4-dinitro-fluorobenzene (DNFB) in a 4:1 acetone:olive oil mixture on the shaved area.
The challenge response was produced on day 7 by applying 10 ml of the DNFB solution used above on the left ear.
The thickness of the ears was measured immediately before and 24 h after the challenge.
The test compounds were suspended in a methocel solution. The methocel solution was prepared by dissolving 30 g of methocel 4000-HG, 45 g of sodium chloride and 25 g of kremo- for EL in 5 litres of water and the obtained solution was sterilized. The methocel solutions including the test com¬ pounds were administered 26 and 2 h before and 22 h after the challenge. The control group was treated with the metho¬ cel solution.
The thickness of the ears is an expression of the inflamma¬ tory response. The inhibitory effect of the test compounds is expressed in per cent after comparison with the control groups. The resultas are found in Table 1.
Table 1
* 4,5-dihydro-l-(3-(trifluoromethyl)-phenyl)-lH-pyrazol-3-amine
Example 2
The effects of Compound P and the known anti-inflammatory agents BW 755 C amd dexamethasone were determined and compared using the croton oil induced inflammation of the mouse ear.
Groups consisting of 10 male CF/1 mice weighting approximate¬ ly 25 g at the start of the experiment were used.
The test compounds were administered suspended in a methocel solution (see Example 1). The animals in the control group were treated with the methocel solution.
Two hours after the administration of the test compounds, 10 ml of a solution of croton oil in acetone (20 mg/ml) were applied on the innerside of one of the earlobes of each mouse.
The thickness of the ears was measured immediately before and three hours after the application of the croton oil solution.
The thickness of the ears in an expression of the inflamma¬ tory response to croton oil. The inhibitory effect of the test compounds is expressed in per cent after comparison with the control group. The results are found in Table 2.
Table 2
The effect on Compound P compared with known anti- inflammatory agents on the croton oil induced inflammation of the mouse ear
This example shows that Compound P inhibits the inflammatory reaction caused by the irritant substance croton oil.
Example 3
A cream containing Compound P as the active ingredient is produced in the following way:
Four grams of Compound P are dissolved in mixture of 380 g of Macrogol 3000 and 555 g Macrogol 400 and 61 g of distil¬ led water are added. The mixture so obtained is homogenized to a cream.
Claims
1. Use of 2,5-dihydro-2-phenyl-3H-pyrazolo(4,3-c)quinoline- 3-one or its pharmaceutically acceptable alkali metal or acid addition salts for the manufacture of a medicament for treatment of inflammatory and allergic disorders.
2. Use according to claim 1 for the treatment of psoriasis.
3. Use according to claim 1 for the treatment of rheumatoid arthritis.
4. Use according to claim 1 for the treatment of inflamma¬ tory bowel disease.
5. A method for treating inflammatory and allergic disor¬ ders comprising administering an effective amount of 2,5-dihydro-2-phenyl-3H-pyrazolo(4,3-c)quino-line3-one or its pharmaceutically acceptable alkali metal or acid ad- dition salts to a mammal suffering from said disorder.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE8903564-6 | 1989-10-26 | ||
SE8903564A SE8903564D0 (en) | 1989-10-26 | 1989-10-26 | NEW USE CONDENSED QUINOLINE COMPOUND |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1991006298A1 true WO1991006298A1 (en) | 1991-05-16 |
Family
ID=20377287
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/SE1990/000673 WO1991006298A1 (en) | 1989-10-26 | 1990-10-19 | New use of condensed quinoline compound |
Country Status (2)
Country | Link |
---|---|
SE (1) | SE8903564D0 (en) |
WO (1) | WO1991006298A1 (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5334595A (en) * | 1992-10-23 | 1994-08-02 | Sterling Winthrop Inc. | Pyrazoloquinolones as anticancer agents |
WO1997034893A1 (en) * | 1996-03-20 | 1997-09-25 | Astra Pharmaceuticals Ltd. | Pharmaceutically useful compounds |
WO2003004495A1 (en) * | 2001-07-04 | 2003-01-16 | Active Biotech Ab | Novel immunomodulating compounds |
US6642249B2 (en) | 2001-07-04 | 2003-11-04 | Active Biotech Ab | Immunomodulating compounds |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4312870A (en) * | 1979-06-21 | 1982-01-26 | Ciba-Geigy Corporation | Pyrazoloquinolines |
-
1989
- 1989-10-26 SE SE8903564A patent/SE8903564D0/en unknown
-
1990
- 1990-10-19 WO PCT/SE1990/000673 patent/WO1991006298A1/en unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4312870A (en) * | 1979-06-21 | 1982-01-26 | Ciba-Geigy Corporation | Pyrazoloquinolines |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5334595A (en) * | 1992-10-23 | 1994-08-02 | Sterling Winthrop Inc. | Pyrazoloquinolones as anticancer agents |
WO1997034893A1 (en) * | 1996-03-20 | 1997-09-25 | Astra Pharmaceuticals Ltd. | Pharmaceutically useful compounds |
WO2003004495A1 (en) * | 2001-07-04 | 2003-01-16 | Active Biotech Ab | Novel immunomodulating compounds |
US6642249B2 (en) | 2001-07-04 | 2003-11-04 | Active Biotech Ab | Immunomodulating compounds |
HRP20031055B1 (en) * | 2001-07-04 | 2008-01-31 | Active Biotech Ab | Novel immunomodulating compounds |
Also Published As
Publication number | Publication date |
---|---|
SE8903564D0 (en) | 1989-10-26 |
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