EP0559728A1 - Aldehydes aromatiques et leurs derives et compositions pharmaceutiques utiles pour le traitement des maladies de la peau et de l'arthrite - Google Patents
Aldehydes aromatiques et leurs derives et compositions pharmaceutiques utiles pour le traitement des maladies de la peau et de l'arthriteInfo
- Publication number
- EP0559728A1 EP0559728A1 EP92900278A EP92900278A EP0559728A1 EP 0559728 A1 EP0559728 A1 EP 0559728A1 EP 92900278 A EP92900278 A EP 92900278A EP 92900278 A EP92900278 A EP 92900278A EP 0559728 A1 EP0559728 A1 EP 0559728A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- atoms
- treatment
- cells
- formula
- compounds
- 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.)
- Withdrawn
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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
-
- 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
- A61K31/11—Aldehydes
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P37/08—Antiallergic agents
Definitions
- compositions thereof useful for the treatment of skin are compositions thereof useful for the treatment of skin
- Present invention concern aromatic aldehydes and derivatives thereof, which are useful for the treatment of diseases which arise due to an elevated cellular proliferation (i.e. the rapid and repeated reproduction by cell division), such as psoriasis, inflammatory diseases, rheumatic diseases and allergic dermatologic reactions.
- Psoriasis for example, is a dermatologic disease which is characterized by rapid turnover of the epidermis.
- patients suffering from psoriasis may also suffer from autoimmune and rheumatic diseases, such as for instance lupus and arthritis.
- psoriasis is treated with hydrocortison derivatives, ditranole, tar salve or, in serious cases, with immuno-depressants such as cytostatica, cyclosporins or the like. All these treatments give rise to unwanted secondary effects.
- the compounds according to present invention are aromatic benzaldehydes or derivatives thereof of the following formula (I):
- Y is H or D
- X 1 and X 2 may be the same or different and may be OR
- R, R 1 and R 2 may be H or an alkyl of 1-5
- Ar is phenyl which may be unsubstituted or substituted in one or several positions by one or more of the following substituents which may be alkyl with 1-5 C-atoms, cycloalkyl of 3-6 C-atoms, halogen, nitro, amino, monoalkylamino or dialkylamino, wherein the alkylgroups have 1-5 C- atoms, OR wherein R may be H or an alkylgroup of 1-5C-atoms; or pharmaceutically acceptable salts thereof.
- alkyl groups herein may be straight-chained or branched, and especially preferred are methyl, ethyl, propyl and t- butyl.
- the halogens may be any of chlorine, bromine, fluorine and iodine.
- the pharmaceutically acceptable salts may be alkali metal salts, such as sodium salts, earth alkali metal salts, such as magnesium or calsium salts, ammoniumsalts, salts with organic aminobases or the like.
- Some of the compounds according to present invention are known as anticancer agents among other from EP215395,
- J63264411, J88009490, J55069510 and EP283139 J63264411, J88009490, J55069510 and EP283139.
- the compounds of formula I may be used for the treatment of diseases such as psoriasis, inflammatory diseases, rheumatic diseases and allergic dermatologic reactions.
- Dermatologic abnormalities such as psoriasis are often characterized by rapid turnover of the epidermis. While normal skin produces ca. 1250 new cells/day/cm 2 of skin consisting of about 27,000 cells, psoriatic skin produces 35,000 new cells/day/cm 2 from 52,000 cells. The cells involved in these diseases are however "normal" cells reproducing rapidly and repeatedly by cell division. While the cell cycle of normal skin cells is approximately 311 hours, this progression through the division cycle is reduced to about 10 to 36 hours for psoriatic skin.
- diseases which may be treated by the compounds of formula I are rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus (SLE), discoid lupus erythematosus (DLE), acne, Bechterew's arthritis, systemic seleroderma and seborrhea.
- Human cells of the established line NHIK 3025 originating from a cervical carcinoma in situ (Nordbye, K. and Oftebro, R., Exp. Cell Res., 58: 458, 1969), Oftebro, R. and Nordbye, K., Exp. Cell Res., 58: 459-460, 1969) were cultivated in medium E2a (Puck et al., J. Exp. Med., 106: 145-165, 1957) supplemented with 20% human (prepared at the laboratory) and 10% horse serum (Grand Island Biological Co.).
- the cells are routinely grown as monolayers in tissue culture flasks. The cells do not move around after they have attached, a quality which enables us to observe the same cells in an inverted microscope for several cell generations.
- the cells were kept in continuous exponential growth by frequent reculturing, i.e. every second and third day, and were obtained by repeated selection of mitotic cells
- the NHIK 3025 cells have a medium cell-cycle time of ⁇ 18 hr, with median G 1 , S 1 and G 2 durations of ⁇ 7, ⁇ 8 and ⁇ 2.5 hr, respectively.
- Zilascorb ( 2 H) was given in the G1- to early S-phases of the cell cycle. Thereafter the time of cell division was recorded.
- the data of table 3 should be evaluated on basis of those of table 1 shoving that 1 mM Zilascorb ( 2 H) reduces protein synthesis to 1.73 %/h from 3.68 %/h which was the protein synthesis in the control. Since NHIK 3025 cells usually have a protein degradation just above 1 %/h, net protein accumulation is not more than 0.7 %/h in the treated cells during treatment. Thus, during treatment the protein doubl ing time is
- the compounds may according to the present invention be administrered in any pharmaceutical formulation suitable for topical or systemic therapy.
- the pharmaceutical preparations may be administrered enterally, parenterally or topically.
- the compounds of formula I may be formulated e.g. as soft or hard gelatine capsules, tablets, granules, grains or powders, dragees, syrups, suspensions, solutions or suppositories.
- the compounds of formula I When administrered topically the compounds of formula I may be formulated as a lotion, salve, ointment, cream, gel, tincture, spray, lotion or the like containing the compounds of formula I in admixture with non-toxic, inert, solid or liquid carriers which are usual in topical preparations. It is especially suitable to use a formulation which protects the active ingredient against air, water and the like.
- the preparations can contain inert or pharmacodynamically active additives. Tablets or granulates e.g. can contain a series of binding agents, filler materials, carrier substances or diluents. Liquid preparations may be present, for example, in the form of a sterile solution. Capsules can contain a filler material or thickening agent in addition to the active ingredient. Furthermore, flavour-improving additives as well as the substances usually used as preserving, stabilizing, moisture-retaining and emulsifying agents, salts for varying the osmotic pressure, buffers and other additives may also be present.
- the dosages in which the preparations are administered can vary according to the mode of use and the route of use, as well as to the requirements of the patient.
- a daily dosage for a systemic therapy for an adult average patient of 70 kg body weight will be about 0.1-50 mg/kg/day preferably 1-15 mg/kg/day.
- the suitable salve or ointment can contain from 0.1-20% by weight of the active ingredient, especially 1-5%.
- the proportion of active ingredient in the pharmaceutical composition will vary depending upon the type of preparation, but may generally be within the range of approximately 0.1 to 20% by weight for oral administration and for absorption through mucous membranes, and about 0.01 to 10% by weight for parenteral administration.
- the pharmaceutical preparation of the compound of formula I can contain an antioxidant, e.r. tocopherol, N-methyl-tocopheramine, butylated hydroxyanisole, ascorbic acid or butylated hydroxytoluene.
- an antioxidant e.r. tocopherol, N-methyl-tocopheramine, butylated hydroxyanisole, ascorbic acid or butylated hydroxytoluene.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Composés répondant à la formule (I) et servant au traitement des cellules qui présentent une prolifération cellulaire anormalement élevée susceptible d'entraîner des maladies telles que le psoriasis, les maladies inflammatoires, les maladies rhumatismales et les réactions dermatologiques allergiques.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9026080 | 1990-11-30 | ||
GB909026080A GB9026080D0 (en) | 1990-11-30 | 1990-11-30 | Pharmaceutical compositions |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0559728A1 true EP0559728A1 (fr) | 1993-09-15 |
Family
ID=10686268
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP92900278A Withdrawn EP0559728A1 (fr) | 1990-11-30 | 1991-11-25 | Aldehydes aromatiques et leurs derives et compositions pharmaceutiques utiles pour le traitement des maladies de la peau et de l'arthrite |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP0559728A1 (fr) |
JP (1) | JPH06503084A (fr) |
AU (1) | AU9035691A (fr) |
CA (1) | CA2095334A1 (fr) |
GB (1) | GB9026080D0 (fr) |
WO (1) | WO1992009276A1 (fr) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NO309815B1 (no) * | 1999-07-05 | 2001-04-02 | Norsk Hydro As | Derivater av 5-nitrofurfural |
CN102973417A (zh) * | 2001-11-16 | 2013-03-20 | 斯美凯有限公司 | 含有携带含氧基团的芳族醛的药物与化妆品组合物 |
US8246969B2 (en) | 2001-11-16 | 2012-08-21 | Skinmedica, Inc. | Compositions containing aromatic aldehydes and their use in treatments |
AU2004241107A1 (en) * | 2003-05-15 | 2004-12-02 | Cutanix Corporation | Compositions containing a combination of a pharmaceutical agent or a cosmetic agent and an oxy group-bearing aromatic aldehyde |
CA2823647C (fr) | 2011-01-07 | 2016-07-19 | Allergan, Inc. | Compositions comprenant des benzaldehydes substitues et leur utilisation pour eclaircir la peau ou traiter des troubles d'hyperpigmenation et d'hypermelanose |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6256423A (ja) * | 1985-09-06 | 1987-03-12 | Kaken Pharmaceut Co Ltd | 悪液質治療改善剤 |
US4874780A (en) * | 1987-03-11 | 1989-10-17 | Norsk Hydro A.S. | Anticancer compounds |
-
1990
- 1990-11-30 GB GB909026080A patent/GB9026080D0/en active Pending
-
1991
- 1991-11-25 CA CA002095334A patent/CA2095334A1/fr not_active Abandoned
- 1991-11-25 WO PCT/NO1991/000147 patent/WO1992009276A1/fr not_active Application Discontinuation
- 1991-11-25 AU AU90356/91A patent/AU9035691A/en not_active Abandoned
- 1991-11-25 EP EP92900278A patent/EP0559728A1/fr not_active Withdrawn
- 1991-11-25 JP JP4500554A patent/JPH06503084A/ja active Pending
Non-Patent Citations (1)
Title |
---|
See references of WO9209276A1 * |
Also Published As
Publication number | Publication date |
---|---|
AU9035691A (en) | 1992-06-25 |
JPH06503084A (ja) | 1994-04-07 |
GB9026080D0 (en) | 1991-01-16 |
WO1992009276A1 (fr) | 1992-06-11 |
CA2095334A1 (fr) | 1992-05-31 |
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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: 19930503 |
|
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 |
|
17Q | First examination report despatched |
Effective date: 19931207 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 19940419 |