A NEW CHEMICAL ENTITY (ENDIPALENE) IN THE TREATMENT OF PSORIASIS

Abstract: In the literature, a correlation between the inhibition of 5-lipooxygenase and anti-inflammatory and immunomodulatory activity sufficient to effectively treat psoriasis, is known. It seems that, in particular, the excellent results can be obtained with lonapalene (6-chloro-2,3-dimethoxynaphthalendioldiacetate). However, the clinical use of lonapalene has not been successful most likely due to the significant number of side effects. With these considerations, after various studies, we have identified a molecule which we have patented with the name of endipalene, which seems to guarantee notable therapeutic results without side effects.

Description: DESCRIPTION A NEW CHEMICAL ENTITY (ENDIPALENE) IN THE TREATMENT OF PSORIASIS TECHNICAL FIELD My invention relates to the field of molecules with two aromatic condensed rings (naphtalenic rings) characterized by a good activity against inflamma - tion through inhibitory actions in one or more pas- sages of the "fall" of the arachidonic acid. BACKGROUND ART From the beginning of the nineties in the medical literature lots of studies appeared about a molecule patented as lonapalene (drawnings, FIG 1) with a great power against inflammation of the skin. Lonapalene ( 6-chloro-2 , 3-dimethoxynaphtalendioldi- acetate) has a statistically significant reduction in the levels of material similar or identical to the chemoattractant arachidonate 5-lipooxygenase product, leukotriene B4 (Black A. K. , LAMP RD..Mailed AT..Cunningham FM.,Hofbauer M. , Greaves MW. ; PHAR- MACOLOGIC AND CLINICAL EFFECTS OF LONAPALENE -RS43- 179- A 5-LIPOOXYGENASE INHIBITOR IN PSORIASIS; JOUR NAL OF INVESTIGATIVE DERMATOLOGY 95 ( 1 ): 50-4 , 1990 jul) A wide variety of agents have been reported as 5-li pooxygenase inhibitors. The majority of the series appear to be lipophilic reducing agents, including phenols, partially saturated. Aromatics and compounds containing heteroatom-hetero atom bonds are the same. Many of these are not sele£ tive 5-LO inhibitors. In vivo sistemic activity for many of these has been in general, disappointing, probably because of poor bioavailability caused by lipophilicity and metabo - lie instability (oxidation and conjugation of pheno lie compounds). However, topically a number of agents have shown promise for skin inflammation, and best of all, lonapalene; (Batt DG. , 5-LIPOXYGENASE INHIBITORS AND THEIR ANTI-INFLAMMATORY ACTIVITIES, PROGRESS IN MEDICINAL CHEMISTRY, 29:1 - 63, 1992). Unfortunately, the clinical utilisation of lonapalene wasn't succesful, probably because of the remarkable side effects. Lots of attempts have been made to find other topical nonsteroidal antipsoriatic agents ana - logues of lonapalene, without any success ; (Venuti MC. , Loe BE., Jones GH. , Young GM. , TOPICAL NONSTEROIDAL AN: TIPSORIATIC AGENTS.2.2,3-ALKYLIDENEDIOXYNAPHTALENE ANA LOGUES OF LONAPALENE, JOURNAL OF MEDICINAL CHEMISTRY, 31(11) :2132-6, 1988 Nov.). (Jones GH. , Venuti MC. , YOUNG JM. , Murthy DV. , Loe BE., Simpson RA. , Berks AH., Spires DA. ,Malonej PJ.,Kruseman M. , et al., TOPICAL NON STEROIDAL ANTIPSORIATIC AGENTS .1.1 , 2 , 3 , 4 , -TETRA- OXYGENATED NAPHTALENE DERIVATIVES, JOURNAL OF MEDICINAL CHEMISTRY, 29(8) :1504-11, 1986 Aug.). DISCLOSURE OF INVENTION Considering what I reported before, my attention tur- ned to find out a molecule as efficacious as lonapale ne avoiding the negative side effects. After a first screening which led me to select molec_u les without halogens, a molecule has been found: 2,6 or 2,7 -dimethoxynaphtalene that I patented with the name of ENDIPALENE. Endipalene seems to have the same action mechanism of lonapalene excluding remarkable side effects. BRIEF DESCRIPTION OF DRAWNINGS The enclosed dra nings show the structural formulas of lonapalene (FIG. 1) and endipalene (FIG.2). BEST MODE FOR CARRYING OUT THE INVENTION I think that endipalene should be used topically, with a concentration between 1% or 2%. We need to continue studying in order to confirm the selective action mechanism (inhibitor of 5-LO) , to check skin absorption, pharmacokinetics , meta- boliεm. We should also confirm the absence of side effects and verify the results after long time. INDUSTRIAL APPLICABILITY If one considers that psoriasis afflicts 2% of the population in North Europe and an equal portion of the Caucasians in the USA and that more than 91% of patients with psoriasis have a relative or first or second degree afflicted with the same disease, it is evident that there is a significant possibility to get success in the field of, if research confirm the positive results.

Claims: CLAIMS Endipalene is an absolute novelty i n the treatment of psoriasis and inflammatory skin diseases. Compounds called naphtalenes , consisting of mono and bicyclic oxy and oxo compounds were subjected to clinical trials in various dermatoses of viral and supposed viral aetiology. Analogues agents or derivatives -(lonapalene) have been tested in psoriasis bioassay screens. Endipalene is a novelty in this field. Therefore my claims are: l)The employment, topically or in other way gived, of endipalene at any concentration and in any soj^ vent treating inflammatory skin deseases and part_i culary psoriasis. 2) The employment, topically or in other way gived, at any concentration and in any solvent, of endipa lene treating diseases in fields different from those illustrated in paragraph n° 1).

Inventors: ENDRICI GIORGIO, ENDRICI, GIORGIO
Applicants: ENDRICI GIORGIO, ENDRICI, GIORGIO
Application year: 1998
Main classification: A61K31
IPC codes: A61K31, A61P17