Patent EA-001216-B1 (EA)
Title: Bicyclic aromatic compounds, pharmaceutical and cosmetic composition based thereof, and use of the cosmetic composition
Inventor: BERNARDON JEAN-MICHEL
IPC: A61K31/435
Filed: 1997-03-05
Abstract: 1. Biaromatic compounds of propinyl of general formula (1):   wherein: -R1 is (1) a radical -CH3 (II) is a radical -CH2-O-R5  (III) is a radical -CO-R6 wherein R5 and R6 have meanings, determined below, -Ar is a radical, selected from radicals of the formulas (a)-(e):    wherein R5 and R7 have meanings, determined below, -X is a radical of the formula:    wherein R8  and R9 have meanings, determined below, -R2 and R3, same or different, represent: (I) a hydrogen atom, (II) alkyl, having at least, 3 carbon atoms, from which carbon connected with phenyl radical, at least is substituted with 2 carbon atoms, (III) a radical -OR5,  (IV) a radical -SR5,  wherein R5 has the meaning, determined below, and R2 and R3 together can form with adjacent aromatic cycle a cycle with 5 or 6 sections, which can be substituted  with methyl groups and/or can be interrupted  by atom of oxygen or sulpfur, and R2 and R3  can not simultaneously have the above mentioned meanings (I), (III) and (IV),  -R4 and R7, same or different, represent  a hydrogen atom, a halogen atom, a linear or branched alkyl, having 1-20 carbon atoms, a radical -OR5,  -R5 is a hydrogen, a lower alkyl or a radical -COR10, wherein R10 have the meanings, determined above, -R6 is: (a) hydrogen, (b) lower alkyl, (c) radical of formula:   wherein R' and R" have meanings, determined below, (d) a radical -OR11,  wherein R11 has the meaning, determined below, -R8 and R9, same or different, are hydrogen or lower alkyl, -R10 is lower alkyl, -R11 is hydrogen, linear or branched alkyl, having 1-20 carbon atoms, alkenyl mono- or polyhydroxyalkyl, aryl or aralkyl, which can be substituted with either saccharide residue, or amino acid residue, or peptide, -R' and R", same or different, are hydrogen, lower alkyl, mono- or polyhydroxyalkyl, aryl, which can be substituted either with amino acid residue or saccharide, or together form heterocycle, and salts thereof and optical and geometrical isomers. 2. The compounds as claimed in claim 1, characterised in that they are present as an alkaline or alkali earth metal salts, or zinc or organic amine. 3. The compounds as claimed in claim 1, characterised in that they represent independently or in mixture the group of compounds: -5-(3-tert-butyl-4-methoxyphenyl)-2-thiopheneacrylic acid, -5-(3-tert-butyl-4-methoxyphenyl)-2-thiophenepropiolic acid,  -2-(3-tert-butyl-4-methoxyphenyl)-4-thiopheneacrylic acid,  -4-(3-tert-butyl-4-methoxyphenyl)-2-thiopheneacrylic acid,  -5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)-2-thiopheneacrylic acid, -4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)-2-thiopheneacrylic acid, -4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphtyl)-2-thiopheneacrylic acid, -5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)-2-thiophenepropiolic acid, -3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)phenylpropiolic acid, N-methyl-4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphtyl)-2-pyrroleacrylic acid, -3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphtyl)phenylacrylic acid, N-methyl-4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)-2-pyrroleacrylic acid, -4-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)-2-pyrroleacrylic acid, -3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)phenylacrylic acid, -3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphtyl)phenylpropiolic acid, -2-methoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)phenylacrylic acid, -2-propyloxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)phenylacrylic acid, -2-heptyloxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)phenylacrylic acid, -2-methoxymethoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)phenylacrylic acid, -2-hydroxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)phenylacrylic acid, -3-(3-methoxy-5,6,7,8-tetrahydro-5, 5,8,8-tetramethyl-2-naphtyl)phenylacrylic acid, -3-(3-propyloxy-5,6,7,8-tetrahydro-5, 5,8,8-tetramethyl-2-naphtyl)phenylacrylic acid, -3-(3-heptyloxy-5,6,7,8-tetrahydro-5, 5,8,8-tetramethyl-2-naphtyl)phenylacrylic acid, -3-(3-methoxymethoxy-5,6,7,8-tetrahydro-5, 5,8,8-tetramethyl-2-naphtyl)phenylacrylic acid, -3-(3-hydroxy-5,6,7,8-tetrahydro-5, 5,8,8-tetramethyl-2-naphtyl)phenylacrylic acid, -3-(4,4,7-trimethylthiochroman-6-yl)phenylacrylic acid, -N-ethyl-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)phenylacrylic acid, -N-4(hydroxyphenyl)-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)phenylacrylamide acid, -morpholide-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)phenylacrylic acid, -3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)phenylethylacrylate acid, -3-[3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)phenyl]but-2-enic acid, -4-methoxymethoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)phenylacrylic acid, -4-hydroxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)phenylacrylic acid, -4-methoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)phenylacrylic acid, -4-propyloxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)phenylacrylic acid, -4-heptyloxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)phenylacrylic acid, -3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)phenyl acrolein acid, -3-[3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)phenylnyl]prop-2-ene-1-ol, -Cis-3-[3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)phenyl]but-2-enic acid, -Cis-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)phenylacrylic acid, -5-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)-3-pyridineacrylic acid, -3-(3-butyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphtyl)phenylacrylic acid, -6-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphtyl)-2-pyridineacrylic acid. 4. The compounds as claimed in claim 1, characterised in that at least one, and preferably all the following conditions are fulfilled for them: -R1 is a radical -CO-R6, -Ar represents radicals of the formula (a) or (d), -X is a radical   -R2 and R3 together form with adjacent aromatic cycle a cycle with 5 or 6 sections, which can be substituted  with methyl groups and/or can be interrupted  by atom of oxygen or sulpfur. 5. The application of the compounds of formula (1) as a medicine. 6. The application according to claim 5 as a medicine for treating of dermatological diseases,  connected with keratinization disorders, caused by differentiation and proliferation, in particular, for treating acne vulgaris,  common,  polymorphic, rosacea, cystic, conglobata, senile, as well as secondary acne, caused by solar, medicamental influence, or having professional nature, for treating the other types of keratinization disorders, in particular, ichthyosis, ichthyosis-like conditions, Darier`s disease, palmo-plantar keratodermias, leukoplakias and leukoplakia-like conditions, cutaneous or mucosal (buccal) lichen; for treating other dermatological diseases, connected with keratinization disorders with inflammatory and/or immuno-allergic component and, in particular, all forms of psoriasis, cutis, mucosal or nails, and  psoriatic arthritis, or cutanic atopy such as eczema, or respiratory atopy, as well as hypertrophy of gingivas; the compounds also can be used for treating of some inflammatory processes, which are not connected with keratinization disorders; for treating of dermal or epidermic proliferations, benign and malignant, of virus and unvirus origin, for example, common warts, plane warts and warty epidermodysplasias, oral or florid papillomatosis, and proliferations, which can be caused by ultra-violet rays, in particular, basocellular and spinocellular epitheliomas; for treating other dermatological disorders, such as vesical dermatosis and collagenosis, for treating of several ophthalmologic diseases, in particular, corneopathies; for regeneration  or prevention of skin aging, both caused by age and luminous influence, as well as for reduction of pigmentation and albuminous keratosises, or any pathologies, associated with aging or albuminous aging; for prophylaxis or treating characters of epidermic and/or dermal atrophy, caused by external or systemic corticosteroids, or other forms of cutaneous atrophy; for prophylaxis or treating of cicatrization infractions or for adhesion of cicatrixes, for treating of sebaceous glands functioning disorders, for example, hyperseborrhea acne or common seborrhea, for treating and prophylaxis of cancerous and precancerous conditions; for treating of several inflammatory processes, such as arthritis; for treating of any virus general or cutaneous diseases, for example, Kaposi`s syndrome; for prophylaxis or treating of alopecia; for treating of dermatologic or general diseases with immunologic component; for treating of cardiovascular system diseases, such as arteriosclerosis or hypertension, and also immuno-independent diabetes, for treating of cutaneous diseases, caused by ultra-violet irradiation. 7. The pharmaceutical composition, characterised in that it contains in pharmaceutically acceptable carrier at least one compound according to one of claims 1-4. 8. The composition according to claim 7, characterised in that concentration of compound(s) according to one of claims 1-4 comprises from 0,001 % to 5 % wt of total weight of the composition. 9. The cosmetic composition, characterised in that it contains in cosmetically acceptable carrier at least one compound according to one of claims 1-4. 10. The composition according to claim 9, characterised in that concentration of compound(s) according to one of claims 1-4 comprises from 0,001 % to 3 % wt of total weight of the composition. 11. The application of the cosmetic composition according to one of claims 9 or 10 for body or hair hygiene.