Patent EA-001060-B1 (EA)
Title: Diaromatic propynyl or dienyl compounds, intermediate compounds of pharmacological and cosmetic compositions and usage of cosmetic compositions
Inventor: BERNARDON JEAN-MICHEL
IPC: A61K8/41
Filed: 1997-03-05
Abstract: 1. A diaromatic compound of propinyl or dienyl, having the general formula (I):   in which: R1 is (I) radical -CH3,  (II) radical -CH2-O-R6, (III) radical -O-R6, (IV) radical -CO-R7, wherein R6 and R7 having the meanings given below,  -Ar is a radical corresponding to the following formula (a):   wherein R5 has the meanings given below, -X is a radical of formula:  or or  wherein R8 and R9 have the meanings given below, -R2 and R3, identical or different are: (I) hydrogen atom, (II) a linear or a branched alkyl having from 1 to 20 carbon atoms, (III) a radical -OR6, (IV) a radical -SR6, wherein R6 has the meaning given below, where R2 and R3 taken together, may form, with the adjacent aromatic ring, a 5- or 6-membered ring optionally substituted with methyl groups, and/or may be broken off with oxygen atom or sulphur atom, where R2 and R3 can not have at the same time meanings (I), (III) and (IV) determined above, R4 and R5, identical or different are hydrogen atom, halogen atom, a linear or a branched alkyl having from 1 to 20 carbon atoms, a radical -OR6, moreover, if R4 is a hydroxyl, then R2 and R3 form, with the adjacent aromatic ring, a 5- or 6-membered ring optionally substituted with methyl groups and/or may be broken off with oxygen atom or sulphur atom, R6 is a hydrogen atom, alkyl with 1-12 carbon atoms or a radical -COR10, wherein R10 is defined below, -R7 is: (a) a hydrogen atom, (b) an alkyl with 1-12 carbon atoms, (c) a radical of formula:   wherein R' and R" are defined below, (d) a radical -OR11, (e) a radical -NHOR6, where R11 is defined below,  -R8 and R9, taken separately, or simultaneously are a hydrogen or radical  -OR10, or one of them is a hydrogen atom and the other is an alkyl with 1-12 carbon atoms or, taken together, form the cycle -Y-(CH2)n-Y-, where , where Y is an oxygen or sulphur, n is 2 or 3, -R10 is alkyl with 1-12 carbon atoms , -R11 is a hydrogen atom, a linear or branched alkyl having from 1 to 20 carbon atoms, an alkenyl, a mono- or polyhydroxyalkyl with 3-6 carbon atoms and 2-5 hydroxy groups, aryl or aralkyl, such as benzyl or phenetyl, which are optionally substituted, or residue of sugar, or aminoacidic or peptide residue, -R' and R", which may be identical or different, are a hydrogen atom, an alkyl with 1-12 carbon atoms, a mono- or polyhydroxyalkyl with 3-6 carbon atoms, and 2-5 hydroxy groups, optionally substituted aryl, or residue of aminoacid or sugar, or taken together, form a heterocycle, and salts or optical or geometric isomers thereof. 2. Compounds of general formula (II):   wherein R1 and Ar have the same meanings, which are determined for general formula (I) according claim 1, and R'2 and R'4, identical or different, are a linear or branched alkyl having from 1 to 20 carbon atoms. 3. Compounds according to claim 1or 2, wherein said compounds are salts of alkali metal or alkaline earth metal, zinc, and organic amine. 4. Compounds according to claim 1, characterized in that taken separately or in mixture are the group of the following compounds: -4-[3-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-propynyl] benzoic acid,  -2-hydroxy-4-[3-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-propynyl] benzoic acid, -4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propynyl] benzoic acid, -2-hydroxy-4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propynyl] methylbenzoate, -2-hydroxy-4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propynyl]benzoic acid, -2-hydroxy-4-[3-(3-hydroxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propynyl]benzoic acid, -2-hydroxy-4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propynyl]benzenemethanol, -2-hydroxy-4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propynyl]diethanolamine benzoate, -2-hydroxy-4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propynyl]lithium benzoate, -4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-2-propynyl]benzoic acid, -2-hydroxy-4-[3-(4,4-dimethylthiochroman-6-yl)-1-propynyl]benzoic acid, -2-hydroxy-4-[3-(8,8-dimethyl-5,6,7,8-tetrahydro-2-naphthyl)-1-propynyl]benzoic acid, -2-hydroxy-4-[3-(5,5-dimethyl-5,6,7,8-tetrahydro-2-naphthyl)-1-propynyl]benzoic acid, 4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propynyl] ethylbenzoate, -4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propynyl]benzamide, N-ethyl-4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propynyl]benzamide, -Morpholide 4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propynyl]benzoic acid, N-(4-hydroxyphenyl)-4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propynyl]benzamide, -4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propynyl]benzaldehyde,  -4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propynyl]phenol, -[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propynyl]benzenemethanol, -4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propynyl]toluene, -4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propynyl]hexylbenzoate, N-hydroxy-4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propynyl]benzamide, N-hydroxy-2-hydroxy-4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propynyl]benzamide, -2-methyl-4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propynyl]benzoic acid, -3-methyl-4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propynyl]benzoic acid, -6-[3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)propa-1,2-dienyl]nicotinic acid, -4-[3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)propa-1,2-dienyl]benzoic acid, -2-hydroxy-4-[3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)propa-1,2-dienyl]benzoic acid, -2-hydroxy-4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-butynyl]benzoic acid,  -5-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propynyl]-2-pyridinecarboxylic acid, -4-[3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-1-propynyl]benzoic acid,  -2-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propynyl]-4-thiophenecarboxylic acid,  -2-[3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)-1-propynyl]-4-thiophenecarboxylic acid, -2-hydroxy-4-[3-(3-tert-butyl-4-methoxyphenyl)-1-propynyl]benzoic acid, -2-hydroxy-4-[3-(3-tert-butyl-4-hydroxyphenyl)-1-propynyl]benzoic acid. 5. Compounds according to claim 2, characterized in that taken separately or in mixture are in the group consisting of: -4-[3-(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadien-1-ylyden)-1-propynyl]benzoic acid, -2-hydroxy-4-[3-(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadien-1-ylyden)-1-propynyl]benzoic acid.  6. Compounds according to claims 1 or 2, characterized in that for them at least one or preferably all the following conditions are carried out: -R1 is a radical -CO-R7, -Ar is a radical of formula (a). 7. Compounds according to one of claims 1,3 or 6, characterized in that they correspond to the formula (I), described in claim 1, where R8 and R9, taken separately, either are hydrogen atoms or one of them is hydrogen atom and the other is an alkyl with 1-12 carbon atoms. 8. Usage of the compounds of formulas (I) or (II) according to one of preceding claims as a medicine. 9. Usage in accordance with claim 8, characterized in that a medicine for treating dermatological conditions, associated with keratinization, which are associated with differentiation and proliferation, in particular, common acne, juvenile, polymorphic acne, acne rosacea, cystic acne, acne conglobata, senile acne, as well as nodulocystic acne, for example, solar medication-related acne, or occupational acne; for treating other types of keratinization disorders, in particular, ichthyosis, ichthyosiform states, Darier's disease, palmoplantar keratoderma, leucoplasias and leucoplasiform states, cutaneous or mucous (buccal) lichen; for treating other dermatological conditions associated with keratinization disorders having an inflammatory and/or immunoallergic component and, in particular, different forms of psoriasis, skin, mucous or nails, and even psoriatic arthritis,or skin atopy, such as eczema, or respiratory atopy, and gingival hypertrophy; the compounds can be used for treating of different inflammatory conditions, which are not associated with keratinization disorders; for treating of dermal and epidermal proliferations, these of benign or malignant, which are of viral or non-viral origin, for example, common warts, flat warts, and verruciform epidermodysplasia, oral or florid papillomatoses, and proliferations induced by ultraviolet radiation, in particular, basocellular or spinocellular epithelioma; for treating of other dermal disorders, such as bullosis or collagen disorders; for treating of opthamological disorders, in particular, corneopathies; for renewal and prevention chronological or UV-induced aging of the skin, reducing pigmentation and actinic keratoses, or any pathologies associated with chronological and protein aging; for prophylactics and treating of stigmata of epidermal and/or dermal atrophy induced by local or systemic corticosteroids, and other forms of cutaneous atrophy; for prophylactics and treating of cicatrization disorders; promotion of cicatrization; for treating of disorders of sebaceous function, for example, hyperseborrhea acne or common seborrhea; for treating and prophylactics of cancerous or precancerous conditions; for treating several inflammatory conditions, such as arthritis; for treating of any viral common and dermal conditions, for example, syndrome Koposhi; for prophylactics and treating of alopecia; treating of dermatological or common diseases with immunological component; for treating of cardiovascular conditions, such as arteriosclerosis, and hypertension, and insulin-independent diabetes, and treating of skin disorders associated with UV radiation exposure. 10. A pharmacological composition, characterised in that it contains in pharmaceutically acceptable carrier, at least, one compound in accordance w