RU98121401A - NEW ANALOGUES OF VITAMIN D - Google Patents

Claims (12)

1. The compound of the formula

where X represents hydrogen or hydroxy; R ¹ and R ² , which may be the same or different, are hydrogen or a C ₁ -C ₃ alkyl radical; or R ¹ and R ² taken together with a carbon atom having a group X can form a C ₃ -C ₆ -carbocyclic ring; R ³ means C ₁ -C ₃ -alkyl radical, aryl or aralkyl radical or YR ⁴ , where Y means radicals —CO — S—, —CS — O— or —CS — S— and R ⁴ means C ₁ -C ₃ -alkyl radical or aryl or aralkyl radical; Q represents (CH ₂ ) _n , n is 1-4; R ¹ , R ² and Q, independently, may optionally be substituted with one or more fluorine atoms. 2. A compound of formula I in accordance with claim 1, wherein Q is (CH ₂ ) _n , wherein n is 2 or 3, where X is hydroxy, R ¹ and R ² are methyl or ethyl, and R ³ is methyl or ethyl.  3. Diastereoisomer compounds according to any one of paragraphs. 1, 2 in pure form or a mixture of such diastereoisomers.  4. The diastereoisomer of a compound according to claim 3, having an “A” configuration at C-22.  5. The compound according to claim 1, which is: 1 (S), 3 (R) -dihydroxy-20 (R) - (1-methoxy-4-hydroxy-4-methyl-1-pentyl) -9,10 -seco-pregna-5 (Z), 7 (E), 10 (19) -trien; isomer A, or 1 (S), 3 (R) -dihydroxy-20 (R) - (1-ethoxy-4-hydroxy-4-methyl-1-pentyl) -9,10-seco-pregna-5 (Z ), 7 (E), 10 (19) -trien; isomer A. 6. A method of obtaining a compound of formula I according to claim 1, comprising (Z), 7 (E), 10 (19) -triene with an organometallic reagent R-Met-Hl or R-Met, in which Met represents a suitable metal, such as magnesium or lithium, Hl represents Cl, Br or I and R presents
Q-CR ¹ R ² -X ¹
where X ¹ represents H, HE or OR ⁵ , and R ⁵ represents an alcohol protective group, and R ¹ , R ² and Q have the above values, with the formation of a mixture of two C-22 epimers IIA and IIB

who share; c) alkylation of the compound of formula IIA or IIB of step a) to obtain the corresponding compound IIIA or IIIB, in which R and R ³ are as defined above, or is optionally acylated to obtain the corresponding compound III A or IIIB, where R ³ = YR ⁴ , moreover, Y and R ⁴ have the meanings defined in claim 1:

c) isomerizing the compound of formula IIIA or IIIB of stage b) to obtain the corresponding compound IVA or IVB using UV light in the presence of a triplet sensitizer, such as anthracene,

where R and R ³ are as defined above, d) removing the protecting group of the compound of formula IVA or IVB to obtain the corresponding compound of general formula I.  7. The method according to claim 6, wherein the steps c) and c) are carried out in the reverse order.  8. The method of claim 6, wherein steps c) and d) are carried out in the reverse order.  9. A pharmaceutical composition comprising an effective amount of one or more compounds of claims 1 to 5, together with pharmaceutically acceptable, non-toxic carriers and / or auxiliary agents.  10. The pharmaceutical composition according to claim 9 in unit dosage form containing from 0.1 ppm up to 0.1 wt.% from the mass of the dosage unit of the compounds of formula I.  11. A method of treating and / or preventing a number of disease states characterized by abnormal cell differentiation and / or cell proliferation, such as psoriasis and other keratinization disorders, HIV-associated dermatoses, wound healing, cancer, including skin cancer, and immune system diseases or disorders in the immune system, such as the host versus graft and graft versus host reactions and graft rejection, and autoimmune diseases such as discoid and systemic lupus erythematosus, diabetes mellitus and chronic dermatosis autoimmune type, such as scleroderma and the common vesicle, inflammatory diseases such as rheumatoid arthritis and asthma, as well as a number of other painful conditions, including hyperparathyroidism, especially secondary hyperparathyroidism associated with renal failure, impaired cognitive ability or senile dementia (Alzheimer's disease) and others neurodegenerative diseases, hypertension, acne, alopecia, skin atrophy, for example, steroid-induced skin atrophy, skin aging, including photo-aging, and stimulus Osteogenesis and treatment / prevention of osteoporosis and osteomalacia, including the administration to a patient in need, an effective amount of the pharmaceutical composition according to claim 9.  12. The use of compounds according to any one of paragraphs. 1-5 for the manufacture of a medicinal product for the treatment and prevention of a number of diseases characterized by abnormal cell differentiation and / or cell proliferation, such as psoriasis and other keratinization disorders, HIV-associated dermatoses, wound healing, cancer, including skin cancer, and immune disease diseases or a disorder in the immune system, such as the host versus graft and graft versus host reactions and graft rejection, autoimmune diseases such as discoid and systemic lupus erythematosus, diabetes mellitus t and chronic autoimmune dermatoses, such as scleroderma and the common vesicle, and inflammatory diseases such as rheumatoid arthritis and asthma, as well as a number of other painful conditions, including hyperparathyroidism, especially secondary hyperparathyroidism associated with renal failure, impaired cognitive ability or senile dementia ( Alzheimer's disease) and other neurodegenerative diseases, hypertension, acne, alopecia, skin atrophy, such as steroid-induced skin atrophy, skin aging, including I am photoaging, to stimulate osteogenesis and to treat / prevent osteoporosis and osteomalacia.