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Problems solved by technology
Since conventional hormone preparations or synthetic peptide preparations cannot be taken orally, their administration by injection is cumbersome and expensive compared to small molecule compounds
Method used
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Embodiment 1
[0081] Example 1. Synthesis of 5,6-dichloroindirubin-3'-methoxime (A3051)
[0082] ①Synthesis of intermediate 5',6'-dichloro-[2,3'-dihydroindolylidene]-2'3-dione
[0083]
[0084] 5,6-Dichloroisobutane (500mg, 2.32mmol) was added to a 250mL round bottom flask and dissolved in MeOH (92.80ml) and indoxyl acetate (405.48mg, 2.315mmol) and Sodium carbonate (Na 2 CO 3 ) (637.83mg, 6.02mmol) was stirred at 65°C for 12 hours. Termination of the reaction was checked using TLC (Rf = 0.4; ethyl acetate / hexane = 1 / 2 (v / v)), and the product was cooled until crystalline material formed in ice. When crystals formed, they were filtered off, the solvent was removed, the filtrate was discarded and the product was washed several times with solvent (ethanol / water=1 / 1 (v / v)). The product was filtered to dry in vacuum pump and used in the next step without further purification.
[0089] Example 2. Synthesis of 5-methoxyl indirubin-3'-oxime (A3334)
[0090] ① Synthesis of intermediate 5'-methoxy-[2,3'-dihydroindolinylidene]-2',3-dione
[0091]
[0092] 5-Methoxyisatin (1000 mg, 5.65 mmol) was added to a 250 ml round bottom flask and dissolved in MeOH (225 ml). Add indole acetate (989mg, 5.65mmol) and sodium carbonate (Na 2 CO 3 ) (1496mg, 14.11mmol) was stirred at 65°C for 12 hours. Termination of the reaction was checked using TLC (Rf = 0.4; ethyl acetate / hexane = 1 / 2 (v / v)), and the product was cooled until crystalline material formed in ice. After crystals formed, they were filtered off, the solvent was removed, the filtrate was discarded, and the product was washed several times with solvent (ethanol / water=1 / 1 (v / v)). The resulting water was filtered to dry in a vacuum pump and used in the next step without further purification.
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Abstract
A composition for promoting longitudinal bone growth, according to the present invention, promotes the proliferation of the chondrocytes and the differentiation of the osteoblasts and has effects of simultaneously increasing longitudinal bone length and thickness (bone density), and thus has an advantage of being widely prescribable to various age groups, thereby being usable as a pharmaceutical composition for promoting the growth of longitudinal bone length and thickness. An indirubin derivative according to the present invention has excellent prevention or treatment effects through oral administration and has an excellent competitive price unlike conventional hormone-based therapeutic agents. In addition, unlike conventional therapeutic agents, the pharmaceutical composition for preventing or treating bone diseases of the present invention is a stable compound, which is known to be substantially noncytotoxic to the human body, and is a material of which side effects have not been identified and which has excellent treatment effects for bone diseases and osteogenesis imperfecta.
Description
technical field [0001] The present invention relates to a composition comprising an indirubin derivative as an active ingredient for promoting bone length growth and / or bone thickness improvement, which is used for preventing or treating bone length growth disorder and / or bone density-related diseases, so Said composition comprises an indirubin derivative as an active ingredient. Background technique [0002] Bone is the hardest tissue constituting the human skeleton and has a large amount of bone matrix, which is present throughout the body and plays a key role. From infancy to adulthood, the long bones that make up our arms and legs grow in length and determine the height of our bodies. This process is initiated by chondrocytes in the growth plate of the bone and is important for growth during adolescence because the growth plate is limitedly open. Growth plates gradually close throughout adolescence, and through adulthood, bone growth no longer occurs, but bone still su...
Claims
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