去异丁基环索奈德

简介制备生物活性靶点体外研究去异丁基环索奈德试剂级价格

去异丁基环索奈德

CAS号:161115-59-9
英文名:Desisobutyryl Ciclesonide
中文名:去异丁基环索奈德
CBNumber:CB62487016
分子式:C28H38O6
分子量:470.61
MOL File:161115-59-9.mol

去异丁基环索奈德化学性质

熔点 :129-132?C
沸点 :640.8±55.0 °C(Predicted)
密度 :1.28±0.1 g/cm3(Predicted)
储存条件 :-20°C Freezer
溶解度 :Chloroform (Slightly), Methanol (Slightly)
形态 :Solid
酸度系数(pKa) :12.87±0.10(Predicted)
颜色 :White to Off-White

去异丁基环索奈德性质、用途与生产工艺

简介环索奈德，16α，17α-22R-环己基亚甲基-11β-羟基-1，4-孕甾二烯-3，20-二酮-21-异丁酸酯，是新一代的吸入性非卤代酶糖皮质甾体，具有较高局部抗炎能力，能够有效缓解患者肺部和呼吸道的炎症。它是一种酯类前药，基本无口服的生物利用度，通过内源性酯酶而活化，对全身副作用和咽部副作用极低。
制备 (一）缩醛反应：16α，17α-22R，S-环己基亚甲基-11β-羟基-1，4-孕甾二烯-3，20-二酮-21-醋酸酯（R/S=99：10）反应瓶中加入10g11β，16α，17α-三羟基-1，4-孕甾二烯-3，20-二酮-21-醋酸酯，30ml异丙醇和30ml70%氢氟酸，搅拌溶解，控温至0±2℃，滴加10ml环己基甲醛，保温0±2℃反应2小时，薄层分析至无原料后，稀释于冰水中，过滤，干燥得到11.8g缩醛物(1)。（二）提纯1：16α，17α-22R，S-环己基亚甲基-11β-羟基-1，4-孕甾二烯-3，20-二酮-21-醋酸酯（R/S=99：1）反应瓶中加入缩醛物(1)20g，氯仿30ml，乙醇40ml，加热至55℃搅拌溶解，冷却至-5℃，析出大量白色晶状固体，过滤得15.8g化合物(2)。（三）水解反应：16α，17α-22R，S-环己基亚甲基-11β，21-二羟基-1，4-孕甾二烯-3，20-二酮（R/S=99：1，去异丁基环索奈德）反应瓶中加入30ml甲醇和30ml二氯甲烷，加入10g化合物(2)，通氮气，降温至0℃，于一小时内滴入20ml2%KOH/甲醇溶液，保温0-5℃反应2小时，薄层分析至无原料后，加入适量醋酸中和至PH=7，减压浓缩，甲醇中重结晶，得到7.5g水解物(3)去异丁基环索奈德。
生物活性 Desisobutyryl-ciclesonide 是 Ciclesonide 的活性代谢产物。Desisobutyryl-ciclesonide 对糖皮质激素受体 (glucocorticoid receptor) 具有亲和力。
靶点

Glucocorticoid receptor
体外研究

Ciclesonide, an inhaled corticosteroid with almost no affinity for the glucocorticoid receptor, is highly effective in downregulating in vitro pro-inflammatory activities of airway parenchymal cells when converted into the active metabolite Desisobutyryl-ciclesonide. Peripheral blood mononuclear cell proliferation to C. albicans is dose-dependently inhibited by 0.3-3.0 μM Ciclesonide and Desisobutyryl-ciclesonide but inhibition by Desisobutyryl-ciclesonide is higher. A significant proliferation to PhlP5 is observed only in cultures from atopic subjects: an effective downregulation is already detected at 0.03 μM Ciclesonide and 0.003 μM Desisobutyryl-ciclesonide (complete inhibition at 3 μM Ciclesonide and 0.03 μM Desisobutyryl-ciclesonide). 3 μM Ciclesonide and Desisobutyryl-ciclesonide reduce the PhlP5 -specific T-cell blast proliferation and interleukin 4-producing cell proportion. In PBMCs cultures from atopic patients, both Ciclesonide (CIC) and Desisobutyryl-ciclesonide (des-CIC) induce a dose-dependent downregulation of PhlP5 -induced proliferation. The effect is already significantat 0.03 μM Ciclesonide and at 0.003 μM Desisobutyryl-ciclesonide (p<0.001, each comparison),with an early complete inhibition observed at 3μM Ciclesonide and at 0.03 μM Desisobutyryl-ciclesonide. The inhibitory activity toward PhlP5 -induced PBMC proliferation is higher for Desisobutyryl-ciclesonide than for Ciclesonide at 0.003 μM (p<0.05), 0.03 μM (p<0.001) and 0.3 μM (p<0.05).