- 生物活性
Efaproxiral (RSR13) 是一种血红蛋白 (Hb) 合成变构调节剂, 能降低血红蛋白氧 (O2) 的结合亲和力，增强放射处理中缺氧肿瘤的氧合作用。
- 靶点
haemoglobin (Hb)
- 体外研究
Efaproxiral binds to only one pair of symmetry-related sites in the Hb central water cavity.
Efaproxiral readily crosses the red cell membrane in the presence of serum albumin solutions.
Efaproxiral is not inhibited from entering erythrocytes in the presence of an anion-channel blocking agent (DIDS).
- 体内研究
Efaproxiral (150 mg/kg, i.p.) increase tumor oxygenation，and increase the tumor growth inhibition of radiotherapy over 5 days of treatment.
Efaproxiral reduces hemoglobin-oxygen binding affinity, which facilitates oxygen release from hemoglobin into surrounding tissues and potentially increases the pO(2) of the tumors
Animal Model:
Female C3H/HEJ mice (18–20 g), with radiation-induced fibrosarcoma tumor (RIF-1) cells xenograft
Dosage:
150 mg/kg
Administration:
Intraperitoneal injection; prior to X Irradiation (4 Gy/day), for 5 days
Result:
Significantly increased tumor oxygenation by 8.4 to 43.4 mmHg within 5 days, with maximum increases at 22–31 minutes after treatment.
- 乙丙昔罗是一种合成的变构血红蛋白调节剂，由美国AllosThera-peutics公司首先研制。该化合物是首个放疗增效剂，可用于实体瘤(如脑瘤、乳腺癌脑转移、非小细胞性肺癌脑转移)、心肌梗死、脑中风等缺血、缺性疾病的治疗，可增强氧扩散到低氧肿瘤组织，提高标准放疗效果，是目前与血浆蛋白结合最弱、生理活性最强的变构血红蛋白调节剂。
医药
乙丙昔罗合成方法包括: 1) 4-羟基苯乙酸与过量二氯亚砜反应得4-羟基苯乙酰氯后，与 3，5-二甲基苯胺缩合得酰胺中间体( Ⅱ) ， 再与丙酮、氯仿在氢氧化钠存在下发生缩合反应得到目标产物; 2) 4-羟基苯乙酸与 3，5-二甲基苯胺在不同溶剂( 如二甲苯、1，3，5-三甲苯、五氯化磷、氮气或氩气) 的条件下，直接反应制得酰胺中间体( Ⅱ) ， 再按路线1得到目标产物; 3) 4-羟基苯乙酸与 3，5- 二甲基苯胺在羰基咪唑催化下反应得到中间体 ( Ⅱ) 后，与溴代丁酸乙酯缩合得到酯，最后经碱水解得到目标产物。
