生物活性
SYN115 is a novel, selective adenosine A(2A) receptor antagonist. The selective adenosine A(2A) receptor antagonists have been proposed as therapeutic tools for dopaminergically-relevant diseases. Adenosine A(2a) receptor antagonists reduce symptom severity in Parkinson disease (PD) and animal models. SYN115 produced a highly significant decrease in thalamic CBF, consistent with reduced pallidothalamic inhibition via the indirect pathway. Similar decreases occurred in cortical regions whose activity decreases with increased alertness and externally focused attention, consistent with decreased self-reported sleepiness on SYN115. In cocaine-dependent subjects, SYN115 may produce stimulant-like effects through a unique mechanism of action. We conclude that SYN115 enters the brain and exerts dose-dependent regional effects, the most prominent of these effects is consistent with deactivation of the indirect pathway as predicted by preclinical studies.
化学数据
| 分子量 | 406.5 |
| 分子式 | C19H26N4O4S |
| CAS号 | 870070-55-6 |
| 纯度 | >98% |
| 溶解性（25°C） | DMSO 10 mM |
| 储存和运输条件 | 固体粉末： -20°C 冷藏长期储存
常温运输及临时存放 |
实验操作 来自于公开的文献，仅供相同实验参考（如实验材料、目的不同，请参考其他文献）
| 细胞实验 |
|---|
| 细胞系 | CHO cells |
| 方法 | A1 and A2B adenosine receptor functional assay
CHO cells, expressing recombinant human ARs, were harvested by trypsinization. After centrifugation and re-suspension in medium, cells (~30,000) were plated in 24-well plates in 0.5 mL of medium. After 24 h, the medium was removed, and the cells were incubated at 37℃ for 15 min with 0.5 mL of Dulbecco's Modified Eagle Medium (DMEM) in the presence of adenosine deaminase (ADA) (1 U/mL) and the phosphodiesterase inhibitor Ro20-1724 (20 mM). The pharmacological profile of the compounds towards A2B ARs was evaluated by assessing cAMP accumulation in the absence or presence of the agonist NECA (100 nM). The antagonist profile of the compounds towards A1 ARs was evaluated by assessing their ability to counteract NECA-mediated inhibition of cAMP accumulation in the presence of 1 mM forskolin, as non-selective adenylate cyclase (AC) activator. Cells were incubated in the reaction medium (15 min at 37℃) with different concentrations of target compounds (0.1 nM~1 mM) and then were treated with the agonist. Following incubation, the reaction was terminated by the removal of the medium and the addition of 0.4 N HCl. After 30 min, lysates were neutralized with 4 N KOH, and the suspension was centrifuged at 800 g for 5 min. For the determination of cAMP production, bovine adrenal cAMP binding protein was incubated with [3H]cAMP (2 nM) and 50 ml of cell lysate or cAMP standard (0~160 pmol) at 0℃for 150 min in a total volume of 300 ml. Bound radioactivity was separated by rapid filtration through GF/C glass fiber filters and washed twice with 4 mL 50 mM TriseHCl, pH 7.4. The radioactivity was measured by liquid scintillation spectrometry. |
| 浓度 | 0~1μM |
| 处理时间 | 15 min |
| 动物实验 |
|---|
| 动物模型 | male Swiss albino mice(23~25 g) |
| 配制 | isotonic (NaCl 0.9%) saline solution |
| 剂量 | 3, 10 and 30mg/kg was given immediately after punishment |
| 给药处理 | i.p. |
不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）
| 小鼠 | 大鼠 | 兔 | 豚鼠 | 仓鼠 | 狗 |
| 重量 (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| 体表面积 (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km系数 | 3 | 6 | 12 | 8 | 5 | 20 |
| 动物 A (mg/kg) = 动物 B (mg/kg) × | 动物 B的Km系数 |
| 动物 A的Km系数 |
例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。
储备液配制
以下数据基于产品分子量，对于特殊产品，请参照COA中的储备液配制条件和说明进行操作。
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.46 mL | 12.3001 mL | 24.6002 mL |
| 5 mM | 0.492 mL | 2.46 mL | 4.92 mL |
| 10 mM | 0.246 mL | 1.23 mL | 2.46 mL |
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