(R)-(+)-WIN 55,212-2 甲磺酸盐

概述生物活性靶点体外研究体内研究 (R)-(+)-WIN 55,212-2 甲磺酸盐试剂级价格

CAS号:131543-23-2
英文名:WIN 55,212-2 MESYLATE
中文名:(R)-(+)-WIN 55,212-2 甲磺酸盐
CBNumber:CB8335502
分子式:C28H30N2O6S
分子量:522.62
MOL File:131543-23-2.mol

(R)-(+)-WIN 55,212-2 甲磺酸盐化学性质

储存条件 :Store at +4°C
溶解度 :0.1 M HCl: 0.25 mg/mL
形态 :solid
颜色 :white to off-white
稳定性 :Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months.
InChIKey :FSGCSTPOPBJYSX-OZYVVJTJNA-N
SMILES :S(O)(=O)(=O)C.C(N1CCOCC1)[C@@H]1COC2=CC=CC3C(C(C4=CC=CC5=CC=CC=C45)=O)=C(C)N1C=32 |&1:12,r|

安全信息

WGK Germany :3

(R)-(+)-WIN 55,212-2 甲磺酸盐性质、用途与生产工艺

概述 (R)-(+)-WIN 55,212-2 甲磺酸盐是生产西地那非的原料，西地那非俗称伟哥，因治疗男性勃起功能障碍（ED）而闻名，其实最早是一种为治疗心血管疾病而研发的药物。目前不仅验证了西地那非对ED的治疗作用，而且也证明了西地那非对肺动脉高压等疾病也有治疗作用。西地那非通过抑制磷酸二酯酶5（PDE5），增加阴茎海绵体内环磷酸鸟苷（cGMP）水平，松弛海绵体平滑肌，血液流入海绵体，改善性刺激引起的勃起反应，药效可持续4小时。
生物活性 WIN 55,212-2 Mesylate ((R)-(+)-WIN 55212)是一种有效的 cannabinoid (CB) receptor 的激动剂，对人重组CB2和CB1的Ki值分别为3.3 nM和62.3 nM。 WIN 55,212-2 Mesylate 可调节谷氨酸的传递。
靶点
Target Value
CB2
(Cell-free assay) 3.3 nM(Ki)
CB1
(Cell-free assay) 62.3 nM(Ki)
体外研究

WIN 55,212-2 is more potent in CHO-CB2 cells than in CHO-CB1 cells by a factor of 6O. WIN 55,212-2 has no effect on arachidonic acid release in CHO-CB2 or control CHO cells. WIN 55,212-2 fails to stimulate any increase in intracellular Ca ²⁺ up to 10 μM. In primary cultures of rat cerebral cortex neurons, WIN 55,212-2 (0.01--100 nM) increases extracellular glutamate levels, displaying a bell-shaped concentration-response curve. The facilitatory effect of WIN 55,212-2 (1 nM) is fully counteracted by SR141716A (10 nM), by the replacement of the normal Krebs Ringer-bicarbonate buffer with a low Ca ²⁺ medium (0.2 mM) and by the IP(3) receptor antagonist xestospongin C (1 μM). WIN 55,212-2 evokes CGRP release from TG neurons in vitro (EC ₅₀ =26 μM) in a concentration- and calcium-dependent manner. WIN 55,212-2-2 neither inhibits capsaicin-evokes CGRP release nor does it inhibit forskolin-, isoproteranol- or prostaglandin E2-stimulated cAMP accumulation. WIN 55,212-2 significantly inhibits (EC ₅₀ =1.7 μM) 50 mm K ⁺ -evoked CGRP release by approximately 70%. WIN 55,212-2 inhibition of 50 mm K ⁺ -evoked CGRP release is not reversed by antagonists of cannabinoid type 1 (CB1) receptor, but is mimicks in magnitude and potency (EC ₅₀ =2.7 μM) by its cannabinoid-inactive enantiomer WIN 55,212-2-3.
体内研究

In the prefrontal cortex WIN 55,212-2 (0.1 and 1 mg/kg i.p.) increases dialysate glutamate levels from of the awake rat, while the lower (0.01 mg/kg) and the higher (2 mg/kg) doses are ineffective. Furthermore, the WIN 55,212-2 (0.1 mg/kg)- induced increase of dialysate glutamate levels is counteracted by pretreatment with the selective CB(1) receptor antagonist SR141716A (0.1 mg/kg, i.p.) and by the local perfusion with a low-calcium Ringer solution (Ca ²⁺ 0.2 mM). WIN 55,212-2 (0.5, 1, 3, 5, 10 and 15 mg/kg, i.p.) does not alter the seizure threshold at low doses, while higher doses of the drug significantly increases the threshold in a dose-dependent manner. The anticonvulsant effect of WIN 55,212-2, which is observed with doses as high as 5 mg/kg, can be observed with doses as low as 0.5 mg/kg in groups pre-treated with 20 mg/kg of pioglitazone.