(R)-(+)-WIN 55,212-2 甲磺酸盐
中文名称:
(R)-(+)-WIN 55,212-2 甲磺酸盐
中文同义词:
甲磺酸西地那非(酒溶西地那非);WIN552122 甲磺酸酯;(+)-【2,3-二氢-5-甲基-3-(4-吗啡啉甲基)吡咯[1,2,3-D]-1,4-苯并噁唑琳-6-】-1-萘基甲酮;(+)WIN 55212-2甲磺酸盐;(R)-(+)-WIN 55,212-2 甲磺酸盐;WIN 55212-2 甲磺酸盐;甲磺酸西地那非(Z);水溶性西地那非
英文名称:
WIN 55,212-2 MESYLATE
英文同义词:
(+)-WIN 55,212-2 mesylate - CAS 131543-23-2 - Calbiochem;CS-754;WIN552122;WIN-552122;R(+)-WIN 55,212-2 ,MESYLATE HIGH AFFINIT Y CANNABI;(R)-(+)-(2,3-Dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1.2.3-de]-1,4-benzoxazin-6-yl)-1-naphthalenylmethanonemesy;212-2Mesylate;WIN55;(R)-(+)-[2,3-Dihydro-5-methyl-3[(4-morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate salt
CAS号:
131543-23-2
分子式:
C28H30N2O6S
分子量:
522.61
EINECS号:
1592732-453-0
相关类别:
定制化学品;保健原料;其他生化试剂;原料药;医药原料;原料及中间体;保健减肥原料;Cannabinoid receptor;Cannabinoid;男性保健;男性保健原料;原料
Mol文件:
131543-23-2.mol
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
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)
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.
WGK Germany
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