利伐普坦

概述用途生物活性靶点体外研究体内研究利伐普坦试剂级价格

利伐普坦

CAS号:168079-32-1
英文名:LIXIVAPTAN
中文名:利伐普坦
CBNumber:CB22446529
分子式:C27H21ClFN3O2
分子量:473.93
MOL File:168079-32-1.mol

利伐普坦化学性质

熔点 :>114°C (dec.)
沸点 :626.5±55.0 °C(Predicted)
密度 :1.32
储存条件 :Sealed in dry,Room Temperature
溶解度 :DMSO: soluble20mg/mL, clear
形态 :powder
酸度系数(pKa) :11.86±0.70(Predicted)
颜色 :white to beige
InChIKey :PPHTXRNHTVLQED-UHFFFAOYSA-N

安全信息

WGK Germany :3

利伐普坦性质、用途与生产工艺

概述利希普坦（Lixivaptan，1）是由美国惠氏（wyeth）公司研发的一种非肽类口服选择性精氨酸加压素V2受体拮抗剂，化学名为N-[3-氯-4-(10,11-二氢-5H- 吡咯并[2,1-c][1,4]苯并二氮杂卓-10-基羰基)苯基]-5-氟-2-甲基苯甲酰胺。
用途利希普坦在用于治疗充血性心力衰竭（CHF）、肝硬化并发低钠血症和抗利尿激素分泌失调综合征（SIADH）病人时，其在提高自由水清除率的同时并不影响肾钠的排出，也不会激活神经内分泌系统，并具有较高的安全性和耐受性。
生物活性 Lixivaptan (VPA-985, WAY-VPA 985) 是具有口服活性，选择性的 vasopressin receptor V2 拮抗剂，对人和大鼠的 IC50 值分别为1.2 和 2.3 nM。
靶点

IC50: 1.2 nM (human V2), 2.3 nM (rat V2)
体外研究

Lixivaptan displays competitive antagonist activity at V2 receptors.
体内研究

In conscious dogs, water-loaded with 30 mL/kg (po) and arginine vasopressin (AVP)-treated (0.4 µg/kg in oil, sc), lixivaptan (1, 3, and 10 mg/kg po) increases U _vol over the AVP-treated vehicle group by 438, 1018, and 1133%, respectively, while U _osm decreases from 1222 mOsm/kg (water-loaded and AVP treated vehicle) to 307, 221, and 175 mOsm/kg, respectively. In homozygous Brattleboro rats lacking AVP, lixivaptan at 10 mg/kg po (i.e., 10 times the dose producing V2 antagonist activity) b.i.d. for 5 days, shows a sustained antagonist action without evidence of agonist effects. In a randomized double-blind placebo-controlled ascending single dose study, patients (deprived of fluids overnight before dosing) are dosed orally with 30, 75, or 150 mg of lixivaptan. All three doses increase urine flow and serum sodium concentrations and produced significant dose-related decreases in urinary osmolality. Phase II clinical trials in patients with congestive heart failure, liver cirrhosis with ascites or syndrome of inappropriate antidiuretic hormone have demonstrated that lixivaptan increases water clearance without affecting renal sodium excretion or activating the neurohormonal system.