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- CAS号:
- 168079-32-1
- 英文名:
- LIXIVAPTAN
- 英文别名:
- CS-780;VPA 985;LIXIVAPTAN;Lixivaptan (VPA-985);VPA985;LIXIVAPTAN (VPA 985);N-[3-Chloro-4-(5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-ylcarbonyl)phenyl]-5-fluoro-2-methylbenzamide;N-[3-Chloro-4-(5H-pyrrolo[2,1-c][1,4]benzodiazepine-10(11H)-ylcarbonyl)phenyl]-5-fluoro-2-methylbenzamide;BenzaMide,N-[3-chloro-4-(5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-ylcarbonyl)phenyl]-5-fluoro-2-Methyl-;N-[3-chloro-4-(6,11-dihydropyrrolo[2,1-c][1,4]benzodiazepine-5-carbonyl)phenyl]-5-fluoro-2-methyl-benzamide;N-(3-Chloro-4-(10,11-dihydro-5H-benzo[e]pyrrolo[1,2-a][1,4]diazepine-10-carbonyl)phenyl)-5-fluoro-2-methylbenzamide
- 中文名:
- 利伐普坦
- 中文别名:
- 利赛伐坦;利希普坦;利昔伐坦;利伐普坦;利昔普坦;利昔普坦/利伐普坦;LIXIVAPTAN游离;N-(3-氯-4-(10,11-二氢-5H-苯并[E]吡咯[1,2-A][1,4]二氮杂-10-羰基)苯基)-5-氟-2-甲基苯甲酰胺
- CBNumber:
- CB22446529
- 分子式:
- C27H21ClFN3O2
- 分子量:
- 473.93
- MOL File:
- 168079-32-1.mol
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利伐普坦性质、用途与生产工艺
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。
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。
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。
IC50: 1.2 nM (human V2), 2.3 nM (rat V2)
Lixivaptan displays competitive antagonist activity at V2 receptors.
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.
利伐普坦
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