149709-62-6
149709-62-6 结构式
基本信息
原研900-04
LCZ696原料
LCZ697杂质
LCZ696中间体5
AHU-377(钠盐)
沙库必曲(AHU-377)
LCZ696中间体 10G
LCZ696原研900-04
AHU-377(LCZ696中间体)
AHU-77
AHU-377
Sacubitril(AHU-377)
(2R,4S)-5-([1,1'-Biphenyl]-4-yl)-4-(3-carboxypropanamido)-2-methylpentanoic acid
4-{[(2S,4R)-1-(4-Biphenylyl)-5-ethoxy-4-methyl-5-oxo-2-pentanyl]amino}-4-oxobutanoic acid
(2R,4S)-5-(Biphenyl-4-yl)-4-[(3-carboxypropionyl)amino]-2-methylpentanoic acid ethyl ester
4-[[(2S,4R)-5-ethoxy-4-methyl-5-oxo-1-(4-phenylphenyl)pentan-2-yl]amino]-4-oxobutanoic acid
4-(((2S,4R)-1-([1,1'-Biphenyl]-4-yl)-5-ethoxy-4-methyl-5-oxopentan-2-yl)amino)-4-oxobutanoic a
4-(((2R,4R)-1-([1,1'-biphenyl]-4-yl)-5-ethoxy-4-Methyl-5-oxopentan-2-yl)aMino)-4-oxobutanoic acid
物理化学性质
常见问题列表
该药物临床试验中，针对一个双盲二期试验患者的轻度至中度高血压，对其用于100至400毫克的剂量组合药物，80至320毫克的缬沙坦，200毫克的neprilysin抑制剂或安慰剂。组合药物的效果比仅与缬沙坦等药物效果更为显著，且耐受性良好，无血管性水肿的报告。LCZ696从治疗早期便表现出了可持续的治疗利益：
（1）心血管疾病死亡风险降低20%（p=0.00004）。
（2）心脏衰竭住院率降低21%（p=0.00004）。
（3）全因死亡风险降低16%（p=0.0005）。
（4）总体而言，综合衡量心血管死亡或心脏衰竭住院主要终点，风险降低20%（p=0.0000002）。
LCZ696是一种结合了诺华的Diovan和正处于研究阶段的AHU-377的药物，一些分析人士也对这种药物给予了很高评价并认为诺华公司可能最早将于明年提交FDA审核，一旦获得通过将使诺华公司在心血管药物领域再下一城。
不过，尽管诺华公司对LCZ696表现出很高的期待。但是考虑到其serelaxin在FDA和欧盟医药管理部门的挫折，诺华公司还有很长一段路要走。
The news came straight from Basel as investigators around the world were wrapping up the big scientific meeting of the American College of Cardiology.
IC50: 5 nM (NEP)
Sacubitril (AHU-377) is a single molecule that is comprised of molecular moieties of valsartan, an ARB, and Sacubitril (AHU-377), a neprilysin inhibitor (1:1 ratio). Sacubitril (AHU-377) is converted by enzymatic cleavage of the ethyl ester into the active neprilysin inhibiting metabolite LBQ657. The inactive NEPi precursor, Sacubitril (AHU-377), does not inhibit collagen accumulation in fibroblasts nor cardiac myocyte hypertrophy. In cardiac fibroblasts, the active NEPi LBQ657 had no discernible effects. In contrast, LBQ657 modestly inhibits cardiac myocyte hypertrophy.
In humans, Sacubitril (AHU-377) (t max 0.5-1.1 h) are absorbed quickly. Sacubitril (AHU-377) is converted rapidly into LBQ657 with its t max being reached in 1.9-3.5 h. Mean t 1/2 values for the biologically active LBQ657 is 9.9-11.1 h. In vehicle-treated dogs, ANF increases urinary sodium excretion from 17.3±3.6 to 199.5±18.4 pequivkglmin. This effect is potentiated significantly in animals which receive Sacubitril (AHU-377). Urinary volume is also potentiated in animals which receive an iv administration of Sacubitril (AHU-377).