LCZ696中间体

应用用途生物活性靶点体外研究体内研究 LCZ696中间体试剂级价格

LCZ696中间体

CAS号:1369773-39-6
英文名:AHU-377 (heMicalciuM salt)
中文名:LCZ696中间体
CBNumber:CB72685916
分子式:C48H56CaN2O10
分子量:861.04364
MOL File:1369773-39-6.mol

LCZ696中间体化学性质

熔点 :>140°C (dec.)
密度 :1.24g/cm3 at 20℃
蒸气压 :0.001Pa at 20℃
储存条件 :-20°C
溶解度 :DMSO (Slightly, Heated), Methanol (Slightly)
形态 :powder
颜色 :white to beige
LogP :-0.66-2.9 at 20℃ and pH2-7

安全信息

危险品运输编号 :UN2811 - class 6.1 - PG 3 - EHS - Toxic solids, organic, n.o.s., HI: all

LCZ696中间体性质、用途与生产工艺

应用 LCZ696中间体是有机合成中间体，可用于实验室研发过程和化工医药合成过程中，主要用于分析化学中沙库比曲药物研发的标准品和对照品。
用途
沙必利是一种与缬沙坦联合使用的降压药。这种名为缬沙坦/沙必利的联合药物在试验中被称为LCZ696，并以Entresto品牌销售，是一种治疗心力衰竭的药物。本品用作该药物中间体和杂质对照品，用于药品申报检测等。
生物活性 Sacubitril (AHU-377) hemicalcium salt 是有效的NEP抑制剂，IC50值为5 nM。Sacubitril hemicalcium salt 是研究心力衰竭药物 LCZ696 的一个组分。
靶点

IC50: 5 nM (NEP)
体外研究

Sacubitril (AHU-377) is a single molecule that is comprised of molecular moieties of valsartan, an ARB, and Sacubitril hemicalcium salt, 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 hemicalcium salt, 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.
体内研究

In humans, Sacubitril (AHU-377)(t _max 0.5-1.1 h) are absorbed quickly. Sacubitril hemicalcium salt 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).