中文名称:

LCZ696中间体

中文同义词:

AHU377钙盐;沙库必曲钙盐;AHU-377 钙盐1369773-39-6;HU377钙盐;LCZ696中间体(AHU-377钙盐);(2R,4S)-5-(联苯-4-基)-4-(氨基)-5-(3-羧基-丙酰基氨基)-2甲基-戊酸乙酯钙盐;(2S,4R)-5-(联苯基-4-基)-4-[(3-羧基丙酰基)氨基]-2-甲基戊酸乙酯 钙盐(2:1);原研534-06

英文名称:

AHU-377 (heMicalciuM salt)

英文同义词:

AHU-377 (heMicalciuM salt);(alphaR,gammaS)-gamma-[(3-Carboxy-1-oxopropyl)amino]-alpha-methyl-[1,1-biphenyl]-4-pentanoic acid 4-ethyl ester calcium salt (2:1);(2S,4R)-5-(Biphenyl-4-yl)-4-[(3-carboxypropionyl)amino]-2-methylpentanoic acid ethyl ester,calcium salt(2:1);AHU-377 hemicalcium salt (2:1);Calciumbis(4-{[(1S,3R)-1-([1,1-biphenyl]-4-ylmethyl)-4-ethoxy-3-methyl-4-oxobutyl] amino} -4-oxobutanoate);LCZ696(valsartan + sacubitril) impurity 1;Ethyl (αR,γS)-γ-[(3-carboxy-1-oxopropyl)amino]-α-methyl-[1,1-biphenyl]-4-pentanoate hemicalcium salt;(alphar

CAS号:

1369773-39-6

分子式:

C48H56CaN2O10

分子量:

861.04364

EINECS号:

相关类别:

LCZ696 中间体;医药中间体;杂质对照品;LCZ696中间体;对照品-杂质对照品;抗高血压;化工原料;lcz696;LCZ 696;Pharmaceutical Intermediates;Intermediates

Mol文件:

1369773-39-6.mol

储存条件 

-20°C

形态

powder

颜色

white to beige

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).

危险品运输编号 

UN2811 - class 6.1 - PG 3 - EHS - Toxic solids, organic, n.o.s., HI: all