New Fashion Design for Blood Pressure Medication Hydrochlorothiazide - Sacubitril Hemicalcium – CPF

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New Fashion Design for Blood Pressure Medication Hydrochlorothiazide - Sacubitril Hemicalcium – CPF Detail:

    沙库比曲半钙盐 Sacubitril Hemicalcium 1369773-39-6 In-House
    沙库比曲钠盐 149690-05-1 In-House
    LCZ-4 1426129-50-1 In-House
    LCZ-7 1012341-48-8 In-House
    LCZ-8 1012341-50-2 In-House
    LCZ-9 149690-12-0 In-House

 

Background

AHU-377 hemicalcium salt is a hemicalcium salt form of AHU-377. It is an inhibitor of neprilysin with IC50 value of 5 nM [1].

AHU-377 and the angiotensin II AT1 receptor antagonist valsartan compose LCZ696 in a 1:1 molar ratio. LCZ696 is an angiotensin receptor neprilysin inhibitor. It can reduce blood pressure and may be a novel drug for the treatment of heart failure. AHU-377 is a pro-drug, it can be converted by enzymatic cleavage of the ethyl ester into the active form LBQ657. It is reported that AHU-377(30 and 100 mg/kg, PO) can cause antihypertensive effect in a dose-dependent manner in DAHI-SS rats. But in the DOCA-salt hypertensive rats, it shows a weak reduction [2, 3].

References:
[1] Ksander GM, Ghai RD, deJesus R, Diefenbacher CG, Yuan A, Berry C, Sakane Y, Trapani A. Dicarboxylic acid dipeptide neutral endopeptidase inhibitors. J Med Chem. 1995 May 12; 38(10):1689-700.
[2] Voors AA, Dorhout B, van der Meer P. The potential role of valsartan + AHU377 ( LCZ696 ) in the treatment of heart failure. Expert Opin Investig Drugs. 2013 Aug;22(8):1041-7.
[3] Laxminarayan G Hegde, Cecile Yu, Cheruvu Madhavi et al. Comparative efficacy of AHU-377, a potent neprilysin inhibitor, in two rat models of volume-dependent hypertension. BMC Pharmacology 2011, 11(Suppl 1):P33.

Chemical structure

Sacubitril Hemicalcium

2018 GMP-2
原料药GMP证书201811(captopril ,thalidomide etc)
GMP-of-PMDA-in-Chanyoo-平成28年08月03日 Nantong-Chanyoo-Pharmatech-Co
FDA-EIR-Letter-201901

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