LCZ696

Base Information

• Chemical Name: LCZ696
• CAS No.: 936623-90-4
• Molecular Formula: 2(C24H29N5O3).2(C24H29NO5).5(H2O).6Na
• Molecular Weight: 958.008
• Mol file: 936623-90-4.mol

Synonyms:3-(1-Biphenyl-4-ylMethyl-3-ethoxycarbonyl-1-butylcarbaMoyl)propionate-3'-Methyl-2'-(pentanoyl(2'-(tetrazol-5-ylate)biphenyl-4'-ylMethyl)aMino)butyrate;Valsartan/sacubitril;LCZ696 interMediate;N-(1-oxopentyl)-N-[[2'-(2H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-L-valine, compd. with α-ethyl (αR,γS)-γ-[(3-carboxy-1-oxopropyl)amino]-α-methyl[1,1'-biphenyl]-4-pentanoate, sodium salt, hydrate (2);Valsartan-sacubitril(LCZ696);Entresto;LZC696;[(C24H29N5O3).(C24H29NO5).2.5(H2O).3Na]

Chemical Property of LCZ696

Chemical Property:

• PSA: 207.53000
• LogP: 5.98340
• Solubility.: ≥45.05 mg/mL in DMSO; ≥11.28 mg/mL in H2O; ≥28.5 mg/mL in EtOH

Purity/Quality:

99.5%, ^*data from raw suppliers

LCZ696 ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Description: LCZ696 is a dual angiotensin II receptor antagonist and neprilysin inhibitor that is a combination of the nonpeptide angiotensin II receptor antagonist valsartan and AHU377 , a prodrug of LBQ657 , which is an inhibitor of the zinc metallopeptidase neprilysin., LCZ696 (2-60 mg/kg) induces a dose-dependent decrease in mean arterial pressure in rats expressing human renin and angiotensinogen, a double-transgenic model for angiotensin II-dependent hypertension. Formulations containing LCZ696 are under clinical investigation for the treatment of mild to moderate hypertension and chronic heart failure.
• Clinical Use: LCZ696 (Novartis Pharmaceuticals), a first-in-class inhibitor of dualacting angiotensin-2 type-I receptor and neprilysin inhibitors, was developed as a molecule composed of molecular moieties of valsartan and neprilysin inhibitor prodrug AHU377 in a 1:1 ratio. Several phase 2 randomised clinical trials have been done or are underway in patients with hypertension. In a proof-of-concept randomised trial, LCZ696 was compared with valsartan in 1328 patients with mild-to-moderate hypertension, and provided fully additive reduction of blood pressure. No cases of angio-oedema were reported in the 8 week treatment period. This tolerance should be confirmed, particularly in black patients, for whom omapatrilat resulted in a higher occurrence of angio-oedema than in white patients. Indeed, in the proof-of-concept trial only about 8% of patients were black.

Technology Process of LCZ696

There total 5 articles about LCZ696 which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 91.9%

N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenyl-methyl)-4-amino-(2R)-methylbutanoic acid ethyl ester calcium salt + N-pentanoyl-N-[[2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl]-methyl]-(L)-valine (137862-53-4,137862-87-4) → trisodium [3-((1S,3R)-1-biphenyl-4-yl-methyl-3-ethoxycarbonyl-1-butylcarbamoyl)propionate-(S)-3’-methyl-2’-(pentanoyl{2”-(tetrazol-5-ylate)biphenyl-4’-yl-methyl}amino)butyrate] hemipentahydrate (936623-90-4)

Guidance literature:

N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenyl-methyl)-4-amino-(2R)-methylbutanoic acid ethyl ester calcium salt; With hydrogenchloride; water; In Isopropyl acetate;

N-pentanoyl-N-[[2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl]-methyl]-(L)-valine; With sodium hydroxide; In n-heptane; water; acetone; at 45 ℃; Temperature;

Reference yield: 90.83%

4-(((2S,4R)-1-([1,1'-biphenyl]-4-yl)-5-ethoxy-4-methyl-5-oxopentan-2-yl)amino)-4-oxobutanoic acid (149709-63-7,766480-48-2) + N-pentanoyl-N-[[2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl]-methyl]-(L)-valine (137862-53-4,137862-87-4) → trisodium [3-((1S,3R)-1-biphenyl-4-yl-methyl-3-ethoxycarbonyl-1-butylcarbamoyl)propionate-(S)-3’-methyl-2’-(pentanoyl{2”-(tetrazol-5-ylate)biphenyl-4’-yl-methyl}amino)butyrate] hemipentahydrate (936623-90-4)

Guidance literature:

With sodium hydroxide; In water; acetone; at 25 - 35 ℃; for 1h;

Reference yield: 85.29%

(S)-N-(1-carboxy-2-methyl-prop-1-yl)-N-pentanoyl-N-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-amine disodium salt + sacubitril sodium → trisodium [3-((1S,3R)-1-biphenyl-4-yl-methyl-3-ethoxycarbonyl-1-butylcarbamoyl)propionate-(S)-3’-methyl-2’-(pentanoyl{2”-(tetrazol-5-ylate)biphenyl-4’-yl-methyl}amino)butyrate] hemipentahydrate (936623-90-4)

Guidance literature:

With cyclohexane; at 25 - 35 ℃; for 1h;

upstream raw materials:

N-pentanoyl-N-[[2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl]-methyl]-(L)-valine

4-(((2S,4R)-1-([1,1'-biphenyl]-4-yl)-5-ethoxy-4-methyl-5-oxopentan-2-yl)amino)-4-oxobutanoic acid

α-ethyl (αR,γS)-γ-<(3-carboxy-1-oxopropyl)amino>-α-methyl<1,1'-biphenyl>-4-pentanoate

Refernces

• 1、 -. "SOLID STATE FORMS OF TRISODIUM SALT OF VALSARTAN/SACUBITRIL COMPLEX AND SACUBITRIL". Page/Page column 25; 26; 28; 29; 30; 31; 32. . Retrieved 2017/02/09.
• 2、 -. "Method for preparing LCZ696". Paragraph 0047; 0048; 0049. . Retrieved 2016/10/09.