Sacubitril

A summary of the most common chemical descriptors (InChI Key and SMILES codes) for Sacubitril are summarized together with 3D and 2D structures and relevant physico-chemical properties.

What is the Sacubitril?

The molecule Sacubitril presents a molecular formula of C24H29NO5 and its IUPAC name is 4-[[(2S,4R)-5-ethoxy-4-methyl-5-oxo-1-(4-phenylphenyl)pentan-2-yl]amino]-4-oxobutanoic acid.

Sacubitril (INN; codenamed LCZ696) is an experimental drug in the field of cardiovascular medicine, specifically for the treatment of heart failure. It is a prodrug of the neprilysin inhibitor, LBQ657. It is being developed by Novartis..

In September 2015, the U.S. Food and Drug Administration (FDA) granted fast track status to sacubitril for the treatment of heart failure..

In October 2015, the FDA Advisory Committee voted 12 to 4 in favor of approving sacubitril for the treatment of heart failure. The FDA is expected to make a decision on whether to approve the drug by early 2016..

Sacubitril is a prodrug of LBQ657, which is a neprilysin inhibitor. Neprilysin is an enzyme that breaks down natriuretic peptides, which are hormones that help regulate blood pressure and fluid balance. By inhibiting neprilysin, sacubitril increases the levels of natriuretic peptides in the blood, which leads to a decrease in blood pressure and an increase in urine output..

In clinical trials, sacubitril has been shown to improve symptoms of heart failure and to reduce the risk of hospitalization for heart failure. The most common side effects of sacubitril include headache, dizziness, diarrhea, and nausea..

If approved by the FDA, sacubitril would be the first drug in a new class of heart failure treatments. It would be used in conjunction with an ACE inhibitor or angiotensin receptor blocker..

3D structure

Cartesian coordinates

Geometry of Sacubitril in x, y and z coordinates (Å units) to copy/paste elsewhere. Generated with Open Babel software.

2D drawing

 

Sacubitril PYNXFZCZUAOOQC-UTKZUKDTSA-N chemical compound 2D structure molecule svg
Sacubitril

 

Molecule descriptors

 
IUPAC name4-[[(2S,4R)-5-ethoxy-4-methyl-5-oxo-1-(4-phenylphenyl)pentan-2-yl]amino]-4-oxobutanoic acid
InChI codeInChI=1S/C24H29NO5/c1-3-30-24(29)17(2)15-21(25-22(26)13-14-23(27)28)16-18-9-11-20(12-10-18)19-7-5-4-6-8-19/h4-12,17,21H,3,13-16H2,1-2H3,(H,25,26)(H,27,28)/t17-,21+/m1/s1
InChI KeyPYNXFZCZUAOOQC-UTKZUKDTSA-N
SMILESCCOC(=O)[C@H](C)C[C@@H](Cc1ccc(-c2ccccc2)cc1)NC(=O)CCC(=O)O

Other names (synonyms)

IUPAC nomenclature provides a standardized method for naming chemical compounds. Although this system is widely used in chemistry, many chemical compounds have also other names commonly used in different contexts. These synonyms can come from a variety of sources and are used for a variety of purposes.

One common source of synonyms for chemical compounds is the common or trivial names, assigned on the basis of appearance, properties, or origin of the molecule.

Another source of synonyms are historical or obsolete names employed in the past, however replaced nowadays by more modern or standardized names.

In addition to common and historical names, chemical compounds may also have synonyms that are specific to a particular field or industry.

  • (2R,4S)-5-(biphenyl-4-yl)-4-((3-carboxypropionyl) amino)-2-methylpentanoic acid ethyl ester
  • (2R,4S)-5-Biphenyl-4-yl-4-(3-carboxypropionylamino)-2-methylpentanoic acid ethyl ester
  • (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester
  • (alphaR,gammaS)-gamma-[(3-Carboxy-1-oxopropyl)amino]-alpha-methyl-4-biphenylpentanoic acid alpha-ethyl ester
  • 149709-62-6
  • 17ERJ0MKGI
  • 3-{[(2S,4R)-5-Ethoxy-4-methyl-5-oxo-1-(4-phenylphenyl)pentan-2-yl]carbamoyl}propanoic acid
  • 4-(((2S,4R)-1-([1,1'-biphenyl]-4-yl)-5-ethoxy-4-methyl-5-oxopentan-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-oxobutanoicacid
  • 4-(((2S,4R)-1-([1,1-biphenyl]-4-yl)-5-ethoxy-4-Methyl-5-oxopentan-2-yl)aMino)-4-oxobutanoic acid
  • 4-[[(2S,4R)-5-ethoxy-4-methyl-5-oxo-1-(4-phenylphenyl)pentan-2-yl]amino]-4-oxobutanoic acid
  • AC-28899
  • AHU 377
  • AHU-377
  • AHU-377(Sacubitril)
  • AHU377
  • AM85599
  • AMBZ0404
  • AS-16703
  • D10225
  • DB09292
  • ENTRESTO COMPONENT SACUBITRIL
  • GTPL7857
  • HY-15407
  • J-008612
  • MFCD00920862
  • NCGC00387800-02
  • Neparvis
  • Q17811448
  • SACUBITRIL COMPONENT OF ENTRESTO
  • Sacubitril
  • Sacubitril (JAN/USAN/INN)
  • [1,1'-Biphenyl]-4-pentanoic acid, -[(3-carboxy-1-oxopropyl)amino]-alpha-methyl-, alpha-ethyl ester, (alphaR,S)-
  • [1,1'-Biphenyl]-4-pentanoic acid, gamma-[(3-carboxy-1-oxopropyl)amino]-alpha-methyl-, alpha-ethyl ester, (alphaR,gammaS)-
  • alpha-ethyl (alphaR,gammaS)-gamma-<(3-carboxy-1-oxopropyl)amino>-alpha-methyl<1,1'-biphenyl>-4-pentanoate

Reference codes for other databases

There exist several different chemical codes commonly used in orded to identify molecules:
  • ZINC3792417
  • UNII-17ERJ0MKGI
  • AKOS027321509
  • DTXSID20164370
  • CHEMBL3137301
  • CHEBI:134714
  • SCHEMBL2707112

Physico-Chemical properties

IUPAC name4-[[(2S,4R)-5-ethoxy-4-methyl-5-oxo-1-(4-phenylphenyl)pentan-2-yl]amino]-4-oxobutanoic acid
Molecular formulaC24H29NO5
Molecular weight411.491
Melting point (ºC)
Boiling point (ºC)
Density (g/cm3)
Molar refractivity115.78
LogP4.2
Topological polar surface area92.7

LogP and topological polar surface area (TPSA) values were estimated using Open Babel software.

The n-octanol/water partition coeficient (Kow) data is applied in toxicology and drug research. Kow values are used, to guess the environmental fate of persistent organic pollutants. High partition coefficients values, tend to accumulate in the fatty tissue of organisms. Molecules with a log(Kow) (or LogP) greater than 5 are considered to bioaccumulate.

TPSA values are the sum of the surface area over all polar atoms or molecules, mainly oxygen and nitrogen, also including hydrogen atoms.

In medicinal chemistry, TPSA is used to assess the ability of a drug to permeabilise cells.

For molecules to penetrate the blood-brain barrier (and act on receptors in the central nervous system), TPSA values below 90 Å2 are required. Thus, molecules with a polar surface area greater than 140 Å2 tend to be poorly permeable to cell membranes.