Omapatrilat

Status : investigational

Description

Omapatrilat is an investigational drug that inhibits both neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE). NEP inhibition results in elevated natriuretic peptide levels, promoting natriuresis, diuresis, vasodilation, and reductions in preload and ventricular remodeling. This drug from BMS was not approved by the FDA due to angioedema safety concerns.

Used

For the treatment of hypertension.

Mechanism Of Action

Omapatrilat binds to both angiotensin converting enzyme and neutral endopeptidase. This results in a decrease renin-angiotensin-aldosterone production and increase natriuretic peptidase circulation.

Pharmacodynamics

Omapatrilat is used to treat hypertension. Vasopeptidase inhibitor that simultaneously inhibits angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). Omapatrilat lowers blood pressure by inhibiting the action of the angiotensin converting enzyme (ACE), which causes blood vessels to constrict. But unlike other drugs, omapatrilat also inhibits another enzyme known as neutral endopeptidase (NEP), which helps blood vessels relax. Omapatrilat demonstrated greater reduction in blood pressure than the ACE inhibitor lisinopril in individuals with salt-sensitive hypertension who typically do not respond well to ACE inhibitors.

Toxic Effect

Side effects include hyperkalemia, cough, hypotension, increased SrCr, and dizziness. Dizziness, diarrhea, vision disturbance, hypotension and angioedema

Metabolism

Hepatic

Absorption

The absolute oral bioavailability of omapatrilat is 20% to 30% and the absorption is not affected by food intake.

Chemical Classification

This compound belongs to the class of organic compounds known as n-acyl-alpha amino acids and derivatives. These are compounds containing an alpha amino acid (or a derivative thereof) which bears an acyl group at its terminal nitrogen atom.

N-acyl-alpha amino acids and derivatives

Organic compounds

Organic acids and derivatives

Carboxylic acids and derivatives

Amino acids, peptides, and analogues

Calculated Property

kind Value Source
logP 2.15 ALOGPS
logS -3.7 ALOGPS
Water Solubility 7.69e-02 g/l ALOGPS
logP 2.06 ChemAxon
IUPAC Name (7S,10aS)-5-oxo-4-[(2S)-3-phenyl-2-sulfanylpropanamido]-octahydro-2H-pyrido[2,1-b][1,3]thiazepine-7-carboxylic acid ChemAxon
Traditional IUPAC Name (7S,10aS)-5-oxo-4-[(2S)-3-phenyl-2-sulfanylpropanamido]-octahydropyrido[2,1-b][1,3]thiazepine-7-carboxylic acid ChemAxon
Molecular Weight 408.535 ChemAxon
Monoisotopic Weight 408.117748646 ChemAxon
SMILES [H][C@]12CCC[C@H](N1C(=O)C(CCS2)NC(=O)[C@@H](S)CC1=CC=CC=C1)C(O)=O ChemAxon
Molecular Formula C19H24N2O4S2 ChemAxon
InChI InChI=1S/C19H24N2O4S2/c22-17(15(26)11-12-5-2-1-3-6-12)20-13-9-10-27-16-8-4-7-14(19(24)25)21(16)18(13)23/h1-3,5-6,13-16,26H,4,7-11H2,(H,20,22)(H,24,25)/t13?,14-,15-,16-/m0/s1 ChemAxon
InChIKey InChIKey=LVRLSYPNFFBYCZ-JFKGFPBSSA-N ChemAxon
Polar Surface Area (PSA) 86.71 ChemAxon
Refractivity 106.68 ChemAxon
Polarizability 42.03 ChemAxon
Rotatable Bond Count 5 ChemAxon
H Bond Acceptor Count 4 ChemAxon
H Bond Donor Count 3 ChemAxon
pKa (strongest acidic) 3.77 ChemAxon
pKa (strongest basic) -3.6 ChemAxon
Physiological Charge -1 ChemAxon
Number of Rings 3 ChemAxon
Bioavailability 1 ChemAxon
Rule of Five 1 ChemAxon
Ghose Filter 1 ChemAxon
MDDR-Like Rule 0 ChemAxon

Affected organism

Humans and other mammals

Target within organism

  • Angiotensin-converting enzyme : in Human
  • Neprilysin : in Human