(2S)-1-[(2S)-2-{[(2R)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]pyrrolidine-2-carboxylic acid

• ChemBase ID: 466
• Molecular Formular: C20H28N2O5
• Molecular Mass: 376.44672
• Monoisotopic Mass: 376.19982201
• SMILES: O=C(N1[C@@H](CCC1)C(=O)O)[C@@H](N[C@H](CCc1ccccc1)C(=O)OCC)C
• Canonical SMILES: CCOC(=O)[C@H](N[C@H](C(=O)N1CCC[C@H]1C(=O)O)C)CCc1ccccc1
• InChI: InChI=1S/C20H28N2O5/c1-3-27-20(26)16(12-11-15-8-5-4-6-9-15)21-14(2)18(23)22-13-7-10-17(22)19(24)25/h4-6,8-9,14,16-17,21H,3,7,10-13H2,1-2H3,(H,24,25)/t14-,16+,17-/m0/s1
• InChIKey: GBXSMTUPTTWBMN-UAGQMJEPSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (2S)-1-[(2S)-2-{[(2R)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]pyrrolidine-2-carboxylic acid
• IUPAC Traditional name: vasotec
• Brand Name: Bonuten; Gadopril; Kinfil; Vasotec; Vasotec IV
• Synonyms: Enalapril Maleate; Enalaprila [INN-Spanish]; Enalaprilat; Enalaprilum [INN-Latin]; Enalapril; ENALAPRIL MALEATE

Database IDs

• CAS Number: 75847-73-3
• PubChem SID: 160963929
• PubChem CID: 5362032

CALCULATED PROPERTIES

JChem

• Acid pKa: 3.6713305
• H Acceptors: 5
• H Donor: 2
• LogD (pH = 5.5): 0.29928052
• LogD (pH = 7.4): -1.0552722
• Log P: 0.5877766
• Molar Refractivity: 99.5746 cm^3
• Polarizability: 39.423725 Å^3
• Polar Surface Area: 95.94 Å^2
• Rotatable Bonds: 10
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 0.19
• LOG S: -3.25
• Solubility (Water): 2.13e-01 g/l

PROPERTIES

Physical Property

• Solubility: 0.025g/mL
• Hydrophobicity(logP): 2.1

Product Information

• Purity: 98%

DETAILS

DrugBank - DB00584

• Drug Groups: approved
• Description: Enalapril is a prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is rapidly metabolized in the liver to enalaprilat following oral administration. Enalaprilat is a potent, competitive inhibitor of ACE, the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Enalapril may be used to treat essential or renovascular hypertension and symptomatic congestive heart failure.
• Indication: For the treatment of essential or renovascular hypertension and symptomatic congestive heart failure. It may be used alone or in combination with thiazide diuretics.
• Pharmacology: Enalapril is a prodrug that is rapidly metabolized by liver esterases to enalaprilat following oral administration. Enalapril itself has little pharmacologic activity. Enalaprilat lowers blood pressure by antagonizing the effect of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure using a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may sustain the effects of enalaprilat by causing increased vasodilation and decreased blood pressure.
• Toxicity: Overdosage may result in marked hypotension and stupor. Most common adverse effects include hypotension, headache, dizziness and fatigue.
• Affected Organisms: Humans and other mammals
• Biotransformation: ~ 60% of absorbed dose is extensively hydrolyzed to enalaprilat, primarily by liver esterases
• Absorption: 55-75%, absorption is unaffected by food; enalaprilat (clinically administered IV) is poorly absorbed, 3-12%, due to its high polarity.
• Half Life: < 2 hours for unchanged enalapril in health individuals, may be increased in those with congestive heart failure (3.4 and 5.8 hours for single 5- and 10-mg doses, respectively). The average terminal half life of enalaprilat is 35-38 hours. The effective half life following multiple doses is 11-14 hours.
• Protein Binding: 50-60% of enalaprilat is bound to plasma proteins
• Elimination: Excretion of enalapril is primarily renal.
• References: D.P. Ip and G.S. Brenner, in K. Florey (Editor), Analytical Profiles of Drug Substances, Vol. 16, Aca- demic Press, London, 1987, pp. 207-243.
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

REFERENCES

• D.P. Ip and G.S. Brenner, in K. Florey (Editor), Analytical Profiles of Drug Substances, Vol. 16, Aca- demic Press, London, 1987, pp. 207-243.