(3S)-2-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid

• ChemBase ID: 573
• Molecular Formular: C27H34N2O7
• Molecular Mass: 498.56806
• Monoisotopic Mass: 498.23660144
• SMILES: O=C(N1[C@@H](Cc2c(C1)cc(OC)c(OC)c2)C(=O)O)[C@@H](N[C@@H](CCc1ccccc1)C(=O)OCC)C
• Canonical SMILES: CCOC(=O)[C@@H](N[C@H](C(=O)N1Cc2cc(OC)c(cc2C[C@H]1C(=O)O)OC)C)CCc1ccccc1
• InChI: InChI=1S/C27H34N2O7/c1-5-36-27(33)21(12-11-18-9-7-6-8-10-18)28-17(2)25(30)29-16-20-15-24(35-4)23(34-3)14-19(20)13-22(29)26(31)32/h6-10,14-15,17,21-22,28H,5,11-13,16H2,1-4H3,(H,31,32)/t17-,21-,22-/m0/s1
• InChIKey: UWWDHYUMIORJTA-HSQYWUDLSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (3S)-2-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
• IUPAC Traditional name: moexipril
• Brand Name: Univasc
• Synonyms: Moexiprilum [INN-Latin]; Moexipril HCl; Moexipril hydrochloride; Moexipril

Database IDs

• CAS Number: 103775-10-6
• PubChem SID: 160964036; 46508441
• PubChem CID: 91270

CALCULATED PROPERTIES

JChem

• Acid pKa: 3.462318
• H Acceptors: 7
• H Donor: 2
• LogD (pH = 5.5): 1.1609751
• LogD (pH = 7.4): -0.08144003
• Log P: 1.5021217
• Molar Refractivity: 132.8822 cm^3
• Polarizability: 52.210068 Å^3
• Polar Surface Area: 114.4 Å^2
• Rotatable Bonds: 12
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 1.52
• LOG S: -4.93
• Solubility (Water): 5.85e-03 g/l

PROPERTIES

Physical Property

• Solubility: Soluble (about 10% weight-to-volume) in distilled water at room temperature as HCl salt.
• Hydrophobicity(logP): 2.7

DETAILS

DrugBank - DB00691

• Drug Groups: approved
• Description: Moexipril is a non-sulfhydryl containing precursor of the active angiotensin-converting enzyme (ACE) inhibitor moexiprilat. It is used to treat high blood pressure (hypertension). It works by relaxing blood vessels, causing them to widen. Lowering high blood pressure helps prevent strokes, heart attacks and kidney problems.
• Indication: For the treatment of hypertension.
• Pharmacology: Moexipril is a non-sulfhydryl containing precursor of the active angiotensin-converting enzyme (ACE) inhibitor moexiprilat. It is used to treat high blood pressure (hypertension). It works by relaxing blood vessels, causing them to widen. Lowering high blood pressure helps prevent strokes, heart attacks and kidney problems.
• Toxicity: Human overdoses of moexipril have not been reported. In case reports of overdoses with other ACE inhibitors, hypotension has been the principal adverse effect noted. Single oral doses of 2 g/kg moexipril were associated with significant lethality in mice. Rats, however, tolerated single oral doses of up to 3 g/kg. Common adverse effects include cough, dizziness, diarrhea, flu syndrome, fatigue, pharyngitis, flushing, rash, and myalgia
• Affected Organisms: Humans and other mammals
• Biotransformation: Rapidly converted to moexiprilat, the active metabolite. Conversion to the active metabolite is thought to require carboxyesterases and is likely to occur in organs or tissues, other than the gastrointestinal tract, in which carboxyesterases occur. The liver is thought to be one site of conversion, but not the primary site.
• Absorption: Moexipril is incompletely absorbed, with bioavailability as moexiprilat of about 13% compared to intravenous (I.V.) moexipril (both measuring the metabolite moexiprilat), and is markedly affected by food, which reduces C_max and AUC by about 70% and 40%, respectively, after the ingestion of a low-fat breakfast or by 80% and 50%, respectively, after the ingestion of a high-fat breakfast.
• Half Life: Moexipril elimination half-life is approximately 1 hour. Moexiprilat elimination half-life is 2 to 9 hours.
• Protein Binding: Moexiprilat is approxomately 50% protein bound.
• Elimination: Moexiprilat undergoes renal elimination.
• Distribution: * 183 L
• Clearance: * 441 mL/min
• References: Asmar R, Sayegh F, Tracz W, Hlawaty M, Olszowska M, Jourde M, Vincent M, Goujoun B, Maldonado J: Reversal of left ventricular hypertrophy with the ACE inhibitor moexipril in patients with essential hypertension. Acta Cardiol. 2002 Feb;57(1):31-2. [Pubmed] ; Blacher J, Raison J, Amah G, Schiemann AL, Stimpel M, Safar ME: Increased arterial distensibility in postmenopausal hypertensive women with and without hormone replacement therapy after acute administration of the ACE inhibitor moexipril. Cardiovasc Drugs Ther. 1998 Sep;12(4):409-14. [Pubmed] ; Brogden RN, Wiseman LR: Moexipril. A review of its use in the management of essential hypertension. Drugs. 1998 Jun;55(6):845-60. [Pubmed] ; Cawello W, Boekens H, Waitzinger J, Miller U: Moexipril shows a long duration of action related to an extended pharmacokinetic half-life and prolonged ACE inhibition. Int J Clin Pharmacol Ther. 2002 Jan;40(1):9-17. [Pubmed] ; Chrysant SG, Chrysant GS: Pharmacological and clinical profile of moexipril: a concise review. J Clin Pharmacol. 2004 Aug;44(8):827-36. [Pubmed] ; Chrysant SG, Chrysant GS: Pharmacological profile and clinical use of moexipril. Expert Rev Cardiovasc Ther. 2003 Sep;1(3):345-52. [Pubmed] ; Chrysant GS, Nguyen PK: Moexipril and left ventricular hypertrophy. Vasc Health Risk Manag. 2007;3(1):23-30. [Pubmed] ; Grass GM, Morehead WT: Evidence for site-specific absorption of a novel ACE inhibitor. Pharm Res. 1989 Sep;6(9):759-65. [Pubmed] ; Kalasz H, Petroianu G, Tekes K, Klebovich I, Ludanyi K, Gulyas Z: Metabolism of moexipril to moexiprilat: determination of in vitro metabolism using HPLC-ES-MS. Med Chem. 2007 Jan;3(1):101-6. [Pubmed] ; Persson B, Stimpel M: Evaluation of the antihypertensive efficacy and tolerability of moexipril, a new ACE inhibitor, compared to hydrochlorothiazide in elderly patients. Eur J Clin Pharmacol. 1996;50(4):259-64. [Pubmed] ; Spinar J, Vitovec J: MORE--MOexipril and REgression of left ventricle hypertrophy in combination therapy A multicentric open label clinical trial. Int J Cardiol. 2005 Apr 20;100(2):199-206. [Pubmed] ; Stimpel M, Koch B, Oparil S: Antihypertensive treatment in postmenopausal women: results from a prospective, randomized, double-blind, controlled study comparing an ACE inhibitor (moexipril) with a diuretic (hydrochlorothiazide). Cardiology. 1998 May;89(4):271-6. [Pubmed] ; White CM: Pharmacologic, pharmacokinetic, and therapeutic differences among ACE inhibitors. Pharmacotherapy. 1998 May-Jun;18(3):588-99. [Pubmed] ; White WB, Whelton A, Fox AA, Stimpel M, Kaihlanen PM: Tricenter assessment of the efficacy of the ACE inhibitor, moexipril, by ambulatory blood pressure monitoring. J Clin Pharmacol. 1995 Mar;35(3):233-8. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

REFERENCES

• Stimpel M, Koch B, Oparil S: Antihypertensive treatment in postmenopausal women: results from a prospective, randomized, double-blind, controlled study comparing an ACE inhibitor (moexipril) with a diuretic (hydrochlorothiazide). Cardiology. 1998 May;89(4):271-6. Pubmed
• White CM: Pharmacologic, pharmacokinetic, and therapeutic differences among ACE inhibitors. Pharmacotherapy. 1998 May-Jun;18(3):588-99. Pubmed
• White WB, Whelton A, Fox AA, Stimpel M, Kaihlanen PM: Tricenter assessment of the efficacy of the ACE inhibitor, moexipril, by ambulatory blood pressure monitoring. J Clin Pharmacol. 1995 Mar;35(3):233-8. Pubmed
• Asmar R, Sayegh F, Tracz W, Hlawaty M, Olszowska M, Jourde M, Vincent M, Goujoun B, Maldonado J: Reversal of left ventricular hypertrophy with the ACE inhibitor moexipril in patients with essential hypertension. Acta Cardiol. 2002 Feb;57(1):31-2. Pubmed
• Blacher J, Raison J, Amah G, Schiemann AL, Stimpel M, Safar ME: Increased arterial distensibility in postmenopausal hypertensive women with and without hormone replacement therapy after acute administration of the ACE inhibitor moexipril. Cardiovasc Drugs Ther. 1998 Sep;12(4):409-14. Pubmed
• Brogden RN, Wiseman LR: Moexipril. A review of its use in the management of essential hypertension. Drugs. 1998 Jun;55(6):845-60. Pubmed
• Cawello W, Boekens H, Waitzinger J, Miller U: Moexipril shows a long duration of action related to an extended pharmacokinetic half-life and prolonged ACE inhibition. Int J Clin Pharmacol Ther. 2002 Jan;40(1):9-17. Pubmed
• Chrysant SG, Chrysant GS: Pharmacological and clinical profile of moexipril: a concise review. J Clin Pharmacol. 2004 Aug;44(8):827-36. Pubmed
• Chrysant SG, Chrysant GS: Pharmacological profile and clinical use of moexipril. Expert Rev Cardiovasc Ther. 2003 Sep;1(3):345-52. Pubmed
• Chrysant GS, Nguyen PK: Moexipril and left ventricular hypertrophy. Vasc Health Risk Manag. 2007;3(1):23-30. Pubmed
• Grass GM, Morehead WT: Evidence for site-specific absorption of a novel ACE inhibitor. Pharm Res. 1989 Sep;6(9):759-65. Pubmed
• Kalasz H, Petroianu G, Tekes K, Klebovich I, Ludanyi K, Gulyas Z: Metabolism of moexipril to moexiprilat: determination of in vitro metabolism using HPLC-ES-MS. Med Chem. 2007 Jan;3(1):101-6. Pubmed
• Persson B, Stimpel M: Evaluation of the antihypertensive efficacy and tolerability of moexipril, a new ACE inhibitor, compared to hydrochlorothiazide in elderly patients. Eur J Clin Pharmacol. 1996;50(4):259-64. Pubmed
• Spinar J, Vitovec J: MORE--MOexipril and REgression of left ventricle hypertrophy in combination therapy A multicentric open label clinical trial. Int J Cardiol. 2005 Apr 20;100(2):199-206. Pubmed