N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl}acetamide

• ChemBase ID: 128
• Molecular Formular: C24H33N3O4
• Molecular Mass: 427.53652
• Monoisotopic Mass: 427.24710655
• SMILES: OC(CN1CCN(CC1)CC(=O)Nc1c(cccc1C)C)COc1c(OC)cccc1
• Canonical SMILES: COc1ccccc1OCC(CN1CCN(CC1)CC(=O)Nc1c(C)cccc1C)O
• InChI: InChI=1S/C24H33N3O4/c1-18-7-6-8-19(2)24(18)25-23(29)16-27-13-11-26(12-14-27)15-20(28)17-31-22-10-5-4-9-21(22)30-3/h4-10,20,28H,11-17H2,1-3H3,(H,25,29)
• InChIKey: XKLMZUWKNUAPSZ-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl}acetamide
• IUPAC Traditional name: ranolazine; @ranolazine
• Brand Name: Ranexa
• Synonyms: N-(2,6-Dimethylphenyl)-2-(4-(2-hydroxy-3-(2-methoxy-phenoxy)propyl)piperazin-1-yl)acetamide; N-(2,6-Dimethylphenyl)-4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]-1-piperazineacetamide; (+/-))-Ranolazine; CVT 303; RS 43285-003; Renexa; N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl}acetamide; Ranexa; (-)-Ranolazine; Ranolazine 2HCl; Ranolazine Dihydrochloride; ranolazine; Ranolazine; N-(2,6-Dimethylphenyl)-2-(4-(2-hydroxy-3-(2-methoxyphenoxy)propyl)piperazin-1-yl)acetamide

Database IDs

• CAS Number: 142387-99-3; 95635-55-5
• MDL Number: MFCD00864690
• PubChem SID: 46505145; 160963591
• PubChem CID: 56959

CALCULATED PROPERTIES

JChem

• Acid pKa: 13.600031
• H Acceptors: 6
• H Donor: 2
• LogD (pH = 5.5): 1.1640991
• LogD (pH = 7.4): 2.633176
• Log P: 2.8324604
• Molar Refractivity: 123.4604 cm^3
• Polarizability: 47.363354 Å^3
• Polar Surface Area: 74.27 Å^2
• Rotatable Bonds: 9
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.08
• LOG S: -3.59
• Solubility (Water): 1.10e-01 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; DMSO; Methanol; Very slightly soluble
• Apperance: White Solid
• Melting Point: 119-120°C
• Hydrophobicity(logP): 1.012; 1.6

Safety Information

• Storage Condition: -20°C; -20°C Freezer
• Storage Warning: IRRITANT
• TSCA Listed: false

Product Information

• Purity: 95%; 95+%; 97%
• Salt Data: Free Base

DETAILS

DrugBank - DB00243

• Drug Groups: approved; investigational
• Description: Ranolazine is an antianginal medication. On January 31, 2006, ranolazine was approved for use in the United States by the FDA for the treatment of chronic angina. [Wikipedia]
• Indication: For the treatment of chronic angina. It should be used in combination with amlodipine, beta-blockers or nitrates.
• Pharmacology: Ranolazine has antianginal and anti-ischemic effects that do not depend upon reductions in heart rate or blood pressure. It is the first new anti-anginal developed in over 20 years.
• Toxicity: In the event of overdose, the expected symptoms would be dizziness, nausea/vomiting, diplopia, paresthesia, and confusion. Syncope with prolonged loss of consciousness may develop.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic, metabolized mainly by CYP3A and to a lesser extent by CYP2D6. The pharmacologic activity of the metabolites has not been well characterized.
• Absorption: Absorption is highly variable. After oral administration of ranolazine as a solution, 73% of the dose is systemically available as ranolazine or metabolites. The bioavailability of oral ranolazine relative to that from a solution is 76%.
• Half Life: 7 hours
• Protein Binding: 62%
• Elimination: Ranolazine is metabolized rapidly and extensively in the liver and intestine; less than 5% is excreted unchanged in urine and feces.
• References: Hale SL, Kloner RA: Ranolazine, an inhibitor of the late sodium channel current, reduces postischemic myocardial dysfunction in the rabbit. J Cardiovasc Pharmacol Ther. 2006 Dec;11(4):249-55. [Pubmed] ; Fraser H, Belardinelli L, Wang L, Light PE, McVeigh JJ, Clanachan AS: Ranolazine decreases diastolic calcium accumulation caused by ATX-II or ischemia in rat hearts. J Mol Cell Cardiol. 2006 Dec;41(6):1031-8. Epub 2006 Oct 5. [Pubmed] ; Stone PH, Gratsiansky NA, Blokhin A, Huang IZ, Meng L: Antianginal efficacy of ranolazine when added to treatment with amlodipine: the ERICA (Efficacy of Ranolazine in Chronic Angina) trial. J Am Coll Cardiol. 2006 Aug 1;48(3):566-75. Epub 2006 Jun 15. [Pubmed] ; Chaitman BR, Pepine CJ, Parker JO, Skopal J, Chumakova G, Kuch J, Wang W, Skettino SL, Wolff AA: Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial. JAMA. 2004 Jan 21;291(3):309-16. [Pubmed] ; Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, Murphy SA, Budaj A, Varshavsky S, Wolff AA, Skene A, McCabe CH, Braunwald E: Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial. JAMA. 2007 Apr 25;297(16):1775-83. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1799

Research Area: Cardiovascular Disease
Biological Activity:
Ranolazine(Ranexa) is an antianginal medication. Ranolazine is believed to have its effects via altering the trans-cellular late sodium current. It is by altering the intracellular sodium level that ranolazine affects the sodium-dependent calcium channels during myocardial ischemia in rabbits. Thus, ranolazine indirectly prevents the calcium overload that causes cardiac ischemia in rats. [1]

Toronto Research Chemicals - R122500

Ranolazine is an anti-ischemic agent which modulates myocardial metabolism. Antianginal.

REFERENCES

• Hale SL, Kloner RA: Ranolazine, an inhibitor of the late sodium channel current, reduces postischemic myocardial dysfunction in the rabbit. J Cardiovasc Pharmacol Ther. 2006 Dec;11(4):249-55. Pubmed
• Fraser H, Belardinelli L, Wang L, Light PE, McVeigh JJ, Clanachan AS: Ranolazine decreases diastolic calcium accumulation caused by ATX-II or ischemia in rat hearts. J Mol Cell Cardiol. 2006 Dec;41(6):1031-8. Epub 2006 Oct 5. Pubmed
• Stone PH, Gratsiansky NA, Blokhin A, Huang IZ, Meng L: Antianginal efficacy of ranolazine when added to treatment with amlodipine: the ERICA (Efficacy of Ranolazine in Chronic Angina) trial. J Am Coll Cardiol. 2006 Aug 1;48(3):566-75. Epub 2006 Jun 15. Pubmed
• Chaitman BR, Pepine CJ, Parker JO, Skopal J, Chumakova G, Kuch J, Wang W, Skettino SL, Wolff AA: Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial. JAMA. 2004 Jan 21;291(3):309-16. Pubmed
• Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, Murphy SA, Budaj A, Varshavsky S, Wolff AA, Skene A, McCabe CH, Braunwald E: Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial. JAMA. 2007 Apr 25;297(16):1775-83. Pubmed
• Chaitman, B.R., et al.: J. Am. Coll. Cardial., 43, 1375 (2004)
• McCormack, J.G., et al.: Gen. Pharmacol., 30, 639 (2004)
• Schofield, J.A.H., et al.: Expert Opin. Invest. Drugs, 11, 117 (2004)