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Identification
NameLercanidipine
Accession NumberDB00528  (APRD00193)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Lercanidipine is a calcium channel blocker of the dihydropyridine class.

It is sold under various commercial names including Zanidip.

Structure
Thumb
Synonyms
Lercanidipine
Lercanil
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIV7XTJ4R0BH
CAS number100427-26-7
WeightAverage: 611.7272
Monoisotopic: 611.299536059
Chemical FormulaC36H41N3O6
InChI KeyInChIKey=ZDXUKAKRHYTAKV-UHFFFAOYSA-N
InChI
InChI=1S/C36H41N3O6/c1-24-31(34(40)44-6)33(28-18-13-19-29(22-28)39(42)43)32(25(2)37-24)35(41)45-36(3,4)23-38(5)21-20-30(26-14-9-7-10-15-26)27-16-11-8-12-17-27/h7-19,22,30,33,37H,20-21,23H2,1-6H3
IUPAC Name
3-{1-[(3,3-diphenylpropyl)(methyl)amino]-2-methylpropan-2-yl} 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
SMILES
COC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OC(C)(C)CN(C)CCC(C1=CC=CC=C1)C1=CC=CC=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassDiphenylmethanes
Direct ParentDiphenylmethanes
Alternative Parents
Substituents
  • Diphenylmethane
  • Phenylpropylamine
  • Nitrobenzene
  • Dihydropyridinecarboxylic acid derivative
  • Aralkylamine
  • Dihydropyridine
  • Hydropyridine
  • Dicarboxylic acid or derivatives
  • Vinylogous amide
  • Alpha,beta-unsaturated carboxylic ester
  • Enoate ester
  • Methyl ester
  • Organic nitro compound
  • Tertiary aliphatic amine
  • Tertiary amine
  • Organic nitrite
  • C-nitro compound
  • Carboxylic acid ester
  • Azacycle
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Allyl-type 1,3-dipolar organic compound
  • Organic oxoazanium
  • Enamine
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organic salt
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Organic zwitterion
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of Hypertension, management of angina pectoris and Raynaud's syndrome
PharmacodynamicsLercanidipine, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Lercanidipine is similar to other peripheral vasodilators. Lercanidipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.
Mechanism of actionBy deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, Lercanidipine inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9474
Blood Brain Barrier-0.9611
Caco-2 permeable-0.7039
P-glycoprotein substrateSubstrate0.9085
P-glycoprotein inhibitor IInhibitor0.9132
P-glycoprotein inhibitor IIInhibitor0.8957
Renal organic cation transporterNon-inhibitor0.7439
CYP450 2C9 substrateNon-substrate0.8448
CYP450 2D6 substrateNon-substrate0.8924
CYP450 3A4 substrateSubstrate0.7579
CYP450 1A2 substrateInhibitor0.6321
CYP450 2C9 inhibitorInhibitor0.7247
CYP450 2D6 inhibitorInhibitor0.5933
CYP450 2C19 inhibitorInhibitor0.7625
CYP450 3A4 inhibitorInhibitor0.5715
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7709
Ames testNon AMES toxic0.5517
CarcinogenicityNon-carcinogens0.668
BiodegradationNot ready biodegradable0.9895
Rat acute toxicity2.8614 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.5761
hERG inhibition (predictor II)Non-inhibitor0.6908
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP6.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000156 mg/mLALOGPS
logP6.42ALOGPS
logP6.41ChemAxon
logS-6.6ALOGPS
pKa (Strongest Basic)9.36ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area113.69 Å2ChemAxon
Rotatable Bond Count14ChemAxon
Refractivity177.85 m3·mol-1ChemAxon
Polarizability65.78 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis Reference

Bandi Parthasaradhi Reddy, Kura Rathnakar Reddy, Rapolu Raji Reddy, Dasari Muralidhara Reddy, Dandamudi Satish Kumar, " NOVEL PROCESS FOR THE PREPARATION OF LERCANIDIPINE." U.S. Patent US20090227800, issued September 10, 2009.

US20090227800
General References
  1. Lin TH, Voon WC, Yen HW, Huang CH, Su HM, Lai WT, Sheu SH: Lercanidipine and losartan effects on blood pressure and fibrinolytic parameters. Kaohsiung J Med Sci. 2006 Apr;22(4):177-83. [PubMed:16679299 ]
  2. Martinez ML, Lopes LF, Coelho EB, Nobre F, Rocha JB, Gerlach RF, Tanus-Santos JE: Lercanidipine reduces matrix metalloproteinase-9 activity in patients with hypertension. J Cardiovasc Pharmacol. 2006 Jan;47(1):117-22. [PubMed:16424795 ]
  3. Agrawal R, Marx A, Haller H: Efficacy and safety of lercanidipine versus hydrochlorothiazide as add-on to enalapril in diabetic populations with uncontrolled hypertension. J Hypertens. 2006 Jan;24(1):185-92. [PubMed:16331117 ]
External Links
ATC CodesC09DB08C08CA13C09BB02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcetaminophenThe metabolism of Lercanidipine can be increased when combined with Acetaminophen.
AmobarbitalThe metabolism of Lercanidipine can be increased when combined with Amobarbital.
AtazanavirThe serum concentration of Lercanidipine can be increased when it is combined with Atazanavir.
Atracurium besylateLercanidipine may increase the neuromuscular blocking activities of Atracurium besylate.
BoceprevirThe serum concentration of Lercanidipine can be increased when it is combined with Boceprevir.
ButabarbitalThe metabolism of Lercanidipine can be increased when combined with Butabarbital.
ButalbitalThe metabolism of Lercanidipine can be increased when combined with Butalbital.
CaffeineThe metabolism of Lercanidipine can be increased when combined with Caffeine.
Calcium AcetateThe therapeutic efficacy of Lercanidipine can be decreased when used in combination with Calcium Acetate.
Calcium carbonateThe therapeutic efficacy of Lercanidipine can be decreased when used in combination with Calcium carbonate.
Calcium ChlorideThe therapeutic efficacy of Lercanidipine can be decreased when used in combination with Calcium Chloride.
Calcium citrateThe therapeutic efficacy of Lercanidipine can be decreased when used in combination with Calcium citrate.
Calcium gluconateThe therapeutic efficacy of Lercanidipine can be decreased when used in combination with Calcium gluconate.
CeritinibThe serum concentration of Lercanidipine can be increased when it is combined with Ceritinib.
CimetidineThe serum concentration of Lercanidipine can be increased when it is combined with Cimetidine.
Cisatracurium besylateLercanidipine may increase the neuromuscular blocking activities of Cisatracurium besylate.
ClarithromycinThe serum concentration of Lercanidipine can be increased when it is combined with Clarithromycin.
ClopidogrelThe therapeutic efficacy of Clopidogrel can be decreased when used in combination with Lercanidipine.
CobicistatThe serum concentration of Lercanidipine can be increased when it is combined with Cobicistat.
CyclosporineThe serum concentration of Cyclosporine can be increased when it is combined with Lercanidipine.
DarunavirThe serum concentration of Lercanidipine can be increased when it is combined with Darunavir.
DoxazosinDoxazosin may increase the hypotensive activities of Lercanidipine.
EfavirenzThe serum concentration of Lercanidipine can be decreased when it is combined with Efavirenz.
ErythromycinThe metabolism of Lercanidipine can be decreased when combined with Erythromycin.
FluconazoleThe serum concentration of Lercanidipine can be increased when it is combined with Fluconazole.
FosphenytoinThe serum concentration of Fosphenytoin can be increased when it is combined with Lercanidipine.
IdelalisibThe serum concentration of Lercanidipine can be increased when it is combined with Idelalisib.
IndinavirThe serum concentration of Lercanidipine can be increased when it is combined with Indinavir.
ItraconazoleThe serum concentration of Lercanidipine can be increased when it is combined with Itraconazole.
KetoconazoleThe serum concentration of Lercanidipine can be increased when it is combined with Ketoconazole.
Magnesium chlorideThe risk or severity of adverse effects can be increased when Lercanidipine is combined with Magnesium chloride.
Magnesium citrateThe risk or severity of adverse effects can be increased when Lercanidipine is combined with Magnesium citrate.
Magnesium hydroxideThe risk or severity of adverse effects can be increased when Lercanidipine is combined with Magnesium hydroxide.
Magnesium oxideThe risk or severity of adverse effects can be increased when Lercanidipine is combined with Magnesium oxide.
Magnesium salicylateThe risk or severity of adverse effects can be increased when Lercanidipine is combined with Magnesium salicylate.
Magnesium SulfateThe risk or severity of adverse effects can be increased when Lercanidipine is combined with Magnesium Sulfate.
MethohexitalThe metabolism of Lercanidipine can be increased when combined with Methohexital.
MetoprololLercanidipine may increase the hypotensive activities of Metoprolol.
NafcillinThe metabolism of Lercanidipine can be increased when combined with Nafcillin.
NefazodoneThe serum concentration of Lercanidipine can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Lercanidipine can be increased when it is combined with Nelfinavir.
NitroprussideLercanidipine may increase the hypotensive activities of Nitroprusside.
PancuroniumLercanidipine may increase the neuromuscular blocking activities of Pancuronium.
PentobarbitalThe metabolism of Lercanidipine can be increased when combined with Pentobarbital.
PhenobarbitalThe metabolism of Lercanidipine can be increased when combined with Phenobarbital.
PhenoxybenzaminePhenoxybenzamine may increase the hypotensive activities of Lercanidipine.
PhentolaminePhentolamine may increase the hypotensive activities of Lercanidipine.
PhenytoinThe serum concentration of Phenytoin can be increased when it is combined with Lercanidipine.
PosaconazoleThe serum concentration of Lercanidipine can be increased when it is combined with Posaconazole.
PrazosinPrazosin may increase the hypotensive activities of Lercanidipine.
RifabutinThe serum concentration of Lercanidipine can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Lercanidipine can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Lercanidipine can be decreased when it is combined with Rifapentine.
RitonavirThe serum concentration of Lercanidipine can be increased when it is combined with Ritonavir.
RocuroniumLercanidipine may increase the neuromuscular blocking activities of Rocuronium.
SaquinavirThe serum concentration of Lercanidipine can be increased when it is combined with Saquinavir.
SecobarbitalThe metabolism of Lercanidipine can be increased when combined with Secobarbital.
SilodosinSilodosin may increase the hypotensive activities of Lercanidipine.
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Lercanidipine.
SulfisoxazoleThe metabolism of Lercanidipine can be decreased when combined with Sulfisoxazole.
TamsulosinTamsulosin may increase the hypotensive activities of Lercanidipine.
TelaprevirThe serum concentration of Lercanidipine can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Lercanidipine can be increased when it is combined with Telithromycin.
TerazosinTerazosin may increase the hypotensive activities of Lercanidipine.
VecuroniumLercanidipine may increase the neuromuscular blocking activities of Vecuronium.
VoriconazoleThe serum concentration of Lercanidipine can be increased when it is combined with Voriconazole.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Voltage-gated calcium channel activity
Specific Function:
This protein is a subunit of the dihydropyridine (DHP) sensitive calcium channel. Plays a role in excitation-contraction coupling. The skeletal muscle DHP-sensitive Ca(2+) channel may function only as a multiple subunit complex.
Gene Name:
CACNG1
Uniprot ID:
Q06432
Molecular Weight:
25028.105 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Burnier M, Pruijm M, Wuerzner G: Treatment of essential hypertension with calcium channel blockers: what is the place of lercanidipine? Expert Opin Drug Metab Toxicol. 2009 Aug;5(8):981-7. doi: 10.1517/17425250903085135. [PubMed:19619074 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxygen binding
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular Weight:
57108.065 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxygen binding
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A7
Uniprot ID:
P24462
Molecular Weight:
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23