Identification

Name
Lercanidipine
Accession Number
DB00528  (APRD00193)
Type
Small Molecule
Groups
Approved, 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
  • Lercanidipino
  • Lercanil
Categories
UNII
V7XTJ4R0BH
CAS number
100427-26-7
Weight
Average: 611.7272
Monoisotopic: 611.299536059
Chemical Formula
C36H41N3O6
InChI Key
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

Pharmacology

Indication

For the treatment of Hypertension, management of angina pectoris and Raynaud's syndrome

Pharmacodynamics

Lercanidipine, 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 action

By 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.

TargetActionsOrganism
AVoltage-dependent calcium channel gamma-1 subunit
inhibitor
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Lercanidipine.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Lercanidipine.
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidLercanidipine may increase the hypotensive activities of 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
2,4-thiazolidinedioneThe risk or severity of hypoglycemia can be increased when Lercanidipine is combined with 2,4-thiazolidinedione.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Lercanidipine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Lercanidipine.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Lercanidipine.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Lercanidipine.
6-Deoxyerythronolide BThe metabolism of Lercanidipine can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Lercanidipine.
Food Interactions
Not 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
Human Metabolome Database
HMDB0014669
PubChem Compound
65866
PubChem Substance
46508865
ChemSpider
59276
ChEBI
135930
ChEMBL
CHEMBL250270
Therapeutic Targets Database
DAP001261
PharmGKB
PA164769058
Wikipedia
Lercanidipine
ATC Codes
C09DB08 — Valsartan and lercanidipineC08CA13 — LercanidipineC09BB02 — Enalapril and lercanidipine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentHypertension,Essential2
3CompletedTreatmentHigh Blood Pressure (Hypertension)1
4CompletedTreatmentCardiovascular Disease (CVD) / Chronic Kidney Disease (CKD) / Hypertension,Essential / Strokes1
4CompletedTreatmentHigh Blood Pressure (Hypertension)1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Hypertension,Essential1
4RecruitingTreatmentProteinuria / Renal Insufficiency,Chronic1
4Unknown StatusTreatmentHigh Blood Pressure (Hypertension) / Human Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedNot AvailableHigh Blood Pressure (Hypertension)1
Not AvailableRecruitingNot AvailableObesity, Morbid1
Not AvailableTerminatedTreatmentHigh Blood Pressure (Hypertension) / Microvascular Angina1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylmethanes
Direct Parent
Diphenylmethanes
Alternative Parents
Nitrobenzenes / Dihydropyridinecarboxylic acids and derivatives / Nitroaromatic compounds / Aralkylamines / Dicarboxylic acids and derivatives / Vinylogous amides / Methyl esters / Enoate esters / Trialkylamines / Amino acids and derivatives
show 9 more
Substituents
Diphenylmethane / Dihydropyridinecarboxylic acid derivative / Nitrobenzene / Nitroaromatic compound / Dihydropyridine / Aralkylamine / Dicarboxylic acid or derivatives / Hydropyridine / Methyl ester / Enoate ester
show 28 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not 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...
Gene Name
CACNG1
Uniprot ID
Q06432
Uniprot Name
Voltage-dependent calcium channel gamma-1 subunit
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
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 un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
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. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  3. 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 un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
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]
  2. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]

Drug created on June 13, 2005 07:24 / Updated on November 05, 2018 17:48