Details of the Drug

General Information of Drug (ID: DMJPGUA)

Drug Name
MANIDIPINE
Synonyms
manidipine; 89226-50-6; Franidipine; 120092-68-4; Manidipine 6300; 3-(2-(4-Benzhydrylpiperazin-1-yl)ethyl) 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate; Iperten; Artedil; Manidipine [INN]; Manidipine (Manyper); C35H38N4O6; CHEMBL312176; Manidipine (INN); 2-(4-Diphenylmethyl-1-piperazinyl)ethyl methyl-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate; 2-[4-(diphenylmethyl)piperazin-1-yl]ethyl methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridin
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 3 Molecular Weight (mw) 610.7
Logarithm of the Partition Coefficient (xlogp) 5.6
Rotatable Bond Count (rotbonds) 11
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 9
ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 1.5 h [1]
Elimination
63% of drug is eliminated in the feces and 31% in the urine as metabolites [1]
Half-life
The concentration or amount of drug in body reduced by one-half in 7.95 hours [1]
Metabolism
The drug is metabolized via the CYP enzymes to pyridine derivatives and diphenylmethane derivatives [1]
Chemical Identifiers
Formula
C35H38N4O6
IUPAC Name
5-O-[2-(4-benzhydrylpiperazin-1-yl)ethyl] 3-O-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
Canonical SMILES
CC1=C(C(C(=C(N1)C)C(=O)OCCN2CCN(CC2)C(C3=CC=CC=C3)C4=CC=CC=C4)C5=CC(=CC=C5)[N+](=O)[O-])C(=O)OC
InChI
InChI=1S/C35H38N4O6/c1-24-30(34(40)44-3)32(28-15-10-16-29(23-28)39(42)43)31(25(2)36-24)35(41)45-22-21-37-17-19-38(20-18-37)33(26-11-6-4-7-12-26)27-13-8-5-9-14-27/h4-16,23,32-33,36H,17-22H2,1-3H3
InChIKey
ANEBWFXPVPTEET-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
4008
ChEBI ID
CHEBI:135849
CAS Number
89226-50-6
DrugBank ID
DB09238
TTD ID
D08TVA
INTEDE ID
DR1001

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Trypanosoma Cruzipain (Trypano CYSP) TTEAID7 CYSP_TRYCR Inhibitor [2]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [3]
Cytochrome P450 2J2 (CYP2J2) DERSX5P CP2J2_HUMAN Substrate [4]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Androgen receptor (AR) OTUBKAZZ ANDR_HUMAN Gene/Protein Processing [5]
Bile acid receptor (NR1H4) OTWZLPTB NR1H4_HUMAN Gene/Protein Processing [5]
Cytochrome b-245 light chain (CYBA) OT16N9ZO CY24A_HUMAN Gene/Protein Processing [6]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Gene/Protein Processing [7]
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Gene/Protein Processing [7]
Cytochrome P450 2J2 (CYP2J2) OTJBTEH8 CP2J2_HUMAN Gene/Protein Processing [4]
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Gene/Protein Processing [5]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Gene/Protein Processing [6]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Gene/Protein Processing [5]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Gene/Protein Processing [8]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 Manidipine: a review of its use in hypertension. Drugs. 2001;61(12):1777-99.
2 Colloid formation by drugs in simulated intestinal fluid. J Med Chem. 2010 May 27;53(10):4259-65.
3 Effect of grapefruit juice on the disposition of manidipine enantiomers in healthy subjects. Br J Clin Pharmacol. 2006 May;61(5):533-7.
4 Inhibitory effects of antihypertensive drugs on human cytochrome P450 2J2 activity: Potent inhibition by azelnidipine and manidipine. Chem Biol Interact. 2019 Jun 1;306:1-9.
5 Quantitative high-throughput profiling of environmental chemicals and drugs that modulate farnesoid X receptor. Sci Rep. 2014 Sep 26;4:6437. doi: 10.1038/srep06437.
6 Effect of manidipine on gene expression and protein level of oxidative stress-related proteins: p22phox and HO-1: relevance for antihypertensive and anti-remodeling effects. J Cardiovasc Pharmacol. 2004 Apr;43(4):531-8. doi: 10.1097/00005344-200404000-00008.
7 Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol. 2000 Feb-Mar;55(11-12):843-52.
8 Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.