Details of the Drug

General Information of Drug (ID: DM4V6JA)

Drug Name

Cilazapril

Synonyms

Cilazaprilum; Cilazil; Dynorm; Inhibace; Inibace; Justor; Vascace; CILAZAPRIL MONOHYDRATE; Cilazapril anhydrous;Cilazapril hydrate; Cilazaprilum [Latin]; Cilazapril (INN); Cilazapril (USAN); Cilazapril (anhydrous); Cilazapril hydrate (JAN); Cilazapril, Anhydrous; Inhibace (TN); Ro 31-2848; Ro 31-2848 monohydrate; Ro 34-2848; Ro-312848; Ro-31-2848; Cilazapril [USAN:INN:BAN:JAN]; (1S,9S)-9-(((S)-1-Carboxy-3-phenylpropyl)amino)octahydro-10-oxo-6H-pyridazino(1,2-a)(1,2)diazepine-1-carboxylic acid 9-ethyl estermonohydrate; (4S,7S)-7-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]-6-oxo-1,2,3,4,7,8,9,10-octahydropyridazino[1,2-a]diazepine-4-carboxylic acid; (4S,7S)-7-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]-6-oxo-1,2,3,4,7,8,9,10-octahydropyridazino[1,2-a]diazepine-4-carboxylic acid hydrate

Indication

Disease Entry	ICD 11	Status	REF
Congestive heart failure	BD10	Approved	[1]
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Therapeutic Class

Antihypertensive Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

417.5

Logarithm of the Partition Coefficient (xlogp)

0.6

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [2]
Bioavailability: 60% of drug becomes completely available to its intended biological destination(s) [3]
Clearance: The renal clearance of drug is 10.8 L/h []
Elimination: 0% of drug is excreted from urine in the unchanged form [2]
Half-life: The concentration or amount of drug in body reduced by one-half in 1 - 4 hours [4]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.3422 micromolar/kg/day [5]
Water Solubility: The ability of drug to dissolve in water is measured as 1 mg/mL [2]

Chemical Identifiers

Formula: C22H31N3O5
IUPAC Name: (4S,7S)-7-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]-6-oxo-1,2,3,4,7,8,9,10-octahydropyridazino[1,2-a]diazepine-4-carboxylic acid
Canonical SMILES: CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]2CCCN3CCC[C@H](N3C2=O)C(=O)O
InChI: InChI=1S/C22H31N3O5/c1-2-30-22(29)18(13-12-16-8-4-3-5-9-16)23-17-10-6-14-24-15-7-11-19(21(27)28)25(24)20(17)26/h3-5,8-9,17-19,23H,2,6-7,10-15H2,1H3,(H,27,28)/t17-,18-,19-/m0/s1
InChIKey: HHHKFGXWKKUNCY-FHWLQOOXSA-N

Cross-matching ID

PubChem CID: 56330
ChEBI ID: CHEBI:3698
CAS Number: 88768-40-5
DrugBank ID: DB01340
TTD ID: D04GKO

Repurposed Drugs (RPD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Angiotensin-converting enzyme (ACE)	TTL69WB	ACE_HUMAN	Inhibitor	[6]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Adiponectin (ADIPOQ)	OTNX23LE	ADIPO_HUMAN	Gene/Protein Processing	[7]
Angiotensin-converting enzyme (ACE)	OTDF1964	ACE_HUMAN	Drug Response	[8]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Protein Interaction/Cellular Processes	[9]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Congestive heart failure

ICD Disease Classification

BD10

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Angiotensin-converting enzyme (ACE)	DTT	SLC33A1	2.62E-01	-0.01	-0.06

Molecular Expression Atlas (MEA)

MEA Detail

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References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6459).
2	BDDCS applied to over 900 drugs
3	Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
4	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
6	Triple pharmacological blockade of the renin-angiotensin-aldosterone system in nondiabetic CKD: an open-label crossover randomized controlled trial. Am J Kidney Dis. 2008 Sep;52(3):486-93.
7	Combination of an ACE inhibitor and indapamide improves blood pressure control, but attenuates the beneficial effects of ACE inhibition on plasma adiponectin in patients with essential hypertension. Circ J. 2009 Dec;73(12):2282-7. doi: 10.1253/circj.cj-09-0387. Epub 2009 Sep 29.
8	[A prospective study on the cough mechanism induced by angiotensin-converting enzyme inhibitors in patients with hypertension]. Zhonghua Jie He He Hu Xi Za Zhi. 2004 Sep;27(9):581-4.
9	Effects of angiotensin converting enzyme inhibitors and calcium antagonists on atrial natriuretic peptide release and action and on albumin excretion rate in hypertensive insulin-dependent diabetic patients. Am J Hypertens. 1992 Nov;5(11):837-46. doi: 10.1093/ajh/5.11.837.