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], [2]

Therapeutic Class

Antihypertensive Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

417.5

Topological Polar Surface Area (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 [3]
Bioavailability: 60% of drug becomes completely available to its intended biological destination(s) [4]
Clearance: The renal clearance of drug is 10.8 L/h [5]
Elimination: 0% of drug is excreted from urine in the unchanged form [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 1 - 4 hours [6]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.3422 micromolar/kg/day [7]
Water Solubility: The ability of drug to dissolve in water is measured as 1 mg/mL [3]

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

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	[8]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

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

Jump to Detail Molecular Expression Atlas of This Drug

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	Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
3	BDDCS applied to over 900 drugs
4	Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
5	An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
6	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
7	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
8	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.
9	Determination of bezafibrate, methotrexate, cyclophosphamide, orlistat and enalapril in waste and surface waters using on-line solid-phase extracti... J Environ Monit. 2009 Apr;11(4):830-8.
10	Central angiotensin II controls alcohol consumption via its AT1 receptor. FASEB J. 2005 Sep;19(11):1474-81.
11	Using ACE inhibitors appropriately. Am Fam Physician. 2002 Aug 1;66(3):461-8.
12	Efficacy of benazepril hydrochloride to delay the progression of occult dilated cardiomyopathy in Doberman Pinschers. J Vet Intern Med. 2009 Sep-Oct;23(5):977-83.
13	Moexipril for treatment of primary biliary cirrhosis in patients with an incomplete response to ursodeoxycholic acid. Dig Dis Sci. 2010 Feb;55(2):476-83.
14	Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
15	Fixed combination perindopril-amlodipine (Coveram) in the treatment of hypertension and coronary heart disease. Rev Med Liege. 2009 Apr;64(4):223-7.
16	Selective reduction of central pulse pressure under angiotensin blockage in SHR: role of the fibronectin-alpha5beta1 integrin complex. Am J Hypertens. 2009 Jul;22(7):711-7.
17	Angiotensin-converting enzyme inhibition and novel cardiovascular risk biomarkers: results from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study. Am Heart J. 2009 Feb;157(2):334.e1-8.
18	Involvement of vascular angiotensin II-forming enzymes in the progression of aortic abdominal aneurysms in angiotensin II- infused ApoE-deficient m... J Atheroscler Thromb. 2009 Jun;16(3):164-71.