NAV

Temocapril

Identification

Generic Name
Temocapril
DrugBank Accession Number
DB08836
Background

Temocapril is a prodrug-type angiotensin-I converting enzyme (ACE) inhibitor not approved for use in the United States, but is approved in Japan and South Korea. Temocapril can also be used in hemodialysis patients without risk of serious accumulation.

Type
Small Molecule
Groups
Experimental, Investigational
Structure
 3D
Similar Structures
Weight
Average: 476.609
Monoisotopic: 476.143963396
Chemical Formula
C23H28N2O5S2
Synonyms
  • Temocapril
  • Temocaprilum
External IDs
  • CS-622

Pharmacology

Indication

Temocapril is an ACE inhibitor primarily indicated in the treatment of hypertension and congestive heart failure, diabetic nephropathy, and improvement of prognosis for coronary artery diseases (including acute myocardial infarction).

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug events
Improve clinical decision support with information oncontraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events & improve clinical decision support.
Learn more
Pharmacodynamics

Temocapril is a prodrug of its active metabolite (and diacid form) temocaprilat which contains a thiazepine ring. Temocaprilat has slightly higher potency than enalaprilat in ACE inhibition isolated from rabbit lung. ACE inhibitors exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.). When compared with other Angiotensin-converting Enzyme Inhibitors, temocapril's advantages include a rapid onset of action and what research suggests is tighter vascular ACE binding than enalaprilat.

Mechanism of action
Target Actions 生物
UAngiotensin-converting enzyme
inhibitor
 Humans
Absorption

Temocapril is rapidly absorbed in the gastrointestinal tract and converted into the diacid (active) metabolite, which inhibits ACE in plasma.

Volume of distribution

Not Available

Protein binding

99.5%, including those with renal impairment.

Metabolism
Not Available
Route of elimination

Temocapril is eliminated primarily through the liver and kidneys.

Half-life

13.1 hours in patients with normal liver function.

Clearance

19.4% urinary recovery.

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including:blackbox warnings, adverse reactions, warning & precautions, & incidence rates.
Learn more
Improve decision support & research outcomes with our structured adverse effects data.
Learn more
Toxicity

In rats, whether or male or female, the LD50 values of temocapril were higher than 5000 mg/kg.

Pathways
Pathway Category
Temocapril Metabolism Pathway Drug metabolism
Temocapril Action Pathway Drug action
Pharmacogenomic Effects/ADRsBrowse all" title="" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug InteractionsLearn More" title="" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction
Integrate drug-drug
interactions in your software
Acebutolol Acebutolol may increase the hypotensive activities of Temocapril.
Aceclofenac The risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Aceclofenac is combined with Temocapril.
Acemetacin The risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Acemetacin is combined with Temocapril.
Acetylcysteine The excretion of Temocapril can be decreased when combined with Acetylcysteine.
Acetylsalicylic acid The therapeutic efficacy of Temocapril can be decreased when used in combination with Acetylsalicylic acid.
Agrostis gigantea pollen The risk or severity of adverse effects can be increased when Temocapril is combined with Agrostis gigantea pollen.
Agrostis stolonifera pollen The risk or severity of adverse effects can be increased when Temocapril is combined with Agrostis stolonifera pollen.
Alclofenac The risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Alclofenac is combined with Temocapril.
Aldesleukin Aldesleukin may increase the hypotensive activities of Temocapril.
Alfentanil Alfentanil may decrease the antihypertensive activities of Temocapril.
Identify potential medication risks
Easily compare up to 40 drugs with our drug interaction checker.
Get severity rating, description, and management advice.
Learn more
Food Interactions
Not Available

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
Ingredient UNII CAS InChI Key
Temocapril hydrochloride 8G820I95VP 110221-44-8 XDDQNOKKZKHBIX-ASBZXGSUSA-N
International/Other Brands
Acecol (Sankyo)

Categories

ATC Codes
C09AA14 — Temocapril
Drug Categories
Chemical TaxonomyProvided byClassyfire
Description
This compound belongs to the class of organic compounds known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Dipeptides
Alternative Parents
Alpha amino acid esters/Aralkylamines/Fatty acid esters/Dicarboxylic acids and derivatives/Benzene and substituted derivatives/Thiophenes/Tertiary carboxylic acid amides/Heteroaromatic compounds/Amino acids/Lactams
show 9 more
Substituents
Alpha-amino acid ester/Alpha-amino acid or derivatives/Alpha-dipeptide/Amine/Amino acid/Amino acid or derivatives/Aralkylamine/Aromatic heteromonocyclic compound/Azacycle/Benzenoid
show 24 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
18IZ008EU6
CAS number
111902-57-9
InChI Key
FIQOFIRCTOWDOW-BJLQDIEVSA-N
InChI
InChI=1S/C23H28N2O5S2/c1-2-30-23(29)17(11-10-16-7-4-3-5-8-16)24-18-15-32-20(19-9-6-12-31-19)13-25(22(18)28)14-21(26)27/h3-9,12,17-18,20,24H,2,10-11,13-15H2,1H3,(H,26,27)/t17-,18-,20-/m0/s1
IUPAC Name
2-[(2S,6R)-6-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}-5-oxo-2-(thiophen-2-yl)-1,4-thiazepan-4-yl]acetic acid
SMILES
CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]1CS[C@@H](CN(CC(O)=O)C1=O)C1=CC=CS1

References

一般引用
  1. Tsuji A: Transporter-mediated Drug Interactions. Drug Metab Pharmacokinet. 2002;17(4):253-74. [Article]
  2. Furuta S, Kiyosawa K, Higuchi M, Kasahara H, Saito H, Shioya H, Oguchi H: Pharmacokinetics of temocapril, an ACE inhibitor with preferential biliary excretion, in patients with impaired liver function. Eur J Clin Pharmacol. 1993;44(4):383-5. [Article]
  3. Nakashima M, Yamamoto J, Shibata M, Uematsu T, Shinjo H, Akahori T, Shioya H, Sugiyama K, Kawahara Y: Pharmacokinetics of temocapril hydrochloride, a novel angiotensin converting enzyme inhibitor, in renal insufficiency. Eur J Clin Pharmacol. 1992;43(6):657-9. [Article]
  4. Yasunari K, Maeda K, Nakamura M, Watanabe T, Yoshikawa J, Asada A: Pharmacological and clinical studies with temocapril, an angiotensin converting enzyme inhibitor that is excreted in the bile. Cardiovasc Drug Rev. 2004 Fall;22(3):189-98. [Article]
  5. Clearance of Temocapril and Enalapril during Haemodialysis Treatment [Link]
Human Metabolome Database
HMDB0061720
KEGG Drug
D08566
PubChem Compound
443874
PubChem Substance
175427114
ChemSpider
391964
ChEBI
135771
ChEMBL
CHEMBL2110627
ZINC
ZINC000003808778
Drugs.com
Drugs.com Drug Page
Wikipedia
Temocapril
MSDS
Download (569 KB)

Clinical Trials

Clinical TrialsLearn More" title="" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Property Value Source
melting point (°C) decomposes at 187 Not Available
water solubility <1 mg/mL Not Available
Predicted Properties
Property Value Source
Water Solubility 0.00342 mg/mL ALOGPS
logP 2.46 ALOGPS
logP 2.04 Chemaxon
logS -5.1 ALOGPS
pKa (Strongest Acidic) 3.88 Chemaxon
pKa (Strongest Basic) 5.14 Chemaxon
Physiological Charge -1 Chemaxon
Hydrogen Acceptor Count 5 Chemaxon
氢供体数 2 Chemaxon
Polar Surface Area 95.94 Å2 Chemaxon
Rotatable Bond Count 11 Chemaxon
Refractivity 124.1 m3·mol-1 Chemaxon
Polarizability 49.28 Å3 Chemaxon
Number of Rings 3 Chemaxon
Bioavailability 1 Chemaxon
Rule of Five Yes Chemaxon
Ghose Filter Yes Chemaxon
Veber's Rule No Chemaxon
MDDR-like规则 Yes Chemaxon
Predicted ADMET Features
Property Value Probability
Human Intestinal Absorption + 0.9707
Blood Brain Barrier - 0.8501
Caco-2 permeable - 0.6871
P-glycoprotein substrate Substrate 0.8016
P-glycoprotein inhibitor I Non-inhibitor 0.6373
P-glycoprotein inhibitor II Non-inhibitor 0.9056
Renal organic cation transporter Non-inhibitor 0.8744
CYP450 2C9 substrate Non-substrate 0.6676
CYP450 2D6 substrate Non-substrate 0.8686
CYP450 3A4 substrate Substrate 0.5082
CYP450 1A2 substrate Non-inhibitor 0.7748
CYP450 2C9 inhibitor Non-inhibitor 0.6996
CYP450 2D6 inhibitor Non-inhibitor 0.8016
CYP450 2C19 inhibitor Inhibitor 0.5371
CYP450 3A4 inhibitor Non-inhibitor 0.746
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7297
Ames test Non AMES toxic 0.7962
Carcinogenicity Non-carcinogens 0.8965
Biodegradation Not ready biodegradable 0.9584
Rat acute toxicity 2.3397 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9862
hERG inhibition (predictor II) Inhibitor 0.5523
ADMET data is predicted usingadmetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (163 KB)
Spectra
Spectrum Spectrum Type Splash Key
Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets tounlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Details 1.Angiotensin-converting enzyme
Kind
Protein
生物
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin. Also able to inactivate bradykinin, a potent...
Gene Name
ACE
Uniprot ID
P12821
Uniprot Name
Angiotensin-converting enzyme
分子量
149713.675 Da
References
  1. Furuta S, Kiyosawa K, Higuchi M, Kasahara H, Saito H, Shioya H, Oguchi H: Pharmacokinetics of temocapril, an ACE inhibitor with preferential biliary excretion, in patients with impaired liver function. Eur J Clin Pharmacol. 1993;44(4):383-5. [Article]

Transporters

Details 1.Solute carrier family 15 member 1
Kind
Protein
生物
Humans
Pharmacological action
Unknown
General Function
Proton-dependent oligopeptide secondary active transmembrane transporter activity
Specific Function
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products.
Gene Name
SLC15A1
Uniprot ID
P46059
Uniprot Name
Solute carrier family 15 member 1
分子量
78805.265 Da
References
  1. Tsuji A: Transporter-mediated Drug Interactions. Drug Metab Pharmacokinet. 2002;17(4):253-74. [Article]
Details 2.Solute carrier organic anion transporter family member 1A2
Kind
Protein
生物
Humans
Pharmacological action
Unknown
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
分子量
74144.105 Da
References
  1. Ishizuka H, Konno K, Naganuma H, Nishimura K, Kouzuki H, Suzuki H, Stieger B, Meier PJ, Sugiyama Y: Transport of temocaprilat into rat hepatocytes: role of organic anion transporting polypeptide. J Pharmacol Exp Ther. 1998 Oct;287(1):37-42. [Article]

Drug created at February 20, 2013 00:04 / Updated at February 03, 2022 21:15