Temocapril
Explore a selection of our essential drug information below, or:
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
- 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).
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- 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 Organism UAngiotensin-converting enzyme inhibitorHumans - 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 outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- 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/ADRs
- Not Available
Interactions
- Drug Interactions
- 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 softwareAbaloparatide Abaloparatide may increase the hypotensive activities of Temocapril. 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. - Food Interactions
- Not Available
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- 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 by Classyfire
- 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
- General References
- Tsuji A: Transporter-mediated Drug Interactions. Drug Metab Pharmacokinet. 2002;17(4):253-74. [Article]
- 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]
- 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]
- 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]
- Clearance of Temocapril and Enalapril during Haemodialysis Treatment [Link]
- External Links
- 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 Trials
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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 Hydrogen Donor Count 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 Rule 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
Spectra
- Mass Spec (NIST)
- Download (163 KB)
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0udi-3300900000-07c0bde728f9e7cad38a Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-0000900000-84818080b199ac6e669d Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-2004900000-b1261cda8d33e9f21b0b Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0059-0221900000-c846f1fbf2343385789d Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-047l-2191400000-391bf8dad8d45d6aaffc Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-004l-4950200000-5ee63f7afebc934344a7 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0fsr-3942300000-d1dd383916e79c083f59 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 215.0759595 predictedDarkChem Lite v0.1.0 [M-H]- 211.9510595 predictedDarkChem Lite v0.1.0 [M-H]- 198.24147 predictedDeepCCS 1.0 (2019) [M+H]+ 215.2060595 predictedDarkChem Lite v0.1.0 [M+H]+ 212.4727595 predictedDarkChem Lite v0.1.0 [M+H]+ 200.63702 predictedDeepCCS 1.0 (2019) [M+Na]+ 215.7173595 predictedDarkChem Lite v0.1.0 [M+Na]+ 212.0414595 predictedDarkChem Lite v0.1.0 [M+Na]+ 206.54955 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins, thereby playing a key role in the regulation of blood pressure, electrolyte homeostasis or synaptic plasticity (PubMed:15615692, PubMed:20826823, PubMed:2558109, PubMed:4322742, PubMed:7523412, PubMed:7683654). Composed of two similar catalytic domains, each possessing a functional active site, with different selectivity for substrates (PubMed:10913258, PubMed:1320019, PubMed:1851160, PubMed:19773553, PubMed:7683654, PubMed:7876104). Plays a major role in the angiotensin-renin system that regulates blood pressure and sodium retention by the kidney by converting angiotensin I to angiotensin II, resulting in an increase of the vasoconstrictor activity of angiotensin (PubMed:11432860, PubMed:1851160, PubMed:19773553, PubMed:23056909, PubMed:4322742). Also able to inactivate bradykinin, a potent vasodilator, and therefore enhance the blood pressure response (PubMed:15615692, PubMed:2558109, PubMed:4322742, PubMed:6055465, PubMed:6270633, PubMed:7683654). Acts as a regulator of synaptic transmission by mediating cleavage of neuropeptide hormones, such as substance P, neurotensin or enkephalins (PubMed:15615692, PubMed:6208535, PubMed:6270633, PubMed:656131). Catalyzes degradation of different enkephalin neuropeptides (Met-enkephalin, Leu-enkephalin, Met-enkephalin-Arg-Phe and possibly Met-enkephalin-Arg-Gly-Leu) (PubMed:2982830, PubMed:6270633, PubMed:656131). Acts as a regulator of synaptic plasticity in the nucleus accumbens of the brain by mediating cleavage of Met-enkephalin-Arg-Phe, a strong ligand of Mu-type opioid receptor OPRM1, into Met-enkephalin (By similarity). Met-enkephalin-Arg-Phe cleavage by ACE decreases activation of OPRM1, leading to long-term synaptic potentiation of glutamate release (By similarity). Also acts as a regulator of hematopoietic stem cell differentiation by mediating degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP) (PubMed:26403559, PubMed:7876104, PubMed:8257427, PubMed:8609242). Acts as a regulator of cannabinoid signaling pathway by mediating degradation of hemopressin, an antagonist peptide of the cannabinoid receptor CNR1 (PubMed:18077343). Involved in amyloid-beta metabolism by catalyzing degradation of Amyloid-beta protein 40 and Amyloid-beta protein 42 peptides, thereby preventing plaque formation (PubMed:11604391, PubMed:16154999, PubMed:19773553). Catalyzes cleavage of cholecystokinin (maturation of Cholecystokinin-8 and Cholecystokinin-5) and Gonadoliberin-1 (both maturation and degradation) hormones (PubMed:10336644, PubMed:2983326, PubMed:7683654, PubMed:9371719). Degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP) and amyloid-beta proteins is mediated by the N-terminal catalytic domain, while angiotensin I and cholecystokinin cleavage is mediated by the C-terminal catalytic region (PubMed:10336644, PubMed:19773553, PubMed:7876104)
- Specific Function
- actin binding
- Gene Name
- ACE
- Uniprot ID
- P12821
- Uniprot Name
- Angiotensin-converting enzyme
- Molecular Weight
- 149713.675 Da
References
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Electrogenic proton-coupled amino-acid transporter that transports oligopeptides of 2 to 4 amino acids with a preference for dipeptides. Transports neutral and monovalently charged peptides with a proton to peptide stoichiometry of 1:1 or 2:1 (By similarity) (PubMed:15521010, PubMed:18367661, PubMed:19685173, PubMed:26320580, PubMed:7896779, PubMed:8914574, PubMed:9835627). Primarily responsible for the absorption of dietary di- and tripeptides from the small intestinal lumen (By similarity). Mediates transepithelial transport of muramyl and N-formylated bacterial dipeptides contributing to recognition of pathogenic bacteria by the mucosal immune system (PubMed:15521010, PubMed:9835627)
- Specific Function
- dipeptide transmembrane transporter activity
- Gene Name
- SLC15A1
- Uniprot ID
- P46059
- Uniprot Name
- Solute carrier family 15 member 1
- Molecular Weight
- 78805.265 Da
References
- Tsuji A: Transporter-mediated Drug Interactions. Drug Metab Pharmacokinet. 2002;17(4):253-74. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Na(+)-independent transporter that mediates the cellular uptake of a broad range of organic anions such as the endogenous bile salts cholate and deoxycholate, either in their unconjugated or conjugated forms (taurocholate and glycocholate), at the plasmam membrane (PubMed:19129463, PubMed:7557095). Responsible for intestinal absorption of bile acids (By similarity). Transports dehydroepiandrosterone 3-sulfate (DHEAS), a major circulating steroid secreted by the adrenal cortex, as well as estrone 3-sulfate and 17beta-estradiol 17-O-(beta-D-glucuronate) (PubMed:11159893, PubMed:12568656, PubMed:19129463, PubMed:23918469, PubMed:25560245, PubMed:9539145). Mediates apical uptake of all-trans-retinol (atROL) across human retinal pigment epithelium, which is essential to maintaining the integrity of the visual cycle and thus vision (PubMed:25560245). Involved in the uptake of clinically used drugs (PubMed:17301733, PubMed:20686826, PubMed:27777271). Capable of thyroid hormone transport (both T3 or 3,3',5'-triiodo-L-thyronine, and T4 or L-tyroxine) (PubMed:19129463, PubMed:20358049). Also transports prostaglandin E2 (PubMed:19129463). Plays roles in blood-brain and -cerebrospinal fluid barrier transport of organic anions and signal mediators, and in hormone uptake by neural cells (By similarity). May also play a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons (PubMed:25132355). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel (PubMed:23243220). Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO1A2
- Uniprot ID
- P46721
- Uniprot Name
- Solute carrier organic anion transporter family member 1A2
- Molecular Weight
- 74144.105 Da
References
- 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 August 02, 2024 07:31