Temocapril

Synonyms :
Temocaprilum

Status : experimental

Category

Angiotensin-Converting Enzyme Inhibitors

Therapeutic Classification

ACE INHIBITORS, PLAIN

CARDIOVASCULAR SYSTEM
AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
ACE INHIBITORS, PLAIN
Antihypertensive Agents

Description

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.

Used

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).

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.

Toxic Effect

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

Absorption

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

Half Life

13.1 hours in patients with normal liver function.

Protein Binding

99.5%, including those with renal impairment.

Elimination Route

Temocapril is eliminated primarily through the liver and kidneys.

Clearance

19.4% urinary recovery.

Chemical Classification

This compound belongs to the class of organic compounds known as alpha amino acid esters. These are ester derivatives of alpha amino acids.

Alpha amino acid esters

Organic compounds

Organic acids and derivatives

Carboxylic acids and derivatives

Amino acids, peptides, and analogues

Salt : Temocapril Hydrochloride

Chemical Name

Temocaprilum

Calculated Property

kind Value Source
logP 2.46 ALOGPS
logS -5.1 ALOGPS
Water Solubility 3.42e-03 g/l ALOGPS
logP 2.04 ChemAxon
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 hydrochloride ChemAxon
Traditional IUPAC Name [(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 hydrochloride ChemAxon
Molecular Weight 513.07 ChemAxon
Monoisotopic Weight 512.120641135 ChemAxon
SMILES Cl.CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]1CS[C@@H](CN(CC(O)=O)C1=O)C1=CC=CS1 ChemAxon
Molecular Formula C23H29ClN2O5S2 ChemAxon
InChI InChI=1/C23H28N2O5S2.ClH/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);1H/t17-,18-,20-;/s2 ChemAxon
InChIKey InChIKey=XDDQNOKKZKHBIX-ZXTPIAIONA-N ChemAxon
Polar Surface Area (PSA) 95.94 ChemAxon
Refractivity 124.1 ChemAxon
Polarizability 49.28 ChemAxon
Rotatable Bond Count 11 ChemAxon
H Bond Acceptor Count 5 ChemAxon
H Bond Donor Count 2 ChemAxon
pKa (strongest acidic) 3.88 ChemAxon
pKa (strongest basic) 5.14 ChemAxon
Physiological Charge -1 ChemAxon
Number of Rings 3 ChemAxon
Bioavailability 0 ChemAxon
Rule of Five 0 ChemAxon
Ghose Filter 0 ChemAxon
MDDR-Like Rule 1 ChemAxon

Affected organism

Humans and other mammals

Target within organism

  • Angiotensin-converting enzyme : in Human