Temocapril HCl is the hydrochloride of Temocapril, which is a long-acting angiotensin-converting enzyme (ACE) inhibitor, it is used for the treatment of hypertension. Temocapril is a prodrug-type 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.
Physicochemical Properties
| Molecular Formula | C23H28N2O5S2.HCL | |
| Molecular Weight | 513.07 | |
| Exact Mass | 512.12 | |
| CAS # | 110221-44-8 | |
| Related CAS # | Temocapril;111902-57-9;Temocapril-d5;1356840-03-3 | |
| PubChem CID | 443873 | |
| Appearance | White to off-white solid powder | |
| Boiling Point | 717.4ºC at 760 mmHg | |
| Melting Point | 196-200ºC (dec) | |
| Flash Point | 387.7ºC | |
| Vapour Pressure | 1.34E-21mmHg at 25°C | |
| Index of Refraction | 1.628 | |
| LogP | 1.284 | |
| Hydrogen Bond Donor Count | 3 | |
| Hydrogen Bond Acceptor Count | 8 | |
| Rotatable Bond Count | 11 | |
| Heavy Atom Count | 33 | |
| Complexity | 644 | |
| Defined Atom Stereocenter Count | 3 | |
| SMILES | CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]2CS[C@@H](CN(C2=O)CC(=O)O)C3=CC=CS3.Cl |
|
| InChi Key | XDDQNOKKZKHBIX-ASBZXGSUSA-N | |
| InChi Code | InChI=1S/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-;/m0./s1 | |
| Chemical 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 | |
| Synonyms |
|
|
| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
|
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | The prodrug of Temocaprilat, an ACE inhibitor, is Temocapril hydrochloride. Temoprilat hydrochloride is easily absorbed by the small intestine and then processed by CES1 (human carboxylesterase 1) in the liver to produce its active metabolite, temoprilat [1]. The inhibitory effects of AngI and RS (N-acetyl tetradecapeptide renin substrate) on SHR neurogenic vasodilation are lessened by temocapril hydrochloride (500 nM) [2]. Temocapril hydrochloride (0.1–10 μM; 24 h) induces the redox protein TRX, but does not change the production of Mn-SOD and Cu/ZnSOD, two antioxidant enzymes [3]. |
| ln Vivo | Improved thioredoxin expression in cardiomyocytes and amelioration of autoimmune myocarditis are two benefits of temopril hydrochloride (10 mg/kg; oral; 21 days) [3]. For four weeks, temopril hydrochloride (30 mg/kg; oral; daily) reduces renal ACE activity, plasma, and angiotensin I-induced hypertension, but not renal Ang II levels [4]. |
| Cell Assay |
Cell proliferation assay [3] Cell Types: cultured neonatal rat cardiomyocytes Tested Concentrations: 0.1 μM, 1 μM, 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: TRX protein expression was enhanced 1.9 times at 10 μM without affecting TRX2 and Cu/Zn -SOD or Mn-SOD protein expression. |
| Animal Protocol |
Animal/Disease Models: Experimental autoimmune myocarditis (EAM) rat model [3] Doses: 10 mg/kg Route of Administration: po (oral gavage); water management; 21-day Experimental Results: Improve EAM and prevent cellular protein oxidation. The expression of redox regulatory protein TRX in cardiomyocytes is enhanced. Animal/Disease Models: Male Sprague Dawley rats [1] Doses: 30 mg/kg Route of Administration: Orally, one time/day for 4 weeks Experimental Results: Inhibition of Ang I-induced increase in blood pressure. |
| References |
[1]. In vitro evaluation of inhibitory effects of antidiabetic and antihyperlipidemic drugs on human carboxylesterase activities. Drug Metab Dispos. 2010 Dec;38(12):2173-8. [2]. Angiotensin inhibits neurotransmission of calcitonin gene-related peptide-containing vasodilator nerves in mesenteric artery of spontaneously hypertensive rats. J Pharmacol Exp Ther. 1998 Feb;284(2):508-15. [3]. Temocapril treatment ameliorates autoimmune myocarditis associated with enhanced cardiomyocyte thioredoxin expression. Cardiovasc Res. 2002 Aug 1;55(2):320-8. [4]. Angiotensin-converting enzyme inhibitor does not suppress renal angiotensin II levels in angiotensin I-infused rats. J Pharmacol Sci. 2013;122(2):103-8. |
| Additional Infomation | Temocapril hydrochloride is a dipeptide. |
Solubility Data
| Solubility (In Vitro) |
|
|||
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.05 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.05 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (4.05 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9491 mL | 9.7453 mL | 19.4905 mL | |
| 5 mM | 0.3898 mL | 1.9491 mL | 3.8981 mL | |
| 10 mM | 0.1949 mL | 0.9745 mL | 1.9491 mL |