Imidapril HCl (TA-6366; TA-6366; Tanatril), the hydrochloride salt of imidapril, is a potent angiotensin-converting enzyme (ACE) inhibitor with IC50 of 2.6 nM, approved in 1993 for use as an antihypertensive drug and for the treatment of chronic heart failure. As a prodrug, imidapril is converted by hydrolysis in the liver into its active form imidaprilat. Imidaprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Imidaprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.

Physicochemical Properties

Molecular Formula	C20H27N3O6.HCL
Molecular Weight	441.91
Exact Mass	441.166
CAS #	89396-94-1
Related CAS #	Imidapril;89371-37-9;Imidapril-d3 hydrochloride;1356017-30-5
PubChem CID	5485193
Appearance	White to off-white solid powder
Boiling Point	577ºC at 760 mmHg
Melting Point	38-42ºC
LogP	1.142
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	10
Heavy Atom Count	30
Complexity	619
Defined Atom Stereocenter Count	3
SMILES	CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N2[C@@H](CN(C2=O)C)C(=O)O.Cl
InChi Key	LSLQGMMMRMDXHN-GEUPQXMHSA-N
InChi Code	InChI=1S/C20H27N3O6.ClH/c1-4-29-19(27)15(11-10-14-8-6-5-7-9-14)21-13(2)17(24)23-16(18(25)26)12-22(3)20(23)28;/h5-9,13,15-16,21H,4,10-12H2,1-3H3,(H,25,26);1H/t13-,15-,16-;/m0./s1
Chemical Name	(4S)-3-[(2S)-2-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]propanoyl]-1-methyl-2-oxoimidazolidine-4-carboxylic acid;hydrochloride
Synonyms	TA-6366;TA 6366;TA6366;
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	Matrix metalloproteinase (MMP) plays a critical role in the development of ventricular remodeling after acute myocardial infarction (AMI). Imidapril, an angiotensin-converting enzyme inhibitor, has been shown to inhibit MMP activity. We investigated whether imidapril inhibits plasma MMP activities and attenuates ventricular remodeling in patients with AMI in comparison with enalapril. We enrolled 70 patients with AMI. All patients underwent primary percutaneous coronary intervention and were randomly assigned either to imidapril (n = 35) or to enalapril (n = 35) treatment. Left ventriculography was performed in acute (day 14) and chronic (6 months) phases, and plasma MMP-2 and MMP-9 activities were measured by zymography. Any changes in left ventricular end-diastolic volume index and ejection fraction from acute to chronic phases did not differ between the 2 groups. The plasma MMP-2 and MMP-9 activities at day 14 were both significantly decreased compared with those at day 1 in both groups (all P < 0.05). At 6 months, MMP-9 activity still remained decreased in both groups (P < 0.05 vs. day 1). Overall, there were no differences between the 2 groups both in plasma MMP-2 and MMP-9 activities. These results demonstrate that imidapril exerts inhibitory effects on plasma MMP activities and attenuates left ventricular remodeling in patients with AMI similar to enalapril.[1]
References	J Cardiovasc Pharmacol.2014 Jun;63(6):528-32.
Additional Infomation	Imidapril hydrochloride is a dipeptide. Imidapril Hydrochloride is the hydrochloride salt of imidapril, an angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. As a prodrug, imidapril is converted by hydrolysis in the liver into its active form imidaprilat. Imidaprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Imidaprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.

Solubility Data

Solubility (In Vitro)

DMSO:88 mg/mL (199.1 mM) Water:54 mg/mL (122.19 mM) Ethanol:29 mg/mL (65.6 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.66 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 25.0 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: ≥ 2.5 mg/mL (5.66 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 25.0 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: ≥ 2.5 mg/mL (5.66 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 40 mg/mL (90.52 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2629 mL	11.3145 mL	22.6290 mL
	5 mM	0.4526 mL	2.2629 mL	4.5258 mL
	10 mM	0.2263 mL	1.1315 mL	2.2629 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.