Cilazapril Monohydrate (Ro 31-2848) is a potent angiotensin-converting enzyme (ACE) inhibitor used for the treatment of hypertension and congestive heart failure. Cilazapril is a prodrug that is hydrolyzed after absorption to its main metabolite cilazaprilat. It is known that the diacid form of Cilazapril is more potent that enalapril at inhibiting ACE.

Physicochemical Properties

Molecular Formula	C22H31N3O5.H2O
Molecular Weight	435.51
Exact Mass	435.237
CAS #	92077-78-6
Related CAS #	Cilazapril;88768-40-5
PubChem CID	56329
Appearance	White to off-white solid powder
Boiling Point	598.1ºC at 760mmHg
Melting Point	98° (dec)
Flash Point	315.5ºC
LogP	1.797
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	9
Heavy Atom Count	31
Complexity	608
Defined Atom Stereocenter Count	3
SMILES	CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]2CCCN3CCC[C@H](N3C2=O)C(=O)O.O
InChi Key	JQRZBPFGBRIWSN-YOTVLOEGSA-N
InChi Code	InChI=1S/C22H31N3O5.H2O/c1-2-30-22(29)18(13-12-16-8-4-3-5-9-16)23-17-10-6-14-24-15-7-11-19(21(27)28)25(24)20(17)26;/h3-5,8-9,17-19,23H,2,6-7,10-15H2,1H3,(H,27,28);1H2/t17-,18-,19-;/m0./s1
Chemical Name	(4S,7S)-7-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]-6-oxo-1,2,3,4,7,8,9,10-octahydropyridazino[1,2-a]diazepine-4-carboxylic acid;hydrate
Synonyms	Ro 31-2848 monohydrate;Ro31-2848 monohydrate;Ro-31-2848 monohydrate;Ro-31 2848 monohydrate;
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
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	In vitro activity: Cilazapril is one of the angiotensin-converting enzyme inhibitors (ACE inhibitors) used for hypertension.
ln Vivo	Cilazapril (1 mg/kg, daily) tends to decrease and the higher dose (10 mg/kg, daily) significantly decreases systolic blood pressure (SBP) in subtotal nephrectomized rats. Cilazapril attenuates the further development of protein uria in a dose-dependent manner in subtotal nephrectomized rats. Cilazapril attenuates the increase in plasma fibrinogen concentration and serum albumin concentration in a dose-dependent manner. Cilazapril reduces serum MCP-1 concentration in the nephrectomized rats. Cilazapril decreases hepatic fibrinogen synthesis through the alleviation of the local inflammatory process and the improvement of hypoalbuminemia. Cilazapril normalizes systolic arterial pressure to 121 mm Hg (SD) in the treated SHR-SP rats. Cilazapril decreases systolic arterial pressure to a nearly normal level and prevents hypertensive retinal vascular changes, probably by improving endothelial function. Cilazapril results in a marked decrease in the Kd of the renal arginine vasopressin (AVP) receptor and an increase in the plasma AVP level in the spontaneously hypertensive rat. Cilazapril exerts a rapid, complete, and persistent antihypertensive effect in the spontaneously hypertensive rats (SHR) in vivo but has no effect on SAP in the normotensive Sprague-Dawley rat. Cilazapril treatment depresses heart performance (28-35%) in SHR but has no effect in the Sprague-Dawley rats. Cilazapril decreases blood pressure to control values and reduces HW:BW in hyperthyroid rats.
Animal Protocol	1 mg/kg Rats
References	J Pharmacol Sci.2004 Jan;94(1):67-72;Life Sci.1999;64(3):PL27-39.
Additional Infomation	Cilazapril monohydrate is a hydrate that is the monohydrate of cilazapril. It is used for the treatment of hypertension and heart failure. It has a role as an antihypertensive agent, an EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor and a prodrug. It contains a cilazapril. One of the ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACE inhibitors) used for hypertension. It is a prodrug that is hydrolyzed after absorption to its main metabolite cilazaprilat. See also: Cilazapril (annotation moved to).

Solubility Data

Solubility (In Vitro)

DMSO:87 mg/mL (199.8 mM) Water:<1 mg/mL Ethanol:87 mg/mL (199.8 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 3 mg/mL (6.89 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 30.0 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: ≥ 3 mg/mL (6.89 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 30.0 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: ≥ 3 mg/mL (6.89 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 30.0 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	2.2962 mL	11.4808 mL	22.9616 mL
	5 mM	0.4592 mL	2.2962 mL	4.5923 mL
	10 mM	0.2296 mL	1.1481 mL	2.2962 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.