Perindopril Erbumine (also called S9490-3; Pirindopril; ACEON; Perindopril tert-butylamine; Perstarium), the tert-butylamine salt of perindopril, is a long acting and brain penetrant ACE (angiotensin-converting enzyme) inhibitor with anti-hypertensive effects. It inhibits ACE with an IC50 of 1.05 nM and has been approved for use in the treatment of hypertension and heart failure. Perindopril Erbumine can suppress the increase in hippocampal ACE activity and improves cognition in PS2APP-transgenic mice. Perindopril Erbumine displays a higher binding affinity for the bradykinin binding sites than the angiotensin I binding sites of ACE. Perindopril Erbumine inhibits the angiotensin- and Aβ42-to-Aβ40-converting activity of mutated ACE containing two active domains (F-ACE) with IC50 of 0.03-0.1 μM, and 0.01-0.03 μM, respectively.

Physicochemical Properties

Molecular Formula	C19H32N2O5.C4H11N
Molecular Weight	441.6
Exact Mass	441.32
CAS #	107133-36-8
Related CAS #	Perindopril;82834-16-0
PubChem CID	441313
Appearance	White to off-white solid powder
Density	1.15 g/cm3
Boiling Point	537.4ºC at 760mmHg
Melting Point	126-128ºC
Flash Point	278.8ºC
LogP	3.713
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	9
Heavy Atom Count	31
Complexity	549
Defined Atom Stereocenter Count	5
SMILES	CCC[C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@H]2CCCC[C@H]2C[C@H]1C(=O)O.CC(C)(C)N
InChi Key	IYNMDWMQHSMDDE-MHXJNQAMSA-N
InChi Code	InChI=1S/C19H32N2O5.C4H11N/c1-4-8-14(19(25)26-5-2)20-12(3)17(22)21-15-10-7-6-9-13(15)11-16(21)18(23)24;1-4(2,3)5/h12-16,20H,4-11H2,1-3H3,(H,23,24);5H2,1-3H3/t12-,13-,14-,15-,16-;/m0./s1
Chemical Name	(2S,3aS,7aS)-1-[(2S)-2-[[(2S)-1-ethoxy-1-oxopentan-2-yl]amino]propanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylic acid;2-methylpropan-2-amine
Synonyms	S 9490; S-9490;Pirindopril;S9490;S 9490-3;S9490-3;ACEON; Perindopril tert-butylamine; Perstarium; S 9490 3; S 94903.
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	In vitro activity: Perindopril Erbumine displays a higher binding affinity for the bradykinin binding sites than the angiotensin I binding sites of the angiotensin-converting enzyme (ACE) with bradykinin/angiotensin I selectivity ratio of 1.44. Perindopril Erbumine inhibits the angiotensin- and Aβ42-to-Aβ40-converting activity of mutated ACE containing two active domains (F-ACE) with IC50 of 0.03-0.1 μM, and 0.01-0.03 μM, respectively. Perindopril Erbumine (~2 μM) displays no significant cytotoxicity towards SCC-VII and KB cells, but can significantly reduce the production of angiotensin II and the transcription of VEGF in KB cells in a concentration-dependent manner.
ln Vivo	Oral administration of Perindopril Erbumine at 2 mg/kg/day has a significant inhibitory effect on SCC-VII tumor growth, and reduces blood vessel formation surrounding the tumors in vivo due to the suppression of VEGF-induced angiogenesis. Administration of Perindopril Erbumine at 2 mg/kg/day displays a strong inhibitory effect of the BNL-HCC tumor growth in rats similar to that of 20 mg/kg/day and in contrast to the AT1-R antagonist candesartan or losartan which at the dose of 20 mg/kg/day has no inhibitory effect. Administration of Perindopril Erbumine at 3 mg/kg/day significantly inhibits LPS-induced apoptosis by 6.4% in RAECs in vivo than that of ramipril by 3.2%. Administration of Perindopril Erbumine (1 mg/kg/day) significantly suppresses the hippocampal ACE activity, and prevents cognitive impairment and brain injury in rats with Alzheimers disease (AD).
Animal Protocol	Dissolved in DMSO, and diluted in saline; 1 or 2 mg/kg/day; p.o. Female BALB/c nude mice injected with SCC-VII cells
Toxicity/Toxicokinetics	Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Limited information indicates that only low levels of perindopril and its active metabolite are found in breastmilk, which is consistent with other drugs in this class. Amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants. ◉ Effects in Breastfed Infants Ten infants were breastfed (extent not stated) by mothers were taking perindopril 5 to 20 mg daily. All infants grew and developed normally according to their parents. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date.
References	Eur J Pharmacol.2007 Dec 22;577(1-3):1-6;J Biol Chem.2009 Nov 13;284(46):31914-20.
Additional Infomation	Perindopril erbumine is an addition compound. It has a role as an antihypertensive agent and an EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor. It contains a perindopril(1-). Perindopril Erbumine is the tert-butylamine salt of perindopril, the ethyl ester of a non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor with antihypertensive activity. Upon hydrolysis, perindopril erbumine is converted to its active form perindoprilat, inhibiting ACE and the conversion of angiotensin I to angiotensin II; consequently, angiotensin II-mediated vasoconstriction and angiotensin II-stimulated aldosterone secretion from the adrenal cortex are inhibited and diuresis and natriuresis ensue. An angiotensin-converting enzyme inhibitor. It is used in patients with hypertension and heart failure. See also: Perindopril (has active moiety); Perindoprilat (has active moiety).

Solubility Data

Solubility (In Vitro)	DMSO:<1 mg/mL Water: 88 mg/mL (199.3 mM) Ethanol:88 mg/mL (199.3 mM)
Solubility (In Vivo)	Solubility in Formulation 1: 100 mg/mL (226.45 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication. Solubility in Formulation 2: Saline: 30 mg/mL  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2645 mL	11.3225 mL	22.6449 mL
	5 mM	0.4529 mL	2.2645 mL	4.5290 mL
	10 mM	0.2264 mL	1.1322 mL	2.2645 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.