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87333-19-5 molecular structure
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(2S,3aS,6aS)-1-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]-octahydrocyclopenta[b]pyrrole-2-carboxylic acid

ChemBase ID: 63
Molecular Formular: C23H32N2O5
Molecular Mass: 416.51058
Monoisotopic Mass: 416.23112213
SMILES and InChIs

SMILES:
O=C(N1[C@@H]2[C@H](C[C@H]1C(=O)O)CCC2)[C@@H](N[C@@H](CCc1ccccc1)C(=O)OCC)C
Canonical SMILES:
CCOC(=O)[C@@H](N[C@H](C(=O)N1[C@H]2CCC[C@H]2C[C@H]1C(=O)O)C)CCc1ccccc1
InChI:
InChI=1S/C23H32N2O5/c1-3-30-23(29)18(13-12-16-8-5-4-6-9-16)24-15(2)21(26)25-19-11-7-10-17(19)14-20(25)22(27)28/h4-6,8-9,15,17-20,24H,3,7,10-14H2,1-2H3,(H,27,28)/t15-,17-,18-,19-,20-/m0/s1
InChIKey:
HDACQVRGBOVJII-JBDAPHQKSA-N

Cite this record

CBID:63 http://www.chembase.cn/molecule-63.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
(2S,3aS,6aS)-1-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]-octahydrocyclopenta[b]pyrrole-2-carboxylic acid
IUPAC Traditional name
ramipril
(2S,3aS,6aS)-1-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]-octahydrocyclopenta[b]pyrrole-2-carboxylic acid
Brand Name
Acovil
Altace
Carasel
Cardace
Delix
Hytren
Lostapres
Pramace (discontinued)
Quark
Ramace
Triatec
Tritace
Unipril
Vesdil
Hypren
Synonyms
Ramiprilum [Latin]
Ramipril
Ramipro
Tritace
Altace
Prilace
(2S,3aS,6aS)-1-((S)-2-(((S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino)propanoyl)octahydrocyclopenta[b]pyrrole-2-carboxylic acid
[2S,3aS,6aS]-1-[(2S)-2-[[(1S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]octahydrocyclopenta[b]pyrrole-2-carboxylic acid
Ramipril
(2S,3aS,6aS)-1-[(2S)-2-[[(1S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]octahydrocyclopenta[b]pyrrole-2-carboxylic Acid
Cardace
Delix
HOE-498
Pramace
Ramace
Unipril
Vesdil
(2S,3aS,6aS)-1-[(2S)-2-[[(1S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl-d3]octahydrocyclopenta[b]pyrrole-2-carboxylic Acid
Altace-d3
Cardace-d3
Delix-d3
HOE-498-d3
Pramace-d3
Ramace-d3
Acovil
Hypren
Quark
Triatec
(2S,3aS,6aS)-1-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]-octahydrocyclopenta[b]pyrrole-2-carboxylic acid
Unipril-d3
Ramipril-d3
CAS Number
87333-19-5
MDL Number
MFCD00865775
PubChem SID
160963526
46506390
24724586
PubChem CID
5362129

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem ALOGPS 2.1
Acid pKa 3.74893  H Acceptors
H Donor LogD (pH = 5.5) 1.2103999 
LogD (pH = 7.4) -0.18272619  Log P 1.4738114 
Molar Refractivity 111.1868 cm3 Polarizability 44.21084 Å3
Polar Surface Area 95.94 Å2 Rotatable Bonds 10 
Lipinski's Rule of Five true 
Log P 0.92  LOG S -4.03 
Solubility (Water) 3.90e-02 g/l 

PROPERTIES

PROPERTIES

Physical Property Safety Information Pharmacology Properties Product Information Bioassay(PubChem)
Solubility
3.5mg/L expand Show data source
Aqueous Alkali expand Show data source
Chloroform expand Show data source
Dichloromethane expand Show data source
Dimethyl Sulfoxide, expand Show data source
DMSO expand Show data source
DMSO: ~18 mg/mL expand Show data source
Methanol expand Show data source
Apperance
white powder expand Show data source
White Solid expand Show data source
Melting Point
104-106°C expand Show data source
106-108°C expand Show data source
Hydrophobicity(logP)
1.54 expand Show data source
2.9 expand Show data source
Storage Condition
-20°C expand Show data source
-20°C Freezer expand Show data source
RTECS
GY5879600 expand Show data source
MSDS Link
Download expand Show data source
Download expand Show data source
German water hazard class
2 expand Show data source
Personal Protective Equipment
Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter expand Show data source
Storage Temperature
2-8°C expand Show data source
Target
Ras expand Show data source
Gene Information
human ... ACE(1636) expand Show data source
Mechanism of Action
ACE inhibitor expand Show data source
Angiotensin converting enzyme inhibitor expand Show data source
Purity
≥98% (HPLC) expand Show data source
95% expand Show data source
Salt Data
Free Base expand Show data source
Certificate of Analysis
Download expand Show data source
Description
Isomers (3:1) expand Show data source
Application(s)
Antihypertensive agent expand Show data source
Hypotensive expand Show data source
Empirical Formula (Hill Notation)
C23H32N2O5 expand Show data source

DETAILS

DETAILS

DrugBank DrugBank Selleck Chemicals Selleck Chemicals InterBioScreen InterBioScreen Sigma Aldrich Sigma Aldrich TRC TRC
DrugBank - DB00178 external link
Item Information
Drug Groups approved
Description Ramipril is a prodrug belonging to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is metabolized to ramiprilat in the liver and, to a lesser extent, kidneys. Ramiprilat is a potent, competitive inhibitor of ACE, the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Ramipril may be used in the treatment of hypertension, congestive heart failure, nephropathy, and to reduce the rate of death, myocardial infarction and stroke in individuals at high risk of cardiovascular events.
Indication For the management of mild to severe hypertension. May be used to reduce cardiovascular mortality following myocardial infarction in hemodynamically stable individuals who develop clinical signs of congestive heart failure within a few days following myocardial infarction. To reduce the rate of death, myocardial infarction and stroke in individuals at high risk of cardiovascular events. May be used to slow the progression of renal disease in individuals with hypertension, diabetes mellitus and microalubinuria or overt nephropathy.
Pharmacology Ramipril is an ACE inhibitor similar to benazepril, fosinopril and quinapril. It is an inactive prodrug that is converted to ramiprilat in the liver, the main site of activation, and kidneys. Ramiprilat confers blood pressure lowing effects by antagonizing the effect of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure using a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may sustain the effects of ramiprilat by causing increased vasodilation and decreased blood pressure.
Toxicity Symptoms of overdose may include excessive peripheral vasodilation (with marked hypotension and shock), bradycardia, electrolyte disturbances, and renal failure. The most likely adverse reactions are symptoms attributable to its blood-pressure lowing effect. May cause headache, dizziness, asthenia, chest pain, nausea, peripheral edema, somnolence, impotence, rash, arthritis, and dyspnea.
LD50 = 10933 mg/kg (orally in mice).
Affected Organisms
Humans and other mammals
Biotransformation Hepatic metabolism accounts for 75% of total ramipril metabolism. 25% of hepatic metabolism produces the active metabolite ramiprilat via liver esterase enzymes. 100% of renal metabolism converts ramipril to ramiprilat. Other metabolites, diketopiperazine ester, the diketopiperazine acid, and the glucuronides of ramipril and ramiprilat, are inactive.
Absorption The extent of absorption is at least 50-60%. Food decreases the rate of absorption from the GI tract without affecting the extent of absorption. The absolute bioavailabilities of ramipril and ramiprilat were 28% and 44%, respectively, when oral administration was compared to intravenous administration.
Half Life Plasma concentrations of ramiprilat decline in a triphasic manner. Initial rapid decline represents distribution into tissues and has a half life of 2-4 hours. The half life of the apparent elimination phase is 9-18 hours and that of the terminal elimination phase is > 50 hours. Two elimination phases occur as a result of ramiprilat's potent binding to ACE and slow dissociation from the enzyme. The half life of ramiprilat after multiple daily doses (MDDs) is dose-dependent, ranging from 13-17 hours with 5-10 mg MDDs to 27-36 hours for 2.5 mg MDDs.
Protein Binding Protein binding of ramipril is about 73% and that of ramiprilat about 56%.
References
Cacciapuoti F, Capasso A, Mirra G, De Nicola A, Minicucci F, Gentile S: Prevention of left ventricular hypertrophy by ACE-inhibitor, ramipril in comparison with calcium-channel antagonist, felodipine. Int J Cardiol. 1998 Jan 31;63(2):175-8. [Pubmed]
Kleinert S: HOPE for cardiovascular disease prevention with ACE-inhibitor ramipril. Heart Outcomes Prevention Evaluation. Lancet. 1999 Sep 4;354(9181):841. [Pubmed]
External Links
Wikipedia
RxList
PDRhealth
Drugs.com
Selleck Chemicals - S1793 external link
Research Area
Description Cardiovascular Disease
Biological Activity
Description Ramipril (Altace) is an angiotensin-converting enzyme (ACE) inhibitor with IC50 of 5 nM.
Targets ACE
IC50 5 nM [1]
In Vitro Ramipril is an angiotensin-converting enzyme (ACE) inhibitor with IC50 of 5 nM. [1] Ramipril enhances the activity of ACE-associated CK2 and the phosphorylation of ACE Ser1270 in cultured endothelial cells, but is unable to activate JNK or stimulate the nuclear accumulation of c-Jun in endothelial cells expressing a S1270A ACE mutant or in ACE-deficient cells. Prolonged Ramipril treatment increases ACE expression in primary cultures of human endothelial cells and in vivo (mouse lung), which can be prevented by pretreatment with the JNK inhibitor SP600125. [2] Ramipril displays little enhanced effect on the rate of in vitro endothelial apoptosis induced by the serum deprivation method. [3]
In Vivo Chronic in vivo administration of Ramipril to rats at a dosage that has similar hypotensive effects in vitro HUVECs significantly reduces the rate of LPS-induced apoptosis compared to the other ACE inhibitors, which contrasts with the apoptosis effect in vitro. [3] Ramipril inhibits systolic blood pressure (SBP) with IC50 of 1.97 mg/kg in spontaneously hypertensive rats (SHR). When in combination with AT1-receptor blockade by candesartan–cilexetil increases SBP reduction synergistically rather than additively. [4] Administration of Ramipril to spontaneously hypertensive rats (SHR) produces significant inhibition of aorta ACE and lung ACE with IC50 ~5 mg/kg, but shows little effect for brain ACE ex vivo. [5] Ramipril prevents beta cell dysfunction in osteoprotegerin treated mice through decreasing islet monocyte/macrophage infiltration, fibrosis and apoptosis involving decreasing RAS, growth factor genes and inflammatory molecules expressions. [6]
Clinical Trials Phase IV trails for evaluating the efficacy and safety of Aliskiren versus Ramipril in patients with moderate systolic essential hypertension have been completed.
Features Ramipril is a pro-drug converted to its active metabolite ramiprilat by liver esterase enzymes.
Protocol
Cell Assay [3]
Cell Lines Human umbilical vein endothelial cells (HUVECs)
Concentrations ~1 μM
Incubation Time 24 hours
Methods The HUVECs are pretreated with the active metabolites of Ramipril for 24 hours. A serum deprivation method is used to induce apoptosis in the presence of Ramipril for an additional 24 hours. The rate of apoptosis is then determined using flow cytometry with two makers annexinV fluorescein isothiocyanate (FITC+) and propidium iodide (PI).
Animal Study [4]
Animal Models Male spontaneously hypertensive rats
Formulation Dissolved in distilled water by using gum arabic (10% w/v)
Doses 0.03-10 mg/kg
Administration Gavage, every day
References
[1] Stevens BR, et al. Comp Biochem Physiol C, 1988, 91(2), 493-497.
[2] Kohlstedt K, et al. Circ Res, 2004, 94(1), 60-67.
[3] Ceconi C, et al. Cardiovasc Drugs Ther, 2007, 21(6), 423-429.
[4] Raasch W, et al. J Hypertens, 2004, 22(3), 611-618.
[5] Cushman DW, et al. Br J Clin Pharmacol, 1989, 28, 115S-131S.
[6] Toffoli B, et al. Mol Cell Endocrinol, 2011, 331(1), 136-142.
Sigma Aldrich - R0404 external link
Biochem/physiol Actions
Angiotensin converting enzyme (ACE) inhibitor.
Toronto Research Chemicals - R111003 external link
A labelled antihypertensive. An angiotensin converting enzyme (ACE) inhibitor, converted to active, diacid metabolite.
Toronto Research Chemicals - R111000 external link
An antihypertensive. An angiotensin converting enzyme (ACE) inhibitor, converted to active, diacid metabolite.

REFERENCES

REFERENCES

From Suppliers Google Scholar IconGoogle Scholar PubMed iconPubMed Google Books IconGoogle Books
  • • Cacciapuoti F, Capasso A, Mirra G, De Nicola A, Minicucci F, Gentile S: Prevention of left ventricular hypertrophy by ACE-inhibitor, ramipril in comparison with calcium-channel antagonist, felodipine. Int J Cardiol. 1998 Jan 31;63(2):175-8. Pubmed
  • • Kleinert S: HOPE for cardiovascular disease prevention with ACE-inhibitor ramipril. Heart Outcomes Prevention Evaluation. Lancet. 1999 Sep 4;354(9181):841. Pubmed
  • • Stevens BR, et al. Comp Biochem Physiol C, 1988, 91(2), 493-497.
  • • Kohlstedt K, et al. Circ Res, 2004, 94(1), 60-67.
  • • Ceconi C, et al. Cardiovasc Drugs Ther, 2007, 21(6), 423-429.
  • • Raasch W, et al. J Hypertens, 2004, 22(3), 611-618.
  • • Cushman DW, et al. Br J Clin Pharmacol, 1989, 28, 115S-131S.
  • • Toffoli B, et al. Mol Cell Endocrinol, 2011, 331(1), 136-142.
  • • Teetz, V., et al.: Arzneim.-Forsch., 34, 1399 (1984)
  • • Ruggenenti, P., et al.: Lancet, 352, (1984)
  • • Bosch, J., et al.: Br. Med. J., 324, 1 (1984)
  • • Teetz, V., et al.: Arzneim.-Forsch., 34, 1399 (1984)
  • • Ruggenenti, P., et al.: Lancet, 352, (1984)
  • • Bosch, J., et al.: Br. Med. J., 324, 1 (1984)
  • • Eur. Pat., 1983, Hoechst, 79 022; CA, 100, 52012, (synth)
  • • Paulus, E.F. et al., Acta Cryst. C, 1987, 43, 941, (cryst struct)
  • • Becker, R.H.A. et al., Am. J. Cardiol., 1987, 59, 3D; 18D; 23D, (revs, Ramipril)
  • • Omosu, M. et al., Arzneim.-Forsch., 1988, 38, 1309, (pharmacol)
  • • Ger. Pat., 1989, Hoechst, 3 901 291; CA, 113, 52535z, (synth)
  • • Tabata, S. et al., Arzneim.-Forsch., 1990, 40, 865, (metab)
  • • Aboulenein, H.Y. et al., Anal. Lett., 1991, 24, 2217, (detn)
  • • J. Cardiovasc. Pharmacol., 1991, 18, Suppl. 2, (rev)
  • • Meisel, S. et al., Clin. Pharmacokinet., 1994, 26, 7, (rev, pharmacokinet)
  • • Negwer, M., Organic-Chemical Drugs and their Synonyms, 7th edn., Akademie-Verlag, 1994, 9653, (synonyms)
  • • Frampton, J.E. et al., Drugs, 1995, 49, 440, (rev)
  • • Martindale, The Extra Pharmacopoeia, 32nd edn., Pharmaceutical Press, 1999, 941
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