87269-97-4

Basic information

• Product Name: Ramiprilat
• Synonyms: RAMIPRILAT;RAMIPRILAT HYDRATE;Ramiprilat, ammonium salt;(2S,3aS,6aS)-1-[(2S)-2-[[(1S)-1-Carboxy-3-phenylpropyl]amino]-1-oxopropyl]octahydrocyclopenta[b]pyrrole-2-carboxylic Acid;HOE 498 Diacid;Ramipril Diacid;(2S,3aS,6aS)-1-((S)-N-((S)-1-Carboxy-3-phenylpropyl)alanyl)tetrahydrocyclopenta[b]pyrrole-2-carboxylic acid;(2S,3aS,6aS)-1-[(S)-N-[(S)-1-Carboxy-3-phenylpropyl]alanyl]octahydrocyclopenta[b]pyrrole-2-carboxylic acid
• CAS NO: 87269-97-4
• Molecular Formula: C₂₁H₂₈N₂O₅
• Molecular Weight: 388.46
• Product Categories: Various Metabolites and Impurities;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals
• Mol File: 87269-97-4.mol
• Article Data: 5

Chemical Properties

• Melting Point: 139-141°C
• Boiling Point: 632.2 °C at 760 mmHg
• Flash Point: 336.2 °C
• Appearance: white to off-white solid
• Density: 1.273 g/cm³
• Vapor Pressure: 7.47E-17mmHg at 25°C
• Refractive Index: 1.583
• Storage Temp.: Refrigerator, Under Inert Atmosphere
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 2.20±0.10(Predicted)
• Stability: Hygroscopic
• CAS DataBase Reference: Ramiprilat(CAS DataBase Reference)
• NIST Chemistry Reference: Ramiprilat(87269-97-4)
• EPA Substance Registry System: Ramiprilat(87269-97-4)

Safety Data

• Hazard Codes: Xi
• Statements: 36/38
• Safety Statements: 26-37/39
• Hazardous Substances Data: 87269-97-4(Hazardous Substances Data)

Usage

Description

Ramiprilat is the active metabolite of ramipril and functions as an angiotensin-converting enzyme inhibitor (pKi = 9.08 in human heart) to suppress the conversion of angiotensin I to angiotensin II and the degradation of bradykinin, thereby preventing vasoconstriction. Furthermore, ramiprilat is reported to interfere with the targeting of B2 kinin receptors to endothelial cell membranes further preventing bradykinin signaling. In addition to its cardioprotective effects in both animal models and clinical studies, ramiprilat has been reported to inhibit matrix metalloproteinase-3 and -9 activity in isolated Crohn’s disease fistulas.

Chemical Properties

White to Off-White Solid

Uses

Ramiprilat (Ramipril EP Impurity E) is a metabolite of Ramipril (R111000), and acts as an ACE inhibitor (1). Reduces the need for dialysis among patients previously on angiotensin-converting-enzyme inhibitors (2). Ramipril is used in stroke prevention. (3)

Definition

ChEBI: A dipeptide that is the active metabolite of ramipril. An angiotensin-converting enzyme (ACE) inhibitor, used to treat high blood pressure and congestive heart failure.

in vitro

pretreatment with ramiprilat could significantly attenuate the recovery of b2 kinin receptors in while increasing that from membranes lacking caveolin, and such effect was not because of the inhibition of bradykinin degradation. ramiprilat could also decrease [3h]bradykinin binding to cr membranes. in addition, ramiprilat treatment led to reactivation of the b2 receptor in bradykinin-stimulated cells [1].

in vivo

in previous animal study, when compared with the control rats, diabetic rats showed decreased creatinine clearance rate, increased urinary protein excretion and blood pressure, as well as development of tubulointerstitial fibrosis, glomerulosclerosis, and inflammatory cell infiltration. furthermore, the blocking angiotensin ii with ramipril (the prodrug of ramiprilat) was able to significantly improve all of these parameters [2].

references

[1] t. benzing, i. fleming, a. blaukat, et al. angiotensin-converting enzyme inhibitor ramiprilat interferes with the sequestration of the b2 kinin receptor within the plasma membrane of native endothelial cells. circulation 99(15), 2034-2040 (1999).[2] li c, yang cw, park cw, ahn hj, kim wy, yoon kh, suh sh, lim sw, cha jh, kim ys, kim j, chang ys, bang bk. long-term treatment with ramipril attenuates renal osteopontin expression in diabetic rats. kidney int. 2003 feb;63(2):454-63.[3] warner gt, perry cm. ramipril: a review of its use in the prevention of cardiovascular outcomes. drugs. 2002;62(9):1381-405.

InChI:InChI=1/C21H28N2O5/c1-13(22-16(20(25)26)11-10-14-6-3-2-4-7-14)19(24)23-17-9-5-8-15(17)12-18(23)21(27)28/h2-4,6-7,13,15-18,22H,5,8-12H2,1H3,(H,25,26)(H,27,28)/t13-,15-,16-,17-,18-/m0/s1

Upstream product

• 87333-19-5 Ramipril 

Relevant articles and documents

Stress degradation studies of ramipril by a validated stability-indicating liquid chromatographic method

Ramipril is an angiotensin-converting enzyme inhibitor which has chemical structure susceptible to degradation, therefore in this work forced degradation studies of ramipril were carried out by a developed and validated stability-indicating liquid chromat

In vitro drug metabolism by human carboxylesterase 1: Focus on angiotensin-converting enzyme inhibitors

Carboxylesterase 1 (CES1) is the major hydrolase in human liver. The enzyme is involved in the metabolism of several important therapeutic agents, drugs of abuse, and endogenous compounds. However, no studies have described the role of human CES1 in the activation of two commonly prescribed angiotensinconverting enzyme inhibitors: enalapril and ramipril. Here, we studied recombinant human CES1-and CES2-mediated hydrolytic activation of the prodrug esters enalapril and ramipril, compared with the activation of the known substrate trandolapril. Enalapril, ramipril, and trandolapril were readily hydrolyzed by CES1, but not by CES2. Ramipril and trandolapril exhibited Michaelis-Menten kinetics, while enalapril demonstrated substrate inhibition kinetics. Intrinsic clearances were 1.061, 0.360, and 0.02 ml/min/mg protein for ramipril, trandolapril, and enalapril, respectively. Additionally, we screened a panel of therapeutic drugs and drugs of abuse to assess their inhibition of the hydrolysis of p-nitrophenyl acetate by recombinant CES1 and human liver microsomes. The screening assay confirmed several known inhibitors of CES1 and identified two previously unreported inhibitors: the dihydropyridine calcium antagonist, isradipine, and the immunosuppressive agent, tacrolimus. CES1 plays a role in the metabolism of several drugs used in the treatment of common conditions, including hypertension, congestive heart failure, and diabetes mellitus; thus, there is a potential for clinically relevant drug-drug interactions. The findings in the present study may contribute to the prediction of such interactions in humans, thus opening up possibilities for safer drug treatments. Copyright

Rapid conversion of the new angiotensin converting enzyme inhibitor ramipril to its active metabolite in rats

The rate of conversion of ramipril (Hoe 498), a new angiotensin converting enzyme (ACE) inhibitor, to its active metabolite was compared with that of enalapril. After intravenous administration to rats, ramipril was very rapidly desterified to its active moiety, ramiprilat. The ratio of the active metabolite level to the prodrug level in plasma at 5 min after administration was 10.7 for ramipril, which was about 5 times the ratio for enalapril. The in vitro conversion rates of ramipril were higher than those of enalapril in all rat tissue homogenates examined, including the liver, a main site of metabolism. The apparent Km values of ramipril and enalapril in the liver were 190 and 710 μmol/l, respectively, suggesting that ramipril has a higher affinity for esterase than enalapril. In conclusion, ramipril was superior to enalapril in efficiency of conversion to the active metabolite.