76095-16-4 Usage
Description
Enalapril maleate is the second angiotensin-converting enzyme (ACE) inhibitor to reach the marketplace, following captopril. It is a medication used in the treatment of hypertension and congestive heart failure. Enalapril maleate has a longer effective half-life than captopril, allowing for once or twice-daily dosing, and appears to have a somewhat lower incidence of side effects.
Uses
Used in Pharmaceutical Industry:
Enalapril maleate is used as a long-acting ACE inhibitor and antihypertensive for the treatment of hypertension and congestive heart failure. Its longer half-life and lower side effect profile make it a preferred choice over other ACE inhibitors.
Used in Research:
Enalapril maleate salt is used in research to study diabetic angiopathy in diabetic rats and the inhibition of ACE in hog plasma (IC50=1.2nM). ACE inhibitors, such as enalapril maleate, disrupt the renin-angiotensin-aldosterone system, which plays a crucial role in blood pressure regulation and fluid balance.
Other ACE inhibitors in the market include Enalapril, Enalaprilat dihydrate, Enalaprilat, and Enalapril-d5 Maleate Salt, among others. These compounds are also used for similar applications in the treatment and research of hypertension and related conditions.
Originator
Merck (USA)
Manufacturing Process
N-[1(S)-Ethoxycarbonyl-3-phenylpropyl]-L-alanyl-L-proline maleic acid saltA mixture of 3 g of L-alanyl-L-proline, 5 g of ethyl 2-oxo-4-phenyl-butanoate,
13 g of 3A molecular sieves, and 3.6 g of Raney nickel in 85 ml of ethanol is
hydrogenated at 25°C and at 40 psig of hydrogen until uptake of hydrogen
ceases. The solids are filtered, washed with 80 ml of ethanol and the filtrates
are combined. Assay by high pressure liquid chromatography shows an 87:13
ratio of diastereoisomers in favor of the desired product. Ethanol is removed
under vacuum to afford an oil which is dissolved in 60 ml of water and 20 ml
of ethyl acetate. The pH of the stirred two-phase mixture is adjusted to 8.6
with 50% NaOH. The layers are separated and the water phase is extracted
with 2x20 ml of ethyl acetate. The water phase is adjusted to pH 4.25 with
hydrochloric acid, 12 g of NaCl is dissolved in the water, and product is
extracted with 5x12 ml of ethyl acetate. The extracts are combined and dried
with Na2SO4. The desired product, N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-
L-alanyl-L-proline, is crystallized as its maleate salt by addition of 1.86 g of
maleic acid. After stirring for 4 hours, the salt is filtered, washed with ethyl
acetate and dried to afford 5.2 g of pure product, melting point 150°-151°C.
Therapeutic Function
Antihypertensive
Biochem/physiol Actions
A long-acting angiotensin-converting enzyme inhibitor.
Clinical Use
Angiotensin converting enzyme inhibitor:HypertensionHeart failure
Veterinary Drugs and Treatments
The principle use of enalapril/enalaprilat in veterinary medicine at
present is as a vasodilator in the treatment of heart failure. Recent
studies have demonstrated that enalapril, particularly when used
in conjunction with furosemide, does improve the quality of life
in dogs with heart failure. It is not clear, however, whether it has
any significant effect on survival times. It may also be of benefit
in treating the effects associated with valvular heart disease (mitral
regurgitation) and left to right shunts. It is being explored as
adjunctive treatment in chronic renal failure and protein losing
nephropathies.
While ACE inhibitors are a mainstay for treating hypertension in
humans, they have not been particularly useful in treating hypertension
in dogs or cats.
Drug interactions
Potentially hazardous interactions with other drugs Anaesthetics: enhanced hypotensive effect.Analgesics: antagonism of hypotensive effect and
increased risk of renal impairment with NSAIDs;
hyperkalaemia with ketorolac and other NSAIDsAntihypertensives: increased risk of hyperkalaemia,
hypotension and renal failure with ARBs and
aliskiren.Bee venom extract: possible severe anaphylactoid
reactions when used togetherCiclosporin: increased risk of hyperkalaemia and
nephrotoxicity.Cytotoxics: increased risk of angioedema with
everolimus.Diuretics: enhanced hypotensive effect;hyperkalaemia with potassium-sparing diureticsESAs: increased risk of hyperkalaemia; antagonism
of hypotensive effect.Gold: flushing and hypotension with sodium
aurothiomalate.Lithium: reduced excretion, possibility of enhanced
lithium toxicity.Potassium salts: increased risk of hyperkalaemiaTacrolimus: increased risk of hyperkalaemia and
nephrotoxicity.
Metabolism
Following absorption, oral enalapril is rapidly and
extensively hydrolysed to enalaprilat, a potent angiotensin
converting enzyme inhibitor. Peak serum concentrations
of enalaprilat occur about 4 hours after an oral dose of
enalapril tablet, and the effective half-life is 11 hours.
Excretion of enalaprilat is primarily renal. The principal
components in urine are enalaprilat, accounting for about
40% of the dose, and intact enalapril.
Check Digit Verification of cas no
The CAS Registry Mumber 76095-16-4 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 7,6,0,9 and 5 respectively; the second part has 2 digits, 1 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 76095-16:
(7*7)+(6*6)+(5*0)+(4*9)+(3*5)+(2*1)+(1*6)=144
144 % 10 = 4
So 76095-16-4 is a valid CAS Registry Number.
InChI:InChI=1/C20H28N2O5.C4H4O4/c1-3-27-20(26)16(12-11-15-8-5-4-6-9-15)21-14(2)18(23)22-13-7-10-17(22)19(24)25;5-3(6)1-2-4(7)8/h4-6,8-9,14,16-17,21H,3,7,10-13H2,1-2H3,(H,24,25);1-2H,(H,5,6)(H,7,8)/b;2-1-/t14-,16?,17-;/m0./s1
76095-16-4Relevant articles and documents
PROCESS FOR THE PREPARATION OF AMIDES OF N-[1-(S)-(ETHOXYCARBONYL)-3-PHENYLPROPYL]-L-ALANINE
-
Page/Page column 21, (2015/01/07)
A process for the production of amides of N-[1-(S)-(ethoxycarbonyl)-3-phenylpropyl]-L-alanine is described. The process can be used for the production of key intermediates and finally the ACE inhibitors such as Ramipril, Enalapril, Quinapril, Trandolapril, Delapril and Moexipril starting from N-[1-(S)-(ethoxycarbonyl)-3-phenylpropyl]-L-alanine by the reaction with the appropriate amines.
Soluble alpha-amino acid salts in acetonitrile: practical technology for the production of some dipeptides.
Palomo, Claudio,Palomo, Antonio L,Palomo, Francisco,Mielgo, Antonia
, p. 4005 - 4008 (2007/10/03)
Alpha-amino acids are soluble in acetonitrile when treated with phosphazene bases. As a result, the protection/deprotection events that are usually required for peptide coupling reactions can be minimized. This is illustrated in the synthesis of the important angiotensin-converting enzyme (ACE) inhibitor enalapril. [reaction: see text]
Process for the preparation of compounds having ACE inhibitory action and intermediates in said process
-
, (2008/06/13)
-