Captopril

Base Information

• Chemical Name: Captopril
• CAS No.: 62571-86-2
• Deprecated CAS: 138452-88-7,70903-77-4,225661-74-5
• Molecular Formula: C9H15NO3S
• Molecular Weight: 217.289
• Hs Code.: 29339900
• European Community (EC) Number: 263-607-1
• NSC Number: 757419
• UNII: 9G64RSX1XD
• DSSTox Substance ID: DTXSID1037197
• Nikkaji Number: J3.203D
• Wikipedia: Captopril
• Wikidata: Q421119
• NCI Thesaurus Code: C340
• RXCUI: 1998
• Pharos Ligand ID: DCTASLNAXK1N
• Metabolomics Workbench ID: 43412
• ChEMBL ID: CHEMBL1560
• Mol file: 62571-86-2.mol

Synonyms:(S)-1-(3-Mercapto-2-methyl-1-oxopropyl)-L-proline;Capoten;Captopril;Lopirin;SQ 14,225;SQ 14,534;SQ 14225;SQ 14534;SQ-14,225;SQ-14,534;SQ-14225;SQ-14534;SQ14,225;SQ14,534;SQ14225;SQ14534

Chemical Property of Captopril

Chemical Property:

• Appearance/Colour: white crystalline powder
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 104-108 °C(lit.)
• Refractive Index: -127.5 ° (C=1.7, EtOH)
• Boiling Point: 427 °C at 760 mmHg
• PKA: 3.7, 9.8(at 25℃)
• Flash Point: 212.1 °C
• PSA: 96.41000
• Density: 1.272 g/cm³
• LogP: 0.56580
• Storage Temp.: -20°C Freezer
• Solubility.: H2O: 0.1 g/mL, very slightly hazy, colorless
• Water Solubility.: soluble
• XLogP3: 0.3
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 3
• Exact Mass: 217.07726451
• Heavy Atom Count: 14
• Complexity: 244

Purity/Quality:

99.5% ^*data from raw suppliers

ON ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn, Xi
• Hazard Codes: Xn,Xi
• Statements: 43-63-36/37/38-40
• Safety Statements: 36/37-37/39-26-36-22

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Angiotensin-Converting Enzyme Inhibitors
• Canonical SMILES: CC(CS)C(=O)N1CCCC1C(=O)O
• Isomeric SMILES: C[C@H](CS)C(=O)N1CCC[C@H]1C(=O)O
• Recent ClinicalTrials: Hormone Therapy and Angiotensin-Dependent Arterial and Renal Vasoconstriction in Humans
• Recent EU Clinical Trials: Efficacy of captopril nebulization in Covid-19 patients suffering of SARS-CoV-2 pneumonia.
• Description: Captopril is the most studied of the angiotensin-converting enzyme inhibitors proposed as an antihypertensive drug. It blocks angiotensin-converting enzyme, which suppresses formation of angiotensin II and relieves its vasoconstricting effect on arterial and venous vessels. Overall vascular peripheral tension is reduced, which results in the lowering of arterial pressure.
• Uses: Orally active angiotensin-converting enzyme (ACE) inhibitor anesthetic angiotensin-converting enzyme (ACE) inhibitor,anti-hypertensive Captopril has also been shown to inhibit the formation of angiotensin II, a bioactive peptide that stimulates angiogenesis and increases microvessel density. Captopril demonstrates noncompetitive inhibition of tyrosinase monophenolase activity and competitive inhibition of diphenolase activity
• Therapeutic Function: Antihypertensive
• Biological Functions: Captopril (Capoten) is an orally effective ACE inhibitor with a sulfhydryl moiety that is used in binding to the active site of the enzyme. Captopril blocks the blood pressure responses caused by the administration of angiotensin I and decreases plasma and tissue levels of angiotensin II.
• Clinical Use: Captopril, as well as other ACE inhibitors, is indicated in the treatment of hypertension, congestive heart failure, left ventricular dysfunction after a myocardial infarction, and diabetic nephropathy. In the treatment of essential hypertension, captopril is considered firstchoice therapy, either alone or in combination with a thiazide diuretic. Decreases in blood pressure are primarily attributed to decreased total peripheral resistance or afterload. An advantage of combining captopril therapy with a conventional thiazide diuretic is that the thiazide-induced hypokalemia is minimized in the presence of ACE inhibition, since there is a marked decrease in angiotensin II–induced aldosterone release. If the patient is asymptomatic, captopril can be used as monotherapy in the treatment of congestive heart failure. The use of ACE inhibitors in the treatment of congestive heart failure is supported by results from large-scale clinical trials demonstrating a general reduction in the relative risk of death. In symptomatic patients captopril should be used in conjunction with a diuretic because of the weak natriuretic properties of ACE inhibitors. In combination, captopril will reduce afterload and preload and prevent diuretic-induced activation of the renin–angiotensin system. Finally, ACE inhibitors may slow the progression of congestive heart failure by limiting left ventricular hypertrophy. In the treatment of diabetic nephropathy associated with type I insulin-dependent diabetes mellitus, captopril decreases the rate of progression of renal insufficiency and retards the worsening of renal function.
• 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 NSAIDs. Antihypertensives: increased risk of hyperkalaemia, hypotension and renal failure with ARBs and aliskiren. Bee venom extract: possible severe anaphylactoid reactions when used together. Ciclosporin: increased risk of hyperkalaemia and nephrotoxicity. Cytotoxics: increased risk of angioedema with everolimus. Diuretics: enhanced hypotensive effect; hyperkalaemia with potassium-sparing diuretics. ESAs: 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 hyperkalaemia. Tacrolimus: increased risk of hyperkalaemia and nephrotoxicity

Technology Process of Captopril

There total 33 articles about Captopril which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 93.0%

(2R,S)-3-Acetylthio-2-methylpropanoyl chloride (74345-73-6) + L-proline (147-85-3,25191-13-3,37159-97-0,4305-67-3,4607-28-7) → captopril (62571-86-2)

Guidance literature:

With sodium hydroxide; In water; at -2 - 40 ℃; for 4.66667h; pH=8 - 10;

Reference yield: 87.0%

β-hydroxy-α-methyl-N-acryloyl-(S)-proline (613256-52-3) → captopril (62571-86-2)

Guidance literature:

β-hydroxy-α-methyl-N-acryloyl-(S)-proline; With thionyl chloride; In tetrahydrofuran; at 20 ℃; for 5h;

With ammonium sulfide; In tetrahydrofuran; at 0 - 20 ℃; for 3.5h;

DOI:10.1081/SCC-120017189

Reference yield: 71.0%

sodium hydrogen sulfide dihydrate + N-(3-mercapto-2-D-methylpropanyl)-L-proline + N-(3-chloro-2-D-methylpropanoyl)-L-proline + zinc (7440-66-6) → captopril (62571-86-2,63250-36-2,64838-54-6,112243-88-6,112243-90-0,119238-52-7)

Guidance literature:

With sodium chloride; In water;

upstream raw materials:

(S)-1-((S)-3-tert-Butylsulfanyl-2-methyl-propionyl)-pyrrolidine-2-carboxylic acid tert-butyl ester

1-(3-bromo-2S-methylpropionyl)-pyrrolidine-2S-carboxylic acid

H-Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH₂

Captopril disulfide

Downstream raw materials:

(S)-1-{3-[1-(4-Dimethylamino-3,5-dinitro-phenyl)-2,5-dioxo-pyrrolidin-3-ylsulfanyl]-2-methyl-propionyl}-pyrrolidine-2-carboxylic acid

S-Nitrosocaptopril

1-(1-oxo-2-methylpropyl)-L-proline

captopril trithiocarbonate

Refernces

• 1、 Cushman et al.. "Design of potent competitive inhibitors of angiotensin-converting enzyme. Carboxyalkanoyl and mercaptoalkanoyl amino acids.". . p. 5484,5486. Retrieved 1977.
• 2、 -. "Preparing method of captopril isomer". Paragraph 0032; 0040; 0041; 0042; 0043. . Retrieved 2019/04/26.
• 3、 -. "A process for preparing a renin - angiotensin - aldosterone system dual inhibitor compound of intermediate". Paragraph 0062; 0063; 0064. . Retrieved 2017/04/28.