Candesartan cilexetil

Base Information

• Chemical Name: Candesartan cilexetil
• CAS No.: 145040-37-5
• Molecular Formula: C33H34N6O6
• Molecular Weight: 610.67
• Hs Code.: 29339953
• European Community (EC) Number: 627-030-2
• NSC Number: 758697
• UNII: R85M2X0D68
• DSSTox Substance ID: DTXSID5020239
• Nikkaji Number: J1.640.921I
• Wikidata: Q27075664
• NCI Thesaurus Code: C28903
• RXCUI: 135481
• Pharos Ligand ID: HMANUPN3GABW
• Metabolomics Workbench ID: 67435
• ChEMBL ID: CHEMBL1014
• Mol file: 145040-37-5.mol

Synonyms:1-(cyclohexylocarbonyloxy)ethyl-2-ethoxy-1-(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)-1H-benzimidazole-7-carboxylate;1H-benzimidazolium, 7-carboxy-1-(2-((cyclohexylcarbonyl)oxy)ethyl)-2-ethoxy-1-(2'-(1H-tetrazol-5-yl)(1,1'-biphenyl)-4-yl)-, hydroxide, inner salt, (+-)-;Amias;Atacand;Blopress;candesartan cilexetil;Kenzen;Parapres;TCV 116;TCV-116

Chemical Property of Candesartan cilexetil

Chemical Property:

• Appearance/Colour: White crystalline powder
• Melting Point: 168-170?C
• Refractive Index: 1.665
• Boiling Point: 843.3 ºC at 760 mmHg
• PKA: pKa 3.55 (H2O t=25.0 I=0.025) (Uncertain);5.91(H2O t=25.0 I=0.025) (Uncertain)
• Flash Point: 463.8 ºC
• PSA: 143.34000
• Density: 1.37 g/cm³
• LogP: 6.31910
• Storage Temp.: -20°C Freezer
• Solubility.: DMSO: ≥15mg/mL
• XLogP3: 7
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 10
• Rotatable Bond Count: 13
• Exact Mass: 610.25398283
• Heavy Atom Count: 45
• Complexity: 962

Purity/Quality:

98%, ^*data from raw suppliers

Candesartan cilexetil ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn,N,T
• Statements: 20/21/22-36/37/38-50-48/20-61
• Safety Statements: 26-36-61-45-53

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCOC1=NC2=CC=CC(=C2N1CC3=CC=C(C=C3)C4=CC=CC=C4C5=NNN=N5)C(=O)OC(C)OC(=O)OC6CCCCC6
• Recent ClinicalTrials: A Study to Evaluate the Efficacy and Safety of Amlodipine Besylate and Candesartan Cilexetil in Essential Hypertension Patient Who Are Not Adequately Controlled With Candesartan Cilexetil Monotherapy
• Recent EU Clinical Trials: CandMig III study
• Recent NIPH Clinical Trials: None
• Uses: Candesartan cilexetil is a prodrug of the potent, long-acting, and selective angiotensin II type 1 receptor AT1 antagonist, candesartan. It is rapidly hydrolyzed to candesartan during gastrointestinal absorption. After hydrolysis of candesartan cilexetil to candesartan during gastrointestinal absorption, candesartan selectively competes with angiotensin II for the binding of the angiotensin II receptor subtype 1 AT1 in vascular smooth muscle, blocking angiotensin II-mediated vasoconstriction and inducing vasodilatation. In addition, antagonism of AT1 in the adrenal gland inhibits angiotensin II-stimulated aldosterone synthesis and secretion by the adrenal cortex; sodium and water excretion increase, followed by a reduction in plasma volume and blood pressure. Candesartan cilexetil can be used as pesticide and pharmaceutical intermediates. It can be used as the raw material of antihypertensive drugs. Candesartan is an angiotensin-receptor blocker (ARB)，Angiotensin receptor blockers effectively protect against the harmful effects of the activation of the renin-angiotensin-aldosterone system that occur with hypertension or diabetes.It may be used alone or with other agents to treat hypertension. Unlike angiotensin-converting enzyme (ACE) inhibitors, ARBs do not have the adverse effect of dry cough. Candesartan may be used to treat hypertension, isolated systolic hypertension, left ventricular hypertrophy and diabetic nephropathy. It may also be used as an alternative agent for the treatment of heart failure, systolic dysfunction, myocardial infarction and coronary artery disease.
• Description: Candesartan cilexetil is a prodrug form of the angiotensin II type 1 receptor (AT1) antagonist candesartan . Atacand was launched in Australia, Belgium, Canada, Denmark, Finland, the Netherlands, Norway, Sweden, S. Africa and the US as an antihypertensive agent. Pharmacological studies have indicated Atacand is about 10-fold more potent than Losartan and has a long elimination half-life. Like losartan, Atacand is converted to its active form during GI absorption (via ester hydrolysis). It is a potent antagonist of angiotensin II type 1 receptors. This occurs through tight binding and slow dissociation, and is more potent than ACE inhibitors. It is well tolerated (can be taken by elderly and those with type II diabetes) and has no gender effects.
• Therapeutic Function: Antihypertensive
• Clinical Use: Angiotensin-II antagonist: Hypertension Heart failure
• 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 impairment with ACE-Is and aliskiren. Ciclosporin: increased risk of hyperkalaemia and nephrotoxicity. Diuretics: enhanced hypotensive effect; hyperkalaemia with potassium-sparing diuretics. ESAs: increased risk of hyperkalaemia; antagonism of hypotensive effect. Lithium: reduced excretion, possibility of enhanced lithium toxicity. Potassium salts: increased risk of hyperkalaemia. Tacrolimus: increased risk of hyperkalaemia and nephrotoxicity

Technology Process of Candesartan cilexetil

There total 66 articles about Candesartan cilexetil 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: 98.0%

cilexetil trityl candesartan (170791-09-0) → candesartan cilexetil (145040-37-5)

Guidance literature:

With hydrogenchloride; In methanol; dichloromethane; at -14 - -12 ℃; Temperature; Flow reactor; Large scale;

Reference yield: 93.9%

orthocarbonic acid tetraethyl ester (78-09-1) + 2-(((2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)amino)-3-aminobenzoic acid-1-(((cyclohexyloxy)carbonyl)oxy)ethyl ester (1236156-65-2) → candesartan cilexetil (145040-37-5)

Guidance literature:

With acetic acid; In ethyl acetate; at 30 ℃; Temperature;

Reference yield: 92.3%

orthocarbonic acid tetraethyl ester (78-09-1) + C30H32N6O5*C2H2O4 → candesartan cilexetil (145040-37-5)

Guidance literature:

C₃₀H₃₂N₆O₅*C₂H₂O₄; With potassium carbonate; In ethyl acetate; at 10 - 15 ℃; pH=6 - 7;

orthocarbonic acid tetraethyl ester; In acetic acid; at 0 - 25 ℃; for 15h;

upstream raw materials:

2-Ethoxy-1-[[2'-(N-triphenylmethyltetrazol-5-yl)-biphenyl-4-yl]methyl]benzimidazole-7-carboxylic acid

cilexetil trityl candesartan

1-{[(cyclohexyloxy)carbonyl]oxy}ethyl 1-({4-[2-(1-benzyl-1H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-2-ethoxy-1H-1,3-benzodiazole-7-carboxylate

cyclohexyl (1-iodoethyl)carbonate

Downstream raw materials:

candesartan

(1RS)-1-[[(cyclohexyloxy)carbonyl]oxy]ethyl 2-oxo-3-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-2,3-dihydro-1H-benzimidazole-4-carboxylate

(1RS)-1-[[(cyclohexyloxy)carbonyl]oxy]ethyl 2-ethoxy-1-[[2'-(1-ethyl-1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylate

(1RS)-1-[[(cyclohexyloxy)carbonyl]oxy]ethyl 2-ethoxy-1-[[2'-(2-ethyl-2H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylate

Refernces

• 1、 -. "Candesartan cilexetil intermediate and application thereof". Paragraph 0060-0063. . Retrieved 2020/10/20.
• 2、 -. "A method for preparing ester". Paragraph 0006; 0068; 0084; 0098. . Retrieved 2018/05/24.