Imidapril hydrochloride

Base Information

• Chemical Name: Imidapril hydrochloride
• CAS No.: 89396-94-1
• Molecular Formula: C20H27N3O6^.HCl
• Molecular Weight: 441.912
• European Community (EC) Number: 685-551-0
• UNII: 7NSF9GG1NU
• DSSTox Substance ID: DTXSID7046912
• Wikidata: Q27268625
• NCI Thesaurus Code: C99550
• ChEMBL ID: CHEMBL3183293
• Mol file: 89396-94-1.mol

Synonyms:1-methyl-3-(2-(N-(1-ethoxycarbonyl-3-phenylpropyl)amino)propionyl)-2-oxoimidazolidine-4-carboxylic acid;4-imidazolidinecarboxylic acid, 3-(2-((1-(ethoxycarbonyl)-3-phenylpropyl)amino)-1-oxopropyl)-1-methyl-2-oxo-, monohydrochloride, (4S-(3(R*(R*)),4R*))-;imidapril;imidapril HCl;imidapril hydrochloride;TA 6366;TA-6366;Tanatril

Chemical Property of Imidapril hydrochloride

Chemical Property:

• Melting Point: 38-42oC
• Boiling Point: 577 °C at 760 mmHg
• Flash Point: 302.8 °C
• PSA: 116.25000
• LogP: 1.14290
• Storage Temp.: ?20°C
• Solubility.: H2O: ≥5mg/mL
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 10
• Exact Mass: 441.1666633
• Heavy Atom Count: 30
• Complexity: 619

Purity/Quality:

99% ^*data from raw suppliers

Imidapril (hydrochloride) ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCOC(=O)C(CCC1=CC=CC=C1)NC(C)C(=O)N2C(CN(C2=O)C)C(=O)O.Cl
• Isomeric SMILES: CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N2[C@@H](CN(C2=O)C)C(=O)O.Cl
• Recent EU Clinical Trials: A Phase III, Multicentre, Double-Blind, Randomised, Placebo-Controlled, Parallel Group, Dose-Titration Study of Imidapril Hydrochloride (EG006) in the Treatment of Cancer Cachexia
• Uses: Angiotensin converting enzyme (ACE) inhibitor. Antihypertensive. Imidapril hydrochloride was used as a standard in bioequivalence test by LC/MS method.
• 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 Imidapril hydrochloride

There total 16 articles about Imidapril hydrochloride 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:

t-butyl-(4S)-3-[(2S)-2-[[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]-1-methyl-2-oxo-4-imidazolidinecarboxylate hydrochloride (928142-34-1) → Imidapril hydrochloride (89396-94-1)

Guidance literature:

t-butyl-(4S)-3-[(2S)-2-[[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]-1-methyl-2-oxo-4-imidazolidinecarboxylate hydrochloride; With water; potassium carbonate; In dichloromethane; pH=10;

With hydrogenchloride; In isopropyl alcohol; at 25 - 30 ℃; for 6h;

Reference yield:

2-bromo-4-phenyl butanoic acid (16503-46-1) → Imidapril hydrochloride (89396-94-1)

Guidance literature:

Multi-step reaction with 11 steps

1: 28percent aq. NH₃ / 168 h / Ambient temperature

3: CoCl₂ / H₂O / 72 h / 37 °C / aminoacylase (from Aspergillus oryzae); pH 7

4: SOCl₂

5: 43.6 percent / K₂CO₃ / dimethylsulfoxide / 30 h / Ambient temperature

6: ethyl acetate; diisopropyl ether

7: 96 percent / H₂ / Pd / ethanol / 3 h / 760 Torr / Ambient temperature

8: DCC / tetrahydrofuran / Ambient temperature

9: 1) tBuOK / 1) THF, -50 deg C, 20 min, 2) THF, -30 deg C, 20 min

10: ethyl acetate; diisopropyl ether / 3 h / Ambient temperature

11: 1) K₂CO₃, 2) 15percent HCl/dioxane / 1) H₂O, 2) rt, overnight

With hydrogenchloride; ammonium hydroxide; thionyl chloride; potassium tert-butylate; hydrogen; potassium carbonate; dicyclohexyl-carbodiimide; palladium; In tetrahydrofuran; ethanol; di-isopropyl ether; water; dimethyl sulfoxide; ethyl acetate;

DOI:10.1021/jm00122a003

Reference yield:

D,L-homophenylalanine (1012-05-1) → Imidapril hydrochloride (89396-94-1)

Guidance literature:

Multi-step reaction with 10 steps

2: CoCl₂ / H₂O / 72 h / 37 °C / aminoacylase (from Aspergillus oryzae); pH 7

3: SOCl₂

4: 43.6 percent / K₂CO₃ / dimethylsulfoxide / 30 h / Ambient temperature

5: ethyl acetate; diisopropyl ether

6: 96 percent / H₂ / Pd / ethanol / 3 h / 760 Torr / Ambient temperature

7: DCC / tetrahydrofuran / Ambient temperature

8: 1) tBuOK / 1) THF, -50 deg C, 20 min, 2) THF, -30 deg C, 20 min

9: ethyl acetate; diisopropyl ether / 3 h / Ambient temperature

10: 1) K₂CO₃, 2) 15percent HCl/dioxane / 1) H₂O, 2) rt, overnight

With hydrogenchloride; thionyl chloride; potassium tert-butylate; hydrogen; potassium carbonate; dicyclohexyl-carbodiimide; palladium; In tetrahydrofuran; ethanol; di-isopropyl ether; water; dimethyl sulfoxide; ethyl acetate;

DOI:10.1021/jm00122a003

upstream raw materials:

tert-Butyl (4S)-3-<(2S)-2-amino>propionyl>-1-methyl-2-oxoimidazolidine-4-carboxylate Hydrogenmaleate

2-bromo-4-phenyl butanoic acid

D,L-homophenylalanine

2-(acetylamino)-4-phenylbutanoic acid

Downstream raw materials:

[1(S)-(ethoxycarbonyl)-3-phenylpropyl]-(S)-alanine

ethyl 2-amino-4-phenyl-(2S)-butyrate

(4S)-1-methyl-3-{(2S)-2-[N-((1S)-1-carboxy-3-phenylpropyl)amino]propionyl}-2-oxo-imidazolidine-4-carboxylic acid

C₂₀H₂₅N₃O₅

Refernces

• 1、 Hayashi, Kimiaki,Nunami, Ken-ichi,Kato, Jyoji,Yoneda, Naoto,Kubo, Masami,et al.. "Studies on Angiotensin Converting Enzyme Inhibitors. 4. Synthesis and Angiotensin Converting Enzyme Inhibitory Activities of 3-Acyl-1-alkyl-2-oxoimidazolidine-4-carboxylic Acid Derivatives". . p. 289 - 297. Retrieved 2007/10/02.