Astemizole

Base Information

• Chemical Name: Astemizole
• CAS No.: 68844-77-9
• Molecular Formula: C28H31FN4O
• Molecular Weight: 458.579
• Hs Code.: 2933992600
• European Community (EC) Number: 272-441-9
• NSC Number: 759570,329963
• UNII: 7HU6337315
• DSSTox Substance ID: DTXSID9020110
• Nikkaji Number: J18.595G
• Wikipedia: Astemizole
• Wikidata: Q423437
• NCI Thesaurus Code: C28834
• Pharos Ligand ID: 6C6P2LAYLAUN
• Metabolomics Workbench ID: 42959
• ChEMBL ID: CHEMBL296419
• Mol file: 68844-77-9.mol

Synonyms:Alermizol;Alonga, Astemizol;Astemina;Astemizol Alonga;Astemizol ratiopharm;Astemizole;Astesen;Emdar;Esmacen;Fustermizol;Hismanal;Histaminos;Hubermizol;Laridal;Paralergin;R 43 512;R-43-512;R43512;ratiopharm, Astemizol;Retolen;Rifedot;Rimbol;Romadin;Simprox;Urdrim

Chemical Property of Astemizole

Chemical Property:

• Appearance/Colour: White powder
• Vapor Pressure: 1.19E-15mmHg at 25°C
• Melting Point: 172.9 °C
• Refractive Index: 1.623
• Boiling Point: 627.3 °C at 760 mmHg
• PKA: pKa 4.85(H2O t=25.0 I=0.025) (Uncertain);8.69(H2O t=25.0 I=0.025) (Uncertain)
• Flash Point: 333.2 °C
• PSA: 42.32000
• Density: 1.2 g/cm³
• LogP: 5.36220
• Storage Temp.: Store at +4°C
• Solubility.: DMSO: >20mg/mL
• Water Solubility.: It is soluble in DMSO (25 mg/ml ), ethanol (25 mg/ml), chloroform, methanol, and water (partly miscible).
• XLogP3: 6
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 8
• Exact Mass: 458.24818979
• Heavy Atom Count: 34
• Complexity: 599

Purity/Quality:

98%,99%, ^*data from raw suppliers

Astemizole ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 22-36/37/38
• Safety Statements: 26-36

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: COC1=CC=C(C=C1)CCN2CCC(CC2)NC3=NC4=CC=CC=C4N3CC5=CC=C(C=C5)F
• Uses: Astemizole is a histamine H1-receptor antagonist with IC50 of 4.7 nM. Astemizole is also a potent inhibitor of ether à-go-go 1 (Eag1) and Eag-related gene (Erg) potassium channels. Astemizole has antineoplastic and antipruritic effects. Nonsedating-type histamine H1-receptor antagonist. Potential for combination therapy with antivancer drugs such as doxorubicin in resistant leukemia. Antihistaminic Astemizole is used for preventing and treating severe seasonal and chronic allergic rhinitis, allergic conjunctivitis, hives, Quinke’s edema, other allergic conditions and dermatitis. Synonyms of this drug are hismanal, histazol, and others.
• Description: Astemizole belongs to the second-generation class of non-sedating, non-anticholinergic antihistamines. Its non-sedating properties appear to result from its poor penetration of the blood brain barrier. As a result it shows no potentiation of CNS depressants, including alcohol. Its long half-life allows once-daily dosing.
• Therapeutic Function: Antiallergic, Antihistaminic

Technology Process of Astemizole

There total 22 articles about Astemizole 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: 90.0%

4-amino-1-(2-(4-methoxyphenyl)ethyl)piperidine (85098-70-0) + 2-chloro-1-(4-fluorobenzyl)-1H-benzimidazole (84946-20-3) → 1-(4-methoxyphenethyl)piperidin-4-amine hydrochloride (108555-25-5) + astemizole (68844-77-9)

Guidance literature:

In neat (no solvent); at 145 ℃; for 16h; Schlenk technique; Inert atmosphere; Sealed tube;

DOI:10.1021/acs.joc.1c01467

Reference yield: 72.0%

4-amino-1-(2-(4-methoxyphenyl)ethyl)piperidine (85098-70-0) + 2-chloro-1-(4-fluorobenzyl)-1H-benzimidazole (84946-20-3) → astemizole (68844-77-9)

Guidance literature:

With potassium carbonate; In neat (no solvent); at 170 ℃;

DOI:10.1021/acsinfecdis.8b00272

Reference yield: 70.0%

(1H-benzimidazol-2-yl)-(1-(2-(4-methoxyphenyl)ethyl)piperidin-4-yl)amine (104472-63-1) + 4-Fluorobenzyl bromide (459-46-1) → astemizole (68844-77-9)

Guidance literature:

With sodium hydroxide; In acetonitrile; for 6h; Reflux;

DOI:10.1021/acs.joc.1c01467

upstream raw materials:

methanesulfonic acid-2-(4-methoxyphenyl)ethyl ester

1-[(4-fluorophenyl)methyl]-N-(4-piperidinyl)-1H-benzimidazol-2-amine dihydrobromide

1-(2-Chloroethyl)-4-methoxybenzene

O-desmethyl astemizole

Downstream raw materials:

O-desmethyl astemizole

2-<4-<2-<4-<<1-<(4-fluorophenyl)methyl>-1H-benzimidazol-2-yl>amino>-1-piperidinyl>ethyl>phenoxy>acetamide

Methyl-carbamic acid 4-(2-{4-[1-(4-fluoro-benzyl)-1H-benzoimidazol-2-ylamino]-piperidin-1-yl}-ethyl)-phenyl ester

Carbonic acid 4-(2-{4-[1-(4-fluoro-benzyl)-1H-benzoimidazol-2-ylamino]-piperidin-1-yl}-ethyl)-phenyl ester methyl ester

Refernces

• 1、 Fan, Guang-Gao,Jiang, Bo-Wen,Sang, Wei,Cheng, Hua,Zhang, Rui,Yu, Bao-Yi,Yuan, Ye,Chen, Cheng,Verpoort, Francis. "Metal-Free Synthesis of Heteroaryl Amines or Their Hydrochlorides via an External-Base-Free and Solvent-Free C-N Coupling Protocol". . p. 14627 - 14639. Retrieved 2021/11/01.
• 2、 -. "Cardiovascular safety assay". Page/Page column 6-7. . Retrieved 2008/06/13.