1-[(4-fluorophenyl)methyl]-N-{1-[2-(4-methoxyphenyl)ethyl]piperidin-4-yl}-1H-1,3-benzodiazol-2-amine

• ChemBase ID: 519
• Molecular Formular: C28H31FN4O
• Molecular Mass: 458.5703432
• Monoisotopic Mass: 458.24818985
• SMILES: Fc1ccc(Cn2c(NC3CCN(CC3)CCc3ccc(OC)cc3)nc3c2cccc3)cc1
• Canonical SMILES: COc1ccc(cc1)CCN1CCC(CC1)Nc1nc2c(n1Cc1ccc(cc1)F)cccc2
• InChI: InChI=1S/C28H31FN4O/c1-34-25-12-8-21(9-13-25)14-17-32-18-15-24(16-19-32)30-28-31-26-4-2-3-5-27(26)33(28)20-22-6-10-23(29)11-7-22/h2-13,24H,14-20H2,1H3,(H,30,31)
• InChIKey: GXDALQBWZGODGZ-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 1-[(4-fluorophenyl)methyl]-N-{1-[2-(4-methoxyphenyl)ethyl]piperidin-4-yl}-1H-1,3-benzodiazol-2-amine
• IUPAC Traditional name: astemizole
• Brand Name: Alermizol; Astemisan; Astemisol; Astemison; Hismanal; Histamen; Histaminos; Histazol; Kelp; Laridal; Metodik; Nono-Nastizol A; Paralergin; Retolen; Waruzol
• Synonyms: Astemizole; 1-[(4-Fluorophenyl)methyl]-N-[1-[2-(4-methoxyphenyl)ethyl]-4-piperidinyl]-1H-benzimidazol-2-amine; Astemisan; Hismanal; Histamen; Paralergin; R 42512; R 43512; Retolen; Waruzol; 1-(4-Fluorobenzyl)-2-(1-[4-methoxyphenethyl]piperidin-4-yl)aminobenzimidazole; Astemizole; 1-(4-fluorobenzyl)-2-(1-(4-methoxyphenethyl)piperidin-4-yl)aminobenzimidazole

Database IDs

• CAS Number: 68844-77-9
• EC Number: 272-441-9
• MDL Number: MFCD00153919
• PubChem SID: 160963982; 46508569
• PubChem CID: 2247

CALCULATED PROPERTIES

JChem

• H Acceptors: 4
• H Donor: 1
• LogD (pH = 5.5): 1.4488908
• LogD (pH = 7.4): 3.9728467
• Log P: 5.3896523
• Molar Refractivity: 135.6432 cm^3
• Polarizability: 52.523415 Å^3
• Polar Surface Area: 42.32 Å^2
• Rotatable Bonds: 8
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 5.92
• LOG S: -5.58
• Solubility (Water): 1.20e-03 g/l

PROPERTIES

Physical Property

• Solubility: 432 mg/L; Chloroform; DMSO: >20 mg/mL; Methanol
• Apperance: powder; White Solid
• Melting Point: >175°C (dec.)
• Hydrophobicity(logP): 5.8

Safety Information

• Storage Condition: desiccated; protect from light; Refrigerator
• RTECS: DD8968000
• European Hazard Symbols: Harmful (Xn)
• German water hazard class: 3
• Risk Statements: 22-36/37/38
• Safety Statements: 26-36
• GHS Pictograms: GHS07
• GHS Signal Word: Warning
• GHS Hazard statements: H315-H319-H335
• GHS Precautionary statements: P261-P305 + P351 + P338
• Storage Temperature: 2-8°C

Product Information

• Purity: ≥98% (HPLC); 98%
• Empirical Formula (Hill Notation): C28H31FN4O

DETAILS

DrugBank - DB00637

• Drug Groups: approved; withdrawn
• Description: Astemizole is a long-acting, non-sedating second generation antihistamine used in the treatment of allergy symptoms. It was withdrawn from market by the manufacturer in 1999 due to the potential to cause arrhythmias at high doses, especially when when taken with CYP inhibitors or grapefruit juice.
• Indication: Astemizole was indicated for use in the relieving allergy symptoms, particularly rhinitis and conjunctivitis. It has been withdrawn from the market however due to concerns of arrhythmias.
• Pharmacology: Astemizole is a second generation H₁-receptor antagonist. It does not significantly cross the blood brain barrier and therefore does not cause drowsiness or CNS depression at normal doses.
• Toxicity: LD₅₀=2052mg/kg in mice
• Affected Organisms: Humans and other mammals
• Biotransformation: Almost completely metabolized in the liver and primarily excreted in the feces.
• Absorption: Rapidly absorbed from the gastrointestinal tract.
• Half Life: 1 day
• Protein Binding: 96.7%
• References: Wang X, Hockerman GH, Green HW 3rd, Babbs CF, Mohammad SI, Gerrard D, Latour MA, London B, Hannon KM, Pond AL: Merg1a K+ channel induces skeletal muscle atrophy by activating the ubiquitin proteasome pathway. FASEB J. 2006 Jul;20(9):1531-3. Epub 2006 May 24. [Pubmed] ; Chong CR, Chen X, Shi L, Liu JO, Sullivan DJ Jr: A clinical drug library screen identifies astemizole as an antimalarial agent. Nat Chem Biol. 2006 Aug;2(8):415-6. Epub 2006 Jul 2. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Sigma Aldrich - A2861

Biochem/physiol Actions
Astermizole is a potent hERG potassium channel blocker (IC50 of 0.9 nM) and may used as a pharmacological chaperone to correct folding defects and restore protein function for some mutated forms of hERG channels. It has also been studied for treatment of malaria, hERG and hEAG channel function in cancer and as a second generation antihistamine H-1 antagonist.
Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. A2861.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

Toronto Research Chemicals - A790030

Nonsedating-type histamine H1-receptor antagonist. Potential for combination therapy with antivancer drugs such as doxorubicin in resistant leukemia. Antihistaminic.

REFERENCES

• Wang X, Hockerman GH, Green HW 3rd, Babbs CF, Mohammad SI, Gerrard D, Latour MA, London B, Hannon KM, Pond AL: Merg1a K+ channel induces skeletal muscle atrophy by activating the ubiquitin proteasome pathway. FASEB J. 2006 Jul;20(9):1531-3. Epub 2006 May 24. Pubmed
• Chong CR, Chen X, Shi L, Liu JO, Sullivan DJ Jr: A clinical drug library screen identifies astemizole as an antimalarial agent. Nat Chem Biol. 2006 Aug;2(8):415-6. Epub 2006 Jul 2. Pubmed
• Wauquier, A., et al.: Eur. J. Pharmacol., 72, 245 (1981)
• Laduron, P.M., et al.: Mol. Pharmacol., 21, 294 (1981)
• Richards, D.M., et al.: Drugs, 28, 38 (1981)
• Al-Obaid, A.M., et al.: Anal. Profiles Drug Subs., 20, 173 (1981)
• Ishikawa, M., et al.: Biol.