CAS 68844-77-9|Retolen|Astemison|astemizole|Histamen|Histaminos|1-[(4-fluorophenyl)methyl]-N-{1-[2-(4-methoxyphenyl)ethyl]piperidin-4-yl}-1H-1,3-benzodiazol-2-amine|Kelp|Laridal|Hismanal|Nono-Nastiz...

General Information

Structure

Molecular Formula

C₂₈H₃₁FN₄O

Molecular Mass

458.5703432

Exact Mass

458.24818985

Charge

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

Canonic Smiles

COc1ccc(cc1)CCN1CCC(CC1)Nc1nc2c(n1Cc1ccc(cc1)F)cccc2

Isomeric Smiles

Fc1ccc(Cn2c(NC3CCN(CC3)CCc3ccc(OC)cc3)nc3c2cccc3)cc1

Calculated Properties

JChem

H Acceptors

H Donor

LogD (pH = 5.5)

1.4488908

LogD (pH = 7.4)

3.9728467

Log P

5.3896523

Molar Refractivity

135.6432

Polarizability

52.523415

Polar Surface Area

42.32

Rotatable Bonds

Lipinski's Rule of Five

false

ALOGPS 2.1

Log P

5.92

LOG S

-5.58

Solubility (Water)

1.20e-03 g/l

Data Source

Academic Data

Commercial Catalog

Data Source

Names and Identifiers

Brand Name

RetolenAstemisonHistamenHistaminosKelpLaridalHismanalNono-Nastizol AHistazolAlermizolAstemisolMetodikAstemisanParalerginWaruzol

IUPAC Traditional name

astemizole

IUPAC name

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

Synonyms

Astemizole1-(4-Fluorobenzyl)-2-(1-[4-methoxyphenethyl]piperidin-4-yl)aminobenzimidazoleAstemizole1-(4-fluorobenzyl)-2-(1-(4-methoxyphenethyl)piperidin-4-yl)aminobenzimidazoleRetolenHistamenWaruzolAstemisanR 42512ParalerginR 43512Hismanal1-[(4-Fluorophenyl)methyl]-N-[1-[2-(4-methoxyphenyl)ethyl]-4-piperidinyl]-1H-benzimidazol-2-amine

Names and Identifiers

Registration numbers

PubChem SID

PubChem CID

CAS Number

EC Number

MDL Number

Registration numbers

Properties

Product Information

Empirical Formula (Hill Notation)

C28H31FN4O

Purity

≥98% (HPLC)

98%

Certificate of Analysis

Download link

Properties

Related Proteins

No Data Available

Click here to submit data

Molecular Spectra

No Data Available

Click here to submit data

Molecule 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approved; withdrawn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 It was withdrawn from market by the manufacturer in 1999 due to the potential to cause arrhythmias at high doses, especially when when taken with CYP inhibitors or grapefruit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.

TRC

A790030

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

Molecule Details

References

PubChem Literature

From Data Sources

• 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

• Laduron, P.M., et al.: Mol. Pharmacol., 21, 294 (1981)

• Wauquier, A., et al.: Eur. J. Pharmacol., 72, 245 (1981)

• Ishikawa, M., et al.: Biol.

• Richards, D.M., et al.: Drugs, 28, 38 (1981)

• Al-Obaid, A.M., et al.: Anal. Profiles Drug Subs., 20, 173 (1981)

References

Bioactivity

PubChem BioAssay

Bioactivity

Data Source

Academic Data

Commercial Catalog

Names and Identifiers

Brand Name

RetolenAstemisonHistamenHistaminosKelpLaridalHismanalNono-Nastizol AHistazolAlermizolAstemisolMetodikAstemisanParalerginWaruzol

IUPAC Traditional name

astemizole

IUPAC name

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

Synonyms

Registration numbers

PubChem SID

PubChem CID

CAS Number

EC Number

MDL Number

Properties

Product Information

Empirical Formula (Hill Notation)

C28H31FN4O

Purity

≥98% (HPLC)

98%

Certificate of Analysis

Download link

Molecule Details

DrugBank

DB00637

Drug Groups

approved; withdrawn

Description

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

• 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

TRC

A790030

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

References

PubChem Literature

From Data Sources

• 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

• Laduron, P.M., et al.: Mol. Pharmacol., 21, 294 (1981)

• Wauquier, A., et al.: Eur. J. Pharmacol., 72, 245 (1981)

• Ishikawa, M., et al.: Biol.

• Richards, D.M., et al.: Drugs, 28, 38 (1981)

• Al-Obaid, A.M., et al.: Anal. Profiles Drug Subs., 20, 173 (1981)

Bioactivity

PubChem BioAssay

Molecule

ID:519