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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/10/01 11:21:38」(JST)
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Clemizole
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| Systematic (IUPAC) name |
|
1-[(4-chlorophenyl)methyl]-2-(pyrrolidin-1-ylmethyl)benzimidazole
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| Identifiers |
| CAS Number |
442-52-4 |
| ATC code |
none |
| PubChem |
CID 2782 |
| ChemSpider |
2680 |
| UNII |
T97CB3796L Y |
| ChEBI |
CHEBI:52140 |
| ChEMBL |
CHEMBL1407943 |
| NIAID ChemDB |
033090 |
| Chemical data |
| Formula |
C19H20ClN3 |
| Molar mass |
325.84 g/mol |
SMILES
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Clc1ccc(cc1)Cn3c(nc2ccccc23)CN4CCCC4
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InChI
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InChI=1S/C19H20ClN3/c20-16-9-7-15(8-10-16)13-23-18-6-2-1-5-17(18)21-19(23)14-22-11-3-4-12-22/h1-2,5-10H,3-4,11-14H2
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Key:CJXAEXPPLWQRFR-UHFFFAOYSA-N
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Clemizole is an antihistamine.
Synthesis
Benzimidazoles substituted with an alkylamine at position 2 have a venerable history as H1 antihistaminic agents. The standard starting material for many benzimidazoles consists of phenylenediamine, or its derivatives.
Clemizole synthesis:
[1][2]
Reaction of that compound with chloroacetic acid can be rationalized by invoking initial formation of the chloromethyl amide. Imide formation with the remaining free amino group closes the ring to afford th 2-chloromethyl benzimidazole (3). Displacement of halogen with pyrrolidine affords the alkylation product. The proton on the fused imidazole nitrogen is then removed by reaction with sodium hydride. Treatment of the resulting anion with α,4-dichlorotoluene gives the H1 antihistaminic agent clemizole (5).
See also
References
- ^ Jerchel, D.; Fischer, H.; Kracht, M. (1952). "Zur Darstellung der Benzimidazole". Justus Liebigs Annalen der Chemie. 575 (2): 162. doi:10.1002/jlac.19525750204.
- ^ GB 703272 ; M. Schenck, W. Heinz, U.S. Patent 2,689,853 (both 1954 to Schering AG).
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Histaminergics
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Receptor
(ligands) |
| H1 |
- Agonists: 2-Pyridylethylamine
- Betahistine
- Histamine
- HTMT
- UR-AK49
- Antagonists: First-generation: 4-Methyldiphenhydramine
- Alimemazine
- Antazoline
- Azatadine
- Bamipine
- Benzatropine (benztropine)
- Bepotastine
- Bromazine
- Brompheniramine
- Buclizine
- Captodiame
- Carbinoxamine
- Chlorcyclizine
- Chloropyramine
- Chlorothen
- Chlorphenamine
- Chlorphenoxamine
- Cinnarizine
- Clemastine
- Clobenzepam
- Clocinizine
- Cloperastine
- Cyclizine
- Cyproheptadine
- Dacemazine
- Decloxizine
- Deptropine
- Dexbrompheniramine
- Dexchlorpheniramine
- Dimenhydrinate
- Dimetindene
- Diphenhydramine
- Diphenylpyraline
- Doxylamine
- Embramine
- Etodroxizine
- Etybenzatropine (ethylbenztropine)
- Etymemazine
- Fenethazine
- Flunarizine
- Histapyrrodine
- Homochlorcyclizine
- Hydroxyethylpromethazine
- Hydroxyzine
- Isopromethazine
- Isothipendyl
- Meclozine
- Medrylamine
- Mepyramine (pyrilamine)
- Mequitazine
- Methafurylene
- Methapyrilene
- Methdilazine
- Moxastine
- Orphenadrine
- Oxatomide
- Oxomemazine
- Phenindamine
- Pheniramine
- Phenyltoloxamine
- Pimethixene
- Piperoxan
- Pipoxizine
- Promethazine
- Propiomazine
- Pyrrobutamine
- Talastine
- Thenalidine
- Thenyldiamine
- Thiazinamium
- Thonzylamine
- Tolpropamine
- Tripelennamine
- Triprolidine
- Second/third-generation: Acrivastine
- Alinastine
- Astemizole
- Azelastine
- Bamirastine
- Barmastine
- Bepiastine
- Bepotastine
- Bilastine
- Cabastinen
- Carebastine
- Cetirizine
- Clemastine
- Clemizole
- Clobenztropine
- Desloratadine
- Dorastine
- Ebastine
- Efletirizine
- Emedastine
- Epinastine
- Fexofenadine
- Flezelastine
- Ketotifen
- Latrepirdine
- Levocabastine
- Levocetirizine
- Linetastine
- Loratadine
- Mapinastine
- Mebhydrolin
- Mizolastine
- Moxastine
- Noberastine
- Octastine
- Olopatadine
- Perastine
- Pibaxizine
- Piclopastine
- Quifenadine (phencarol)
- Rocastine
- Rupatadine
- Setastine
- Sequifenadine (bicarphen)
- Talastine
- Temelastine
- Terfenadine
- Vapitadine
- Zepastine
- Non-generational: Atypical antipsychotics (e.g., aripiprazole, asenapine, clozapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone, zotepine)
- Tetracyclic antidepressants (e.g., amoxapine, loxapine, maprotiline, mianserin, mirtazapine, oxaprotiline)
- Tricyclic antidepressants (e.g., amitriptyline, butriptyline, clomipramine, desipramine, dosulepin (dothiepin), doxepin, imipramine, iprindole, lofepramine, nortriptyline, protriptyline, trimipramine)
- Typical antipsychotics (e.g., chlorpromazine, flupenthixol, fluphenazine, loxapine, perphenazine, prochlorperazine, thioridazine, thiothixene)
- Unknown/unsorted: Belarizine
- Elbanizine
- Flotrenizine
- Napactadine
- Tagorizine
- Trelnarizine
- Trenizine
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| H2 |
- Agonists: Amthamine
- Betazole
- Dimaprit
- Histamine
- HTMT
- Impromidine
- UR-AK49
- Antagonists: Bisfentidine
- Burimamide
- Cimetidine
- Dalcotidine
- Donetidine
- Ebrotidine
- Etintidine
- Famotidine
- Isolamtidine
- Lafutidine
- Lamtidine
- Lavoltidine (loxtidine)
- Lupitidine
- Metiamide
- Mifentidine
- Niperotidine
- Nizatidine
- Osutidine
- Oxmetidine
- Pibutidine
- Quisultazine (quisultidine)
- Ramixotidine
- Ranitidine
- Roxatidine
- Sufotidine
- Tiotidine
- Tuvatidine
- Venritidine
- Xaltidine
- Zolantidine
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| H3 |
- Agonists: α-Methylhistamine
- Cipralisant
- Histamine
- Imetit
- Immepip
- Immethridine
- Methimepip
- Proxyfan
- Antagonists: A-349,821
- A-423,579
- ABT-239
- ABT-652
- AZD5213
- Betahistine
- Burimamide
- Ciproxifan
- Clobenpropit
- Conessine
- Enerisant
- GSK-189,254
- Impentamine
- Iodophenpropit
- Irdabisant
- JNJ-5207852
- MK-0249
- NNC 38-1049
- PF-03654746
- Pitolisant
- SCH-79687
- Thioperamide
- VUF-5681
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| H4 |
- Agonists: 4-Methylhistamine
- α-Methylhistamine
- Histamine
- OUP-16
- VUF-8430
- Antagonists: JNJ-7777120
- Mianserin
- Thioperamide
- Toreforant
- VUF-6002
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Transporter
(inhibitors) |
| VMATs |
| TAAR1 inactive |
- Amiodarone
- APP
- AZIK
- Bietaserpine
- Deserpidine
- Dihydrotetrabenazine
- Efavirenz
- GBR-12935
- GZ-793A
- Ibogaine
- Ketanserin
- Lobeline
- Methoxytetrabenazine
- NBI-98854
- Reserpine
- Rose bengal
- SD-809
- Tetrabenazine
- Vanoxerine (GBR-12909)
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| TAAR1 active |
- Amphetamine
- Methamphetamine
- MDMA
- Phenethylamine
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Enzyme
(inhibitors) |
| HDC |
- Catechin
- Meciadanol
- Naringenin
- Tritoqualine
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| HNMT |
- Amodiaquine
- Diphenhydramine
- Harmaline
- Metoprine
- Quinacrine
- SKF-91,488
- Tacrine
|
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| DAO |
- Pimagedine (aminoguanidine)
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| Others |
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English Journal
- Clemizole Hydrochloride is a Novel and Potent Inhibitor of Transient Receptor Potential Channel TRPC5.
- Richter JM1, Schaefer M1, Hill K2.
- Molecular pharmacology.Mol Pharmacol.2014 Aug 19. pii: mol.114.093229. [Epub ahead of print]
- TRPC5 is a nonselective, Ca2+ permeable cation channel which belongs to the large family of transient receptor potential channels. It is predominantly found in the central nervous system with a high expression density in the hippocampus, the amygdala and the frontal cortex. Several studies confirm t
- PMID 25140002
- Selective inhibition of heme oxygenase-2 activity by analogs of 1-(4-chlorobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole (clemizole): Exploration of the effects of substituents at the N-1 position.
- Vlahakis JZ1, Vukomanovic D, Nakatsu K, Szarek WA.
- Bioorganic & medicinal chemistry.Bioorg Med Chem.2013 Nov 1;21(21):6788-95. doi: 10.1016/j.bmc.2013.07.050. Epub 2013 Aug 8.
- Several analogs based on the lead structure of 1-(4-chlorobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole (clemizole) were synthesized and evaluated as novel inhibitors of heme oxygenase (HO). Many of the compounds were found to be potent and highly selective for the HO-2 isozyme (constitutive),
- PMID 24021581
- Using chimeric mice with humanized livers to predict human drug metabolism and a drug-drug interaction.
- Nishimura T1, Hu Y, Wu M, Pham E, Suemizu H, Elazar M, Liu M, Idilman R, Yurdaydin C, Angus P, Stedman C, Murphy B, Glenn J, Nakamura M, Nomura T, Chen Y, Zheng M, Fitch WL, Peltz G.
- The Journal of pharmacology and experimental therapeutics.J Pharmacol Exp Ther.2013 Feb;344(2):388-96. doi: 10.1124/jpet.112.198697. Epub 2012 Nov 8.
- Interspecies differences in drug metabolism have made it difficult to use preclinical animal testing data to predict the drug metabolites or potential drug-drug interactions (DDIs) that will occur in humans. Although chimeric mice with humanized livers can produce known human metabolites for test su
- PMID 23143674
Related Links
- Clemizole Penicillin is a medicine available in a number of countries worldwide. A list of US medications equivalent to Clemizole Penicillin is available on the Drugs.com website. ... Drugs.com provides accurate and independent ...
- Sigma-Aldrich offers Sigma-C5040, Clemizole hydrochloride for your research needs. Find product specific information including CAS, MSDS, protocols and references. ... Biochem/physiol Actions H 1 histamine receptor ...
Related Pictures
★リンクテーブル★
[★]
- 英
- clemizole
- 化
- clemizole hydrochloride 塩酸クレミゾール、ウンデシル酸クレミゾール clemizole undecylate
ニュース
- 抗ヒスタミン薬・クレミゾールはHCV感染の治療薬として有望
- 微小流体チップによるC型肝炎ウイルス薬の探索
- Nature Biotechnology 26 (9), Sep 2008
- ………Glenn、Quakeらの研究チームは、HCVの非構造タンパク質4B（NS4B）がHCVのRNAゲノムの結合で役割を担っており、この結合相互作用を阻害すればHCVの複製が抑えられて新たな治療介入法につながるという仮説の検証を始めた。………研究チームは、微小流体装置による小規模の二次スクリーニングで、1,280種の小分子化合物のライブラリーから、NS4BとウイルスRNAの結合を阻害する化合物18種を確認した。そのうち6種は培養細胞で抗ウイルス活性を示し、1種（塩酸クレミゾール）はウイルスの複製を著明に阻害した。NS4B領域またはHCVマイナスRNA鎖の3′末端に変異をもつクレミゾール耐性HCVレプリコンを選択することで、クレミゾールは真のHCV阻害剤であることが確認された。……… (参考)
参考
- http://www.natureasia.com/japan/biotechnology/highlights/article.php?i=68228
[★]
ウンデシル酸クレミゾール