clodazon
{{Short description|Antidepressant}}
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{{Infobox drug
| drug_name = Clodazon
| image = Clodazon.svg
| width = 250px
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| CAS_number = 4755-59-3
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| PubChem = 20883
| IUPHAR_ligand =
| DrugBank =
| ChemSpiderID = 19652
| UNII = X82H6JOC4H
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| ChEMBL = 2110801
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| synonyms = AW 14'2446
| C=22 | H=25 | N=3 | O=3
| StdInChI=1S/C18H20ClN3O/c1-20(2)11-6-12-21-16-10-9-14(19)13-17(16)22(18(21)23)15-7-4-3-5-8-15/h3-5,7-10,13H,6,11-12H2,1-2H3
| StdInChIKey = VWXGRWMELBPMCU-UHFFFAOYSA-N
| SMILES = CN(C)CCCN1C2=C(C=C(C=C2)Cl)N(C1=O)C3=CC=CC=C3
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Clodazon (AW 142446) is an antidepressant drug investigated in Germany in the 1960s. In animal models, clodazon inhibits the catalepsy induced by tetrabenazine and it potentiates the effect of catecholamines, both effects being of the order experienced with imipramine. In clinical trials, about 2/3 of the patients showed a positive antidepressive effect with few side effects.
Pharmacology:{{cite journal | vauthors = Stille G, Lauener H, Eichenberger E | title = Ein Antidepressivum aus der Gruppe der 2-Benzimidazolinone. | journal = International Pharmacopsychiatry | date = August 1968 | volume = 1 | issue = 3-4 | pages = 214–210 | doi = 10.1159/000467934 }}{{cite journal | vauthors = Arnold OH, Guss OH | title = [Clinical experiences with the antidepressive agent AW 14'2446 (Clodazon)] | journal = Wiener Medizinische Wochenschrift | volume = 119 | issue = 7 | pages = 130–133 | date = February 1969 | pmid = 5772001 }}
Synthesis
The synthesis of clodazon is delineated in the patent: BE659364 (1965) idem Hunziker Fritz, US3338916 (1967 to A Wander S A Dr).
5-Chloro-2-nitrodiphenylamine [25781-92-4] (1) is reduced to 5-chloro-N-phenylbenzene-1,2-diamine [68406-47-3] (2). Treatment of this with phosgene (caution) would give 3-phenyl-5-chloro-benzimidazolin-2-one [54986-47-9] (3). Base catalyzed treatment of this with 1-bromo-3-chloropropane provided PC20506309 (structure not shown). Displacement of the remaining halogen atom leaving group by dimethylamine completes the construction of sidechain and thus the synthesis of clodazon (4).
[54986-47-9] ~98%:{{cite journal | vauthors = Bianchi M, Butti A, Rossi S, Barzaghi F, Marcaria V | title = Compounds With Antiulcer and Antisecretory Activity. I: 3-Aryl-benzimidazolin-2-ones and -thiones | journal = European Journal of Medicinal Chemistry | date = 1981 | volume = 16 | issue = 4 | pages = 321–326 }}~90%:{{cite journal | vauthors = Pizzotti M, Cenini S, Quici S, Tollari S |title=Role of alkali halides in the synthesis of nitrogen containing heterocycles by reductive carbonylation of aromatic nitro-derivatives catalysed by Ru3(CO)12 |journal=Journal of the Chemical Society, Perkin Transactions 2 |date=1994 |issue=4 |pages=913 |doi=10.1039/p29940000913}}
The crystal structure is monoclinic with space group P21/c with unit cell parameters a=5.898 b=31.911 c=10.817 Å with β=103.52°. Unit cell volume is 1989.3 Å3.{{cite journal | vauthors = Lambert P, Evrard G, Durant F, Germain G, Declercq JP |title=5-Chloro-1-[3-(dimethylamino)propyl]-1,3-dihydro-3-phenyl-2 H -benzimidazol-2-one monohydrochloride monohydrate (clodazone) |journal=Acta Crystallographica Section B Structural Crystallography and Crystal Chemistry |date=1 August 1978 |volume=34 |issue=8 |pages=2656–2658 |doi=10.1107/S0567740878008894|bibcode=1978AcCrB..34.2656L }}
References
{{Reflist}}
{{Antidepressants}}
{{Monoamine reuptake inhibitors}}
{{Tricyclics}}
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Category:Tricyclic antidepressants