32943-25-2Relevant articles and documents
Reactive metabolites of desipramine and clomipramine: The kinetics of formation and reactivity with DNA
Korobkova, Ekaterina A.,Nemeth, John,Cadougan, Mikeisha,Venkatratnam, Abhishek,Bassit, Mohanram,Azar, Nikolay
, p. 340 - 345 (2012)
Tricyclic antidepressants (TCAs), along with phenothyazines and some industrial chemicals, are shown to react with enzymes that exhibit peroxidase activity. These reactions result in the formation of reactive intermediates having unpaired electrons. The peroxidase oxidation and reactivity of two TCAs, desipramine and clomipramine, were investigated. As a model of peroxidase, horseradish peroxidase (HRP) was employed. The products of the peroxidase catalyzed oxidation of desipramine and clomipramine were identified as N-dealkylated compounds iminodibenzyl and 3-chloroiminodibenzyl using the GC/MS technique. Both drugs formed broad UV/vis absorption spectra in the presence of HRP and H2O2, indicating the formation of a radical cations - reactive intermediate of the oxidation reaction. The dynamics of the formation of the desipramine intermediate was studied using UV/vis spectroscopy. The extinction coefficient was measured for the reactive intermediate, 7.80 × 103 M-1 cm-1, as well as the apparent Michaelis-Menten and catalytic constants, 4.4 mM and 2.3 s-1, respectively. Both desipramine and clomipramine degraded DNA in the presence of HRP/H2O2, as was revealed by agarose gel electrophoresis and PCI extraction. Manipulating the kinetic parameters of drug's radical formation and determining the extent of degradation to biomolecules could be potentially used for designing effective agents exhibiting specific reactivity.
High-purity clomipamine hydrochloride and preparation method thereof
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Paragraph 0082; 0089; 0094-0096; 0106; 0110-0111; 0118; 0122, (2020/11/23)
The invention relates to high-purity clomipamine hydrochloride and a preparation method thereof. Specifically, the preparation method comprises the following steps: reacting bromochloropropane with dimethylamine in the presence of alkali to obtain an intermediate I compound; adding 3-chlor-5-acetyl diphenyl imide and potassium hydroxide into toluene, and heating for reaction to obtain an intermediate II; adding potassium carbonate, potassium hydroxide into the intermediate II, and heating reactants, then adding a mixed solution of the intermediate I compound and methylbenzene, continuously heating to finish the reaction, then cooling the reaction solution, and adding water for extraction to obtain an organic layer containing clomipamine; concentrating the previous product under reduced pressure to obtain an oily substance, adding acetone, dropwise adding hydrochloric acid for acidification, crystallizing, centrifuging to obtain a crystal, and drying to obtain a clomipamine hydrochloride crude product; and adding the obtained clomipamine hydrochloride crude product and a solvent into a reaction kettle, heating for dissolving, adding medicinal carbon for reflux decolorization treatment, filtering for decarburization, cooling for crystallization, filtering for crystallization, and drying to obtain a clomipamine hydrochloride finished product. The method has the effects described in the specification.
Enhancing Reactivity and Selectivity of Aryl Bromides: A Complementary Approach to Dibenzo[b,f]azepine Derivatives
Casnati, Alessandra,Fontana, Marco,Coruzzi, Giovanni,Aresta, Brunella Maria,Corriero, Nicola,Maggi, Raimondo,Maestri, Giovanni,Motti, Elena,Della Ca', Nicola
, p. 4346 - 4352 (2018/09/14)
Dihydrodibenzo[b,f]azepines and dibenzo[b,f]azepines can be efficiently synthesized from aryl bromides, o-bromoanilines and norbornene or norbornadiene by means of palladium catalysis. This protocol gives access to dibenzo[b,f]azepine core containing a variety of electron-withdrawing substituents on both aromatic rings and complements the previously reported methodology where electron rich aryl iodides were preferentially used. The presence of KI, even in sub-stoichiometric amount, is crucial for this three-component reaction. The proper addition of iodide anions has a dramatic effect on reaction rate and selectivity. A formal three-step synthesis of the tricyclic antidepressant Clomipramine (Anafranil) is also described.
