- Comparative analysis of in vivo and in silico toxicity evaluation of the organoiodine compounds towards D. magna using multivariate chemometric approach: A study on the example of amiodarone phototransformation products
-
In the present study the photochemical fate of organoiodine compound – amiodarone was performed. The drug turned out to be highly susceptible to UV–Vis irradiation, especially in the presence of humic substances and organic matrix. Qualitative LC-MS analysis revealed formation of twelve – mainly previously unreported – transformation products (TPs). Four major TPs were submitted to the toxicity analysis with the use of D. magna. All of the tested TPs presented higher toxic potential than the parent compound. The phenolic TPs were approximately 100 times more toxic than amiodarone. Toxic properties of the major TPs resulted in steadily increasing toxic potential of the photo-generated mixture over the time of irradiation. Moreover, the experimental toxicity data, concerning the TPs, were compared with results estimated by 6 in silico models with the use of a multivariate chemometric analysis. The results showed that the applied computational methods were able neither to correctly predict toxic properties of the studied compounds, nor the trends in change of their toxic parameters. Additional validation of in silico models ability to predict toxicity of iodinated organic compounds showed that the studied computational methods do not present sufficient prediction ability. Therefore their estimations concerning organoiodines should be verified using experimental tests.
- Skibiński, Robert,Trawiński, Jakub
-
-
- Method for preparing amiodarone hydrochloride
-
The invention discloses a method for preparing amiodarone hydrochloride, which comprises the following steps: by taking 2-butylbenzofuran and p-acetoxybenzaldehyde as raw materials, carrying out aldol reaction under Lewis acid catalysis and heating conditions, simultaneously carrying out hydroxyl oxidation, deacetylation and iodination reaction on the product in the presence of iodine and alkali, and then reacting the product with N, N-diethyl chloroethylamine, and salifying to obtain amiodarone hydrochloride. According to the method, only a catalytic amount of Lewis acid is needed, strong acidic aluminum chloride is not needed, reaction conditions are milder, byproducts are few, post-treatment is easy, and three wastes are greatly reduced; the whole route is simple to operate, the used reagents are cheap, easy to obtain and non-toxic, and the method is very suitable for industrial production.
- -
-
-
- Preparation method of amiodarone hydrochloride
-
The invention relates to a preparation method of amiodarone hydrochloride. According to the preparation method, synthesis of intermediate 2-butylbenzofuran is realized under effect of a catalyst, a cocatalyst, and an acid binding agent, through Sonogashira coupling cyclization reaction of 2-iodo phenol and 1-acetylene in an organic solvent at a 2-iodo phenol to 1-acetylene molar ratio of 1:09-1.3,wherein reaction temperature ranges from 30 to 60 DEG C, and reaction time ranges from 12 to 38h. Compared with the prior art, the advantages are that: operation is simplified; operation convenienceand product stability are improved; controlling of the ratio of the catalyst to the materials is capable of increasing the purities and yields of intermediates; no column chromatography purifying is needed; cost is reduced; production efficiency is increased at the same time; and convenience is provided for industrial large scale production.
- -
-
-
- Lewis Acid-Catalyzed Synthesis of Benzofurans and 4,5,6,7-Tetrahydrobenzofurans from Acrolein Dimer and 1,3-Dicarbonyl Compounds
-
2,3-Disubstituted benzofurans were synthesized from acrolein dimer and 1,3-dicarbonyl compounds by using N-bromosuccinimide as an oxidizing agent. The method was used to synthesize two commercial drug molecules, benzbromarone and amiodarone. The proposed mechanism of the reaction involves a N-bromosuccinimide (NBS)-assisted autotandem catalysis with Lewis acid catalyst. To proof the proposed mechanism, an intermediate was isolated successfully, which can be converted to 4,5,6,7-tetrahydrobenzofurans.
- Huang, Wenbo,Xu, Jing,Liu, Changhui,Chen, Zhiyan,Gu, Yanlong
-
p. 2941 - 2950
(2019/02/26)
-
- Amiodarone hydrochloride preparation method
-
The invention belongs to the field of medicine, and especially relates to an amiodarone hydrochloride preparation method. The method takes 2-hydroxybenzaldehyde and 2-alkyl halohexoic acid ester as the raw materials to prepare 2-butylbenzofuran, 2-butylbenzofuran is taken as the raw material, and is subjected to the steps of friedel-crafts acylation, demethylation, iodination, etherification and salt forming to obtain the amiodarone hydrochloride. By employing the method, the raw materials have the advantages of low cost and easy acquisition, the process is simple, and 2-butylbenzofuran and amiodarone hydrochloride with high purity and high yield can be obtained, the cost is low, the waste water is little, and the method is suitable for industrial production.
- -
-
-
- Trace amine-associated receptor 1 (TAAR1) is activated by amiodarone metabolites
-
Amiodarone (Cordarone, Wyeth-Ayerst Pharmaceuticals) is a clinically available drug used to treat a wide variety of cardiac arrhythmias. We report here the synthesis and characterization of a panel of potential amiodarone metabolites that have significant structural similarity to thyroid hormone and its metabolites the iodothyronamines. Several of these amiodarone derivatives act as specific agonists of the G protein-coupled receptor (GPCR) trace amine-associated receptor 1 (TAAR1). This result demonstrates a novel molecular target for amiodarone derivatives with potential clinical significance.
- Snead, Aaron N.,Miyakawa, Motonori,Tan, Edwin S.,Scanlan, Thomas S.
-
supporting information; experimental part
p. 5920 - 5922
(2009/05/31)
-
- Structure effect relationships of amiodarone analogues on the inhibition of thyroxine deiodination
-
Objectives: Amiodarone (AMI) has proven to be a potent anti-arrhythmic compound. Due to the structural similarity between AMI and thyroid hormone, it is possible that the drug could inhibit the activity of the 5'-thyroxine- deiodinase. Methods: AMI analogues resulting from (1) dealkylation, (2) deiodination and (3) deamination were synthesised and used as inhibitors in an in vitro biotransformation reaction of thyroxine (T4) to 3,3',5'- triiodothyronine (T3). Using high-performance liquid chromatography and ultraviolet detection for quantifying T3, it was found that the 5'-T4 deiodinase type I was involved in the reaction. On separate occasions, AMI or an AMI analogue was added to the reaction as an inhibitor. Results: All studied AMI analogues inhibited 5'-T4 deiodination competitively (K(i) value range 25-360 μM). In the concentration range of 1-1000 μM, AMI and its N- desethylated, deiodinated analogues inhibited 5'-T4 deiodination very weakly. AMI analogues with a hydroxyl group at the 4-position were strong inhibitors. Moreover, diiodo-AMI analogues inhibited 5'-T4 deiodination more strongly than their corresponding monoiodo- or deiodinated derivatives. Conclusion: It is likely that the degraded products of AMI could be responsible for thyroid dysfunction toxicosis in AMI therapy.
- Ha,Stieger,Grassi,Altorfer,Follath
-
p. 807 - 814
(2007/10/03)
-
- Furans, benzofurans, and thiophenes useful in the treatment of insulin resistance and hyperglycemia
-
This invention provides compounds of Formula I having the structure: wherein R1, R2, R3, R4, R5, R6, R7, R8, W, X, Y, and Z are as defined in the specification, or a pharmaceutically acceptable salt thereof, which are useful in treating metabolic disorders related to insulin resistance or hyperglycemia.
- -
-
-
- Phenyl oxo-acetic acids useful in the treatment of insulin resistance and hyperglycemia
-
This invention provides compounds of Formula I having the structure wherein: A, B, R1, R2, R3, R4, R5, and R6 are as defined in the specification, or a pharmaceutically acceptable salt thereof, which are useful in treating metabolic disorders related to insulin resistance or hyperglycemia.
- -
-
-