40877-09-6Relevant articles and documents
Structure-Kinetic Profiling of Haloperidol Analogues at the Human Dopamine D2 Receptor
Fyfe, Tim J.,Kellam, Barrie,Sykes, David A.,Capuano, Ben,Scammells, Peter J.,Lane, J. Robert,Charlton, Steven J.,Mistry, Shailesh N.
supporting information, p. 9488 - 9520 (2019/11/11)
Haloperidol is a typical antipsychotic drug (APD) associated with an increased risk of extrapyramidal side effects (EPSs) and hyperprolactinemia relative to atypical APDs such as clozapine. Both drugs are dopamine D2 receptor (D2R) antagonists, with contrasting kinetic profiles. Haloperidol displays fast association/slow dissociation at the D2R, whereas clozapine exhibits relatively slow association/fast dissociation. Recently, we have provided evidence that slow dissociation from the D2R predicts hyperprolactinemia, whereas fast association predicts EPS. Unfortunately, clozapine can cause severe side effects independent of its D2R action. Our results suggest an optimal kinetic profile for D2R antagonist APDs that avoids EPS. To begin exploring this hypothesis, we conducted a structure-kinetic relationship study of haloperidol and revealed that subtle structural modifications dramatically change binding kinetic rate constants, affording compounds with a clozapine-like kinetic profile. Thus, optimization of these kinetic parameters may allow development of novel APDs based on the haloperidol scaffold with improved side-effect profiles.
Method for preparing 4-cypro methylene phenylboronic acid
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Paragraph 0021, (2017/08/31)
The invention discloses a method for preparing a 4-cypro methylene phenylboronic acid, and relates to the technical field of organic synthesis. The chlorobenzene is taken as the starting material, is subjected to a friedel-crafts reaction to generate 4-butanoyl chloride chlorobenzene, is subjected to a ring-closure reaction to generate 4-cypro formyl chlorobenzene, is subjected to a reduction reaction to generate 4-cypro methylene chlorobenzene, and is finally subjected to a Grignard boric acid reaction to generate the 4-cypro methylene phenylboronic acid. The cheap chlorobenzene, which is easy to get, is taken as the starting material, the preparation cost is remarkably lowered, the total molar yield of the product of 4-cypro methylene phenylboronic acid prepared through the 4-cypro methylene phenylboronic acid, the ring-closure reaction, the reduction reaction and the Grignard boric acid reaction is more than 35%, the production of the product is guaranteed on the basis of the low cost, and the method is suitable for industrial production.
Synthetic method of gamma-chlorobutanone derivatives
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Paragraph 0039-0041, (2017/07/22)
The invention discloses a synthetic method of gamma-chlorobutanone derivatives, and relates to a production method of inner-end and distal-end chlorinated aliphatic ketones in the technical field of chemical synthesis. Acetonitrile is taken as a solvent, manganese chloride is taken as a catalyst, tert-cyclobutanol, TMSCI (trimethylchlorosilane) and IBX (2-iodoxybenzoic acid) are subjected to a reaction, and a crude product is obtained; an organic solvent is removed through reduced-pressure concentration; the crude product is subjected to chromatography on a silica gel column with an organic solvent, and a refined product can be obtained. A synthetic route is shown in the specification, wherein R is aryl or alkyl. The raw materials used in the whole reaction process are cheap and easily available, a substrate adopted in the method has wide application range, and the whole reaction is simple and easy to operate and higher in yield; the reaction cost is reduced greatly.
