7682-20-4Relevant articles and documents
Synthesis of an analogue of the substance P C-terminal hexapeptide with modification at the glutaminyl and methioninyl residues and increased activity in NK-2 receptor type: Structure-activity relationships
Manolopoulou,Poulos,Tsegenidis
, p. 949 - 954 (1992)
Analogues of [Orn6]-SP6-11 have been synthesized in which the Met11 residue is replaced by Hse(CH3), Hse(Bzl), Nva(5-OCH3), Nva(5-OBzl) and Abu. These analogues were tested in 3 in vitro preparations representative of NK-1, NK-2 and NK-3 receptor types. The Hse(Bzl) analogue is 16.6-fold more potent than the parent hexapeptide at the NK-2 receptor and 2.4-fold more potent at the NK-3 receptor. The Nva(5-OCH3) analogue showed weak antagonist activity in NK-2 and NK-3 receptor types, being a full agonist at NK-1. It is concluded from structure-activity correlations that the role of Met11 side chain in substance P is associated with activity and/or efficacy, as appropriate modifications in the side chain may result either in agonists with increased activity compared to the parent hexapeptide or selective agonists or may induce antagonism.
Preparation method of L-2-aminobutanamide hydrochloride
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Paragraph 0020; 0026; 0029; 0035; 0038; 0044, (2021/06/21)
The invention relates to the technical field of preparation of chiral drug intermediates, and discloses a preparation method of L-2-aminobutanamide hydrochloride, which comprises the following steps: dropwise adding ethyl 2-bromobutyrate into stronger ammonia water, and carrying out chemical reaction in a closed container to prepare a prefabricated mixture; According to the preparation method of the L-2-aminobutanamide hydrochloride, ethyl 2-bromobutyrate is used as an initial raw material, and the medical intermediate L-2-aminobutanamide hydrochloride is prepared through ammonolysis and chiral resolution. Compared with the traditional preparation method, the preparation method adopts a chiral reagent (+)-mandelic acid with low raw material price and racemic 2-aminobutanamide hydrochloride to form diastereoisomers, the L-2-aminobutanamide hydrochloride is obtained through resolution by utilizing the difference of the dissolving properties of the diastereoisomers in ethanol, the optical purity and the chemical purity of the product are high, and the technical scheme has the advantages of mild reaction conditions, short reaction steps, high yield, stable product quality and easy realization of industrial production.
Method for preparing levetiracetam
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Paragraph 0077; 0080; 0083; 0087; 0089; 0093; 0095; 0099, (2020/02/14)
The invention relates to a method for preparing levetiracetam. The method comprises the following steps: reacting aminobutyric acid in lower alcohol and thionyl chloride to obtain an intermediate I; adding ammonia water to continue the reaction, and adding hydrochloric acid to adjust the pH value to about 3 to salify to obtain a salified intermediate II refined product; reacting the intermediate II in the presence of KOH in the presence of a catalyst and dichloromethane, and then adding 4-chlorobutyryl chloride to continuously react; adding water to hydrolyze, adjusting the pH to be weakly alkaline by using diluted hydrochloric acid, and crystallizing to obtain a levetiracetam crude product; decolorizing and crystallizing in ethyl acetate to obtain a refined product of levetiracetam. The invention also relates to the levetiracetam prepared by the method and pharmaceutical application thereof, for example, the levetiracetam can be used for treating or preventing epilepsy, Parkinson's disease, dyskinesia, migraine, tremor, idiopathic tremor, bipolar disorder, chronic pain, neuropathic pain, or bronchial, asthma or allergic diseases.
