- Enantioselective resolution of Rac-terbutaline and evaluation of optically pure R-terbutaline hydrochloride as an efficient anti-asthmatic drug
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Terbutaline is a β2-adrenoceptor agonist for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Among the two isomers of terbutaline (TBT 2), R-isomer was found to be the potent enantiomer in generating therapeutic effect, while S-isomer has been reported to show side effects. In this study, R-terbutaline hydrochloride (R-TBH 6) was synthesized through chiral resolution from the racemic terbutaline sulfate (rac-TBS 1) with 99.9% enantiomeric excess (ee) in good overall yield (53.6%). Further, R-TBH 6 nebulized solution was prepared in half dosage of Bricanyl, which is a marketed product of racemic terbutaline and evaluated in vitro aerosol performance and in vivo anti-asthmatic effect on guinea pigs via. pulmonary delivery. From the investigation, it is evident that R-TBH 6 nebulized solution of half dosage performed similar fine aerosol characteristics and anti-asthmatic effect with Bricanyl.
- Beng, Huimin,Zhang, Hao,Jayachandra,Li, Junxiao,Wu, Jie,Tan, Wen
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- Preparation method of terra
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The invention provides a preparation method of terra, and relates to the technical field of chemical synthesis. The preparation method comprises the following steps: (a) reacting compound 1 with halogenated oxirane through Suzuki to obtain compound 2. (b) Compound 2 was reacted with tert-butylamine to yield terbutaline. Suzuki Reaction is creatively applied to preparation of terbutaline, the reaction steps are greatly shortened, the processes of protecting groups and deprotection are avoided by using the bromination reaction, the reaction conditions are mild, the reaction process is easy to control, and the safety coefficient is high. Raw materials are simple and easy to obtain, and the industrial cost is saved. The product yield is high. The purity is high, and the process route of a product with higher quality can be industrially produced.
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- Preparation method of terbutaline
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The invention belongs to the field of pharmacy, and particularly relates to a preparation method of terbutaline. The method comprises: S1, adding a compound I and dichloromethane into a reaction kettle, stirring and dissolving, and then adding anhydride, S2, after the reaction is finished, adding dilute alkaline water into the system, fully stirring and washing, collecting a dichloromethane phase,and carrying out reduced pressure distillation to obtain a yellow oily matter, namely a compound II, S3, adding the compound II, ethyl acetate, tert-butylamine, sodium hydroxide and an oxidation protective agent into the reaction kettle, and S4, after the reaction in the step S3 is finished, adding purified water into the system to wash the reaction solution in the step S3, collecting an ethyl acetate phase, and carrying out reduced pressure distillation on the ethyl acetate phase to obtain terbutaline. According to the technical scheme provided by the invention, the post-reaction treatment difficulty is reduced, so that an intermediate compound is easily separated from a reaction system, meanwhile, side reactions such as epoxy bond hydrolysis are avoided, and the stability and yield of the final product terbutaline are improved.
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Paragraph 0038; 0042-0043
(2020/12/05)
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- Preparation method of terbutaline sulfate
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The invention relates to the field of preparation of chemicals, in particular to a preparation method of terbutaline sulfate. The invention provides a preparation method of terbutaline sulfate. With simple and low-cost acetophenone as an initial raw material, the terbutaline is prepared through five-step reaction; then the terbutaline is subjected to salifying and purification to obtain terbutaline sulfate. According to the method disclosed by the invention, the total synthesis route of terbutaline is effectively shortened, so that the method is simple in intermediate purification, single in reaction solvent, simple in process, mild in reaction condition, easy to operate, high in total yield and more suitable for industrial production; the burden of workshop waste liquid treatment and purification is relieved, the three wastes and reaction energy consumption are reduced, the whole route is combined, research and control of raw material medicine impurities are better facilitated, and working hours are shortened technically and the three wastes and reaction energy consumption are reduced technically.
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- Preparation method of terbutaline sulfate
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The invention discloses a preparation method of terbutaline sulfate, wherein the method comprises the following steps: carrying out a bromination reaction on 3,5-dihydroxyacetophenone as a raw material by using a bromination reagent without hydroxyl protection, carrying out reduction and ring closing, carrying out a ring-opening reaction with tert-butylamine, and finally forming a salt with sulfuric acid to obtain terbutaline sulfate. According to the method, the defects of requirement of deprotection after hydroxyl protection, use of various high-risk highly toxic reagents, long reaction stepand low yield in the prior art are overcome.
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Paragraph 0017; 0029; 0032; 0034; 0037; 0039; 0042; 0044
(2020/04/29)
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- Novel preparation method of terbutaline sulfate
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The invention belongs to the field of organic synthesis of medicines, and concretely relates to a novel preparation method of a medicine terbutaline sulfate for treating bronchial spasm caused by bronchial asthma, chronic bronchitis, emphysema and other lung diseases. The synthesis route of the preparation method comprises the following steps: reacting 3,5-dihydroxybenzaldehyde with acetic anhydride to generate a compound I; reacting the compound I with trimethyloxosulfonium halide to generate a compound II; reacting the compound II with tert-butylamine to generate terbutaline; and salifying the terbutaline to generate the terbutaline sulfate. The method has the advantages of avoiding of dangerous chemical reagents, low price of adopted reagents, mild reaction conditions, and suitablenessfor industrial amplification.
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Paragraph 0039; 0042; 0044; 0047; 0049; 0052
(2020/03/13)
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- Method for synthesizing terbutaline
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The invention discloses a method for synthesizing terbutaline. The method comprises the following steps: reacting a compound I with selenium dioxide to obtain a compound II; reacting the compound II with tert-butylamine to obtain a compound III; reacting the compound III with a reducing agent to obtain a compound IV; and reacting the compound IV with a catalyst to remove benzyloxy to obtain terbutaline. The synthesis method has the advantage that the generation of impurity alpha-bromo-3, 5-dibenzyloxyacetophenone is avoided.
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Paragraph 0034; 0041-0042
(2020/02/10)
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- Preparation method for terbutaline hemisulfate
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The invention discloses a preparation method for terbutaline hemisulfate. The method comprises the following steps: by adopting 3, 5-resacetophenone as a raw material, performing bromination reaction by directly using a bromination reagent without protecting hydroxide radical, then reducing carbanyl group; condensing with tert-butylamine, finally, forming salt with sulfuric acid, thereby obtaining terbutaline hemisulfate. The method can overcome the defects of deprotection after hydroxide radical protection, usage of various high-risk toxic reagents, long reaction steps and low yield in the present technology.
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Paragraph 0012; 0026; 0031
(2017/08/30)
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- Compositions and methods for inducing adipose tissue cell death
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Pharmaceutical compositions, methods for increasing the rate of apoptosis in adipose tissue cells, and methods of reducing adipose tissue mass in a host, are described. One exemplary pharmaceutical composition, among others, includes at least one catecholamine in combination with a pharmaceutically acceptable carrier. The catecholamine is present in a dosage level effective to increase the rate of apoptosis in adipose tissue cells in a host.
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- Combined doses
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The present invention discloses a method and a pharmaceutical dry powder combined dose for the prophylaxis or treatment of a respiratory disorder in a mammalian host by inhalation of a metered dry powder combined dose of finely divided dry medication powders. At least one dry powder medicament is selected from a first group of bronchodilating medicaments and at least one dry powder medicament from a second group of anti-inflammatory medicaments. A metered dry powder medicinal combined dose comprising separately metered deposits of medicinally suitable quantities of each of the selected medicaments is prepared, in which the sum of the metered deposits constitutes the metered quantities of powder of the combined dose and the medicinal combined dose is introduced into an adapted inhaler device for a generally simultaneous delivery of the medicinal combined dose during the course of a single inhalation by a user, such that the delivered medicinal combined dose is composed of a high proportion of mixed de-aggregated fine particles of the selected medicaments, whereby an desired therapeutic or treating effect to the user is achieved.
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- Pharmaceutical formula
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The present invention concerns a pharmacological vehicle or carrier system, which makes possible administration of the active ingredient with a high absorption thereof in the blood circulation of the patient treated therewith, in particular also in the case of oral administration. The pharmacological vehicle system according to the invention comprises ultrafine particles of a reaction product of a reactive derivative of an at least dibasic inorganic acid or an alkane-carboxylic acid having 2 or 3 carboxyl groups and optionally one or two hydroxy groups, wherein one bond of the dibasic inorganic acid or one carboxy group of the alkane-carboxylic acid is bonded to a pharmacological active ingredient containing a hydroxy group, SH group and/or a primary or secondary amino group having a ractive hydrogen atom on this group, and the other bond is bonded to the free hydroxy group of a glycerolipid having at least one free hydroxy group on the glycerol. The invention further concerns these reaction products and a process for the preparation of ultrafine particles of these reaction products.
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- Orally active bronchospasmolytic compounds and their preparation
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Novel compounds are disclosed having useful activity as bronchodilators of improved longevity of action and reduced incidence of side effects. These compounds are described by the formula: EQU1 wherein R1 is a member of the class consisting of tertiary butyl and cyclobutyl, and R2 is a hydrogen or 2 to 5 carbon atom acyl radical, and pharmaceutically acceptable salts thereof. The activity of these compounds is compared to previously known bronchodilators such as 1-(3', 5'-dihydroxyphenyl)-2-(isopropylamino)-ethanol, having the common name orciprenaline, and 1-(3', 4'-dihydroxyphenyl-2-isoproplyamino-ethanol, having the common name isoprenaline.
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