39 results about "Zolmitriptan" patented technology

A method of treatment or prevention of headache, migraine or cluster headaches, which method comprises co-administration of a therapeutically effective amount of the compound 1-[N2-[3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxochinazolin-3-yl)-1-piperidinyl]-carbonyl]-D-tyrosyl]-L-lysyl]-4-(4-pyridinyl)-piperazine [BIBN4096BS] or a physiologically acceptable salt thereof and a therapeutically effective amount of a second active antimigraine drug, particularly sumatriptan, zolmitriptan or dihydroergotamin or a physiologically acceptable salt thereof, as well as to the corresponding pharmaceutical compositions and the preparation thereof.

The invention provides a Zolmitriptan quick-release formulation which can further improve the dissolving degree of the main medicament, greatly increase the absorbing velocity of the medicament in stomach and intestine, thus making the curative effect exert completely. Based on the physics and chemistry nature of the Zolmitriptan, adjuvant having specific disintegration and dissolving boosting actions for grease solving Zolmitriptan is selected from a plurality of medicinal findings through experiment.

In particular, zolmitriptan or a pharmaceutically acceptable salt thereof, which includes a) Preparation of the diazonium salt of the aniline hydrochloride (II); followed by reduction and acidification to give hydrazine (III); b) In situ Reaction of the hydrazine hydrochloride (III) with α-keto-δ-valerolactone, to give the hydrazone (IV); c) Fischer indole synthesis of the hydrazone (IV), to give the pyranoindolone of formula (V); d) Transesterification of the pyranoindolone (V) to provide the compound (VI), in which R means a straight or branched C1-C4 alkyl; e) Conversion of the hydroxyl group of the compound (VI) into dimethylamino to give the indolecarboxylate (VII), in which R means a straight or branched C1-C4 alkyl; f) Saponification of the 2-carboalkoxy group of the compound (VII), to provide indolecarboxylic acid (VIII); g) Decarboxylation of the indolecarboxylic acid (VIII), to provide zolmitriptan and, eventually, to provide a pharmaceutically acceptable salt thereof.

The invention relates to the technical field of drug synthesis, and particularly relates to a synthetic method of kyprolis. The synthetic method comprises the following steps: carrying out condensation reaction on morpholine-4-base acetic acid, L-homophenylalanine ester and salt, and then carrying out decarboxylation protection to generate a compound V; carrying out the condensation reaction on the decarboxylation, the salt and N-Boc-L-leucine, and then carrying out deamination protection to generate a compound VI; carrying out the condensation reaction on the compound V and the compound VI, and then carrying out decarboxylation protection to generate a compound VII; carrying out the condensation reaction on the compound VII and a compound VIII to obtain the kyprolis. The method disclosed by the invention can be used for enhancing the reaction yield by adopting a converging synthetic method; the used reagent is easy, convenient, easy to obtain and less in pollution. The process disclosed by the invention only relates to the condensation and deprotection between amino acids and is simple and controllable in reaction and suitable for industrial production.

The preparation method of a compound of a carfilzomib intermediate of the present invention uses L-leucine V as a raw material, and undergoes amidation reaction with di-tert-butyl dicarbonate under alkaline conditions to generate compound IV; ,N'-carbonyldiimidazole reacts with N,O-dimethylhydroxylamine hydrochloride under the action of Weinreb amidation reaction to generate compound Ⅲ, compound Ⅲ reacts with ethylmagnesium halide solution to generate compound Ⅱ, compound Ⅱ reacts with formaldehyde Or paraformaldehyde undergoes aldol condensation reaction to generate carfilzomib intermediate compound Ⅰ ((S)-4-(tert-butoxycarbonylamino)-2,6-dimethyl-1-hepten-3-one) . The invention avoids the use of expensive reagent 2-bromopropene and uses ethylmagnesium chloride, which conforms to the design principles of easy-to-obtain raw materials and simple operation. The synthesis route of the invention has mild conditions, excellent or good synthesis yield in each step, and is suitable for industrial production.

The present invention relates to an amide borate for detecting bortezomib intermediate purity, wherein the amide borate is a compound having the following structure formula, the compound is an optically pure compound II or a diastereoisomer II', and X is fluorine, chlorine, bromine or iodine. According to the present invention, the amide borate is used for rapid detection of the optical purity of the bortezomib key intermediate (R)-leucine borate, wherein the fluorescent chromophore protection group is introduced into the (R)-leucine borate with the simple one-step chemical reaction to obtain the amino borate derivative having strong ultraviolet absorption, wherein the derivative can be provided for quantitatively and rapidly detecting the optical purity through HPLC. The method has characteristics of simple process operation, high sensitivity and high accuracy.

The present invention provides a convenient and industrially viable process for preparation of Zolmitriptan (I) having desired purity. The invention specifically relates to a method for isolating (S)-4-(4-hydrazinobenzyl)-1,3-oxazolidin-2-one hydrochloride (IIIa) of desired purity by separating the undesired inorganic side products such as stannous hydroxide by manipulation of pH at different stages and finally treating with N,N-dimethylamino butyraldehyde diethyl acetal in an acidic medium to provide Zolmitriptan (I) conforming to regulatory specifications.

The invention belongs to the technical field of organic synthesis, and in particular relates to a preparation method of a zolmitriptan intermediate. The present invention takes (S)-4-(4-nitrobenzyl)-2-oxazolidinone as raw material, adopts palladium carbon and ammonium formate to react with it, and prepares zolmitriptan intermediate (S)- 4‑(4‑aminobenzyl)‑2‑oxazolidinone. The invention adopts ammonium formate and palladium charcoal for reduction, has low reaction temperature, simple post-treatment, is environmentally friendly, and the catalyst can be recycled and used mechanically. Adopting the present invention, the yield is above 95%, and the purity is above 98%.

In the preparation of zolmitriptan of formula III the reduction of the diazonium salt to (5)-4-(4-hydrazinobenzyl)-1,3-oxazolidin-2-one of formula IV is performed in a more concentrated mixture and by the effect on an alkali metal disulphite, preferably sodium disulphite. A zolmitriptan toluene solvate, characterized by a toluene content of 9 to 14% by weight according to the gas chromatography determination and by a maximum of the corresponding mass loss at temperatures of about 111° C. in the gravimetric analysis record. A zolmitriptan toluene solvate, showing strong Raman bands at the wave numbers of 1443 and 1354 cm−1, characteristic for the crystal lattice of zolmitriptan with built-in toluene, and further marked bands at 1004 and 786 cm−1, characteristic for toluene.