Zentiva K.s.

University of California

Ludek Ridvan

Lukas Placek

Tomas Pekarek

Monika Zatopkova

Kamal Jarrah

Petr Hruby

Josef Cinibulk

Yi Liu

Alexander Star

Jindrich Richter

Ondrej Dammer

Hana Stepankova

Stanislav Radl

Lukas Krejcik

Natalia Csokova

Gary James Miller

Miroslav Kuchar

Michal Voslar

Anna Zerzanova

Hana Brusova

Norbert Nagel

Winfried Heyse

Tomas Chvojka

Josef Beranek

Michal Zapadlo

Jan Holan

Lucie Krumbholcova

Gregor Sedmak

The present invention relates to novel solid forms of agomelatine (I), specifically novel phaamaceutically acceptable cocrystals thereof, as well as to methods of preparing them. Three pharmaceutically acceptable cocrystals of (I) that have physico-chemical properties acceptable for pharmaceutical development were obtained. 

Pharmaceutically acceptable cocrystals of N-[2-(7-methoxyl-1-naphtyl)ethyl]acetamide and methods of their preparation

The invention deals with new salts of the desvenlafaxine base of formula (I) with oxalic acid, the new salts being the hydrogen oxalate of formula (II) in the proportion of desvenlafaxine:oxalic acid of 1:1 and hemioxalate of formula (III) in the proportion of desvenlafaxine:oxalic acid of 2:1. 

Salts of desvenlafaxine and a method of their preparation

A method for the preparation of a duloxetine hydrochloride salt from a duloxetine base, comprising the steps of: reacting duloxetine base with concentrated hydrochloric acid in ethylmethylketone; and crystallizing duloxetine hydrochloride salt from said concentrated hydrochloric acid in ethylmethylketone.

Method for the preparation of (S)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine hydrochloride (duloxetine)

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&#xb0; C. in the gravimetric analysis record. A zolmitriptan toluene solvate, showing strong Raman bands at the wave numbers of 1443 and 1354 cm1, characteristic for the crystal lattice of zolmitriptan with built-in toluene, and further marked bands at 1004 and 786 cm1, characteristic for toluene. 

Method for the preparation of zolmitriptan

A method of preparation of (S)-N-methyl-3-(1-naphthyloxy)-3-(2-mienyl)propylamine of Formula (I) and its pharmaceutically acceptable salts, comprising a) reaction of (RS)-N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine with optically active D-tartaric acid or an acid salt derived from D-tartaric acid forming a mixture of diastereoisomeric salts of N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine and D-tartaric acid (2:1), b) isolation of the salt (S)-N,N-dimethyl-3-(naphthyloxy) -3-(2-thienyl)propylamine/D-tartrate (2:1) from the mixture of diastereoisomeric salts in an organic solvent, water or a mixture thereof and release of (S)-N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine by action of an inorganic or organic base, c) demethylation of (S)-N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine by action of an alkylchloroformate of formula ClCOOR (R=C-Calkyl, or C-Caryl or alkylraryl), especially phenyl, ethyl or methyl chloroformate, and d) hydrolytic release of the duloxetine base of formula I and optionally conversion of the base to a salt with the respective acid, or salt of a weak base. 

[object Object]

A method of preparation of (S)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine of formula (I) or its pharmaceutically acceptable salt, in which (RS)-N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine of formula (III) is reacted with an optically active acid, after which a crystallization is made of that diastereoisomer which yields, by reaction with an inorganic or organic base, (S)-N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine of formula (S)-III, which is then demethylated using alkylchloroformates, followed by a hydrolysis and optional conversion of the compound of formula (I) to its salt. 

Nanotubes are treated with poly{(5-alkoxy-m-phenylenevinylene)-co-[(2,5-dioctyloxy-p-phenylene)vinylene]} (PAmPV) polymers and derivatives thereof to provide noncovalent functionalization of the nanotubes which increases solubility and enhances other properties.

Noncovalent functionalization of nanotubes

Growing community of inventors

Prague, Czechia

Ludek Ridvan