Univerzita Palackeho V Olomouci

Ustav Organicke Chemie a Biochemie Av Cr, V.v.i.

Univerzita Karlova V Praze

Palacky University Olomouc

Univerzita Karlova V Praze, Prirodovedecka Fakulta

Institute of Experimental Botany of the Academy of Sciences of the Czech Republic

Institute of Organic Chemistry and Biochemistry Ascr, V.v.i.

Univerzita Palackeho

Helmholtz Zentrum Munchen

Ustav Organicke Chemie a Biochemie Akademie Ved Ceske Republiky, V.v.i.

Ustav Anorganicke Chemie Akademie Ved Ceske Republiky, V.v.i.

Palacký University in Olomouc

Univerzita

Cyclacel Limited

Fyziologicky Ustav Av Cr, V.v.i.

Marian Hajduch

Miroslav Strnad

Peter Martin Fischer

Jiri Voller

Petr Dzubak

Jan Sarek

Michal Hocek

Libor Havlicek

Jiri Bartek

Martin Mistrik

Michal Svoboda

Zdenek Skrott

Pavla Spácilová

Petr Cigler

Jerzy Adamski

Petr Naus

Petr Bartunek

David Sedlak

Gabriele Moeller

Radek Zboril

Sabina Smolen

Martin Kotora

David Biedermann

Lenka Radova

Petr Krejci

Eva Prchalova

Pavel Hradil

Jan Hlavac

Olga Caletkova

Piers Collier

Jiri Brynda

Jonathan D Hull

Bohumir Gruner

Marek Svoboda

Tomas Kubelka

Vaclav Mik

Pavel Mader

Jan Kucka

Paul M Blaney

Vaclav Sicha

Anna Tokarenko

Mario Bakardjiev

Marta Dziechciarkova

Josef Holub

Pavlina Maloy Rezacova

Ondrej Stepanek

Ondrej Sedlacek

Lucia Veselovska

Michal Tichy

Katerina Novakova

Zbynek Novy

Milos Petrik

Ivo Frydrych

Madhusudhan Reddy Kollaredy

Bohumir GRÜNER

John R Ferguson

Martin Sladek

Alena Sumova

Martin HrubÝ

Khushboo Agrawal

Rita Hrabakova

Josef Srovnal

Hana Kovarova

Pavel Svec

Miroslav Hruska

Marketa Dokonalova

A complex particle form of dithiocarbamate-metal compound and at least one ligand, that is a polymer or a detergent is disclosed. The complex particle form is obtained by a process having a sequential or simultaneous addition of individual components, resulting in their self-assembling. The dry form or aqueous dispersion of the complex particle form is suitable for medicinal per-oral, topical and parenteral administration and for therapy and imaging of cancer.

Molecular complex assembly particles comprising bis-R1,R2-dithiocarbamate-metal complex and a ligand, method of preparation and use thereof

A particulate form of dithiocarbamate-metal complex and at least one blood protein. The particulate form is obtained by a process having a sequential or simultaneous addition of individual components, resulting in their self-assembling. The aqueous dispersion of the particulate form is suitable for parenteral, oral and topical administration and for therapy and visualization of cancer.

Bioavailable dithiocarbamate-metal complex particles, method of preparation and use thereof

Substituted pyridopyrrolopyrimidine ribonucleosides of general formula I, wherein R is as described in the independent claim, preferably R is selected from the group comprising thiophen-3-yl, furan-2-yl, furan-3-yl, benzofuran-2-yl, methylsulfanyl, methoxy, amino, dimethylamino, methyl; and pharmaceutically acceptable salt thereof, their optical isomers and mixtures of such optical isomers. Compounds according to the invention show strong cytostatic and cytotoxic effects on cell lines of tumor origin in a wide variety of diseases including tumors of different histogenetic origin.

Substituted pyridopyrrolopyrimidine ribonucleosides for therapeutic uses

15&#x3b2;-substituted derivatives of estrone of general formula I wherein R, R, R, R, Rare independently selected from the group consisting of: C-Calkyl, C-Calkoxy, C-Chalogenalkyl, halogen, COORwherein Ris C-Calkyl; H, OH; optionally, R, Rand Rare each formed by a hydrogen atom, while Rand Rtogether form an aryl group, preferably naphthyl, in which the aromatic ring in position C-15 can be mono-, di-, tri-, tetra- and penta-substituted with substituents R-R. Compounds of the invention may be used for diagnosis and possibly also for the treatment of estrogen-dependent diseases.

15&#x3b2;-substituted estrone derivatives as selective inhibitors of 17&#x3b2;-hydroxysteroid-dehydrogenases, method of preparation and use thereof

Substituted heteropentadieno-pyrrolopyrimidine ribonucleosides of general formula I, where R is selected from the group comprising furan-2-yl, furan-3-yl, benzofuran-2-yl, methylsulfanyl, methoxy, amino, dimethylamino, methyl or chloro, and pharmaceutically acceptable salt thereof, their optical isomers and mixtures of such optical isomers.

Substituted heteropentadieno-pyrrolopyrimidine ribonucleosides for therapeutic use

A group of substituted thienopyrrolopyrimidine ribonucleosides of general formula I, in which R shows strong cytostatic and cytotoxic activities preferably against cancer cell lines of broad spectrum of diseases including tumors of various histogenetic origin.

Substituted thienopyrrolopyrimidine ribonucleosides for therapeutic use

Compounds of Formula I and a pharmaceutically acceptable salt thereof, an optical isomer thereof, or a mixture of optical isomers thereof, as well as compositions which include such compounds and therapeutic methods that utilize such compounds and/or compositions.

Substituted 7-deazapurine ribonucleosides for therapeutic uses

Derivatives of boron cluster compounds of general formula I and their pharmaceutically acceptable salts and solvates, and their specific inhibition effect on the enzyme carbonic anhydrase IX, a protein overexpressed in cancer tissues. Methods of synthesis and the use of the novel derivatives. These inhibitors of human carbonic anhydrase IX can be used as active compounds of pharmaceuticals for diagnostics and/or therapy of cancer diseases. 

Carbonic anhydrase inhibitors and method of their production

The invention describes novel triterpenoid 2-deoxy glycosides of general formula I, wherein at least one of the substituents Xand Rcontains a 2-deoxy glycosidic group, method of preparation thereof, their cytotoxic activity and a pharmaceutical formulation containing these compounds.

Triterpenoid 2-deoxy glycosides, method of preparation thereof and use thereof as medicaments

The invention relates to a method of preparation of a soluble formulation of water-insoluble pentacyclic and tetracyclic terpenoids, wherein the water-insoluble terpenoid having a free carboxylic, hydroxy or amino functional group is derivatized on this functional group with a substituent selected from the group comprising substituents of general formula Xa bound to the hydroxy group of the terpenoid, wherein Xa is &#x2014;OC&#x2014;R&#x2014;COOH, substituents of general formula Xa bound to the amino group of the terpenoid, wherein Xa is &#x2014;OC&#x2014;R&#x2014;COOH, quarternary ammonium substituents of general formula Xb bound to the carboxy group of the terpenoid, wherein Xb is &#x2014;(CH2)nN+R3Y&#x2014;, quarternary ammonium substituents of general formula Xc bound to the carboxy group of the terpenoid, wherein Xc je &#x2014;(CH2)nR+Y&#x2014;, substituents of general formula Xd bound to the carboxy group of the terpenoid, wherein Xd represents &#x2014;R&#x2014;COOH, glycosylic substituents Xe bound by alpha or beta glycosidic bond to the hydroxy group or to the carboxy group of the terpenoid, wherein Xe is selected from the group comprising glucosyl, galactosyl, arabinosyl, rhamnosyl, lactosyl, cellobiosyl, maltosyl and the 2-deoxyanalogues thereof, and subsequently, the prepared derivative is dissolved in the solution containing water, a cyclodextrin and optionally pharmaceutically acceptable auxiliary substances, forming an inclusion derivative with the cyclodextrin. Object of the invention is further a soluble formulation of a pentacyclic or tetracyclic triterpenoid, containing an inclusion complex of the derivatized pentacyclic or tetracyclic terpenoid with a cyclodextrin, and optionally water and pharmaceutically acceptable auxiliary substances and further a pharmaceutical composition containing the soluble formulation.

Method of preparation of a soluble formulation of water-insoluble pentacyclic and tetracyclic terpenoids, a soluble formulation of a pentacyclic or tetracyclic terpenoid and a pharmaceutical composition containing this soluble formulation

The invention relates to a method for determining the sensitivity of patients suffering from a cancer disease towards targeted biological therapy based on the inhibition of signaling pathways of the members of HER family (e.g., HER-1, HER-2, HER-3 and HER-4) by determining the expression of the biomarker S6 kinase or its post-translationally modified form or of the biomarkers of the activation of S6 kinase or their post-translationally modified forms in the tumor.

Method for determining the sensitivity of patients suffering from a cancer disease to biological therapy

Derivatives of 2-phenyl-3-hydroxyquinoline-4(1H)-one of the general formula (II), where X represents a nitro group, amino group, and Y represents an atom of halogen, oxygen or sulphur substituted by Cto Calkyl or phenyl group, whereby both the alkyl and phenyl group may be further substituted and the substituents may be identical or different, or by nitrogen substituted independently by hydrogen, Cto Calkyl, Cto Calkyl, which may be substituted among others by halogen, hydroxy, Cto Calkoxy or Cto Calkylamino group, or may form a saturated or unsaturated heterocyclic ring with 5 to 7 atoms, where the individual ring atoms comprise atoms of carbon, and any of the carbon atoms may be substituted by an atom of nitrogen, sulphur or oxygen, X and Y together form an imidazo group, or imidazo group substituted by Cto Calkyl, which may be substituted among others by halogen, hydroxy, Cto Calkoxy or Cto Calkylamino group, CHO or acetylgroup, or a heterocyclic ring with 5 to 6 atoms, where the ring atoms may be further substituted. Methods of preparation of these compounds are described. In addition, their cytostatic, cytotoxic, antiproliferation and immunosuppressive activity is described including examples of their potential pharmacological and pharmaceutical utilization. 

Derivatives of 2-phenyl-3-hydroxyquinoline-4(1H)-one and methods of their preparation and utilization

The invention relates to a method of preparation and isolation of betulin diacetate from birch bark from paper mills and its optional processing to betulin, wherein the birch bark is ground, mixed with two- to twenty-fold excess volume of water and is stirred so that all birch bark is dipped, then the fraction of the birch bark which floats on the surface is collected, said collected fraction is dried at the temperature in the range of from 50 to 85&#xb0; C. and the betulin contained in the dried birch bark is then subjected to an acetylation reaction, after the acetylation the birch bark is dried at the temperature of from 50 to 100&#xb0; C. and the formed betulin diacetate is then isolated from the birch bark by supercritical extraction of the birch bark with carbon dioxide at the pressure of 28-35 MPa and the temperature of from 50 to 100&#xb0; C. and subsequently, the supercritical extract is recrystallized for direct use or for further processing. The further processing can be basic hydrolysis of the re-crystallized betulin diacetate to betulin.

Method of preparation and isolation of betulin diacetate from birch bark from paper mills and its optical processing to betulin

The present invention relates to the use of a compound of formula (I), or a pharmaceutically acceptable salt, crystal form, complex, hydrate, or hydrolysable ester thereof, in the preparation of a medicament for treating a patient suffering from leukaemia, cancer or other proliferative disorder. A further embodiment relates to the use a compound of formula (I) in an assay for detecting the phosphorylation state of cellular substrates. The present invention also relates to novel compounds of formula (I), and the chemical synthesis thereof. 

Triterpenoid derivatives

The present invention relates to the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, in therapy. Prefereably, the compound may be used for treating a patient suffering from leukaemia, cancer or other proliferative disorder. A further embodiment relates to the use of a compound of formula (I) in an assay for detecting the phosphorylation and acetylation state of cellular substrates. The present invention also relates to novel compounds of formula (Ia).

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Moravsky Beroun, Czechia

Marian Hajduch