Centre National De La Recherche Scientifique

Universitéde Strasbourg

Johns Hopkins University

Martial Ruat

Hélène Faure

André Mann

Maurizio Taddei

Elisabeth Traiffort

Fabrizio Manetti

Antonio Solinas

Angèle Schoenfelder

Angele Schoenfelder

Robert H Dodd

Pierre Jean-Paul Potier

Albane Kessler

Philippe Marcel Dauban

Hermine Roudaut

Tatiana Gorojankina

Solomon H Snyder

Gabriele V Ronnett

Loren Walensky

Lucile Hoch

Hélène Véronique Faure

François Meunier

Seana O'Regan

The present invention relates to the use of acylthiourea or acylurea derivatives for the treatment of pathologies involving a tissue dysfunction associated with a deregulation of the Hedgehog protein signalling pathway, and also to novel acylthiourea or acylurea derivatives as such, to their use as a medicinal product, and to pharmaceutical compositions containing them.

N-acylthiourea and N-acylurea inhibitors of the Hedgehog protein signalling pathway

The present invention relates to compounds which are quinolinone derivatives of general formula (I) capable of modulating the activity, in particular of inducing the differentiation, of stem and progenitor cells; these compounds are of use in the treatment of disorders related to a stem differentiation defect; the invention also relates to novel compounds among these quinolinone derivatives and to pharmaceutical compositions containing the same. 

Quinolinone derivatives

The invention relates to compounds of formula (I), and the use thereof as a drug, particularly for the treatment of tumors associated with hyperactivation of the hedgehog protein signaling pathway, treatment of neurodegenerative diseases, treatment of diseases related to cerebral development (holoprosencephaly), for stem cell monitoring treatment of cerebrovascular accidents and cardiovascular accidents, treatment of diseases involving oligodendrocytes and diseases involving neurolemmocytes, for application thereof in vitro for modulating human or animal stem cell renewal, and for the treatment of diabetes. The invention also relates to pharmaceutical compositions having a compound of formula (I). The invention also relates to a method for radio-marking compounds having formula (I), the marked compounds, and the use of the compounds as research tools, and method for screening and/or identifying ligands in the Smoothened receptor (Smo) binding sites, methods for identifying agonists and antagonists of the Smoothened receptor, and a method for identifying cells.

Compounds modulating the hedgehog protein signaling pathway, marked forms thereof, and applications

The present invention relates to the use of quinolinone derivatives of general formula (I), ligands of the Smo receptor or of related receptors which target a binding site of the receptor which is different from the known ligand binding sites, as research tools for identifying modulators of the Smo receptor or of related receptors, characterizing the Hedgehog signalling pathway and diagnosis; the invention also relates to kits containing said derivatives of general formula (I). 

Use of quinolinone derivatives as a research tool

The present invention relates to acyl guanidine derivatives modulating the hedgehog protein signaling pathway to be used as drugs, in particular for treating diseases involving a tissue dysfunction associated with a deregulation of the hedgehog protein signaling pathway, as well as to pharmaceutical compositions containing same. The present invention also relates to novel acyl guanidine derivatives as such.

Acyl guanidine derivatives modulating the hedgehog protein signaling pathway

The invention relates to a novel use of compounds having formula (I), including mifepristone (RU 486 or RU 38 486) and the derivative salts thereof, for the preparation of a medicament that can modulate (activate or inhibit) the Hedgehog protein signalling pathway, which is intended for the treatment of pathologies involving a tissue dysfunction linked to deregulation of said pathway.

Use of mifepristone and derivatives therefor as Hedgehog protein signaling pathway modulators and applications of same

The invention concerns the identification of a novel family of CTL (Choline Transporter Like) genes, in particular hCTL1 and hCTL2, involved in the metabolism and/or transport of choline in cells such as the intestinal tract cells, nervous cells, in particular motoneurons, sensitive neurons, neurons of the nucleus dorsalis of the spinal cord and oligodendrocytes. The invention opens up new prospects in particular for the treatment of familial dysautonomia, and Tangier disease. More generally, the identification of CTL genes enables to develop new strategies for treating diseases of the nervous system, in particular neurodegenerative demyelenating diseases, particularly Alzheimer disease, Parkinson disease and Huntington disease.

Choline transport like (CTL) membrane proteins involved in choline transport

The invention concerns diamines of general formula (I), wherein: A represents a group A1 or A2 of general formula (II); B represents a group B1 or B2 of general formula (III); X represents a SO, CH, C&#x2550;O or COO; YZ represents a group of formula CH(R25)&#x2014;CH(R26) or CH(R27)&#x2550;(R28), and R1 to R28, identical or different, represent independently of one another, a hydrogen or halogen atom or an alkyl, cycloalkyl, CN, NO, hydroxy, aryl, aralkyl, alkoxy, aryloxy, amino, alkylamino, dialkylamino, cycloalkylamino, arylamino, arylalkylamino, diarylamino diarylalkylamino, trihalogenoalkyl or trihalogenoalkoxy group, provided that in the group A1, at least one of the radicals R1, R2, R3, R4 or R5 represents the hydrogen atom when the other four do not represent the hydrogen atom and in the group B1, at least one of the radicals R13, R14, R15, R16 or R17 represents the hydrogen atom when the other four do not represent the hydrogen atom, and their salts with a pharmaceutically acceptable acid, in the form of racemic mixture or their optically pore isomers. The invention also concerns their preparation, pharmaceutical compositions comprising them and their use as CaSR activity modulator and as medicine particularly designed for the treatment of psychological diseases and disorders involving CaSR activity modulation.

Diamines having a CaSR modulating activity

The invention concerns compounds of general formula (I) wherein: the group X represents a &#x2014;NR4, &#x2014;CH&#x2550;N or &#x2014;CHR5-NR4-group; the group Y represents an oxygen or sulphur atom or a NR, &#x2014;CR5, &#x2014;CHR5-, &#x2014;CR5=CR6- or &#x2014;CHR5-CHR6 group provided that when group X represents the &#x2014;CH&#x2550;N&#x2014; or &#x2014;CHR5-NR4-group, group Y represents an oxygen or a sulphur atom or a Nr, &#x2014;CR5 or &#x2014;CHR group; the group R represents a hydrogen atom or an alkyl, aryl or aralkyl group; the groups R1, R5 and R6, identical or different, represent each a hydrogen or halogen atom or an alkyl or alkoxy group; the group R2 represents a hydrogen atom or an alkyl group; the group R3 represents an aryl group; and the group R4 represents a hydrogen atom, an alkyl, aryl, aralkyl, alkylsulphonamide, arylsulphonamide or aralkylsulphonamide group; and their salt with a pharmaceutically acceptable acid, in the form of a racemic mixture and their optically pure isomer. The invention also concerns their preparation, pharmaceutical compositions containing them and their use as CaSR activity modulator and as medicine for preferably treating diseases or physiological disorders involving the intervention of CaSR activity modulation. 

Calcium receptor active molecules and method for preparing same

The present invention provides a nucleic acid comprising a sequence that encodes a sperm receptor that is related to, but is different from, a receptor of the odorant receptor family. The present invention also provides a method of obtaining a nucleic acid that comprises a sequence that encodes a sperm receptor, as well as a means of using the elements of the invention in a method of contraception, a method of detecting autoimmune infertility, and a method of affecting fertility.

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Orsay, France

Martial Ruat