Institut National De La Sante Et De La Recherche Medicale

Pharmaleads

Other

Centre National De La Recherche Scientifique

Institut Pasteur

Université De Technologie De Compiègne

Societe Civile Bioprojet

Kos Therapeutics, Inc.

Bernard P Roques

Marie-Claude Fournie-Zaluski

Jeanne-Marie Lecomte

Hervé Poras

Jean-Charles Schwartz

Pierre Corvol

Catherine Llorens-Cortes

Guido Kroemer

Johan Hoebeke

Michel Wurm

Nicolas Inguimbert

Bruno Charpentier

Tanja Ouimet

Marie Claude Fournie Zaluski

Christine Anne

Etienne Daniel Francois Jacotot

Lena Edelman

Catherine Brenner-Jean

Anne-Sophie Belzacq

Pierre Renard

Caroline Bennejean

Elizabeth Scalbert

Serge Turcaud

Nathalie Luciani

Hugues De Rocquigny

Herv&eacute; Poras

Huixiong Chen

Xuixiong Chen

Marie-Claude Fourni&eacute;-Zaluski

Isabelle Marseigne

Marie C Fournie-Zaluski

The present invention concerns a pharmaceutically acceptable salt of a compound of the following formula (I): HN—CH(R)—CHS—S—CH—CH(R—CONH—CH(R)—COOR(I) and more particularly an acid addition salt thereof, and the compositions comprising the same, for use in the prevention or treatment of trigeminal nerve pain, in particular migraines or trigeminal neuralgia.

Amino acid derivatives containing a disulfanyl group as an inhibitor of NEP and APN for the prevention and treatment of trigeminal nerve pain

The present invention concerns a pharmaceutically acceptable salt of a compound of the following formula (I): HN&#x2014;CH(R)&#x2014;CHS&#x2014;S&#x2014;CH&#x2014;CH(R&#x2014;CONH&#x2014;CH(R)&#x2014;COOR(I) and more particularly an acid addition salt thereof, and the compositions comprising the same, for use in the prevention or treatment of trigeminal nerve pain, in particular migraines or trigeminal neuralgia.

Amino acid derivatives containing a disulfanyl group in the form of an NEP and APN inhibitor for the prevention and treatment of trigeminal nerve pain

The present invention relates to a compound of the following general formula (I): R&#x2014;NH&#x2014;CH(R)&#x2014;P(&#x2550;O)(OR)&#x2014;CH&#x2014;C(R)(R)&#x2014;CONH&#x2014;CH(R)&#x2014;COOR(I) or a pharmaceutically acceptable salt of the latter, an isomer or a mixture of isomers in any proportions, especially a mixture of enantiomers, and in particular a racemic mixture, for which Rrepresents a &#x2014;C(&#x2550;O)&#x2014;O&#x2014;C(R)(R)&#x2014;OC(&#x2550;O)&#x2014;Rgroup; Rrepresents an optionally substituted hydrocarbon-based chain, an aryl or heteroaryl group or a methylene group substituted by a heterocycle; Rrepresents a hydrogen atom or a &#x2014;C(R)(R)&#x2014;OC(&#x2550;O)&#x2014;Rgroup; Rand Rform, together with the carbon that bears them, a saturated hydrocarbon-based ring or an optionally substituted piperidine ring or Rrepresents a hydrogen atom and Rrepresents a phenyl or a benzyl that is optionally substituted, a heteroaromatic ring or a methylene group substituted by a heterocycle; Rrepresents an optionally substituted hydrocarbon-based chain or a phenyl or a benzyl that is optionally substituted; and Rrepresents a hydrogen atom or a benzyl, alkyl, heteroaryl, alkylheteroaryl, &#x2014;CHMe-COOR, &#x2014;CHR&#x2014;OC(&#x2550;O)Rand &#x2014;CHR&#x2014;OC(&#x2550;O)ORgroup. The present invention also relates to the use of these compounds as a medicinal product, and in particular for the treatment of pain, more advantageously neuropathic and neuroinflammatory pain, to their method of synthesis and also to the compositions containing them.

Aminophosphinic derivatives that can be used in the treatment of pain

Mixed inhibitors of aminopeptidase N and neprilysin are disclosed. Pharmaceutical compositions containing at least one of these compounds, used alone or in combination with morphine and derivatives thereof, endocannabinoids and inhibitors of endocannabinoid metabolism, GABA derivatives such as gabapentin or pregabalin, duloxetine or methadone, can be used as an analgesic, anxiolytic, antidepressant or anti-inflammatory.

Mixed inhibitors of aminopeptidase N and neprilysin

The present invention relates to a compound of the following general formula (I): R&#x2014;NH&#x2014;CH(R)&#x2014;P(&#x2550;O)(OR)&#x2014;CH&#x2014;C(R)(R)&#x2014;CONH&#x2014;CH(R)&#x2014;COOR(I) or a pharmaceutically acceptable salt of the latter, an isomer or a mixture of isomers in any proportions, especially a mixture of enantiomers, and in particular a racemic mixture, for which Rrepresents a &#x2014;C(&#x2550;O)&#x2014;O&#x2014;C(R)(R)&#x2014;OC(&#x2550;O)&#x2014;Rgroup; Rrepresents an optionally substituted hydrocarbon-based chain, an aryl or heteroaryl group or a methylene group substituted by a heterocycle; Rrepresents a hydrogen atom or a &#x2014;C(R)(R)&#x2014;OC(&#x2550;O)&#x2014;Rgroup; Rand Rform, together with the carbon that bears them, a saturated hydrocarbon-based ring or an optionally substituted piperidine ring or Rrepresents a hydrogen atom and Rrepresents a phenyl or a benzyl that is optionally substituted, a heteroaromatic ring or a methylene group substituted by a heterocycle; Rrepresents an optionally substituted hydrocarbon-based chain or a phenyl or a benzyl that is optionally substituted; and Rrepresents a hydrogen atom or a benzyl, alkyl, heteroaryl, alkylheteroaryl, &#x2014;CHMe&#x2014;COOR, &#x2014;CHR&#x2014;OC(&#x2550;O)ORand &#x2014;CHR&#x2014;OC(&#x2550;O)ORgroup. The present invention also relates to the use of these compounds as a medicinal product, and in particular for the treatment of pain, more advantageously neuropathic and neuroinflammatory pain, to their method of synthesis and also to the compositions containing them.

The disclosure relates to novel compounds of the formula (I) RNH&#x2014;CH(R)CH&#x2014;S&#x2014;S&#x2014;CH&#x2014;C(R)(R)&#x2014;CONH&#x2014;C(R)(R)&#x2014;COOR, in which Ris a (acyloxy)alkyl carbamate-C(O)&#x2014;O&#x2014;C(R)(R)&#x2014;OC(O)&#x2014;Rgroup; Ris a hydrocarbon chain, a methylene radical substituted by a heterocycle, Ris a hydrogen atom and Ris a phenyl or benzyl radical, a heteroaryl, a methylene group substituted by a heterocycle or Rand Rform together a saturated cycle; Rand Rare hydrogen, a hydrocarbon chain, a phenyl or benzyl radical or Rand Rform together a saturated cycle; Ris hydrogen, a phenyl or benzyl radical, a group of the formula CR(R)C(O)ORor OCR(R)OC(O)Ror OCR(R)OC(O)OR. The disclosure also relates to the use of these compounds as a drug, and to a pharmaceutical composition containing said compounds and a pharmaceutically acceptable carrier. The disclosure further relates to the combined use of at least one cannabinoid derivative and/or morphine or one derivative thereof and/or Gaba derivatives for enhancing the analgesic and anti-depressive effect of the compounds of the formula (I).

Amino acid derivatives, method for preparing same, and therapeutic use thereof

The invention relates to novel compounds of formula (I): HN&#x2014;CH(R)&#x2014;CH&#x2014;S&#x2014;S&#x2014;CH&#x2014;CH(R)&#x2014;CONH&#x2014;R, wherein Ris a hydrocarbon chain, phenyl or benzyl radical, methylene radical substituted by a 5 or 6 atom heterocycle; Ris a phenyl or benzyl radical, a 5 or 6 atom aromatic heterocycle, methylene group substituted by a 5 or 6 atom heterocycle; Ris a CH(R)&#x2014;COORradical, wherein Ris hydrogen, an OH or OR group, a saturated hydrocarbon group, a phenyl or benzyl radical and ORis hydrophile ester, or 5 or 6 membered heterocycle comprising several heteroatoms selected from a group consisting of nitrogen, sulphur and oxygen, with at least two nitrogene atoms, wherein said heterocycle is substitutable by an alkyl C-C, phenyl or benzyl radical. The use of the inventive compounds in the form of drugs, a pharmaceutical composition comprising said compounds, a pharmaceutically acceptable excipient, the use in conjunction of at least one type of cannabinoid derivative for potentiating the analgesic and antidepressant effect of the novel compounds of formula (I) and/or morphine or the derivatives thereof are also disclosed.

Aminoacid derivatives containing a disulfanyl group in the form of mixed disulfanyl and aminopeptidase N inhibitors

A peptide substrate selectively recognisable by a botulinum toxin A, BoNT/A containing a Nop-(Z)-Pya fragment in the peptide structure thereof, wherein Z is an aminoacid chain, preferably RA and the fragment is cleaved by the toxin.

Peptide substrates recognizable by a botulinum toxin A, BoNT/A and the use thereof

The invention is directed to the induction of mitochondrial membrane permeabilization via the physical and functional interaction of the HIV-1 Vpr protein with the mitochondrial inner membrane protein ANT (adenine nucleotide translocator, also called adenine nucleotide translocase or ADP/ATP carrier). Reagents and methods for inducing and/or inhibiting the binding of Vpr to ANT, mitochondrial membrane permeabilization, and apoptosis are provided.

Screening methods for the identification of inhibitors of human immunodeficiency virus (HIV) viral protein R (Vpr) binding to the adenine nucleotide translocator (ANT)

The invention relates to derivatives of 4,4'-dithiobis-(3-aminobutane-1-sulfonates) of formula (1), of use for the treatment and prevention of primary and secondary arterial hypertension.

Derivatives of 4,4'-dithiobis-(3-aminobutane-1-sulfonates) and compositions comprising the same

The invention relates to the bis-hydrochloride of 4,4'-dithiobis-(3-aminobutane-1-sodium sulphonate) and the bis-trifluoracetate of 4,4&#x2032;-dithiobis-(3-aminobutane-1-sulphonate of 2,2-dimethylpropyl). The invention also relates to a pharmaceutical composition comprising one of said compounds and to the use of one of said compounds for the production of a medicament. The invention is suitable for use in a treatment method for hypertension and indirectly- or directly-linked illnesses.

Derivatives of 4,4'-dithiobis-(3-aminobutane-1-sulfphonates) and compositions containing same

Novel compounds of general formula (I), are provided with inhibitory properties for the type B botulism toxin activity, along with methods for preparation thereof and corresponding pharmaceutical compositions. 

Type B botulism toxin inhibitors

The invention concerns the use of a PyA-(Z)-pNF group in a substrate for detecting, identifying and/or analyzing by fluorometry peptidases or proteases capable of cleaving the or a bond between a PyA and pNF and/or compounds with inhibiting or activating activity with respect to enzymes capable of cleaving said bond.

Fluorescence detection of proteases or peptidases

A peptide substrate is identified by type BoNT/B botulinus toxin, characterized in that it incorporates in its structure a fragment of formula PYA-(Z)-pNF, wherein Z represents one or several amino acids, said fragment being cleavable by said toxin.

Growing community of inventors

Saint Maurice, France

Bernard P Roques