Institut National De La Sante Et De La Recherche Medicale

Institut Pasteur

Université De Droit Et De La Santé De Lille 2

Institut Pasteur Korea

Centre National De La Recherche Scientifique

Université De Lille

Centre Hospitalier Universitaire De Lille

Apteeus

Priscille Brodin

Stewart T Cole

Claude Leclerc

Benoit Deprez

Nicolas Willand

Alain Baulard

Roland Brosch

Laleh Majlessi

Jaeseung Kim

Sunhee Kang

SaeYeon Lee

Caroline Demangel

Auguste Genovesio

Min Jung Seo

Zaesung No

Alexander S Pym

Denis Philippe Cedric Fenistein

Thierry Christophe

Ji Youn Nam

Fanny Anne Ewann

Heekyoung Jeon

Young Mi Kim

Matthieu Frederik Desroses

Terence Beghyn

Vincent Villeret

Marion Flipo

Jonathan Cechetto

Laurence Agouridas-Dutot

Benoît Deprez

Lucie Maingot

Eun Hye Kim

Eunjung Park

Olivier Sperando

Jang Jiyeon

Jamung Heo

Baptiste Villemagne

Monica Contreras Dominguez

Matthieu Frédérik Desroses

Sandrine Belouzard

Heo Jamung

The present invention concerns a spiroisoxazoline compound of general formula (I): in which m and n are 0 or 1, R1 represents, inter alia, an optionally substituted alkyl chain, in particular substituted with fluorine or with a cyclic group, and R2 is chosen from phenyl and optionally substituted benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the heterocycles having 5 or 6 vertices comprising at least one atom chosen from S, N and O. The present invention also concerns the use of this compound as a drug, in particular in the treatment of bacterial and mycobacterial infections such as tuberculosis in combination with an antibiotic that is active against bacteria and/or mycobacteria, said compound potentiating the activity of said antibiotic.

Spiroisoxazoline compounds having an activity potentiating the activity of an antibiotic

The present invention concerns a compound of general formula (I): in which n=0 or 1, R1 represents an optionally substituted alkyl chain, in particular substituted alkyl chain, in particular substituted with fluorine, X is chosen from N and CH, and R2 is chosen from optionally substituted phenyl and benzyl, wherein the heterocycles having 6 vertices comprise one, two or three nitrogen atoms. The present invention also concerns the use of this compound as a medicament, in particular in the treatment of bacterial and mycobacterial infections such as tuberculosis in combination with an antibiotic that is active against bacteria and/or mycobacteria, said compound potentiating the activity of said antibiotic.

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The present invention concerns compounds of general formula (I): in which Y and Z are chosen from CH and N; T is chosen from CO or SO; n is 1 to 3; R1 represents a group chosen, for example, from C1-C3 alkyl chains unsubstituted or substituted by fluorine, the unsubstituted or substituted cyclic, cyano, azido, alkoxy and phenyl groups; and R is chosen from the azido, cyano, alkinyl and 2-benzothiazolyl groups and an optionally substituted aromatic heterocycle with five vertices; and the use thereof in the treatment of bacterial and mycobacterial infections such as, for example, tuberculosis, leprosy and atypical mycobacterial infections. The present invention also concerns pharmaceutical compositions comprising, as the active ingredient, at least one of the abovementioned compounds and optionally an antibiotic activatable via the EthA pathway.

Compounds for use in the treatment of mycobacterial infections

The present invention relates to small molecule compounds and their use in the treatment of bacterial infections, in particular Tuberculosis.

Anti-infective compounds

The present invention relates to 4H-pyrido[1,2-a]pyrimidin-4-one compounds and their use in the treatment of bacterial infections, in particular Tuberculosis.

The present invention relates to a strain ofBCG or, wherein said strain has integrated part or all of the RD1 region responsible for enhanced immunogenicity of the tubercle bacilli, especially the ESAT-6 and CFP-10 genes. These strains will be referred as theBCG::RD1 or::RD1 strains and are useful as a new improved vaccine for preventing tuberculosis and as a therapeutical product enhancing the stimulation of the immune system for the treatment of bladder cancer.

A genetically modified strain oforBCG is provided, wherein the genetically modified strain comprises at least one modified sequence comprising SEQ ID NO: 1, SEQ ID NO: 2, or both, having at least one mutation at T2, Q4, F8, A14, L28, L29, W43, G45, Y51, Q55, Q56, N66, M83, V90, M93, or F94 in SEQ ID NO:1; or at least one mutation at Q3, F7 A13, L27, W42, G44, Y50, Q54, N65, N67, M82, V89, M92, or F93 in SEQ ID NO:2, or a deletion at the terminal end of less than 20 amino acids. In a preferred embodiment, the mutation is at least one of T2H, Q4L, F8I, AI4R, L28A, L29S, W43R, G45T, Q55I, Q56A, N66I, N67A, M83I, V90R, M93T, or F94Q in SEQ ID NO:1, and Q3L, F7I, A13R, L27A, L28S, W42R, Q44T, Q54I, N65I, M82I, V89R, M92T, and F93Q in SEQ ID NO:2. Similarly, the genetically modified strain may also secrete ESAT-6 with a hexa-histidine tag, tetra-cysteine tag, or FLAG-tag, a GFP-fusion, or a short truncation at the C-terminal end of less than 20 amino acids.

The present invention relates to a strain ofBCG or, wherein said strain has integrated part or all of the RD1 region responsible for enhanced immunogenicity of the tubercle bacilli, especially the ESAT-6 and CFP-10 genes. These strains will be referred as theBCG::RDI or::RD1 strains and are useful as a new improved vaccine for preventing tuberculosis and as a therapeutical product enhancing the stimulation of the immune system for the treatment of bladder cancer. These strains are also useful for the expression and presentation of heterologous antigens and molecule that are of therapeutic or prophylactic interest.

Growing community of inventors

Paris, France

Priscille Brodin