Rhone-poulenc Sante

Rhone-poulenc Rorer S.a.

Aventis Pharma S.a.

Université Joseph Fourier

Laboratoire Roger Bellon

Phone-poulenc Sante

Jean-Marc Paris

Jean-Claude Barriere

Claude Cotrel

Daniel Farge

Jean-Pierre Corbet

Denis Thibaut

Jean-Dominique Bourzat

Francis Blanche

Gilles Dutruc-Rosset

Jo&euml;l Crouzet

Laurent Debussche

Xavier Radisson

Jean-Pierre Bastart

Nathalie Bamas-Jacques

V&eacute;ronique Blanc

Alain Commercon

Marie-Christine Dubroeucq

Michel Barreau

Christian L Renault

Joel Crouzet

Alain Famechon

Gerard Taurand

Jean-Luc Decout

Guy Picaut

Philippe Girard

Jean-Francois Desconclois

Patrick Lefevre

Bertrand Bonnavaud

Pascal Anger

Michel Kryvenko

Jerome Desire

Isabelle Baussanne

Martine Largeron

Maurice Fleury

Marie-Christine Dubroueucq

Eric Bacque

Marc P Lavergne

Véronique Blanc

Isabelle Baussane

Jérôme Desire

This invention concerns compounds with the formula: in which:

Synthesis of novel neamine derivatives and use thereof as antibacterial agents

Novel group B streptogramin-like compounds of general formula (I), and a method for preparing streptogramines by mutasynthesis using a mutated micro-organism to influence the biosynthesis of at least one of the precursors of group B streptogramins are disclosed. Novel nucleotide sequences involved in the biosynthesis of said precursors, and their uses, are also disclosed.

Streptogramins and method for preparing same by mutasynthesis

Purified form of streptogramines, characterised in that it contains at least one component from group B streptogramines of general formula (I), wherein R is Me or Et, R is H or OH, and R is substituted benzyl of general formula (III), such that 1) if R is H, R is NR R , wherein one of R and R is H or an Me radical and the other is Me, and R&prime; is Cl or Br, or R is (C3-5)alkenyl if R and R are Me, or 2) R is H and R&prime; is halogen, alkylamino or dialkylamino, an ether-oxide residue, alkylthio, (C1-3)alkyl or trihalogenomethyl, or R is halogen, (C2-4)alkylamino, (C2-4)dialkylamino or methyl ethyl amino, pyrrolidino alkenyl alkyl amino, dialkylamino, an alkyl cycloalkylmethyl amino radical or in ether-oxide residue, alkylthio, alkylthiomethyl, (C1-6)alkyl, aryl or trihalogenomethyl, and R&prime; is H, or R is halogen, amino, alkylamino or dialkylamino, an ether-oxide residue, an alkylthio radical, (C1-6)alkyl or trihalogenomethyl and R&prime; is halogen, alkylamino or dialkylamino, an ether-oxide residue or alkylthio, (C1-3)alkyl, cocrystallised with one or more minor components of group A of general formula (II) wherein R&Prime; is H, Me or Et.

Purified form of streptogramines, preparation of same and pharmaceutical compositions containing them

The invention provides a method for preparing streptogramins using genetically-modified microorganisms to influence the biosynthesis of at least one of the precursors of the group B streptogramins. Cultures of the genetically-modified microorganisms are supplemented with a least one precursor that is different from the streptogramin precursor whose biosynthesis is altered and the streptogramins produced are recovered.

Streptogramins for preparing same by mutasynthesis

Streptogramin derivatives, their preparation and pharmaceutical

This invention relates to a novel 1,8 benzo[b]naphythyridine derivative of general formula (I), ##STR1## wherein R is H or a hydroxy, amino or alkylamino radical optionally substituted by amino or hydroxy, or R is dialkylamino of which the alkyl portions may form, with the nitrogen atom, a 5- or 6-membered heterocyclic ring which optionally contains a further heteroatom chosen from nitrogen, oxygen or sulphur, or R is C.sub.3-6 cycloalkylamino or an alkanylamino, N-alkyl N-alkanylamino or aminoalkylphenylamino radical; R.sub.1 and R.sub.2, which are the same or different, are in positions 2 and 3 and represent H, alkyl, C.sub.2-4 alkenyl, phenyl, or substituted phenyl, or R.sub.1 and R.sub.2 are in position 2 and represent alkyl; R.sub.3 is H or alkyl, fluoroalkyl, carboxyalkyl, C.sub.3-6 cycloalkyl, fluorophenyl, difluorophenyl, alkyloxy or alkylamino; and R.sub.4 is H or F, wherein the C.sub.1-4 alkanyl and alkyl radicals are linear or branched; stereoisomeric forms thereof or mixtures of these; and salts and hydrated forms thereof. These novel derivatives are useful as antimicrobials.

1,8 benzonaphthyridine derivatives and antimicrobial compositions

Process for preparing taxane derivatives, new derivatives obtained and

Salts derived from 26-(dialkylaminoalkylsulphonyl)pristinamycin IIB

Streptogramin derivatives and their preparation

This invention relates to a process for preparing synergistic derivatives of formula (I), in which Y is hydrogen or dimethylamino, from pristinamycin I.sub.A or from virginiamycin, via a Mannich base, followed by elimination of the amine introduced. ##STR1##

Pristinaymcinia or virginiamycin derivatives and their preparation

Quinoline derivatives of formula: ##STR1## in which either R.sub.1 denotes trifluoromethyl, R.sub.2 and R.sub.3 form, together with the nitrogen atom to which they are attached, morpholino and R.sub.4 denotes a 4-methylphenyl, 4-chlorophenyl, 2-, 3- or 4-fluorophenyl, 4-methoxyphenyl, 4-methyl-3-fluorophenyl, 2,4-difluorophenyl or 4-aminophenyl,

Quinolyloxyacetamides

The invention provides new synergistin derivatives of formula ##STR1## in which Y is hydrogen or dimethylamino and R is a 3- or 4-quinuclidinyl radical, the isomers thereof and their mixtures, and their salts, also the preparation thereof. These compounds may be made by reaction of the corresponding 5-methylene compounds with the appropriate mercaptoquinuclidine. The products of formula (I), optionally combined with pristinamycin II.sub.A or a derivative of pristinamycin II.sub.B of the formula ##STR2## are useful as antimicrobials.

Synergistin derivatives and pharmaceutical compositions which contain

Pristinamycin II.sub.B derivatives of formula I in which R represents: ##STR1## either a 4- to 7-membered nitrogen-containing heterocyclic radical, optionally containing 1 or more other hetero atoms chosen from nitrogen, oxygen and sulphur in the sulphoxide or sulphone form, and unsubstituted or substituted by alkyl,

New process for the preparation of pristinamycin II.sub.B derivatives

The invention provides compounds of formula: ##STR1## in which R=H, halogen, alkyl, alkyloxy, alkythio, NH.sub.2, alkylamino, dialkylamino or CF.sub.3, R.sub.3 =H or alkyl,

3-phenyl-2-propeneamine derivatives, their preparation and composition

The invention provides compounds of formula: ##STR1## in which R=H, halogen, alkyl, alkyloxy, alkythio, NH.sub.2, alkylamino, dialkylamino or CF.sub.3, R.sub.3 =H or alkyl, either R.sub.4 and R.sub.5 =H and R.sub.1 and R.sub.2 =H or alkyl, optionally substituted by alkenyl (2 to 4 C) or alternatively R.sub.1 and R.sub.2 form together a saturated heterocyclic ring containing 4 to 7 ring members and optionally containing another heteroatom such as O, S or N optionally substituted by alkyl, or R.sub.4 =H, R.sub.1 =H or alkyl and R.sub.2 and R.sub.5 together form an alkylene (3 to 4 C) radical and (i) either A=alkyl or phenyl which is unsubstituted or substituted by one or two substituents chosen from halogen, alkyl, alkyloxy, alkylthio, NH.sub.2, alkylamino, dialkylamino, NO.sub.2 or CF.sub.3 or alternatively A=pyridyl, benzyl or cycloalkyl (3 to 6C), Y=S, SO or SO.sub.2 or a radical: ##STR2## in which R.sub.6 =H or alkyl and R.sub.7 =H or alkylcarbonyl, alkyloxycarbonyl, alkylaminocarbonyl or benzoyl, optionally substituted by one or two halogen, alkyl, alkyloxy, alkylthio, NH.sub.2, alkylamino, dialkylamino, NO.sub.2 or CF.sub.3 groups, (ii) or Y and A together form a 1-hydroxycycloalkyl radical, the ring of which contains 5 or 6 C, optionally joined to a benzene ring, it being understood that the alkyl radicals and alkyl parts contain 1 to 4 C as a straight or branched chain, and that the invention relates to all the possible geometric and optical isomers as well as their mixtures. These compounds are useful as antidepressants.

3-phenyl-2-propeneamine derivatives, their preparation and compositions

Growing community of inventors

Vaires-sur-Marne, France

Jean-Marc Paris