Merrell Dow Pharmaceuticals

Merrell Toraude Et Compagnie

Aventis Pharma Limited

Fritz E Gerhart

Philippe Bey

Pierre Mamont

Michel Jung

Viviane Van Dorsselaer

Daniel Schirlin

Daniel G Schirlin

Eugene L Giroux

Albert Sjoerdsma

Bernhard Neises

Michael Kolb

Ekkehard H Bohme

Nikolaus J Seiler

Michael Jung

Wolfgang Frieben

William Higgins

Michel J Jung

Joseph P Burkhart

Gem-dihalo-1,8-diamino-4-aza-octane derivatives useful as antiproliferative or antitumor agents.

Gem-dihalo-1, 8-diamino-4-aza-octanes

This invention relates to ornithine derivatives substituted at the 5 position with an R group which can be a --CH.sub.2 F, --CHF.sub.2, --CHClF, --C.tbd.CH, --CH.dbd.CH.sub.2, or --CH.dbd.C.dbd.CH.sub.2 group and the pharmaceutically acceptable acid addition salts thereof which are specific inhibitors of OAT and can be used in the treatment of conditional deficiencies of ornithine.

5-substituted ornithine derivatives

Gem-dihalo-1,8-diamino-4-aza-octanes

The large scale preparation of ethyl 2,2-difluoro-4- pentenoate and 2-fluorinated methyl aminoacetonitriles by reaction of 2-H-perfluoroethyl allyl ether and n-butyl lithium and fluoromethylacetonitrile and a Grignard reagent, respectively, is largly unsuccessful because of side reactions which convert intermediate products and reactants to undesired products. Applicants have overcome these problems by performing the reactions with cooling in a continuous manner in a flow reactor with short residence time.

Continuous large-scale production of ethyl 2,2-difluoro-4-pentenoate and

Gem-dihalo and gem-tetrahalo-1,12-diamino-4,9-diazadodecane derivatives useful as antiproliferative or antitumor agents.

Gem-dihalo and tetrahalo-1,12-diamino-4,9-diaza-dodecanes

This invention relates to amino acid, dipeptide and tripeptide derivatives of 2,6-diamino-3-haloheptanedioic acids, processes for preparing the same, and their use as antibacterial agents.

Derivatives of 2,6-diamino-3-haloheptanedioic acid

Gem-dihalo and gem-tetrahalo-1,12-diamino-4,9-diaza-dodecane derivatives useful as antiproliferative or antitumor agents.

Process for preparing 5-vinyl-2-pyrrolidinone and intermediates therefor

Novel fluorinated diamine derivatives are inhibitors of ornithine decarboxylase enzyme and have the following general Formula I: ##STR1## wherein: R.sub.c represents hydrogen or carboxy;

Decarboxylase-inhibiting fluorinated pentane diamine derivatives

Fluorinated alkenylene diamine compounds are inhibitors of ornithine decarboxylase enzyme in vivo and have the following formula: ##STR1## wherein: R.sub.a represents hydrogen or R.sub.2, where R.sub.2 is as defined below;

Fluorinated pentene diamine derivatives

Fluorinated diaminobutane derivatives

Novel fluorinated alkenylene diamine derivatives are inhibitors of ornithine decarboxylase enzyme and have the following general Formula I: ##STR1## wherein: R.sub.c represents hydrogen or --COR.sub.5, where R.sub.5 is as defined below;

Fluorinated diaminopentene derivatives

Fluorinated aminobutyric acid and diaminobutane compounds in vivo are inhibitors of gamma-aminobutyric acid transaminase and have the following formula: ##STR1## wherein: Y represents hydrogen or fluorine;

Fluorinated amino-butyric acid and diaminobutane derivatives

Certain .alpha.-(fluoromethyl or difluoromethyl)-.alpha.-aminoacetonitriles are prepared by treating the appropriate .alpha.-(fluoromethyl or difluoromethyl) ketimine magnesium halide with hydrogen cyanide or with an alkali metal cyanide or ammonium cyanide and a proton source. The products are useful as intermediates for making .alpha.-(fluoromethyl or difluoromethyl)-.alpha.-amino acids having pharmacological activity.

Growing community of inventors

Kehl-Leutesheim, Germany

Fritz E Gerhart