Other

Nederlandse Organisatie Voor Toegepast-natuurwetenschappelijk Onderzoek

Goldschmidt Ag

Rijksuniversiteit Te Leiden

Nederlandse Hartstichting

Jacobus Hubertus Van Boom

Gijsbert Arie Van Der Marel

Louis Hartog Cohen

Mark Overhand

Elsbet Jantine Pieterman

Nicolaas Johannes Meeuwenoord

Nicolette Voskuyl

Richard Jan Baptist Henrikus Nouel Van Den Berg

Steven Hendrik Leonard Verhelst

Brigitte Elisa Anna Burm

Herman Steven Overkleeft

Adrianus Petrus Valentijn

Theodorus Josephus Van Berkel

Hans Van Den Elst

Ericus Anna Biessen

This invention relates to a method for the production of a sphingoid base according to formulacomprising the steps of

Process for the synthesis of sphingosine

Novel peptide-like FPP-analogues suitable for inhibiting protein:prenyl transferases, such as protein:geranylgeranyl transferase-1, and other prenyl pyrophosphate-consuming enzymes such as squalene synthase and geranylgeranyl pyrophosphate synthase are disclosed.

Inhibitors of prenylated pyrophosphate consuming enzymes

Protein:prenyl transferase inhibitors

Triantennary cluster glycosides, their preparation and use

The invention provides a method for inhibiting protein isoprenylation by administration of a polyisoprenyl pyrophosphate analogue. The polyisoprenyl pyrophosphate analogue may have formula 1, ##STR1## wherein: Pren represents a C.sub.10 -C.sub.30 terpenoid group or a derivative thereof; A.sup.1, A.sup.2, A.sup.3 and A.sup.4 independently represent a direct bond or a C.sub.1 -C.sub.4 alkylene or alkenylene group, optionally having substituents selected from methyl, hydroxy, methoxy, mercapto, methylthio, amino, methylamino, dimethylamino, halogen and a group having formula --X.sup.5 --A.sup.5 --P(.dbd.Z.sup.2)Y.sup.2 Y.sup.3 ; A.sup.5 represents a direct bond or a C.sub.1 -C.sub.4 alkylene or alkenylene group; X.sup.1, X.sup.2, X.sup.3, X.sup.4 and X.sup.5 independently represent a direct bond, oxygen, sulphur, imino or methylimino; Y.sup.1, Y.sup.2 and Y.sup.3 independently represent hydroxy, alkoxy, mercapto, alkylthio, amino, mono- or di-alkylamino, alkyl, alkenyl, alkynyl, cycloalkyl, aryl or arylalkyl, whereby one of Y.sup.1, Y.sup.2 and Y.sup.3 may also represent a C.sub.7 -C.sub.30 alkyl or alkenyl group or a group having formula --X.sup.5 --A.sup.5 --P(.dbd.Z.sup.2)Y.sup.2 Y.sup.3 and two of Y.sup.1, Y.sup.2 and Y.sup.3 may together represent an oxygen or sulfur atom or an imino or methylene group; Z.sup.1 and Z.sup.2 independently represent oxygen or sulphur; and n is 0, 1 or 2; or a pharmaceutically acceptable salt thereof. The invention further provides a pharmaceutical composition containing such a polyisoprenyl pyrophosphate analogue, which composition is suitable for the treatment of carcinomas such as by the inhibition of the isoprenylation of a member of the ras protein family.

Method for the treatment of diseases related with protein isoprenylation

Growing community of inventors

Oegstgeest, Netherlands

Jacobus Hubertus Van Boom