Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...
Patent
1994-12-02
1998-10-27
Goldberg, Jerome D.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Phosphorus containing other than solely as part of an...
514102, 514103, A61K 3166
Patent
active
058278389
ABSTRACT:
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.
REFERENCES:
Kolodyazhay: et al, Dopov. Akad. Nauk Ukr, RSR, Ser B: GEOL, KHIM, Biol. Nauki (1987), (7), 51-3.
The original reference will be presented in due course.
Cohen Louis Hartog
Valentijn Adrianus Petrus Robertus Marie
Van Boom Jacobus Hubertus
Van Der Marel Gijsbert Arie
Goldberg Jerome D.
Nederlandse Organisatie Voor Toegepast-Natuurwetenschappelijk On
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