Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2002-09-13
2004-12-14
Kifle, Bruck (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
Reexamination Certificate
active
06831090
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to epothilone derivatives, methods for the preparation of the derivatives and intermediates therefor.
BACKGROUND OF THE INVENTION
Epothilones are macrolide compounds which find utility in the pharmaceutical field. For example, Epothilones A and B having the structures:
Epothilone A R=H
Epothilone B R=Me
have been found to exert microtubule-stabilizing effects similar to TAXOL and hence cytotoxic activity against rapidly proliferating cells, such as, tumor cells or other hyperproliferative cellular disease, see
Angew. Chem. Int. Ed. Engl
., 1996, 35, No. 13/14.
SUMMARY OF THE INVENTION
The present invention relates to compounds of the formula
Q is selected from the group consisting of
G is selected from the group consisting of alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo,
W is O or N R
12
;
X is O, S, or H, H;
Y is selected from the group consisting of O; H, OR
13
; OR
14
, OR
14
; NOR
15
; H, NOR
16
; H, NR
17
R
18
; H, H; or CHR
19
; OR
14
OR
14
can be a cyclic ketal;
B is selected from the group consisting of H, OR
20
, or OCOR
21
, and NR
22
R
23
;
D is selected from the group consisting of NR
24
R
25
or saturated heterocycle (such as piperidinyl, pyrrolidinyl, and the like);
R
1
, R
2
, R
3
, and R
4
are selected from H or lower alkyl;
R
15
, R
16
, R
17
, R
18
, and R
19
are selected from the group H, alkyl, substituted alkyl, or aryl;
R
6
, R
7
, R
13
, R
14
, R
20
, and R
21
are selected from the group H, alkyl, or substituted alkyl;
R
5
, R
8
, R
9
, R
22
, R
24
, R
26
, and R
27
are selected from the group consisting of H, alkyl, substituted alkyl, aryl, heteroaryl, cycloalkyl, or heterocyclo;
R
12
, R
23
, and R
25
are selected from the group consisting of H, alkyl, substituted alkyl, aryl, heteroaryl, cycloalkyl, heterocyclo, R
26
C═O, R
27
SO
2
, hydroxy, O-alkyl or O-substituted alkyl;
and any salts, solvates or hydrates thereof
Proviso
The present invention does not include compounds of formula I wherein
W and X are both O; and
R
1
, R
2
, R
3
, R
4
are methyl; and
R
5
is H or methyl; and
G is 1-methyl-2-(2-methyl-4-thiazolyl)ethenyl; and
Q is
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Victory S.F.,
Borzilleri Robert M.
Höfle Gerhard
Leibold Thomas
Vite Gregory D.
Bristol--Myers Squibb Company
Kifle Bruck
Patel Rena
Winslow Anastasia P.
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