Anticancer agent

Details Anticancer agent Anticancer agent

1999-07-12

2002-03-19

Goldberg, Jerome D. (Department: 1614)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Ester doai

C514S558000, C514S559000, C514S560000

Reexamination Certificate

active

06359000

ABSTRACT:

BACKGROUND OF THE INVENTION
The invention relates to methods of treating cancer with naturally occurring terpenoid, steroid, and polyketide compounds and derivatives or analogs thereof.
SUMMARY OF THE INVENTION
The invention features a method of treating cancer which includes administering to patient an effective anticancer amount of a pharmaceutical composition containing one or more compounds having the formula (I):
In formula (I), A is C
2-10
1-methylalkyl, 1-(C
1-10
alkyloxy)ethyl, 1-(C
1-10
alkylthio)ethyl, C
2-10
hydroxycarbonylalkyl, C
2-10
alkenyl, C
2
alkenylene, X
1
(CH—)R
1
, or X
1
(C—)R
1
, wherein X
1
is H, F, Cl, Br, I, C
1-10
alkyl, C
2-10
alkenyl, C
2-10
alkenylene (where A is X
1
(C—)R
1
), C
1-10
haloalkyl, OR
i
, SR
i
, NR
i
R
ii
, or NR
i
(C═O)R
ii
, each of R
i
and R
ii
being independently selected from H, C
1-10
alkyl, C
3-6
heteroaryl, and (C
6-14
aryl)(C
0-6
alkyl); and R
1
is H or methyl, or ═O where A is X
1
(C—)R
1
. Each of R
a
and R
b
is selected independently from H, C
1-6
alkyl, C
1-6
haloalkyl, and C
1-6
alkenyl, except that where A is C
2-10
alkenylene, R
b
is deleted. X
2
is H, F, Cl, Br, I, NO
3
, SO
4
, C
1-10
alkyl, C
1-10
haloalkyl, OR
iii
, O(C═O)R
iii
, SR
iii
, NR
iii
R
iv
, or NR
iii
(C═O)R
iv
, wherein each of R
iii
and R
iv
is independently selected from H, C
1-10
alkyl, and (C
6-14
aryl)(C
0-6
alkyl) Each of Y
1
and Y
2
is independently selected from H, C
1-10
alkyl, OR
v
, SR
v
, NR
v
R
vi
, and NR
v
(C═O) R
vi
, wherein each of R
v
and R
vi
is independently selected from H, C
1-10
alkyl, and (C
6-14
aryl)(C
0-6
alkyl); or Y
1
and Y
2
, taken together, are ═O, ═S, ═NR
vii
, ═NOR
vii
, or ═CHR
vii
in the E or Z configuration, wherein R
vii
is H, C
1-10
alkyl, (C
6-14
aryl)(C
0-10
alkyl), or (C
1-10
alkyl)(C
6-14
aryl). Z is H, C
1-10
alkyl, C
2-10
alkenyl, or a monovalent C
1-30
organic moiety, said moiety being bonded to the carbon which is also bonded to Y
1
and Y
2
by a heteroatom selected from O, S, and N. The invention also features pharmaceutically acceptable salts or esters of formula (I). Compounds for use in this method include, for example, the compound 3390, and synthetic intermediates of the disclosed compounds, such formulae (II) and (III).
The invention also features a method of treating cancer, comprising administering to a patient an effective amount of a pharmaceutical composition including a compound of the formula (VI) and a pharmaceutically acceptable carrier.
In formula VI, each of R
1
and R
2
is independently selected from H, C
1-10
alkyl, C
1-10
alkoxy, C
2-10
alkenyl, C
2-10
alkenoxy, C
6-10
aryl, substituted or unsubstituted C
6-10
arylcarbonyloxy, and C
2-10
acyloxy; or R
1
and R
2
taken together are ═O or substituted or unsubstituted C
1-10
alkylenedioxy, carbonyldioxy, and other carbonyl-protecting groups. When there is no double bond between C-7 and C-11, each of R
3
, R
4
and R
5
is independently selected from C
1-10
alkyl, C
1-10
alkoxy, and C
1-10
acyloxy; or R
4
and R
5
taken together are ═O, C
1-10
alkylidene, or C
1-10
alkenylidene. When there is a double bond between C-7 and C-11, R
5
is absent.
R
6
is C
1-10
alkylamino or C
1-10
alkylthio when there is no double bond between C-9 and C-10; R
6
is absent when there is a double bond between C-9 and C-10. X is OH, OR
p
where R
p
is C
1-10
alkyl, C
6-10
aryl, C
2-10
acyl, C
6-10
arylcarbonyl, tri(C
1-6
alkyl)silyl, and other hydroxy-protecting groups, or Y having the formula:
Z is —(C═O)—NH—, —(C═O)—O—, or —O—. Each of r
a
-r
h
is independently selected from H, methyl, halomethyl, hydroxy, and OR
p
, where R
p
is C
1-10
alkyl, C
6-10
aryl, C
2-10
acyl, C
6-10
arylcarbonyl, and other hydroxy-protecting groups, provided that at least two of r
a
-r
h
are hydroxyl groups which do not form a gem-diol. The invention includes a pharmaceutically acceptable salt or ester of a disclosed compound.
Treating cancer in a patient includes achieving, partially or substantially, one or more of the following: arresting the growth or spread of a cancer, reducing the extent of a cancer (e.g., reducing size of a tumor or reducing the number of affected sites), inhibiting the growth rate of a cancer, and ameliorating or improving a clinical symptom or indicator associated with a cancer (such as tissue or serum components).
Other features and advantages of the present invention will be apparent from the following detailed description, and also from the appended claims.


REFERENCES:
Bohlmann et al., “Neue Eremophilene Aus Südafrikanischen Senecio-Arten”,Phytochem.,17:1337-41 (1978).
Neuenschwander et al., “63. Struktur der Sesquiterpene von Petasites hybridus (L.) G.M. et ACH.: Petasol-und Isopetasol-Abkömmlinge”,Helvetica Chimica Scta,62:609-34 (1979).
Yamakawa et al., “Steroselective Total Synthesis of (±)-Eremofortin B, A Sesquiterpenoid Mycotoxin ofPenicillium roqueforti”, Chem. Letters, The Chem. Soc. of Japan,pp. 929-32 (1981).
Tirilly et al., “A Fungitoxic Sesquiterpene from Hansfordia Pulvin ATA”,Phytochem.,22(9):2082-83 (1983).
Kim et al., “A Brassinolide-Inhibitor KM-01, Its Isolation and Structure Elucidation from a FungusDrechslera avenae”, Tetrahedron Letters,35(11):1731-34 (1994).
Yoshizawa et al., “Incorporation of13C-Labelled 5-epi-Aristolochene into Capsidiol in Green Pepper Seedlings”,Biosci. Biotech. Biochem.,58(2)305-308 (1994).
Abstracts,Dictionary of Natural Products on CD-ROM,Release 3:2, pp. 1-8 (1995).
Kim et al., “Biological Activity of Brassinosteroid Inhibitor KM-01 Produced by a FungusDrechslera avenae”, Biosci. Biotech. Biochem.,59(8)1394-97 (1995).
Witschel et al., “Synthese der Pestwurzinhaltsstoffe (+)-Petasin und (+)-Isopetasin”,Tetrahedron Letters,36(19):3325-28 (1995).

Affiliated with

Also associated with

Rating

Anticancer agent does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Anticancer agent, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Anticancer agent will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2847951