Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
2001-06-07
2003-10-14
Peselev, Elli (Department: 1623)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C514S025000
Reexamination Certificate
active
06632797
ABSTRACT:
Growth factors comprise a family of polypeptides with a manyfold of properties regulating for example cell proliferation and cell metabolism. As being multi-functional molecules, they may stimulate or inhibit cell proliferation as well as affect cell function depending on the type of the target cells and the presence of other signal peptides. The family of polypeptides include for example platelet derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factors (TGF-, TGF-&bgr;), insulin like growth factors (IGF-1, IGF-2), fibroblast growth factors (a FGF, b FGF), vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and bone morphogenetic proteins (BMP).
The activities of these growth factors are considered to be casual components of several conditions such as cardiovascular conditions, for example diabetes, inflammatory conditions for example rheumatoid arthritis, analgetic conditions, viral conditions, carcinogenic conditions, several eye diseases and wound healing.
Angiogenesis is under normal conditions under stringent control but in many pathological conditions e.g. solid tumours, rheumatoid arthritis, diabetic retinopathy and artherosclerosis unregulated vessel proliferation occurs. The angiogenetic process is controlled by a balance between many positive and negative regulating signals where growth factors such as TGF, FGF and VEGF play a dominant role.
Under normal conditions in the body growth factor activity is to a large extent regulated by the interactions with heparin and heparan sulfate. The interaction between these polyanionic glycosaminoglycans and growth factors is thought to be of functional significance serving as storage depots for growth factors and protecting them from various degradative processes (Vlodavsky, I., Fuks, Z., Ishai-Michaeli, R., Bashkin, P., Levi, E., Korner, G., Bar-Shavit, R., and Klagsbrun, M. (1991) J. Cell. Biochem. 45, 167-176).
Under some circumstances the administration of growth factors as therapeutic agents has been utilized. However the limited stability of this type of molecules reduces their activity before reaching the target in the body.
Under abnormal conditions when growth factor regulation is required to a larger extent than in the normal situation, the administration of heparin and derivatives of heparin has been considered. However the administration of these type of compounds renders side-effects like anticoagulant activity which limits their possible usage.
Other sulphonated compounds like suramin, a polysulphonated napthylurea, has been shown to have activity in the treatment of adrenocortical carbinoma but the limitation also for this type of compounds is the narrow margin between the dose required to achieve anti-tumor activity and the dose leading to the onset of toxic side effects.
According to the present invention the use of a compound containing a high density, negatively charged domain of vicinally oriented radicals for the preparing of a medicament providing a growth factor modulating activity in mammals including man is described.
The present invention more specifically relates to the use of these compounds in a method of treating angio genesis in tumor conditions.
In preferred embodiments of the invention the negatively charged domain comprises, at least three vicinal phosphorus-containing radicals,
The invention also relates to the use of a compound wherein the phosphorus-containing radicals have the following formula:
wherein
V
1
to V
4
are Y
8
m6
T
o3
U
T
o1
to T
o3
are (CH
2
)
n
, CHCH, or CH
2
CHCHCH
2
;
o1 to o3 are 0 or 1;
n is 0 to 4;
U is R
1
Y
9
m7
, CY
10
Y
11
R
2
, SY
12
Y
13
Y
14
R
3
, PY
15
Y
16
Y
17
R
4
R
5
,
Y
18
PY
19
Y
20
Y
21
R
6
R
7
, CH
2
NO
2
, NHSO
2
R
8
, or NHCY
22
Y
23
R
9
;
m1 to m7 are 0 to 1;
Y
1
to Y
23
are NR
10
, NOR
11
, O, or S;
and where R
1
to R
11
are
i) hydrogen
ii) a straight or branched saturated or unsaturated alkyl residue containing 1-22 carbon atoms
iii) a saturated or unsaturated aromatic or non-aromatic homo- or heterocyclic residue containing 3-22 carbon atoms and 0-5 heteroatoms consisting of nitrogen, oxygen or sulfur
iv) a straight or branched saturated or unsaturated alkyl residue containing 1-22 carbon atoms substituted with a saturated or unsaturated aromatic or non-aromatic homo- or heterocyclic containing 3-22 carbon and 0-5 heteroatoms consisting of nitrogen, oxygen or sulfur
v) an aromatic or non-aromatic homo- or heterocyclic residue containing 3-22 carbon and 0-5 heteroatoms consisting of nitrogen, oxygen or sulfur substituted with a straight or branched saturated or unsaturated alkyl residue containing 1-22 carbon atoms. in the said groups ii-v the residues and/or the substituents the thereof being substituted with 0-6 of the following groups: hydroxy, alkoxy, aryloxy, acyloxy, carboxy, alkoxycarbonyl, alkoxycarbonyloxy, aryloxycarbonyl, carbamoyl, fluoro, chloro, bromo, azido, cyano, oxo, oxa, amino, imino, alkylamino, arylamino, acylamino, arylazo, nitro, alkylthio or alkylsulfonyl.
The streight or branched saturated or unsaturated alkyl residue in groups i-v above can be exemplified by methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, eicosyl, heneicosyl, doeicosyl, isopropyl, isobutyl, isopentyl, isohexyl, isoheptyl, isooctyl, isononyl, isodecyl, isodoecosyl, 2-butyl, 2-pentyl, 2-hexyl, 2-heptyl, 2-octyl, 2-nonyl, 2-decyl, 2-doeicosyl, 2-methylbutyl, 2-methylpentyl, 2-methylhexyl, 2-methylheptyl, 2-methyloctyl, 2-methylnonyl, 2-methyldecyl, 2-methyleicosyl, 2-ethylbutyl, 2-ethylpentyl, 2-ethylhexyl, 2-ethylheptyl, 2-ethyloctyl, 2-ethylnonyl, 2-ethyldecyl, 2-ethyleicosyl, tertbutyl, ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl undecenyl, dodecenyl, tridecenyl, tetradecenyl, pentadecenyl, hexadecenyl, heptadecenyl, octadecenyl, nonadecenyl, eicosenyl, heneicosenyl, doeicosenyl, butadienyl, pentadienyl, hexadienyl, heptadienyl, octadienyl, nonadienyl, decadienyl, doeicodienyl, ethynyl, propynyl, doeicosynyl.
The saturated or unsaturated aromatic or non-aromatic homo- or heterocyclic residue in groups i-v above can be exemplified by cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl, cyclotridecyl, cyclotetradecyl, cyclopentadecyl, cyclohexadecyl, cycloheptadecyl, cyclooctadecyl, cyclononadecyl, cycloeicosyl, cycloheneicosyl, cyclodoeicosyl, adamantyl, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, cyclononenyl, cyclodecenyl, phenyl, biphenyl, naphthyl, hydroxyphenyl, aminophenyl, mercaptophenyl, fluorophenyl, chlorophenyl, azidophenyl, cyanophenyl, carboxyphenyl, alkoxyphenyl, acyloxyphenyl, acylphenyl, oxiranyl, thiiranyl, aziridinyl, oxetanyl, thietanyl, azetidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolidinyl, tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, quinuclidinyl, dioxanyl, dithianyl, trioxanyl, furyl, pyrrolyl, thienyl, pyridyl, quinolyl, benzofuryl, indolyl, benzothienyl, oxazolyl, imidazolyl, thiazolyl, pyridazinyl, pyrimidyl, pyrazinyl, purinyl, or a carbohydrate.
Substituents may be selected from the group of: hydroxy, alkoxy, aryloxy, acyloxy, carboxy, alkoxycarbonyl, alkoxycarbonyloxy, aryloxycarbonyl, aryloxycarbonyloxy, carbamoyl, fluoro, chloro, bromo, azido, cyano, oxo, oxa, amino, imino, alkylamino, arylamino, acylamino, nitro, alkylthio, alkylsulfonyl.
Furthermore the invention relates to the use of a compound wherein the phosphorus-containing radicals have the following formula:
wherein V
1
and V
2
are the same or different and are OH, (CH
2
) OH, COOH, CONH
2
, CONOH,
(CH
2
)
p
COOH, (CH
2
)
p
CONH
2
, (CH
2
)
p
CONOH, (CH
2
)
p
SO
3
H, (CH
2
)
p
SO
3
NH
2
, (CH
2
)
p
NO
2
, (CH
2
)
p
PO
3
H
2
, O(CH
2
)
p
OH, O(CH
2
)
p
COOH, O(CH
2
)
p
CONH
2
, O(CH
2
)
p
CONOH, O(CH
2
)
p
SO
3
H, O(CH
2
)
p
SO
3
NH
2
, O(CH
2
)
p
PO
3
H
2
or CF
2
COOH
p is 1 to 4
In this embodiment of the invention
LandOfFree
Method of treating angiogenesis does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method of treating angiogenesis, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method of treating angiogenesis will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3119528