Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2002-09-05
2004-03-16
Davis, Zinna Northington (Department: 1625)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S352000, C514S357000, C514S354000, C514S438000, C514S445000, C546S309000, C546S314000, C546S334000, C546S339000, C549S029000, C549S062000, C549S078000
Reexamination Certificate
active
06706725
ABSTRACT:
The invention relates, as novel and useful industrial products, to biaromatic compounds which are vitamin D analogues. The invention also relates to a process for preparing them and to their use in pharmaceutical compositions intended for use in human or veterinary medicine, or alternatively in cosmetic compositions.
The compounds according to the invention have pronounced activity in the fields of cell proliferation and differentiation and find applications more particularly in the topical and systemic treatment of dermatological (or other) complaints associated with a keratinization disorder, complaints with an inflammatory and/or immunoallergic component and hyperproliferation of tissues of ectodermal origin (skin, epithelium, etc.), whether benign or malignant. These compounds can also be used to combat ageing or the skin, whether light-induced or chronological, and to treat cicatrization disorders.
The compounds according to the invention can also be used in cosmetic compositions for body and hair hygiene.
Vitamin D is an essential vitamin for preventing and treating mineralization defects of cartilage (rickets) and of bone (osteomalacia), and even of certain forms of osteoporosis in elderly people. However, it is now accepted that its functions extend well beyond regulating bone metabolism and calcium homeostasis. Among these functions, mention may be made of its action on cell proliferation and differentiation and the control of the immune defences. Their discovery has opened the way to novel therapeutic approaches in dermatology, carcinology and in the field of autoimmune diseases and that of organ or tissue transplants.
An efficient therapeutic supply has long been confounded by the toxicity of this vitamin (occasionally fatal hypercalcaemia). Structural analogues of vitamin D are currently synthesized, some of which conserve only the differentiating properties and have no action on calcium metabolism.
One of the aims of the present invention is to propose novel compounds which are structural analogues of vitamin D and which show selective activity on cell proliferation and differentiation without displaying any hypercalcaemiant nature.
Another aim of the present invention is to propose novel compounds which are analogues of vitamin D and which are more readily synthesized and thus more economical than those known previously.
Thus, the present invention relates to compounds which can be represented by the general formula (I) below:
in which:
R
1
represents a hydrogen atom, a CH
3
radical or a radical —(CH
2
)
s
—OR
4
,
R
2
represents a radical —(CH
2
)
t
—OR
5
, s, t, R
4
and R
5
having the meanings given below,
X—Y represents a bonding group chosen from the bonding groups of formulae (a) to (i) below:
R
6
and W having the meanings given below,
Z represents a ring chosen from the rings of formulae (j) to (n) below:
R
7
and R8 having the meanings given below, it being understood that when Z represents the rings of formula (k), (l) or (m), then X—Y cannot represent a bonding group of formula (c) or (d),
it being understood that when Z represents a ring of formula (n), then X—Y preferably represents a bonding group of formula (c) or (d),
R
3
represents an alkyl chain containing from 4 to 8 carbon atoms substituted with one or more hydroxyl groups, it being possible for the hydroxyl groups to be protected in the form of acetoxy, methoxy or ethoxy, trimethylsilyloxy, tert-butyldimethylsilyloxy, tetrahydropyranyloxy and optionally also:
substituted with one or more lower alkyl or cycloalkyl groups and/or
substituted with one or more halogen atoms and/or
substituted with one or more CF
3
groups and/or
in which one or more carbon atoms of the chain are replaced with oxygen, sulphur or nitrogen atoms, it being possible for the nitrogen atoms to be optionally substituted with lower alkyl radicals and/or
in which one or more single bonds of the chain are replaced with one or more double and/or triple bonds,
R
3
being positioned on the ring para or meta to the bonding group X—Y,
s and t, which may be identical or different, being 1 or 2,
R
4
and R
5
, which may be identical or different, represent a hydrogen atom, an acetyl radical, a benzoyl radical, a trimethylsilyl radical, a tert-butyldimethylsilyl radical or a tetrahydropyranyl radical,
R
6
represents a hydrogen atom or a lower alkyl radical,
W represents an oxygen or sulphur atom or an —NH— radical which can optionally be substituted with a lower alkyl radical,
R
7
represents a hydrogen atom or a lower alkyl radical,
R
8
represents a hydrogen atom, a lower alkyl radical or a halogen atom.
The invention is also directed towards the optical and geometrical isomers of the said compounds of formula (I), as well as towards the salts thereof when X—Y represent a bonding group of formulae (c) and (h) and W represents an —NH— radical optionally substituted with a lower alkyl radical.
When the compounds according to the invention are in the form of salts, they are pharmaceutically or cosmetically acceptable salts obtained by addition of an inorganic or organic acid, in particular hydrochloric acid, sulphuric acid, acetic acid, fumaric acid, hemisuccinic acid, maleic acid or mandelic acid.
According to the present invention, the expression “lower alkyl radical” means a linear or branched radical containing from 1 to 6 carbon atoms, and preferably methyl, ethyl, isopropyl, tert-butyl and hexyl radicals.
The expression “cycloalkyl radical” means a cyclic or polycyclic alkane radical containing from 3 to 10 carbon atoms. The cycloalkyl radical is preferably chosen from a cyclopropyl, cyclopentyl or cyclohexyl radical.
The expression “halogen atom” preferably means a fluorine, chlorine or bromine atom.
Among the compounds of formula (I) falling within the context of the present invention, mention may be made in particular of the following:
(E)-7-[5-(3,4-bis-hydroxymethyl-phenoxymethyl)-2-thienyl]-3-ethyloct-6-en-3-ol
(E)-7-[4-(3,4-bis-hydroxymethyl-phenoxymethyl)-2-thienyl]-3-ethyloct-6-en-3-ol
(E)-7-[2-(3,4-bis-hydroxymethyl-phenoxymethyl)-4-thienyl]-3-ethyloct-6-en-3-ol
(E)-7-[5-(3,4-bis-hydroxymethyl-phenoxymethyl)-3-pyridyl]-3-ethyloct-6-en-3-ol
(E)-7-[6-(3,4-bis-hydroxymethyl-phenoxymethyl)-2-pyridyl)-3-ethylnon-6-en-3-ol
(E)-7-[5-(3,4-bis-hydroxymethyl-phenoxymethyl)-2-thienyl]-3-ethylnon-6-en-3-ol
(4E,6E)-7-[5-(3,4-bis-hydroxymethyl-phenoxymethyl)-2-thienyl]-3-ethylnona-4,6-dien-3-ol
(3E,5E)-6-[5-(3,4-bis-hydroxymethyl-phenoxymethyl)-2-thienyl]-1,1,1-trifluoro-2-trifluoromethylocta-3,5-dien-2-ol
(4E,6E)-7-[5-(3,4-bis-hydroxymethyl-phenoxymethyl)-2-thienyl]-1,1,1,2,2-pentafluoro-3-pentafluoroethylnona-4,6-dien-3-ol
(E)-7-[5-(3,4-bis-hydroxymethyl-phenoxymethyl)-3-thienyl]-3-ethyl-4,4-dimethylnon-6-en-3-ol
(E)-7-{5-[2-(3,4-bis-hydroxymethyl-phenyl)ethyl]-2-thienyl}-3-ethylnon-6-en-3-ol
(4E,6E)-7-{5-[2-(3,4-bis-hydroxymethyl-phenyl)ethyl]-2-thienyl}-3-ethylnona-4,6-dien-3-ol
(3E,5E)-6-{5-[2-(3,4-bis-hydroxymethyl-phenyl)ethyl]-2-thienyl}-1,1,1-trifluoro-2-trifluoromethylocta-3,5-dien-2-ol
((4E,6E)-7-{5-[2-(3,4-bis-hydroxymethyl-phenyl)ethyl]-2-thienyl}-1,1,1,2,2-pentafluoro-3-pentafluoro-ethylnona-4,6-dien-3-ol
(4E,6E)-7-[5-(3,4-bis-hydroxymethyl-benzylamino)-2-thienyl]-3-ethylnona-4,6-dien-3-ol
(4E,6E)-7-{5-[(3,4-bis-hydroxymethyl-benzyl)methyl-amino]-2-thienyl}-3-ethylnona-4,6-dien-3-ol
(4E,6E)-7-{5-[(3,4-bis-hydroxymethyl-benzyl)propyl-amino]-2-thienyl}-3-ethylnona-4,6-dien-3-ol
(E)-7-[4-(3,4-bis-hydroxymethyl-phenoxymethyl)-2-thienyl]-3-ethylnon-6-en-3-ol
(4E,6E)-7-[4-(3,4-bis-hydroxymethyl-phenoxymethyl)-2-thienyl]-3-ethylnona-4,6-dien-3-ol
(3E,5E)-6-[4-(3,4-bis-hydroxymethyl-phenoxymethyl)-2-thienyl]-1,1,1-trifluoro-2-trifluoromethylocta-3,5-dien-2-ol
(E)-7-{4-[2-(3,4-bis-hydroxymethyl-phenyl)ethyl]-2-thienyl}-3-ethylnon-6-en-3-ol
(4E,6E)-7
Davis Zinna Northington
Galderma Research & Development S.N.C.
LandOfFree
Vitamin D analogues does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Vitamin D analogues, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Vitamin D analogues will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3224199