Ketotricyclo[5.2.1.0]decane derivatives

Details Ketotricyclo[5.2.1.0]decane derivatives Ketotricyclo[5.2.1.0]decane derivatives

1993-10-19

2001-08-21

Reamer, James H. (Department: 1614)

Drug, bio-affecting and body treating compositions

Topical sun or radiation screening, or tanning preparations

C514S679000, C568S326000, C568S313000

Reexamination Certificate

active

06277357

ABSTRACT:

The invention relates to ketotricyclo[5.2.1.0]-decane derivatives of the formula I
wherein
Phe is a phenyl group which is unsubstituted or substituted by 1 to 5 hydroxyl, alkyl or alkoxy groups having 1 to 10 C atoms,
and to a process for their preparation and their use in cosmetic formulations, in particular for protection from solar radiation, and in pharmaceutical formulations for preventive treatment of inflammations and allergies of the skin or certain types of cancer.
As is known, the skin reacts sensitively to the sun's rays, which can cause common sunburn or erythema, and also more or less severe burns.
However, the sun's rays also have other adverse effects: they cause the skin to lose its elasticity and develop wrinkles and thus lead to premature ageing. Dermatoses can also sometimes be observed. In the extreme case, skin cancer occurs in some people.
It is also desirable to protect hair from photo-chemical damage, in order to prevent changes in color shades, bleaching or damage of a mechanical nature.
It is known that the components contained in cosmetic preparations are not always sufficiently stable to light and decompose under the action of light rays.
As is known, ultraviolet rays with a wavelength of less than 400 nm form the most dangerous part of the sun's rays. It is also known that because of the presence of the ozone layer of the earth's atmosphere, which absorbs some of the solar radiation, the lower limit of the ultraviolet rays which reach the earth's surface is about 280 nm.
It thus appears desirable to provide compounds which can absorb UV rays in a wavelength range of 280 to 400 nm, that is to say also UV-B rays with a wavelength of between 280 and 320 nm, which form a decisive role in the development of solar erythema, and also UV-A rays with a wavelength between 320 and 400 nm, which tan the skin but also age it, promote initiation of an erythematous reaction or intensify this reaction in certain people or can even induce phototoxic or photoallergic reactions.
The sunscreen filters nowadays customary in cosmetics are classified into UVA and UVB filters. While there are good filters in the UVB range (280-320 nm) with substances such as Eusolex® 6300 or Eusolex® 232, those used in the UVA range (320-400 nm) present problems.
Dibenzoylmethanes, such as Parsol® 1789 or Eusolex® 8020, do not have an unlimited stability when exposed to UV irradiation, which on the one hand reduces the effectiveness of the filter in the course of time and on the other hand can promote photosensitizations of the skin in isolated cases. The benzophenones also used as UVA filters have only a limited solubility in the oils used in cosmetics, and they have a relatively low absorption. On the other hand, only a few water-soluble UVA filters are currently known, but their UV absorption is low.
Similar benzylidenecamphor derivatives are known, for. example, from EP 0 390 682; however, these do not have a tricyclodecanone structure.
A compound with the designation (+−)-6-oxobenzylidene(3arH.7acH)-5hexahydro-4t.7t-methanoindane, which is embraced by formula I when Phe is unsubstituted phenyl is cited in Beilstein under number BRN=3196309.
Comparison with the original literature cited (H. A. Bruson, T. W. Riener, J. Am. Chem. Soc 67, 1945, 723-28), shows, however, that it is not the 9-benzylidene-tricyclo[5.2.1.0
2,6
]decan-8-one, according to the invention but 3-benzylidenetricyclo[3.3.2.
1,4
0
1,5
]decan-2-one.
It has been found that ketotricyclo[5.2.1.0]-decane derivatives of the formula I wherein Phe is a phenyl group which is unsubstituted or substituted by 1 to 5 hydroxyl, alkyl or alkoxy groups, in particular an unsubstituted phenyl group, have outstanding UVB filter properties. Their solubility in the oils used in cosmetics is very good, so that use concentrations of up to at least 10% of the formulation are possible even in complicated formulations.
The compounds according to the invention furthermore have an exceptional photostability to UV radiation which by far exceeds the stability of UV filter substances known to date, and are particularly suitable as UVB or UV broad-band filters.
If the extinction in the UVA range has a minimum, this is not a disadvantage, since a UVA filter can be co-incorporated into the formulation without problems.
The compounds of the formula I furthermore can also be used for preventive treatment of inflammations and allergies of the skin and for prevention of certain types of cancer.
In addition to their good properties as filters, the compounds according to the invention are distinguished by a good heat and photochemical stability.
These compounds furthermore offer the advantage of not being toxic or irritating and of being completely harmless to the skin.
They are distributed uniformly in the conventional cosmetic carriers, and can form a continuous film, in particular in fat carriers; they can be applied to the skin in this manner, in order to form an effective protective film.
The invention relates to the compounds of the abovementioned formula I, in particular wherein Phe is unsubstituted phenyl or 1,4-phenyl which is substituted by 1 or 2 alkoxy groups having 1 or 2 C atoms.
Phe is preferably a group of the formula
In this formula, R is a methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl or 1,1,3,3-tetra-methylbutyl radical, a methoxy, ethoxy or 2-ethylhexyloxy radical or hydrogen, preferably hydrogen.
n is 1 to 5, preferably 1 or 2.
The phenyl group is preferably unsubstituted or substituted by one or two alkoxy groups having 1 to 8 C atoms, in particular by methoxy, ethoxy or 2-ethylhexyloxy groups.
Preferred compounds of the formula I are those of the formulae I1 to I8, wherein A is a group of the formula
and
R is alkyl or alkoxy having 1 to 10 C atoms.
The compounds of the formula I are obtained, for example, by a process in which a benzaldehyde derivative of the formula II
Phe—CHO  II
wherein Phe has the meaning given, is reacted with 8-ketotricyclo[5.2.1.0
2,6
] decane in the presence of a base.
The reaction is as a rule carried out in an inert diluent, preferably a protic solvent, in particular an alcohol, such as, for example, methanol, ethanol, isopropanol or tert-butanol, or an aprotic solvent, such as diethyl ether, toluene or cyclohexane, or mixtures of the solvents mentioned. Alkali metal alcoholates, such as, for example, sodium methylate, sodium ethylate or potassium tert-butylate, are preferably employed as the base.
The reaction can be carried out at temperatures between 0° C. and the boiling point of the reaction mixture, and is preferably carried out at 25 to 60° C.
The aldehydes of the formula II are known or are prepared by known methods.
8-Ketotricyclo[5.2.1.0
2,6
] decane is known and is commercially obtainable as an isomer mixture.
The invention also relates to the process for the preparation of the new compounds of the formula I.
The invention furthermore relates to a cosmetic formulation which comprises an active amount of at least one derivative of the above formula I in a cosmetically compatible carrier.
The cosmetic agent according to the invention can be used as an agent for protecting the human epidermis or the hair or as a sunscreen agent.
The invention furthermore relates to a process for protecting the skin and natural or sensitized hair from the sun's rays, an active amount of at least one compound of the formula I being applied to the skin or hair.
“Sensitized hair” means hair which has been subjected to a permanent wave treatment or a dyeing or bleaching process.
The invention furthermore relates to a colored or non-colored light-stabilized cosmetic formulation which comprises an active amount of at least one benzylidene-camphor derivative of the above formula I.
If the cosmetic agent according to the invention is used as an agent for protecting the human epidermis from UV rays, it is present in various forms which are usually used for this type. It can thus be, in parti

Affiliated with

Also associated with

Rating

Ketotricyclo[5.2.1.0]decane derivatives does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Ketotricyclo[5.2.1.0]decane derivatives, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Ketotricyclo[5.2.1.0]decane derivatives will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2517374