WO1988002251A1

WO1988002251A1 - Sunscreen compositions and compounds for use therein

Info

Publication number: WO1988002251A1
Application number: PCT/AU1987/000330
Authority: WO
Inventors: Graham Bird; Neil Fitzmaurice; Walter Clark Dunlap; Bruce Edward Chalker; Wickramasinghe Mudiyanselage Bandaranayake
Original assignee: Ici Australia Operations Proprietary Limited; Australian Institute Of Marine Science
Priority date: 1986-09-26
Filing date: 1987-09-25
Publication date: 1988-04-07

Abstract

Certain compounds of formula (I) and sunscreen compositions comprising as an effective component at least one compound of formula (I), wherein R1 is selected from alkyl, alkenyl, alkynyl, substituted alkyl, substituted alkenyl, phenyl, substituted phenyl, substituted benzyl, cycloalkyl, cycloalkenyl, substituted cycloalkyl, substituted cycloalkenyl and polymeric groups; R2 is selected from hydrogen, alkyl and alkoxy; and wherein R1 and R2 may form a carbocyclic ring which may be substituted; R3 is selected from alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, phenyl, benzoyl, substituted phenyl, substituted benzyl, substituted benzoyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, alkanoyl, substituted alkanoyl, polymeric groups, the group OROROR9 wherein R is a bivalent hydrocarbon radical and R9 is alkyl, alkenyl, phenyl, benzyl, substituted phenyl, substituted benzyl; R4 is alkyl or alkoxy; n is an integer from 0 to 4; and R5 and R6 are independently selected from alkyl, alkoxy, alkanoyl, alkanoyl substituted by hydroxyl or alkoxycarbonyl and R5 and R6 may form a spiro carbocyclic ring which may be substituted with alkyl.

Description

SUNSCREEN COMPOSITIONS AND COMPOUNDS FOR USE THEREIN

The invention relates to sunscreen compositions comprising ultra-violet radiation absorbing compounds to methods of preparing such compositions, and to UV-absorbing compounds of particular use in preparing such compositions. Sunscreen compositions may be used to form a coating for protecting substrates from harmful effects of ultraviolet radiation such as in solar radiation. For example, sunscreen compositions are probably best known for use in the protection of skin against severe erythra edema which can be caused by exposure to sunlight.

Common commercially available UV-agents include, for example, para-aminobenzoic acid derivatives, benzotriazoles, benzophenones, methoxycinnamates and salicylates. It has been proposed, for example in U.K. Patent Application 2,120,549A and French Patent Application 8301391, that certain specific classes of vinylagous amide compounds (enaminoketones) may also be used as UV-absorbing sunscreen agents.

We have observed that certain mycosporinβ amino acids which exist in the living tissue of the Pacific staghem coral Acrooora formosa are functional UV-absorbing agents (λmax 310-332 nm) in corals inhabiting the shallow-water, tropical coral reef environment. While these naturally occurring enaminoketone compounds appear to be potentially attractive as commercial UV-agents, their utility is questionable because of the difficulty of isolating them from their biological source and because of their lack of adequate chemical stability. We have proposed that certain synthetic vinylagous amide analogues of those natural products can be prepared which preserves their characteristic UV-absorbing chromophore within a chemically more stable structure and which typically have UV-absorption maxima (λmax) in the wavelength region 288-340 nanometers (P.C.T. Patent Application PCT/AU85/00242). These synthetic analogues, however, proved to be chemically unstable during prolonged period of formulation and storage. We have now found that a select group of cyclic vinylogous amide compounds which comprise a tetrahydropyridine moiety are particularly suitable for use in sunscreen compositions.

Accordingly we provide a sunscreen composition comprising as an effective component thereof at least one compound of formula I

wherein:

R¹ is selected from the group consisting of: C₁ to C₁₈ alkyl; C₁ to C₉ alkyl substituted with a substituent selected from the group of hydroxy, amino, C₁ to C₉ alkoxy, C₂ to C₉ alkenyloxy, C₁ to C₉ alkanoyl, (C₁ to C₉ alkoxy)carbonyl, carbamoyl, (C₁ to C₆ alkyl)carbamoyl and phenyl; C₂ to C₁₈ alkenyl; C₂ to C₉ alkenyl substituted with a substituent selected from the group consisting of hydroxy, amino, C₁ to C₉ alkoxy, C₂ to C₉ alkenyloxy, C₁ to C₉ alkanoyl, carbamoyl, (C₁ to C₆ alkyl)carbamoyl, and phenyl;C₂ to C₁₈ alkynyl; phenyl; the groups phenyl and benzyl said groups being substituted in the benzene ring with a substituent is selected from the group of C₁ to C₁₂ alkyl, C₁ to C₁₂ alkoxy, C₁ to C₁₂ alkenyloxy, C₁ to C₁₂ alkylamino, N,N-di(C₁ to C₆ alkyl)amino, (C₁ to C₁₂ alkoxy)carbonyl and C₁ to C₁₂ alkanoyl; C₅ to C₇ cycloalkyl; C₅ to C₇ cycloalkenyl; the groups substituted C₅ to C₇ cycloalkyl and substituted C₅ to C₇ cycloalkenyl wherein the substituent is selected from the group of hydroxy, amino, C₁ to C₉ alkyl, C₁ to C₉ alkoxy, and C₁ to C₉ alkenyloxy; polymers of one or more of the monomers selected from ethylene glycol, propylene glycol, styrene and

C₂ to C₄ alkenes, and derivatives of said polymers; and wherein R¹ may optionally link together with R² via a bridging group of formula -(R⁷R⁸C)_m- wherein m is 2 or 3 and R⁷ (which may be the same or different) and R⁸ (which may be the same or different) are independently selected from the group of hydrogen and C₁ to C₆ alkyl;

R³ is selected from the group consisting of: C₁ to C₁₈ alkyl; C₁ to C₉ alkyl substituted with a substituent selected from the group of amino, C₁ to C₉ alkoxy, C₂ to C₉ alkenyloxy, C₁ to C₉ alkanoyl, (C₁ to C₉ alkoxy)carbonyl, carbamoyl, (C₁ to C₉ alkyl)carbamoyl, and phenyl; C₂ to C₁₈ alkenyl; C₂ to C₉ alkenyl substituted with a substituent selected from the group consisting of hydroxy, amino C₁ to C₉ alkoxy, C₂ to C₉ alkenyloxy, C₁ to C₉ alkanoyl, (C₁ to C₉ alkoxy)carbonyl, carbamoyl, (C₁ to C₉ alkyl)carbamoyl and phenyl; C₂ to C₁₈ alkynyl; phenyl; benzoyl; the groups phenyl, benzyl and benzoyl said group being substituted in the benzene ring with a substituent selected from the group of hydroxy, amino, C₁ to C₁₂ alkyl, C₂ to C₁₂ alkenyl, C₁ to C₁₂ alkoxy, C₂ to C₁₂ alkenyloxy, C₁ to C₁₂ alkylamino, N,N-di(C₁ to C₆ alkyl)amino, (C₁ to C₁₂ alkoxy)carbonyl, and C₁ to C₁₂ alkanoyl; C₅ to C₇ cycloalkyl; C₅ to C₇ cycloalkenyl; the groups substituted C₅ to C₇ cycloalkyl and substituted C₅ to C₇ cycloalkenyl wherein the substituent is selected from the group of hydroxy, amino, C₁ to C₉ alkyl, C₁ to C₉ alkoxy, and C₁ to C₉ alkenyloxy; C₁ to C₁₈ alkanoyl; C₂ to C₉ alkanoyl substituted with a substituent selected from the group of hydroxy, amino, C₁ to C₉ alkoxy and C₂ to C₉ alkenyloxy, C₁ to C₉ alkanoyl; carbamoyl, (C₁ to C₆ alkyl)carbamoyl, (C₁ to C₉ alkoxy)carbonyl and phenyl; polymers of one or more monomers selected from ethylene glycol, propylene glycol, styrene and

C₂ to C₄ alkenes, and derivatives of said polymers; and the group -ORORO R⁹ wherein R (which may be the same or different) is a bivalent hydrocarbon radical of 2 to 6 (more preferably 2 to 4) carbon atoms and

R⁹ is a hydrocarbon radical selected from C₁ to C₆ alkyl, C₂ to C₆ alkenyl, phenyl, benzyl, C₁ to C₆ alkyl phenyl and (C₁ to C₆ alkyl)benzyl (more preferably R⁹ is selected from C₁ to C₄ alkyl and C₂ to C₄ alkenyl);

R² is selected from the group consisting of hydrogen, C₁ to C₆ alkyl, C₁ to C₆ alkoxy, and the group wherein R¹ and R² together form a bridging group of formula -(CR⁷R⁸)_m- wherein R⁷, R⁸ and m are as hereinbefore defined;

R⁴ is selected from the group consisting of

C₁ to C₆ alkyl and C₁ to C₆ alkoxy; n is an integer selected from 0 to 4 inclusive; and

R⁵ and R⁶ which may be the same or different are selected from hydrogen, C₁ to C₆ alkyl, C₁ to C₆ alkoxy, C₁ to C₁₀ alkanoyl, C₁ to C₁₀ alkanoyl substituted by carboxyl or (C₁ to C₆ alkoxy)carbonyl and wherein R⁵ and R⁶ may form a spiro-carbocyclic ring by the bridging group of formula II

II

wherein q is 2 or 3 and R¹⁰ and R¹¹ may be the same or different at each carbon unit of the bridge and are independently selected from hydrogen and C₁ to C₈ alkyl.

The composition of the present invention may be applied to a surface to reduce the exposure of the surface to ultra-violet radiation. The composition may be formulated, for example, as a solid, liquid, gel or aerosol and may generally comprise a carrier (extending medium) which adapts the agent for application to a surface.

In a further embodiment of the invention, there is provided a method of preparation of a sunscreen composition comprising mixing at least one compound of formula I with a carrier suitably adapted to allow application of said compound to a surface. Examples of suitable carriers may include oils for example, mineral oils, paraffin, squalene and octyl palmetate and oil/alcohol mixtures.

In a specific example, at least one compound of formula I is combined with a water-insoluble liquid such as a paraffin oil to give an oil phase which is combined with an aqueous phase to form an oil-in-water emulsion in the presence of a suitable emulsifier. The temperature at which the composition is formed is not critical and may be selected in accordance with the nature of to the components thereof. The temperature is typically in the range 0 to 150°C (preferably 0 to 80°) although higher or lower temperatures may be used if desired. Further components such as perfumes, colouring agents, antioxidants and oxygen scavengers may be used in the composition of the present invention. Examples of oxygen scavengers include compounds which in the presence of oxygen are oxidised more readily than the compound of formula I. An example of an oxygen scavenger is sodium thiosulphate. The composition may comprise additives making the composition useful as a cosmetic or phamaceutical.

One or more compounds of formula I may be utilized in the composition of the present invention and generally the concentration of said compound(s) is in the range of 0.5 to 20% by weight of the total composition. However higher or lower concentrations may be used if desired depending on the degree of screening required. Preferably in the compound of formula I R¹ is selected from C₁ to C₁₈ alkyl;

C₁ to C₉ alkyl substituted with a substitutent selected from the group consisting of, hydroxy, amino, C₁ to C₉ alkoxy; C₁ to C₉ alkanoyl and (C₁ to C₉ alkoxy)carbonyl; C₁ to C₁₈ alkenyl; cyclohexyl; phenyl; benzyl; the groups phenyl and benzyl said groups being substituted in the benzene ring with a substituent selected form the group of C₁ to C₉ alkyl, C₂ to C₉ alkenyl, C₁ to C₉ alkoxy, C₁ to C₉ alkylamino, N,N-di(C₁ to C₆ alkyl)amino, C₁ to C₉ alkanoyl and (C₁ to C₉ alkoxy)carbonyl; and wherein R ¹ may optionally link together with R² via a bridging group of formula -CH₂(R⁷R⁸OCH₂- wherein R⁷ and R⁸ are independently selected from hydrogen and C₁ to C₆ alkyl;

R³ is selected from C₁ to C₁₈ alkyl; C₁ to C₉ alkyl substituted with a substituent selected form the group consisting of hydroxy, amino, C₁ to C₉ alkoxy and C₁ to C₉ alkanoyl; C₂ to C₁₈ alkenyl; cyclohexyl; phenyl; benzyl; benzoyl; the groups phenyl, benzyl and benzoyl said groups being substituted in the benzene ring with a substituent selected from the group of C₁ to C₉ alkyl, C₂ to C₉ alkenyl, C₁ to C₉ alkoxy, C₁ to C₉ alkylamino, N,N-di(C₁ to C₆ alkyDamino, C₁ to C₉ alkanoyl and (C₁ to C₉ alkoxy)carbonyl; C₁ to C₁₈ alkanoyl; and C₂ to C₉ alkanoyl substituted with phenyl;

R² is selected from hydrogen and C₁ to C₆ alkyl; and wherein R² may link together with R¹ to form a bridging group of formula -CH₂(R⁷R⁸OCH₂- wherein R⁷ and R⁸ are independently selected from hydrogen and C₁ to C₆ alkyl;

R⁴ is C₁ to C₆ alkyl; and n is from 0 to 4, and

R⁵ and R⁶ are independently selected from hydrogen; the group of formula III

I^II

R¹⁰ and R¹¹ are independently selected from C₁ to C₄ alkyl and hydrogen; and R¹² is selected from hydrogen and C₁ to C₆ alkyl and wherein R⁵ and R⁶ may form a spiro-carbocyclic ring by the bridging group of formula II (a)

II (a)

wherein R¹⁰ and R¹¹ are independently selected from hydrogen and C₁ to C₄ alkyl. Preferably wherein one of R⁵ and R⁶ is the group of formula III then the other is hydrogen.

More preferred R¹ compositions of the invention comprise at least one compound of formula I wherein:

R¹ is selected from the group consisting of C₁ to C₁₈ alkyl; C₁ to C₁₈ alkenyl; phenyl; and benzyl;

R² is hydrogen or C₁ to C₄ alkyl; and wherein R¹ and

R² may form a carbocyclic ring by the bridging group of formula

-CH₂(CR⁷R⁸)CH₂-

wherein R⁷ and R⁸ are independently selected from hydrogen and C₁ to C₄ alkyl;

R³ is selected from C₂ to C₁₈ alkyl; C₁ to C₉ alkyl substituted with a substituent selected from the group consisting of hydroxy and C₁ to C₉ alkoxy; C₁ to C₁₈ alkenyl; benzoyl; benzyl; benzoyl substituted with a substituent selected from C₁ to C₆ alkyl and C₁ to C₆ alkoxy; and C₁ to C₉ alkanoyl; R⁴ is C₁ to C₄ alkyl n is from 0 to 3

R⁵ and R⁶ are selected such that they comply with one of the possibilities selected from the group consisting of (i) R⁵ and R⁶ are independently selected from hydrogen and C₁ to C₄ alkyl; (ii) one of R⁵ and R⁶ is hydrogen and the other is a group of formula III

III

wherein R¹⁰, R¹¹ and R¹² are independently selected from the group consisting of hydrogen and C₁ to C₄ alkyl; and (iii) the group wherein R⁵ and R⁶ form a spiro carbocyclic ring by the group of formula Ila

( II a

wherein R¹⁰ and R¹¹ are independently selected from the group consisting of hydrogen and C₁ to C₄ alkyl. In a particularly preferred group of compositions of the invention the compound of formula I is selected such that

R¹ is selected from the group consisting of C₁ to

C₁₈ alkyl; C₁ to C₁₈ alkenyl; phenyl; and benzyl;

R² is hydrogen or C₁ to C₄ alkyl; and wherein R¹ and R² may form a carbocyclic ring by the bridging group of formula

-CH₂(CR⁷R⁸)CH₂- wherein R⁷ and R⁸ are independently selected from hydrogen and C₁ to C₄ alkyl;

R³ is selected from C₁ to C₁₈ alkyl;

C₂ to C₁₈ alkenyl; benzoyl; benzyl; benzoyl substituted with a substituent selected from C₁ to C₆ alkyl and C₁ to C₆ alkoxy; and C₃ to C₉ alkanoyl;

R is C₁ to C₄ alkyl; n is from 0 to 3; and

R⁵ and R⁶ are independently selected from hydrogen and C₁ to C₄ alkyl.

Many of the compounds for use in preparing of compositions of the inventions are novel compounds .

According to a further embodiment of the invention there is therefore provided a compound of formula I

wherein:

R¹ is selected from the group consisting of: C₁ to C₁₈ alkyl; C₁ to C₉ alkyl substituted with a substituent selected from the group of hydroxy, amino, C₁ to C₉ alkoxy, C₂ to C₉ alkenyloxy, C₁ to C₉ alkanoyl, (C₁ to C₉ alkoxy)carbonyl, carbamoyl, (C₁ to C₆ alkyl)carbamoyl and phenyl; C₂ to C₁₈ alkenyl; C₂ to C₉ alkenyl substituted with a substituent selected from the group consisting of hydroxy, amino, C₁ to C₉ alkoxy, C₂ to C₉ alkenyloxy, C₁ to C₉ alkanoyl, carbamoyl, (C₁ to C₉ alkyl)carbamoyl, and phenyl; C₂ to C₁₈ alkynyl; phenyl; the groups phenyl and benzyl said groups being substituted in the benzene ring with a substituent is selected from the group of C₁ to C₁₂ alkyl, C₁ to C₁₂ alkoxy, C₁ to C₁₂ alkenyloxy, C₁ to C₁₂ alkylamino, N,N-di(C₁ to C₆ alkyl)amino, (C₁ to C₁₂ alkoxy)carbonyl and C₁ to C₁₂ alkanoyl; C₅ to C₇ cycloalkyl; C₅ to C₇ cycloalkenyl; the groups substituted C₅ to C₇ cycloalkyl and substituted C₅ to C₇ cycloalkenyl wherein the substituent is selected from the group of hydroxy, amino, C₁ to C₉ alkyl, C₁ to C₉ alkoxy, and C₁ to C₉ alkenyloxy; polymers of one or more of the monomers selected from ethylene glycol, propylene glycol, styrene and C₂ to C₄ alkenes, and derivatives of said polymers; and wherein R¹ may optionally link together with R2 to form a carbocyclic ring by the bridging group of formula -(R⁷R⁸C)m- wherein m is 2 or 3 and R⁷ (which may be the same or different) and R⁸ (which may be the same or different) are independently selected from the group of hydrogen and C₁ to C₆ alkyl; R³ is selected from the group consisting of: C₂ to C₁₈ alkyl; C₁ to C₉ alkyl substituted with a substituent selected from the group of amino, C₁ to C₉ alkoxy, C₂ to C₉ alkenyloxy, C₁ to C₉ alkanoyl, (C₁ to C₉ alkoxy)carbonyl, carbamoyl, (C₁ to C₆ alkyl)carbamoyl and phenyl; C₂ to C₁₈ alkenyl; C₂ to C₉ alkenyl substituted with a substituent selected from the group consisting of hydroxy, amino C₁ to C₉ alkoxy, C₂ to C₉ alkenyloxy, C₁ to C₉ alkanoyl, (C₁ to C₉ alkoxy)carbonyl, carbamoyl, (C₁ to C₉ alkyl) carbamoyl and phenyl; C₂ to C₁₈ alkynyl; phenyl; benzoyl; the groups phenyl, benzyl and benzoyl said groups being substituted in the benzene ring with a substituent selected from the group of hydroxy, amino, C₁ to C₁₂ alkyl, C₂ to C₁₂ alkenyl, C₁ to C₁₂ alkoxy, C₂ to C₁₂ alkenyloxy, C₁ to C₁₂ alkylamino, N,N-di-(C₁ to C₆ alkyl)amino, (C₁ to C₁₂ alkoxy)carbonyl, and C₁ to C₁₂ alkanoyl; C₅ to C₇ cycloalkyl; C₅ to C₇ cycloalkenyl; the groups substituted C₅ to C₇ cycloalkyl and substituted C₅ to C₇ cycloalkenyl wherein the substituent is selected from the group of hydroxy, amino, C₁ to C₉ alkyl, C₁ to C₉ alkoxy, and C₁ to C₉ alkenyloxy; C₁ to C₁₈ alkanoyl; C₁ to C₉ alkanoyl substituted with a substituent selected from the group of hydroxy, amino, C₁ to C₉ alkoxy and C₂ to C₉ alkenyloxy, C₁ to C₉ alkanoyl; carbomoyl, C₁ to C₆ alkyl)carbamoyl, (C₁ to C₉ alkoxy)carbonyl and phenyl; polymers of one or more monomers selected from ethylene glycol, propylene glycol, styrene and C₂ to C₄ alkenes, and derivatives of said polymers; and the group -OROROR⁹ wherein R (which may be the same or different) is a bivalent hydrocarbon radical of 2 to 6 (more preferably 2 to 4) carbon atoms and R⁹ is a hydrocarbon radical selected from C₁ to C₆ alkyl, C₂ to C₆ alkenyl, phenyl, benzyl, (C₁ to C₆ alkyl) phenyl and (C₁ to C₆ alkyl)benzyl (more preferably R⁹ is selected from C₁ to C₄ alkyl and C₂ to C₄ alkenyl); R² is selected from the group consisting of hydrogen, C₁ to C₆ alkyl, and the group wherein R¹ and R² together form a bridging group of formula

-(CR⁷R⁸)_m- wherein R⁷, R⁸ and m are as hereinbefore defined;

R⁴ is selected from the group consisting of C₁ to C₆ alkyl and C₁ to C₆ alkoxy; n is an integer selected from 0 to 4 inclusive; and R⁵ and R⁶ which may be the same or different are selected from hydrogen, C₁ to C₆ alkyl, C₁ to C₆ alkoxy C₁ to C₁₀ alkanoyl, C₁ to C₁₀ alkanoyl substituted by carboxyl or (C₁ to C₆ alkoxy)carbonyl and wherein R⁷ and R⁸ may form a spiro-carbocylic ring by the bridging group of formula II

(CR¹⁰ R¹¹) II

wherein q is 2 or 3 and R¹⁰ and R¹¹ may be the same or different at each carbon unit of the bridge and are independently selected from hydrogen and C₁ to

C₈ alkyl; with the proviso that when R¹ is methyl R³ is not selected from the group of benzyl, hydroxyethyl and methoxymethyl.

Where reference is made herein to a group comprising an alkyl, alkenyl or alkynyl moiety it will be understood that said moiety may be a straight or branched chain moiety, for example, the group C₁ to C₁₈ alkyl includes straight and branched chain alkyl of 1 to 18 carbon atoms and the group C₁ to C₉ alkoxy includes groups wherein the alkyl portion of the alkoxy group is straight or branched chain of from 1 to 9 carbon atoms. In compounds of formula I, as hereinbefore described the substituents R¹ and/or R³ may be a polymer of one or more of the monomers selected from ethylene glycol, propylene glycol and C₂ to C₄ alkenes and derivatives thereof. Examples of the derivatives may include derivatives comprising at least one group of formula XI (a) or XI (b)

wherein R¹, R², R³, R⁴, R⁵, R⁶ and n are as hereinbefore defined. When the polymer is a polymer of ethylene glycol or propylene glycol examples of derivatives thereof may include ethers formed by a bond of the terminal oxygen with a radical selected from the group of C₁ to C₆ alkyl, phenyl, benzyl, and the groups phenyl and benzyl substituted in the benzene ring with C₁ to C₉ alkyl. Preferably the polymers contain in the range of from 3 to 18 monomeric units.

Preferably in the compounds of the invention of formula I R¹ is selected from C₁ to C₁₈ alkyl; C₂ to C₉ alkyl substituted with a substituent selected from the group consisting of hydroxy, amino, C₁ to C₉ alkoxy, C₁ to C₉ alkanoyl and (C₁ to C₉ alkoxy)carbonyl; C₁ to C₁₈ alkenyl; cyclohexyl; phenyl; benzyl; the groups phenyl and benzyl said groups being substituted in the benzene ring with a substituent selected from the group of C₁ to C₉ alkyl, C₂ to C₉ alkenyl, C₁ to C₉ alkoxy, C₁ to C₉ alkanoyl and (C₁ to C₉ alkoxy)carbonyl; and wherein R¹ may optionally link together with R² by the a bridging group of formula -CH₂(R⁷R⁸C)CH₂- wherein R⁷ and R are independently selected from hydrogen and C₁ to C₆ alkyl; R³ is selected from C₂ to C₁₈ alkyl; C₁ to C₉ alkyl substituted with a substituent selected from the group consisting of hydroxy, amino, C₁ to C₉ alkoxy and C₁ to C₉ alkanoyl; C₂ to C_1g alkenyl; cyclohexyl; phenyl; benzyl; benzoyl; the groups phenyl, benzyl and benzoyl said groups being substituted in the benzene ring with a substituent selected from the group of C₁ to C₉ alkyl, C₂ to C₉ alkenyl, C₁ to C₉ alkoxy, C₁ to C₉ alkanoyl and (C₁ to C₉ alkoxy)carbonyl; C₃ to C₁₈ alkanoyl; and C₂ to C₁₈ alkanoyl substituted with phenyl; R² is selected from hydrogen and C₁ to C₆ alkyl; and wherein R 2 may link together with R¹ to form a carbocyclic ring by the bridging group of formula -CH₂(R⁷R⁸C)CH₂- wherein R⁷ and R⁸ are independently selected from hydrogen and C₁ to C₆ alkyl;

R⁴ is C₁ to C₆ alkyl; n is from 0 to 4; and

wherein R¹⁰, R¹¹ and R¹² are independently selected fromC₁ to C₄ alkyl and hydrogen; and wherein R⁵ and R⁶ may form a spiro-carbocyclic ring by the bridging group of formula II (a)

II (a)

More preferably in compounds of the invention: R¹ is selected from C₁ to C₁₈ alkyl; C₁ to C₆ alkyl substituted with a substituent selected from C₁ to C₆ alkanoyl and (C₁ to C₆ alkoxy)carbonyl; C₁ to C₁₈ alkenyl; phenyl; and benzyl;

R² is selected from hydrogen and C₁ to C₄ alkyl and wherein R¹ and R² may form a carbocyclic ring by the bridging group of formula

-CH₂(R⁷R⁸C)CH₂-

wherein R⁷ and R⁸ are independently selected from hydrogen and C₁ to C₄ alkyl. R³ is selected from C₂ to C₁₈ alkyl; C₁ to C₉ alkyl substituted with a substituent selected from the group consisting of hydroxy and C₁ to C₉ alkoxy; C₁ to C₁₈ alkenyl; benzoyl; benzyl; benzoyl substituted with a substituent selected from C₁ to C₆ alkyl and C₁ to C₆ alkoxy; and C₃ to C₉ alkanoyl; R⁴ is C₁ to C₄ alkyl; n is from 0 to 3; and

III

wherein R¹⁰, R¹¹ and R¹² are independently selected from hydrogen and C₁ to C₄ alkyl; and (iii) the group wherein R⁵ and R⁶ form a spiro carbocyclic ring by the diradical group of formula Ila

II a

wherein R¹⁰ to R¹¹ are independently selected from hydrogen and C₁ to C₄ alkyl.

Even more preferably compound of the invention are compounds of formula I wherein:

R¹ is C₁ to C₉ alkyl; R² is selected from hydrogen and C₁ to C₄ alkyl; and wherein R¹ and R² may form a carbocyclic ring by the bridging group of formula

-CH₂(CR⁸R⁹)CH₂-

wherein R⁸ and R⁹ are methyl; R³ is selected from C₂ to C₉ alkyl, C₂ to C₉ alkenyl; C₁ to C₉ alkyl substituted with a substituent selected from hydroxy, phenyl and C₁ to C₆ alkoxy; benzoyl; benzoyl substituted with a substituent selected from the group consisting of C₁ to C₆ alkyl and C₁ to C₆ alkoxy, and C₁ to C₉ alkanoyl;

R⁴ is selected from C₁ to C₄ alkyl; n is from 0 to 3;

III -

wherein R¹⁰ and R¹¹ are methyl and R¹² is hydrogen or C₁ to C₄ alkyl; and (iii) the group wherein R⁵ and R⁶ form a spiro carbocyclic ring by the diradical group of formula II a

II a

wherein R¹⁰ and R¹¹ are methyl. Preferably when one of R⁵ and R⁶ is not hydrogen or C₁ to C₄ alkyl then n is zero. In the most preferred compounds of the invention: R¹ is seleted from the group consisting of methyl, ethyl, propyl and 4-methylbutyl; R² is hydrogen or methyl; and wherein R¹ and R² may form a carbocyclic ring by the bridging group of formula:

-CH₂(CR⁷R⁸)CH₂-

wherein R⁷ and R⁸ are methyl;

R³ is selected from the group consisting of:C₁ to C₉ alkyl such as

propyl, butyl, 1-methylethyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, hexyl, 2-ethylhexyl, 1-methylpentyl, 1,1-dimethylbutyl, octyl, 1-methylheptyl and 3-methyl-2-butenyl; 2-phenylethyl; benzoyl, 3-methoxybenzoyl; 4-butylbenzoyl; propanoyl; benzyl;and cyclohexyl;

R⁴ is methyl; n is chosen from 0 to 3 and is conveniently zero.

R⁵ and R⁶ are selected such that they comply with one of the possibilities selected from the group consisting of (i) R⁵ and R⁶ are independently selected from hydrogen and methyl; (ii) one of R⁵ and R⁶ is hydrogen and the other is a group of formula III

III

wherein R¹⁰ and R¹¹ are methyl and R₁₂ is ethyl; and (iii) the group wherein R⁵ and R⁶ form a spiro carbocyclic ring by the diradical group of formula IIa. II a

wherein R¹⁰ and R¹¹ are methyl.

One group of compounds of the invention which may be used in preparation of sunscreen compositions include compounds of formula la

wherein

R³, R⁴,R⁵and R⁶ are as hereinbefore defined in relation to compounds of the invention, R¹³ is C₁ to

C₄ alkyl and y is from 0 to 3.

Preferrred compounds of formula la include compounds of formula I (a) (i)

wherein R³, R⁴, R⁵, R⁶, R⁷, R⁸ and n are as hereinbefore defined.

Included in the more preferred compounds of the invention of formula I

are compounds where R⁵ and R⁶ are independently selected from hydrogen, C₁ to C₆ alkyl and C₁ to C₆ alkoxy, preferably from hydrogen and C₁ to C₆ alkyl; more preferably from hydrogen and C₁ to C₄ alkyl such as methyl; and R¹, R², R³, R⁴ and n are as hereinbefore defined.

For example, such compound include compounds wherein R¹ is selected from the group consisting of methyl, ethyl, propyl, 3-methylbutyl; R² is hydrogen; R³ is selected from the group consisting of propyl,

1-methylethyl, butyl, 3-methylbutyl, 2-ethylhexyl and 3-mehtyl-2-butenyl; n is 0; and R⁵ and R⁶ are hydrogen.

The compounds of formula 1(a) (i) include such compounds wherein R⁵ and R⁶ are hydrogen and R³ is as hereinbefore defined and n is 0, that is the compounds of formula 1(a) (ii)

wherein R⁷ and R⁸ are as hereinbefore defined.

When in the compounds of formula I (a) R⁵ and R⁶ comprise the groups of formula III or formula Ila it is preferred that R⁷ is identical with the group R¹⁰ and R⁵ is identical with the group R¹¹. Specific examples of compounds embraced by the invention include.

The compounds of formula I may be prepared by a variety of methods and in a further aspect of the invention there is provided methods for the preparation of compounds of the invention of formula I.

The compounds may generally be derived via a suitable tetrahydropyridine compound of formula IV or via a pyridine derivative of formula V (wherein A are independently selected from hydrogen and R⁴).

IV

The preparation of the compound of formula I from the pyridine derivative of formula V may be carried out by reduction of the compound of formula V for example using hydrogen in the presence of a catalyst (such as palladivim on charcoal catalyst) to give a compound of the invention of formula I(c).

1(c)

The pyridine derivative of formula V may be prepared from the compound of formula VII (wherein A

4 are independently selected from hydrogen and R ) reaction thereof with the compound of formula VI

(wherein L is a leaving group).

_³ L

VI

VII

The preparation of a compound of formula I from the compound of formula IV may be carried out by reacting the compound of formula IV, preferably in the presence of a base, with a compound of formula VI wherein L is a leaving group.

The compound of formula IV having the specific formula IVa may be prepared by reduction of the pyridine of formula VII, for example using hydrogen in the presence of a catalyst such as palladium on charcoal.

Alternatively the compound of formula IV (having the specific formula IVb) may be prepared by chemical reduction of the compound of formula VIII

wherein A which may be the same or different is chosen from hydrogen or R⁴ as hereinbefore defined.

N=C-(CR⁵R⁶)CA₂

VIII

(A is independently selected from hydrogen and R⁴). In compound of formula VI the leaving group

(L) may be chosen by those skilled in the art.

Examples of leaving groups include chloride, bromide, iodide, sulfate, nitrate, methylsulfate, ethylsulfate, tetrafluoroborate, hexafluorophosphate, hexafluoro- antiminate, methanesulfonate, fluorosulfonate, fluoromethanesulfonate and trifluoromethanesulfonate.

An alternative method of preparation of the compound of formula IV may involve reaction of the compound of formula XII with a compound of formula XIII in the presence of a base such as an amine to give the compound of formula XIV and hydrogenation of the compound of formula XIV to give the compound of formula IV(c) which may be converted as herein before described to a compound of the invention of formula I having the specific formula Kb). A preferred example of this alternative method is the reaction of the compound of Xlll with mesityl oxide to give the compound of formula IV which has the formula XV which may be utilised in providing compounds of formula I having & 4, 4, 6-trimethyl substitution in the tetrahydro pyridine ring, for example, the compound methyl 1-butyl-4,4,6-trimethyl-1, 4,5, 6-tetrahydro-3-pyridyl ketone.

(A is independently selected from hydrogen and R⁴) A similar scheme may be used for more direct preparation of the compound of formula I by reaction of the compound of formula XII with a compound of formula XVI followed by hydrogenation of the intermediate of formula XVII to give a compound of the invention of formula Kb).

XVI XVII

There is further provided a process for preparation of a compound of formula I (a) (iii)

I (a)(iii)

wherein R⁵ and R⁶ together from the spiro carbocyclic ring by the diradical group of formula II a

II a

or one of R⁵ and R⁶ is hydrogen and the other is the group of formula III

IX I 1^{0 11} R¹²

and R³, R¹⁰, R¹¹ and R¹² are as hereinbefore defined; which process comprises reacting a compound of formula IX with formaldehyde

IX

in presence of an acid to give a compound of the invention of formula I (a) (iii) wherein R⁵ and R⁶ from said spiro carbocyclic ring of formula IIa; and optionally reacting the spiro carbocyclic moiety with a base of formula X.

12

X

, wherein Mis an alkali metal cation, to provide a compound of the invention of formula I (a) (iii).

TABLE 1b (Cont 'd)

b.

c. -C-CH₂C(CH₃)₂ CH₂CO₂C₂H₅

In a further embodiment of the invention, there is provided a method of screening a surface from ultra-violet radiation, the method comprising applying to the surface a composition comprising a compound of formula I as hereinbefore described. The compositions of the present invention are particularly useful for protection of human skin against harmful effects of sunlight. Human skin is well known to be sensitive to sunlight containing radiation of wavelengths between about 270 nm and 400 nm.

The OV-B region of ultra violet radiation (290-320 nm) has long been known to cause damage to skin but more recently concern has been expressed over the effect of UV-A radiation (above 320 nm).

Compositions of the present invention may be prepared comprising one or more compounds of formula I and may provide screening in the UV-A region, the UV-B region or in both of these regions. Consequently, in one embodiment of the invention there is provided a method of protecting skin from ultra-violet radiation, the method comprising applying to the surface of the skin a composition as hereinbefore described. A specific example of a sunscreen formulation which may be used in preparation of compositions of the present invention includes the following Sunscreen lotion composition % w/w

Methyl para-hydroxy benzoate 0.25

Propyl para-hydroxy benzoate 0.10

Cetyl/Stearyl 2-Ethylhexonoate 2.00 "CARBOMER" 491 thickener (cross linked acrylic 0.45 acid polymer)

Phenyl trimethicone 1.00

Stearic Acid 3.00

Sodium Hydroxide 0.15 Phenoxyethanol 0.30

Isopropyl Isostearate 5.00 Antioxidant (BHA, BHT, ascorbates, tocopherols)0.08

Glyceryl Monostearate & PEG 100 Stearate 1.00

Fragrance 0.10 Sunscreen Compound 6.00

Disodium EDTA 0.05

Treated water 80.52

("CARBOMER" is a trade mark)

The invention is now illustrated by, but in o way limited to, the following examples.

Example 1

Methyl 1-(1-methylethyl)-1,4,5.6-tetrahydro-3- pyridyl ketone (1)

a) 3-acetyl-1,4,5,6-tetrahydropyridine was prepared by hydrogenation of 3-acetyl pyridine in the presence of palladium on carbon according to the method of Freifelder, J.Org.Chem. 29, 2895 (1964).

b) 3-acetyl-1,4,5,6-tetrahydropyridine (20.0 g, 0.16 mole) was added under nitrogen to a mixture of sodium hydride (5.75 g, 0.24 mole) and dry dimethylformamide (50 ml) stirring at 0°C and stirring was continued for 15 minutes. 2-Bromopropane (21.5 g, 0.175 mole) was then added dropwise over 15 min, stirring continued for a further hour at 0°C then overnight at room temperature. The reaction mixture was cautiously added to iced water (100 g) under nitrogen and extracted with diethyl ether (3 x 100 ml). The combined organic phase was extracted with water (150 ml), dried over magnesium sulphate, concentrated under reduced pressure to give methyl 1-(1-methylethyl)- 1,4,5,6-tetrahydro-3-pyridyl ketone (1). The product was distilled as a pale yellow oil (b.pt 97-98°C/0.5 mm Hg). Example 2

Methyl 1-propyl-1 , 4 , 5 , 6-tetrahydro-3-Pyridyl ketone (2)

a) Methyl 1-propyl-1 ,4 ,5, 6-tetrahydro-3-pyridyl ketone was prepared from 3-acetyl-1 , 4 , 5 , 6- tetrahydropyridine and 1-bromopropane according to the procedure of Part b) of Example 1. The product distilled as a pale yellow (b.pt98-100°C/0.5 mm Hg) .

Example 3

Methyl 1-(3-methylbutyl)-1,4,5,6-tetrahydro-3- pyridyl ketone (3)

Methyl 1-(3-methylbutyl)-1,4,5,6-tetrahydro-3- pyridyl ketone was prepared from 3-acetyl-414,5,6- tetrahydropyridine and 1-bromo-3-methylbutane according to the procedure of Part b) of Example 1. The product distilled as a pale yellow oil (b.pt. 103-106°C/0.1 mm Hg).

Example 4

Methyl 1-(3-methyl-2-butenyl)-1,4,5,6-tetrahydro-3- pyridyl ketone (4)

a) A mixture of 3-acetylpyridine (12.1 g, 0.1 mole) and 1-bromo-3-methyl-2-butene (22.3 g, 0.15 mole) was stirred at room temperature under nitrogen overnight. The mixture was diluted with diethyl ether (25 ml) and the cream coloured crystalline solid, 1-(3-methyl-2-butenyl)-3-acetyl pyridinium bromide, was filtered off under nitrogen. b) 1-(3-methyl-2-butenyl)-3-acetyl-pyridinium bromide (27.0 g, 0.1 mole) and triethylamine (10.1 g, 0.1 mole) in ethyl alcohol (50 ml) over 5% palladium on carbon (5 g) was hydrogenated at room temperature and pressure until two molar equivalents of hydrogen was taken up. The catalyst was removed by f iltration and the filtrate concentrated at reduced pressure. The semi-solid residue was diluted with diethyl ether (75 ml) , the solid removed by filtration and the filtrate concentrated under reduced pressure to leave a pale oil which solidified on standing. Recrystallisation from ethanol/water gave the product, methyl 1-( 3-methylbutenyl)-1,4,5,6- tetrahydro-3-pyridyl ketone (4) as a pale yellow crystalline solid m.p. 76-78°C.

Example 5

Methyl 1-(2-ethylhexyl)-1,4,5,6-tetrahydro-3-pyridyl ketone (5)

a) 3-acetyl-1,4,5,6-tetrahydropyridine (20.0 g, 0.16 mole) was added under nitrogen to a mixture of sodium hydride (5.76 g, 0.24 mole) and dry tetrahydrofuran (50 ml) stirring at room temperature. After one hour, l-bromo-2-ethyl hexane (33.8 g, 0.175 mole) was added dropwise over 15 minutes and the mixture stirred overnight at room temperature. The reaction mixture was cautiously added to iced water (100 g) under nitrogen and extracted with diethyl ether (3 x 100 ml). The combined organic phase was dried over magnesium sulphate, concentrated under reduced pressure and the residue distilled to give methyl 1- ( 2-ethylhexyl ) - 1, 4, 5, 6- tetrahydro-3-pyridyl ketone (5 ) as a pale yellow oil (b.pt 140-142°C/0. 1 mm Hg) .

Example 6

Methyl 1-(2-phenylethyl)-1,4,5,6,-tetrahydro-3- pyridyl ketone (6)

a) A mixture of 3-acetyl pyridine (12.1 g, 0.1 mole) and (2-bromoethyl)benzene (37.0 g, 0.2 mole) was heated at 100°C under nitrogen for four hours. After cooling, the mixture was diluted with diethyl ether (25 ml) and the pale brown crystalline solid, 1-(2-phenyl ethyl)-3-acetyl-pyridinium bromide, was filtered off under nitrogen.

b) A solution of 1-(2-phenylethyl)-3-acetyl- pyridinium bromide (30.6 g, 0.1 mole) and triethylamine (10.1 g, 0.1 mole) in ethyl alcohol (50 mole) over 5% palladium on carbon (5 g) was hydrogenated at room temperature and pressure. Upon cessation of hydrogen uptake, the catalyst was filtered and the filtrate concentrated at reduced pressure. The semi-solid filtered and the filtrate concentrated under reduced pressure to leave a pale brown oil, methyl 1-(2-phenyl ethyl)-1,4,5,6-tetrahydro-3-pyridyl ketone (6). Example 7

Methyl 1-benzoyl-l,4,5,6-tetrahydro-3-pyridyl ketone (7)

a) Methyl 1-benzoyl-1,4,5,6-tetrahydro-3-pyridyl ketone was prepared from 3-acetyl-1,4,5,6- tetrahydropyridine and benzoyl chloride according to the procedure of Part b) of Example 1. The product was recrystallised from ethanol/water m.pt. 93-95°C.

Example 8 and Example 9

Methyl 1-(3-methylbutyl)-2-methyl-1,4,5,6-tetrahydro -3-pyridyl ketone (9)

Example 8

a) 4,4-Diacetylbutyronitrile was prepared by addition of acrylonitrile to the sodium salt of acetyl acetone according to the procedure of Johnson et al, J.Chem.Soc (C), 1969, 176.

b) A solution of 4,4-diacetylbutyronitrile (15.3g, 0.1 mole) in ethyl alcohol (50 ml) over Raney nickel (2g) was hydrogenated at room temperature and three atmospheres pressure. After hydrogen uptake had ceased, the catalyst was filtered off and the filtrate concentrated under reduced pressure to give 3-acetyl-2-methyl-1,4,5,6-tetrahydro- pyridine. Example 9

Methyl

1-(3-methylbutyl)-2-methyl-1,4,5,6-tetrahydro-3-pyr- idyl ketone was prepared from 3-acetyl-2-methyl, 1,4,5,6-tetrahydro- pyridine and 1-bromo-3- methylbutene according to the procedure of Part b) of Example 1.

Example 10

Ethyl 1-butyl-l,4,5,6-tetrahydro-3-pyridyl ketone (10)

a) A mixture of ethyl nicotinate (15.1g, 0.1 mole), ethyl propionate (15.3g, 0.15 mole) and sodium ethoxide (10.2g, 0.15 mole) was stirred and heated under nitrogen at 100°C for five hours. After cooling, the mixture was diluted with water (150 ml) extracted with diethyl ether (50 ml) and the aqueous layer made acidic to pH 1 with concentrated hydrochloric acid (50 ml). The aqueous layer was heated at 90°C for two hours, cooled, made alkaline with solid potassium carbonate and extracted with diethyl ether (3 x 75 ml). The dried (magnesium sulphate) organic layer was concentrated and distilled to give ethyl 3-pyridyl ketone (b.pt 97-99°/14mm Hg).

b) Ethyl 3-pyridyl ketone was reacted with 1- bromobutane according to the procedure of Para a) of Example 6 to give 1-butyl(3- pyridinium bromide as a tan coloured crystalline solid. c) 1-Butyl-3-propionyl pyridinium bromide was hydrogenated according to the procedure described in Para, b) at Example B to -give ethyl 1-butyl-1,4,5,6-tetrahydro-3-pyridyl ketone (10). The product was distilled as a pale yellow oil (b.pt. 108-109°C/0.1 mm Hg).

Example 11

Ethyl 1-(3-methylbutyl)-1,4,5,6-tetrahydro-3-pyridyl ketone (11)

a) Ethyl 3-pyridyl ketone was reacted with 1-bromo-3-methylbutane according to the procedure of Parb a) of Example 6 to give 1-(3-methylbutyl)-3-propionyl pyridinium bromide as a pale brown crystalline solid.

b) 1-(3-Methylbutyl)-3-propionyl pyridium bromide was hydrogenated according to the procedure of Parb b) of Example 6 to give ethyl 1-(-3-methylbutyl-1,4,5,6-tetrahydro- 3-pyridyl ketone. The product was distilled as a pale yellow oil (b.pt. 111-112°C/0.02 mm Hg). Example 12

Propyl 1-propyl-1,4,5,6-tetrahydro-3-pyridyl ketone (12)

a) A mixture of ethyl nicotinate (15.1g, 0.1 mole), ethyl butyrate (17.4g, 0.15 mole) and sodium ethoxide (10.2g, 0.15 mole) was stirred and heated under nitrogen at 100°C for five hours. After cooling, the mixture was diluted with water (150 ml), extracted with diethyl ether (50 ml) and the aqueous layer made acidic to pHl with concentrated hydrochloric acid (50 ml). The aqueous layer was heated at 90°C for 2 hours, cooled, and made alkaline with solid potassium carbonate and extracted with diethyl ether (3 x 75 ml). The dried (magnesium sulphate) organic layer was concentrated and distilled to give propyl 3-pyridyl ketone (b.pt.H8-120°C/14 mm Hg).

b) Propyl 3-pyridyl ketone was reacted with 1- bromo-2-propene according to the procedure of

Part a) of Example 4 to give 1-(2-propenyl)- 3-butyryl pyridium bromide as a cream coloured crystalline solid.

c) 1-(2-Propenyl)-3-butyryl pyridinium bromide was hydrogenated according to the procedure described in Part b) of Example 6 to give propyl 1-propyl-1,4,5,6-tetrahydro-3-pyridyl ketone. The product was distilled as a pale yellow oil (b.pt 150-153ºC/0.3 mm Hg) Example 13

Propyl 1-butyl-1,4,5,6-tetrahydro-3-pyridyl ketone (13)

a) Propyl 3-pyridyl ketone was reacted with 1- bromobutane according to the procedure of

Part a) of Example 6 to give 1-butyl-3- butyryl pyridinium bromide as a tan coloured crystalline solid.

b) 1-Butyl-3-butyryl pyridinium bromide was hydrogenated according to the procedure described in Part b) of Example 6 to give propyl 1-butyl-1-4,5,6-tetrahydro-3-pyridyl ketone (13). The product was distilled as a pale yellow oil (b.pt. 120-124°C/0.02 mm Hg).

Example 14

Propyl 1-(3-methylbutyl)-1,4,5,6-tetrahydro-3- pyridyl ketone(14)

a) Propyl 3-pyridyl ketone was reacted with 1-chloro-3-methyl-2-butene according to the procedure of Part a) of Example 4 to give

1-(3-methyl-2-butenyl)-3-butyryl pyridinium chloride as a cream coloured crystalline solid.

b) 1-(3-Methyl-2-butenyl)-3-butyryl pyridinium chloride was hydrogenated according to the procedure described in Part b) of Example 6 to give propyl 1-(3-methylbutyl)-1,4,5, 6- tetrahydro-3-pyridyl ketone (14). The product was distilled as a pale yellow oil (b.pt. 126-129°C/0.02 mm Hg) .

Example 15

4-Methylpentanyl 1-propyl-1,4,5,6-tetrahydro-3- pyridyl ketone(15)

a) A solution of 3-cyanopyridine (26.0g, 0.25 mole) in dry diethyl ether (200 ml) was added dropwise over the hour to the Grignard reagent prepared from 1-bromo-3-methyl butane (40.7 g, 0.27 mole) and magensium (6.8g, 0.26 mole) in dry diethyl ether (50 ml) under nitrogen. The mixture was heated at 35°C for eight hours, cooled to room temperature, and diluted with cold saturated aqueous ammonium chloride solution(200 ml) followed by concentrated hydrochloric acid (50 ml). The mixture was stirred for five hours, the ether layer separated, and the aqeuous layer boiled for two hours. The aqueous layer was neutralised to pH9 with aqueous sodium hydroxide solution and extracted with diethyl ether (3 x 100 ml). The organic phase was dried (magnesium sulphate), concentrated under reduced pressure and distilled to give 3-methylbutyl 3-pyridyl ketone.

b) 3-Methylbutyl 3-pyridyl ketone was reacted with 1-bromo-2-propene according to the procedure of Part a) of Example 4 to give 1-(2-propenyl)-3-(4-methyl)valeryl pyridinium bromide as a tan coloured crystalline solid. c) 1-(2-Propenyl)-3-(4-methyl)valeryl pyridinium bromide was hydr ogenated according to the procedure of Part b) of Example 6 to give 4- methylpentanyl 1-propyl-1,4,5,6-tetrahydro- 3-pyridyl ketone (15) as a yellow oil.

Example 16

Phenyl 1-propyl-1,4,5,6-tetrahydro-3-pyridyl ketone (16)

a) 3-Benzoyl pyridine was reacted with 1-bromo-2-propene according to the procedure of Part a) of Example 4 to give 1-(2-propenyl)-3-benzeyl pyridinium bromide as a tan coloured crystalline solid.

b) 1-(2-Propenyl)-3-benzoyl pyridinium bromide was hydrogenated according to the procedure of Part b) of Example 6 to give phenyl 1- propyl-1,4,5,6-tetrahydro-3-pyridyl ketone (10) as a yellow oil.

Example 17

7,7-Dimethyl-1,2,3,4,7,8-hexahydro-1-propyl-quinolin -5(6H)-one(17)

a) 7,7-Dimethyl-1,2,3,4,7,8-hexahydro-quinolin-5 (6H)-one [prepared by the method of Grob and Kiefer, Helv. Chim Acta., 48 799, (1964)] was reacted with 1-bromopropane according to the procedure of Part (b) of Example 1 to give 7,7-dimethyl-1,2,3,4,7, 8-hexahydro- 1-propyl-quinolin-5(6H)-one (17) as an oil. Example 18

7,7-Dimethyl-1,2,3,4,7,8-hexahydro-1-(3-methylbutyl) -quinoline-5(6H)-one(18)

a ) 7,7-Dimethyl-1,2,3,4,7,8-hexahydro-quinolin- 5(6H)-one was reacted with 1-bromo-3-methyl- butane according to the procedures of Part b) of Example 1 to give 7,7-dimethyl-1,2,3,4,7, 8-hexahydro-1-(3-methylbutyl)-quinolin-5(6H)- one (18) as a pale yellow oil.

Example 19

7-7-Dimethyl-1,2,3,4,7,8-hexahydro-1-benzoyl- quinolln-5(6H)-one(19)

a) 7,7 Dimethyl-1,2,3,4,7,8-hexahydro-quinolin- 5(6H)-one was reacted with benzoyl chloride according to the procedure of Part b) of

Example 1 to give 7,7-dimethyl-1,2,3,4,7,8- hexahydro-1-benzoyl-quinolin-5(6H)-one(19) as a yellow solid.

Example 20 7,7-Dimethyl-1,2,3,4,7,8-hexahydro-1-(3-methoxybenzoyl)-quinolin-5(6H)-one(20)

a) 7,7-Dimethyl-1,2,3,4,7,8-hexahydro-quinolin- 5(6H)-one was reacted with 3-methoxybenzoyl chloride according to the procedure of Part b) of Example 1 to give 7,7-dimethyl-l,2,3,4, 7,8-hexahydro-1-(3-methoxybenzoyl)-quinolin- 5(6H)-one (20) as a pale yellow solid. Example 21

7,7-Dimethyl-1,2.3,4,7,8-hexahydro-1-(4-methoxybenzoyl)-quinoline-5(6H)-one(21)

a) 7,7-Dimethyl-1,2,3,4,7,8-hexahydro-quinoline- 5(6H)-one was reacted with 4-methoxybenzoyl chloride according to the procedure of Part b) of Example 1 to give 7,7-dimethyl-1,2,3,4, 7,8-hexahydro-1-(4-methoxybenzoyl)-quinoline- 5(6H)-one(21) as a yellow waxy solid.

Example 22

7,7-Dimethyl-1,2,3,4.7,8-hexahydro-1-(4-butyl- benzoyl)-quinolin-5(6H)-one(22)

a) 7,7-Dimethyl-1,2,3,4,7,8-hexahydro-quinoline -5(6H)-one was reacted with 4-butylbenzoyl chloride according to the procedure of Part b) of Example 1 to give 7,7-dimethyl-1,2,3,4, 7,8-hexahydro-1-(4-butylbenzoyl)-quinoline- 5(6H)-one(22) as a yellow solid.

Example 23

Preparation of 1,2,3,4,7,8 -hexahydro-1-hexyl-4', 4', 7, 7-tetramethylquinoline-3-spirocyclohexane -2', 5(6H)_ c'-trione (23)

a) A solution of 5,5-dimethyl-3-hexylamino cyclohex-2-enone (26.76 g;0.12 mole), aqueous formaldehyde (37%w/w; 9ml) and 2N hydrochloric acid (40 ml) was stirred at room temperature for 24h. The reaction was chilled on ice and made basic with 4N NH.OH. The resulting solid was collected by filtration, washed with water (3 x 100 ml) and dried in vacuo to give 19.2g (85.3%) of 1,2,3,4,7,8-hexahydro-1-hexyl-4',4',7,7- tetramethylquinoline-3-spirocyclohexane-2', 5(6H),6'-trione, m.p. 111.1 - 113.0°C.

max 314.0 mm ( = 27750)

Example 24

The reaction solution of Example 23 consisting of 5,5-dimethyl-3-hexylaminocyclohex-2-enone (26.76g; 0.12 mole), aqueous formaldehyde (37% w/w; 9 ml) and 2N hydrochloric acid (40 ml) was refluxed for 5 h. The reaction mixture was chilled on ice, made basic with 2N NH.OH, extracted into chloroform (3 x 100 ml) and dried over MgSO₄. Evaporation of the chloroform and crystallisation of the residue from benzene/light petroleum gave 20.6g (91.6%) of 1,2,3,4,7,8-hexahydro-1- hexyl-4',4',7,7- tetramethylquinoline-3- spirocyclohexane-2', 5(6H),6'-trione, m.p. 111.1 - 113.0°C. Example 24

PMR (300 MHz;CDCl₃

- ^{( )} 1 " 6_"

Example 25 -35

Preparation of 1 -substituted-1,2,3,4,7 ,8-hexahydro-

4',4',7,7-tetramethylguinoline-3-spirocyclohexane-

2',5(6H),5 '-trione derivatives

The compound derivatives provided in Example 25 - 35 of the invention were prepared by the general method described in Example 23 or Example 24 and are listed in Table I where the R³ group is defined as the 1-substituent. TABLE 1

1-substituted (R³)-1,2,3,4,7,8-hexahvdro-4' ,4',7,7- tetramethylguinoline-3-spirocyclohexane-2',5(6h),6'- trione derivatives

boiling point (ºC/Torr). Example 36

Preparation of ethyl 3,3-dimethyl-5-(1,2,3,4,5,6,7, 8-octahydro-1-cyclohexyl-7,7-dimethylguinolin-3-yl -5-oxopentanoate(36)

The compound of Example 36 was prepared by a reverse Dieckmann reaction by the general equation (R³ = cyclohexyl):

1,2,3,4,7,8-Hexahydro-1-cyclohexyl-4'4 ,7,7- tetramethylquinoline-3-spirocyclohexane-2', 5(6H) 6'-trione (Example 25;6.6g; 0.0175 mole) was added to ethanolic sodium hydroxide [from sodium(0.9g)]and ethanol (80 ml)]. The mixture was refluxed for 2h and the ethanol evaporated in vacuo. The residue was treated with ice-cold water (100 ml) and the product extracted into chloroform (3 x 50 ml). The chloroform layer was dried over MgSO₄ and evaporated to give the crude ester (3.9g; 54.0% as a pale yellow solid. The product was recrystalised from n-hexane/benzene to give pure ethyl 3,3-dimethyl-5- (1,2,3,4,5,6,7,8-octahydro-1-cyclohexyl-7,7- dimethylquinoline-3-yl)-5-oxopentanoate, m.p. 44-46ºC. max 318.6 mm, = 25,900 Example 37

The compounds of Examples 1 to 24 inclusive were characterised by, and can be identified by their 'H nuclear magnetic resonance spectra. The 'H nuclear magnetic resonance spectra for the compounds of Examples 1 to 23 are recorded in Table 2 below Table 2. UV s ectra 'H N.M.R.

Example 38

1-[1-3-methylbutyl)-1,4,5,6-tetrahydro-3-pyridyl] pentan-2,5-dione (38)

1-[1-(3-methylbutyl)-1,4,5,6-tetrahydro-3-pyridyl] pentan-2,5-dione can be prepared from 1-(3-pyridyl) pentan-2,5-dione [obtained by the method of Steller and Bchreckenburg Chem.Ber., 1078, 2453 (1974)] according to the procedure of Example 14 parts (a) and (b). Example 39

Sunscreen compositions were prepared using the components shown in table 2.

Part Material % w/w

A Water 69.5

B Polypropylene glycol

Meristyl Ether 20.0

Glyceryl Stearate 5.0

Oleth 10 surfactant 5.0

Effective component 0.5

BHT antioxidant ) 0.02/0.2

Sodium thiosulphate )

Separate emulsion formulations were prepared using a mixture of parts A and B for each of compounds No. 3, 5, 13 and 18 as the effective component and the pH was adjusted to 7 by dropwise addition of 1 M NaOH.

Further compositions were prepared using a mixture of part A, B and C for each of compounds 3, 5, 13 and 18 as the effective component.

Claims

1. A sunscreen composition comprising as an effective component thereof at least one compound of formula I.

whereins R⁵ is selected from the group consisting of. C₁ to C₁₈ alkyl; C₁ to C₉ alkyl substituted with a substituent selected from the group consisting of hydroxy, amino, C₁ to C₉ alkoxy, C₂ to C₉ alkenyloxy, C₁ to C₉ alkanoyl, (C₁ to C₉ alkoxy) carbonyl, carbamoyl, (C₁ to C₆ alkyl)carbamoyl and phenyl; C₂ to C₁₈ alkenyl; C₂ to C₉ alkenyl substituted with a substituent selected from the group consisting of hydroxy, amino, C₁ to C₉ alkoxy, C₂ to C₉ alkenyloxy, C₁ to C₉ alkanoyl, carbamoyl, (C₁ to C₆ alkyl)carbamoyl, and phenyl; phenyl; the groups phenyl and benzyl said groups being substituted in the benzene ring with a substituent is selected from the group of C₁ to C₁₂ alkyl, C₁ to C₁₂ alkoxy, C₁ to C₁₂ alkenyloxy, C₁ to C₁₂ alkylamino, N,N-di(C₁to C₉ alkyl)amino, (C₁ to C₁₂ alkoxy)carbonyl and C₁ to C₁₂ alkanoyl; C₅ to C₇ cycloalkyli C₅ to C₇ cycloalkenyl; the groups substituted C₅ to C₇ cycloalkyl and substituted C₅ to C₇ cycloalkenyl wherein the substituent is selected from the group consisting of hydroxy, amino, C₁ to C₉ alkyl, C₁ to C₉ alkoxy. and C₁ to C₉ alkenyloxy; polymers of one or more of the monomers selected from ethylene glycol, propylene glycol, styrene and C₂ to C₄ alkenes, and derivatives of said polymers; and wherein R¹ and R² may form a carbocyclic ring by the bridging group of formula -(R⁷R⁸C)_m- wherein m is 2 or 3 and R⁷ (which may be the same or different) and R⁸ (which may be the same or different) are independently selected from the group of hydrogen and C₁ to C₆ alkyl;

R³ is selected from the group consisting of: C₁ to C₁₈ alkyl; C₁ to C₉ alkyl substituted with a substituent selected from the group of amino, C₁ to C₉ alkoxy, C₂ to C₉ alkenyloxy, C₁ to C₉ alkanoyl,

(C₁ to C₉ alkoxy)carbonyl, carbamoyl, (C₁ to C₆ alkyl)carbamoyl and phenyl; C₂ to C₁₈ alkenyl; C₂ to C₉ alkenyl substituted with a substituent selected from the group consisting of hydroxy, amino C₁ to C₉ alkoxy, C₂ to C₉ alkenyloxy, C₁ to C₉ alkanoyl (C₁ to C₉ alkoxy)carbonyl, carbamoyl, (C₁ to C₉ alkyl) carbamoyl and phenyl; phenyl; benzoyl; the groups phenyl, benzyl and benzoyl said groups being substituted in the benzene ring with a substituent selected from the group consisting of hydroxy, amino, C₁ to C₁₂ alkyl, C₂ to C₁₂ alkenyl, C₁ to C₁₂ alkoxy, C₂ to C₁₂ alkenyloxy, C₁ to C₁₂ alkylamino,

N,N-di(C₁ to C₉ alkyl)amino, (C₁ to C₁₂ alkoxy)carbonyl and C₁ to C₁₂ alkanoyl; C₅ to C₇ cycloalkyl; C₅ to C₇ cycloalkenyl; the groups substituted C₄ to C₇ cycloalkyl and substiuted C₄ to

C₇ cycloalkenyl wherein the substituent is selected from the group of hydroxy, amino, C₁ to C₉ alkyl, C₁ to C₉ alkoxy, and C₂ to C₉ alkenyloxy; C₁ to C₁₈ alkanoyl; C₂ to C₉ alkanoyl substituted with a substituent selected from the group of hydroxy, amino, C₁ to C₉ alkoxy and C₂ to C₉ alkenyloxy, C₁ to C₉ alkanoyl; carbamoyl, (C₁ to C₆ alkyl)carbamoyl, (C₁ to C₉ alkoxy)carbonyl and phenyli polymers of one or more monomers selected from ethylene glycol, propylene glycol styrene and C₂ to C₄ alkenes, and derivatives of said polymers; and the group -OROROR⁹ wherein R (which may be the same or different) is a bivalent hydrocarbon radical of 2 to 6 carbon atoms and R⁹ is a hydrocarbon radical selected from C₁ to C₆ alkyl, C₂ to C₆ alkenyl, phenyl, benzyl, (C₁ to C₆ alkyl) phenyl and

(C₁ to C₆ alkyl)benzyl; R² is selected from the group consisting of hydrogen, C₁ to C₆ alkyl, and the group wherein R¹ and R² form a carbocyclic ring by the bridging group of formula -(CR⁷R⁸)_m- wherein R⁷, R⁸ and m are as hereinbefore defined; R⁴ is selected from the group consisting of C₁ to C₆ alkyl and C₁ to 6₆ alkoxy; n is an integer selected from 0 to 4 inclusive; and R⁵ and R⁶ which may be the same or different are selected from hydrogen, C₁ to C₆ alkyl, C₁ to C₆ alkoxy C₁ to C₁₀ alkanyl, C₁ to C₁₀ substituted by carboxyl or (C₁ to C₁₀ alkoxy) carbonyl and wherein R⁵ and R⁶ may form a spiro-carbocyclic ring by the bridging group of formula II

(CR¹⁰ R¹¹)_q II

wherein:

q is 2 or 3 and R¹⁰ and R¹¹ may be the same or different at each carbon unit of the bridge and are independently selected from hydrogen and C₁ to C₈ alkyl.

2. A sunscreen composition according to claim 1 wherein in the compound of formula I: R¹ is selected from the group consisting of: C₁ to

C₁₈ alkyl; C₁ to C₉ alkyl substituted with a substituent selected from the group consisting of, hydroxy, amino, C₁ to C₉ alkoxy C₁ to C₉ alkanoyl and (C₁ to C₉ alkoxy)carbonyl; C₁ to C₁₈ alkenyl; cyclohexyl; phenyl; benzyl; the groups phenyl and benzyl said groups being substituted in the benzene ring with a substituent selected from the group of C₁ to C₉ alkyl, C₂ to C₉ alkenyl, C₁ to C₉ alkoxy, C₁ to C₉ alkylamino, N,N-di(C₁ to C₆ alkyl)amino, C₁ to C₉ alkanoyl and (C₁ to C₉ alkoxy)carbonyl; and wherein R¹ and R² may form a carbocyclic ring by the bridging group of formula -CH₂(R⁷R⁸C)C_H2- wherein R⁷ and R⁸ are independently selected from hydrogen and

C₁ to C₆ alkyl; R³ is selected from C₁ to C₁₈ alkyl; C₁ to C₉ alkyl substituted with a substituent selected from the group consisting of hydroxy, amino, C₁ to C₉ alkoxy and C₁ to C₉ alkanoyl; C₂ to C₁₈ alkenyl; cyclohexyl; phenyl; benzyl; benzoyl; the groups phenyl, benzyl and benzoyl said groups being substituted in the benzene ring with a substituent selected from the group consisting of C₁ to C₉ alkyl, C₂ to C₉ alkenyl, C₁ to C₉ alkoxy, C₁ to C₉ alkylamino, N,N-di(C₁ to C₆ alkyl)amino, C₁ to Cg alkanoyl and (C₁ to C₉ alkoxy)carbonyl; C₁ to C₁₈ alkanoyl; and C₂ to C₉ alkanoyl substituted with phenyl; R² is selected from hydrogen and C₁ to C₆ alkyl; and wherein R² and R¹ may form a carbocyclic ring by the bridging group of formula -CH₂(R⁷R⁸C)CH₂- wherein R⁷ and R⁸ are independently selected from hydrogen and C₁ to C₆ alkyl;

R⁴ is C₁ to C₆ alkyl; and n is from 0 to 4;

R⁵ and R⁶ are independently selected from hydrogen; group of formula III

(CR¹⁰ R¹¹) III

wherein R¹⁰ and R¹¹ are independently selected from C₁ to C₄ alkyl and hydrogen; and R¹² is selected from hydrogen and C₁ to C₆ alkyl, and wherein R⁵ and R⁶ may form a spiro-carbocyclic ring by the bridging group of formula Ila

II a

wherein R¹⁰ and R¹¹ have independently selected from hydrogen and C₁ to C₄ alkyl.

3. A composition according to claim 1 or claim 2 wherein:

R¹ is selected from the group consisting of C₁ to

C₁₈ alkyl; C₁ to C₁₈ alkenyl; phenyl; and benzyl;

-CH₂(CR⁷R⁸)CH₂-

R³ is selected from C₁ to C₁₈ alkyl; C₂ to C₁₈ alkenyl; benzoyl; benzyl; benzoyl substituted with a substituent selected from C₁ to C₉ alkyl and C₁ to C₆ alkoxy; and C₃ to C₉ alkanoyl;

R⁴ is C₁ to C₄ alkyl;

n is from 0 to 3; and

R⁵ and R⁶ are independently selected from hydrogen and C₁ to C₄ alkyl.

4. A compound of formula I

whereint R¹ is selected from the group consisting of: C₁ to

C₁₈ alkyl; C₁ to C₉ alkyl substituted with a substituent selected from the group consisting of hydroxy, amino, C₁ to C₉ alkoxy, C₂ to C₉ alkenyloxy, C₁ to C₉ alkanoyl, (C₁ to C₉ alkoxy) carbonyl, carbamoyl, (C₁ to C₆ alkyl)carbamoyl and phenyl; C₂ to C₁₈ alkenyl; C₂ to C₉ alkenyl substituted with a substituent selected from the group consisting of hydroxy, amino, C₁ to C₉ alkoxy, C₂ to C₉ alkenyloxy, C₁ to C₉ alkanoyl, carbamoyl, (C₁ to C₉ alkyl)carbamoyl, and phenyl; C₂ to C₁₈ alkynyl; phenyl; the groups phenyl and benzyl said groups being substituted in the benzene ring with a substituent is selected from the group of C₁ to C₁₂ alkyl, C₁ to C₁₂ alkoxy, C₂ to C₁₂ alkenyloxy, C₁ to

C₁₂ alkylamino, N,N-di(C₁ to C₉ alkyl)amino, (C₁ to C₁₂ alkoxy)carbonyl and C₁ to C₁₂ alkanoyl; C₅ to C₇ cycloalkyl; C₅ to C₇ cycloalkenyl; the groups substituted C₅ to C₇ cycloalkyl and substituted C₅ to C₇ cycloalkenyl wherein the substituent is selected from the group consisting of hydroxy, amino, C₁ to C₉ alkyl, C₁ to C₉ alkoxy, and C₁ to C₉ alkenyloxy; polymers of one or more of the monomers selected from ethylene glycol, propylene glycol, styrene and C₂ to C₄ alkenes, and derivatives of said polymers; and wherein R¹ and R² may form a carbocyclic ring by the bridging group of formula

-(R⁷R⁸C)_m- wherein m is 2 or 3 and R⁷ (which may be the same or different) and R⁸ (which may be the same or different) are independently selected from the group of hydrogen and C₁ to C₆ alkyl; R³ is selected from the group consisting of: C₂ to

C₁₈ alkyl; C₁ to C₉ alkyl substituted with a substituent selected from the group consisting of amino, C₁ to C₉ alkoxy, C₂ to C₉ alkenyloxy, C₁ to C₉ alkanoyl, (C₁ to C₉ alkoxy)carbonyl, carbamoyl,

(C₁ to C₉ alkyl)carbamoyl and phenyl; C₂ to C₁₈ alkenyl; C₂ to C₉ alkenyl substituted with a substituent selected from the group consisting of hydroxy, amino C₁ to C₉ alkoxy, C₂ to C₉ alkenyloxy,

C₁ to C₉ alkanoyl, (C₁ to Cg alkoxy)carbonyl, carbamoyl, (C₁ to C₉ alkyl) carbamoyl and phenyl; C₂ to C₁₈ alkynyl; phenyl, benzoyl; the groups phenyl, benzyl and benzoyl said groups being substituted in the benzene ring with a substituent selected from the group consisting of hydroxy, amino, C₁ to C₁₂ alkyl, C₂ to C₁₂ alkenyl, C₁ to C₁₂ alkoxy, C₂ to

C₁₂ alkenyloxy, C₁ to C₁₂ alkylamino, N,N-di(C₁ to C₆ alkyl)amino, (C₁ to C₁₂ alkoxy)carbonyl, and C₁ to C₁₂ alkanoyl; C₅ to C₇ cycloalkyl; C₅ to C₇ cycloalkenyl; the groups substituted C₅ to C₇ cycloalkyl and substituted C₅ to C₇ cycloalkenyl wherein the substituent is selected from the groups of hydroxy, amino, C₁ to C₉ alkyl, C₁ to C₉ alkoxy, and C₁ to C₉ alkenyloxy; C₁ to C₁₈ alkanoyl; C₂ to C₉ alkanoyl substituted with a substituent selected from the group consisting of hydroxy, amino, C₁ to C₉ alkoxy, C₂ to C₉ alkenyloxy, C₁ to C₉ alkanoyl, carbamoyl, C₁ to C₆ alkyl)carbamoyl, (C₁ to C₉ alkoxy)carbonyl and phenyl; polymers of one or more monomers selected from ethylene glycol, propylene glycol, styrene and C₂ to C₄ alkenes, and derivatives of said polymers; and the group -OROROR⁹ wherein R (which may be the same of different) are bivalent hydrocarbon radicals of 2 to 6 carbon atoms and R⁹ is a hydrocarbon radical selected from C₁ to C₆ alkyl, C₂ to C₉ alkenyl phenyl, benzyl, (C₁ to C₆ alkyl) phenyl and (C₁ to C₆ alkyl)benzyl;

R² is selected from the group consisting of hydrogen, C₁ to C₆ alkyl, C₁ to C₆ alkoxy, and the group wherein R¹ and R² may form a carbocyclic ring by the bridging group of formula (CH⁷R⁸)_m- wherein R⁷, R⁸ and m are as hereinabove defined.

R⁴ is selected from the group consisting of C₁ to C₆ alkyl and C₁ to C₆ alkoxy; n is an integer selected from 0 to 4 inclusive; R⁵ and R⁶ which may be the same or different are selected from hydrogen, C₁ to C₆ alkyl, C₁ to C₆ alkoxy, C₁ to C₁₀ alkanoyl, C₁ to C₁₀ alkanoyl substituted by carboxyl or (C₁ to C₆ alkoxy) carbonyl and wherein R⁵ and R⁶ may form a spiro-carbocyclic ring by the bridging group of formula II.

C (CR¹⁰ R¹¹)q II

q is 2 or 3 and R¹⁰ and R¹¹ may be the same or different at each carbon unit of the bridge and are independently selected from hydrogen and C₁ to C₈ alkyl; with the priviso that when R¹ is methyl then R³ is not selected from the group of hydroxyethyl, methoxymethyl and benzyl.

5. A compound according to claim 4 whereint R¹ is selected from C₁ to C₁₈ alkyl; C₁ to C₉ alkyl substituted with a substituent selected from the group consisting of hydroxy, amino, C₁ to C₉ alkoxy,

C₁ to C₉ alkanoyl and (C₁ to C₉ alkoxy)carbonyl; C₁ to C₁₈ alkenyl; cyclohexyl; phenyl; benzyl; the groups phenyl and benzyl said groups being substituted in the benzene ring with a substituent selected from the group of C₁ to C₉ alkyl, C₂ to C₉ alkenyl, C₁ to C₉ alkoxy, C₁ to C₉ alkanoyl and (C₁ to C₉ alkoxy) carbonyl; and wherein R¹ and R² may form a carbocyclic ring by the bridging group of formula -CH₂(R⁷R⁸C)CH₂- wherein R⁷ and R⁸ are independently selected from hydrogen and C₁ to C₆ alkyl;

R³ is selected from C₂ to C₁₈ alkyl; C₁ to C₉ alkyl substituted with a substituent selected from the group consisting of hydroxy, amino, C₁ to C₉ alkoxy and C₁ to C₉ alkanoyl; C₂ to C₁₈ alkenyl; cyclohexyl; phenyl; benzyl; benzoyl; the groups phenyl, benzyl and benzoyl said groups being substituted in the benzene ring with a substituent selected from the group of C₁ to C₉ alkyl, C₂ to C₉ alkenyl, C₁ to C₉ alkoxy, C₁ to C₉ alkanoyl and (C₁ to C₉ alkoxy)carbonyl; C₃ to C₁₈ alkanoyl; and C₂ to C₉ alkanoyl substituted with phenyl;

R² is selected from hydrogen; C₁ and C₆ alkyl; and wherein R¹ and R² may form a carbocyclic ring by the bridging group of formula -CH₂(R⁷R⁸C)CH₂- wherein R⁷ and R⁸ are independently selected from hydrogen and

C₁ to C₉ alkyl;

R⁴ is C₁ to C₆ alkyl; n is from 0 to 4; R⁵ and R⁶ are independently selected from hydrogen; C₁ to C₆ alkyl; the substituted alkanoyl group of formula III

1^{0 11 12} III

wherein R¹⁰, R¹¹ and R¹² are independently selected from C₁ to C₄ alkyl and hydrogen; and wherein R⁵ to R⁶ may form a spiro-carbocyclic ring by the bridging group of formula II a

II a

wherein R¹⁰ and R¹¹ are independently selected from hydrogen and C₁ to C₄ alkyl.

6. A compound according to claim 4 or claim 5 whereint

R¹ is selected from the group consisting of C₁ to C₁₈ alkyl; C₁ to C₆ alkyl substituted with a substituent selected from C₁ to C₆ alkanoyl and (C₁ to C₆ alkoxy) carboxyl; C₁ to C₁₈ alkenyl; phenyl, and benzyl;

-CH₂(CR⁷R⁸)CH₂-

wherein R⁷ and R⁸ are independently selected from hydrogen and C₁ to C ₄ alkyl; R³ is selected from the group consisting of C₂ to C₁₈ alkyl; C₁ to C₉ alkyl substituted with a substituent selected from the group consisting of hydroxy and C₁ to C₉ alkoxy; C₁ to C₁₈ alkenyl; benzoyl; benzyl; benyoyl substituted with a substituent selected from C₁ to C₆ alkyl and C₁ to C₆ alkoxy; and C₃ to C₉ alkanoyl; R⁴ is C₁ to C₄ alkyl n is a from 0 to 3.

R⁵ and R⁶ are selected such that they comply with one of the possibilities selected from the group consisting oft (i)R⁵ and R⁶ are independently selected from hydrogen and C₁ to C₄ alkyl, (ii) one of R⁵ and R⁶ is hydrogen and the other is a group of formula III.

III

wherein R¹⁰, R¹¹ and R¹² are independently selected from the group consisting of hydrogen and C₁ to C₄ alkyl; and (iii) the group wherein R⁵ and R⁶ form a spiro carbocyclic ring by the diradical group of formula Ila.

1¹ Ila

wherein R¹⁰ and R¹¹ are independently selected from the group consisting of hydrogen and C₁ and C₄ alkyl.

7. A compound according to any one of claims 4 to 6 inclusive whereint

R¹ is C₁ to C₉ alkyl;

R² is selected from hydrogen and C₁ to C₄ alkyl;

and wherein R¹ and R² may form a carbocyclic ring by the bridging group of formula

-CH₂(CR⁷R⁸)CH₂-

wherein R⁷ and R⁸ are independently selected from hydrogen and methyl;

R is selected from C₂ ato C₉ alkyl; C₂ to C₉ alkenyl; C₁ to C₉ alkyl substituted with a substituent selected from hydroxy, phenyl and C₁ to C₆ alkoxy; benzoyl; benyoyl substituted with a substituent selected from the group consisting of C₁ to C₆ alkyl and C₁ to C₆ alkoxy; and C₃ to C₉ alkanoyl;

R⁴ is selected from C₁ to C₄ alkyl;

n is from 0 to 3;

R⁵ and R⁶ are selected such that they comply with one of the possibilities selected from the group consisting of

(i) R⁵ and R⁶ are independently selected from hydrogen and C₁ to C₄ alkyl;

(ii) one of R⁵ and R⁶ is hydrogen and the other is a group of formula III ; III

wherein R¹⁰ and R¹¹ are methyl and R¹² is hydrogen or C₁ to C₉ alkyl; and

(iii) the group wherein R⁵ and R⁶ form a spiro carbocyclic ring by the diradical group of formula Ila

CH (CRR C II a

wherein R¹⁰ and R¹¹ are methyl; and wherein when one of R⁵ and R⁶ is not hydrogen or C₁ to C₄ alkyl then n is zero.

8. A compound according to any one of claims 4 to 6 inclusive whereint

R¹ is selected from the group consisting of

C₁ to C₉ alkyl;

R² is hydrogen; and wherein

R¹ and R² may form a carbocyclic ring by the bridging group of formula

- CH₂(CR⁷R⁸)CH₂-

wherein R⁷ and R⁸ are methyl; R³ is selected from the group consisting of C₁ to C₉ alkyl; 2-phenylethyl and cyclohexyl;

R⁴ is methyl

n is chosen from 0 to 3;

R⁵ and R⁶ are selected such that they comply with one of the possibilities selected from the group consisting of (i) R⁵ and R⁶ are independently selected from hydrogen and methyl; (ii) one of R⁵ and R⁶ is hydrogen and the other is a group of formula III .

(CR¹⁰R¹¹)CH₂COR¹² III

wherein R¹⁰ and R¹¹ are methyl and R¹² is ethyl; and

(iii) the group wherein R⁵ and R⁶ form a spiro carbocyclic ring by the diradical group of formula Ila.

II a

wherein R¹⁰ and R¹¹ are methyl;

and wherein when at least one of R⁵ and R⁶ is not hydrogen or methyl then n is zero.

9. A compound of formula I(a)(i)

I (a) (i)

wherein R³, R⁴, R⁵, R⁶, R⁷, R⁸, and n are as herein defined with reference to any one of claims 4 to 8 inclusive.

10 A compound of formula

I (a)(ii)

wherein R³, R⁵, R⁶, R⁷ and R⁸ are as hereinbefore defined according to any one of claims 4 to 8 inclusive.

11. A compound according to claim 10 wherein

R 5 and R6 are selected such that either

(a) R and R form a carbocyclic ring by the diradical group of formula Ila (CR¹⁰ R¹¹) Ila

wherein R¹⁰ and R¹¹ are independently- selected from hydrogen and C₁ to C₄ alkyl; or

(b) one of R⁵ and R⁶ is hydrogen and the other is the group of formula IlIa

(CR¹⁰ R¹¹) III a

wherein R¹⁰, R¹¹ and R¹² are independently selected from hydrogen and C₁ to C₄ alkyl.

12. A compound according to claim 11 wherein in each group of formula Ila and Ilia the groups R¹⁰ and

R¹¹ are both methyl and R¹² is ethyl.

13. A compound of formula

where R⁵ and R⁶ are independently selected from the group consisting of hydrogen, C₁ to C₆ alkyl and C₁ to C₆ alkoxy and R¹, R² R³, R⁴ and n are as defined according to any one of claims 4 to 8 inclusive.

14. A compound according to claim 13 wherein R⁵ and R are independently selected from hydrogen and C₁ to C₆ alkyl.

15. A compound according to claim 14 wherein R⁵ and R⁸ are hydrogen.

16. A compound according to any one of claims 4 to 6 whereint

R¹ is selected from the group consisting of C₁ to

C₁₈ alkyl;

R² is hydrogen;

R³ is selected from the group consisting of C₂ to

C₁₈ alkyl and C₂ to C₁₈ alkenyl;

n is 0;

R⁵ and R⁶ are hydrogen.

17. A compound according to claim 13 wherein:

R¹ is selected from the group consisting of methyl, ethyl, propyl, 3-methylbutyl;

R² is hydrogen;

R³ is selected from the group consisting of propyl,

1-methylethyl, butyl, 3-methylbutyl, 2-ethylhexyl, and 3-methyl-2-butenyl; n is 0; and

R⁵ and R⁶ are hydrogen.

18. A compound selected from the group consisting of

methyl 1-(3-methylbutyl)-1,4,5,6-tetrahydro-3-pyridyl ketone; methyl 1-(3-methyl-2-butenyl)-1,4,5-6-tetrahydro-3-pyridyl ketone; ethyl 1-butyl-1,4,5,6-tetrahydro-3-pyridyl ketone; ethyl 1-(3-methylbutyl)-1,4,5,6-tetrahydro-3-pyridylketone; propyl 1-propyl-1,4,5,6-tetrahydro-3-pyridyl ketone; propyl 1-butyl-l,4,5,6-tetrahydro-3-pyridylketone; propyl-1-(3-methylbutyl)-1,4,5,6-tetrahydro-3-pyridylketone;

4-methylpentyl 1-propyl-l,4,5,6-tetrahydro-3-pyridylketone; phenyl 1-propyl-1,4,5,6,-tetrahydro-3-ρyridyl ketone; and methyl 1-butyl-4,4,6 trimethyl-1,4,5,6-tetrahydro-3-pyridyl ketone.

19. A process for preparing a compound of formula I according to any one of claims 3 to 16 which process comprises eithert

(a) reducing the compound of formula V to give a compound of formula I having the formula I (c); or

(b) reacting the compound of formula IV with a compound of formula VI

20. A process according to claim 18 comprising

(a) Reacting the compound of formula VII with the compound of formula VI to provide a compound of formula V and reducing the compound of formula V to provide a compound of formula I having the formula I (c) ; or (b) Reducing the compound of formula VII to provide a compound of formula IV and reacting the compound of formula IV with a compound of formula VI to provide a compound of formula I having the formula I (e) .

VII

21. A sunscreen composition according to any one of claims 1 to 3 inclusive wherein the compound of formula I is as defined according to one of claims 4 to 17 inclusive.

22. A sunscreen composition according to any one of claims selected from the group of claims 1 to 3 and claim 21 wherein the compound of formula I comprises in the range of from 0.5 to 20% by weight of the total sunscreen composition.

23. A method of screening a surface from ultraviolet radiation the method comprising applying to the surface a composition according to any one of the claims selected from the group of claims 1 to 3, Claim 21 and Claim 22.

24. A method according to claim 21 wherein said surface is the surface of skin.

25. A compound according to any one of claims 4 to 17 inclusive substantially as herein described with reference to any one of Examples 1 to 36 inclusive.