AU609125B2 - Ultra violet light absorbing materials - Google Patents

Description

-,,'CAT1ON ACCEPTED AND AMENDMENTS ALL JW L D 609125 arnmendmen'.ts ii Q :ndr Section 4) .id .s Lcr:ect for printing COMMONWEALTH OF AUSTRALIA pt g o **0 0 0 q 4 0 4 o 0 It f i 1 The Patents Act 1952-1969 Name of Applicant(sm): AUSTRALIAN INSTITUTE OF MARINE SCIENCE Address of Applicant(s) Cape Ferguson, Townsville, Queensland, 4810, Australia Actual Inventor(s): Bruce Edward CHALKER Walter Clark DUNLAP Wick :amasinghe Mudiyanselage

BANDARANAYAKE

G.R. CULLEN COMPANY Dalgety House 79 Eagle Street BRISBANE QLD. 4000

AUSTRALIA.

Address for service: t COMPLETE SPECIFICATION FOR THE INVENTION ENTITLED: "ULTRA-VIOLET LIGHT ABSORBING MATERIALS" The following statement is a full description of the invention including the best method of performing it known to us: To: The Commissioner of Patents D. J. BARRY 2 THIS INVENTION relates to new and useful groups of ultra-violet light absorbing materials and to sunscreen and other compositions incorporating such materials to utilise the ultra-violet absorbing properties of the materials according to the invention.

Chemical compounds which absorb radiation in the ultra-violet portion of the spectrum (hereinafter "UVagents") have a number of commercial applications.

The best known of these are probably their use to provide skin protection from the erythemal effect of sunlight o 0 0o o a 0, materials from degradation and decomposition due to exposure 0 00 So °o to solar radiation, They have also been used for other 00 0 ooooo00 purposes such as energy transfer means in UV-light crosso o linking of polymers, o 0 °0 0 Common commercially available UV-agents include, Soo 0 for example, para-aminobenzoio acid derivatives, 000oooo benzotriazoles, benzophenones, methoxycinnamates and 0000 salicylates. It has been proposed, for example in U.K.

Patent Application 2,120,549A and French Patent Application 0 0 0 00 o 0 83 01391 that certain specific classes of vinylogous amide o ao compounds may also be used 's UV-absorbing sunscreen agents.

However these vinylogous amides were found to be relatively unstable and hence were not considered appropriate for commercial use.

i I 3 All of the abovementioned UV-absorbing materials exhibit strong radiation absorption i' the UV region, the actual value of the absorption maximum being important in relating the compounds to their intended end use. For example, it is known that human skin is particularly sensitive to damage at wavelengths between about 290-320 nm (nanometer), the so-called UV-B region, with some likely carryover of harmful effects into the wavelength in excess of 320 nm, the UV-A region. On the other hand, UV-agents used to protect plastics, paint films or other non-biological 0 o00000 o000 material commonly have absorption maxima in the region of 0 9 0 00 0 0O o 340-355 nm and higher.

0 0 S0o° o In particular, useful UV-agents for sun-screen use 000 0 00"00 will have absorption maxima in excess of about 290 nm. They 0 0 must also have acceptable permanence, stability and ,co, compatibility with the media to which they are to be applied ooo or incorporated. Also, when the UV-agents are to be used on oQoo living tissue, they must be non-toxic and not otherwise 0000 harmful to the host surface.

These various criteria are often in conflict and a Go 0 0 0 a on limit the choice of UV-agents available for specific end 0 00 uses. Furthermore, the final selection, when it is made, is often a compromise in which, for example, efficacy must be sacrificed for stability or freedom from toxic or other sideeffects.

4 We have observed that certain mycosporin amino acids which exist in the living tissue of the Pacific staghorn coral Acropora formosa are functional UV-absorbing agents iX max 310-332 nm) in corals inhabiting the shallow water, tropical coral reef environment. While these appear to be potentially attractive as commercial UV-agents, their utility is questionable because of the difficulty of isolating them from their biological sources and due also to their lack of adequate chemical stability. It has been proposed by us that certain synthetic cyclic vinylogous amide ,0 analogues (enaminoketones) of those natural products can be 0 0 0 o0 0 00 o prepared which preserves their characteristic UV-absorbing oa o °o chromophore and which have UV-absorption maxima (Amax) in the ooo 0 ooooo wavelength region 288-340 namometers Patent 0 0 Application PCT/AU85/00242).

0 0 00 Q We have now found to our surprise that ketimine 0 o0 °o000 derivatives of the abovementioned classes of vinylogous amide .oo compounds are a more stable and efficient (greater molar 0000 absorptivity) class of UV-absorbing compounds.

Accordingly, the present invention in one aspect 0 00 0 1 provides novel UV-absorbing 8 enaminoketimine compounds o oo having the general formula Z R 5

(I)

i i i a~ I---xl wherein: T NR 8 or +NR 8

R

9

X-

Y R, OR,, SR,, or NR 1

R

2 Z H, R3, OR 3

SR

3 or NR 3

R

4 in which: R I to R 9 may be independently selected from hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl groups which groups may be further substituted by halogen, ammonia, primary or secondary amine groups, quaternary ammonium salts, nitro, hydroxyl, alkoxyl, aryloxyl, oxo and carboxylic acid or ester groups; or the groups R. to R 9 when present, may form a carbocyclic ring or R, and R 7 or R, and R 9 when taken together form a o heterocyclio ring which may optionally be further substituted 0 0 by halogen, ammonia, primary or secondary amine groups, uO 0 0oooo0 quaternary ammonium salts, alkyl, nitro, hydroxyl, alkoxyl, o 0 oxo and carboxylic acid or ester groups; and the nitrogen group NR 6

R

7 or the substituents NR3R 4 and/or NRIR 2 when present, 0 oo may have a structure of a primary, secondary or tertiary amine 00 within the broad definition of R I to R, and T NRg or NRgRgX- ,ooo0 may include imino derivatives of primary amino acids, which Sb may be esterified, 0 0 0000 ou oo 0 00 0 0 0 Q0 0 ii i I 6 andprotein :on.tituCnts; and the acid addition and quaternary salts thereof; and where the anion X~ is present where T +NRgR 9 X~ may be halogen, carbonate, carboxylate, perchlorate sulfate or nitrate; with the following provisos: when R6 and P7 are -(CH 2 4-,

R

8 and R 9 are -(CH2) 4 Y and R 5 are -QH 2

CRRCH

2 at least one R is not methyl ooo and more suitably both R groups o o are not methyl; o 0a S"00 when R 6 and R 7 are -(CH 2 )20(CH 2 6 &0 0 o oo 0

R

8 and R 9 are -(CH 2 2 0(CH 2 2 Y and R 5 are -CH 2

CRRCH

2 0 00 o q C at least one R is not S0 0 0 methyl and more suitably both R 0000 ojoo groups are not methyl; and when both R 6 and R 7 are ethyl 02,0o Rg and R 9 are -(CH2) 4 ao o oo Y and R 5 are -CH 2 CRR CH 2 at least one R is not methyl and more suitably both R groups are not methyl.

In a preferred embodiment of the invention there are provided compounds of the formula II hereinafter described wherein ~Lllrp rxr 7 T NR, or Y and R s are -CH 2 CRR CH 2 and R hydrogen or methyl.

Preferably in this embodiment R, and R 8 are selected from cycloalkyl, alkyl, phenyl and benzyl; R 7 and R9 are selected from hydrogen or alkyl; Z represents hydrogen, methyl or methoxyl and X- represents Cl- or I-.

Also R 6 and R7 or R 8 and R 9 when taken together may also represent a methylene group to form a carbocyclic ring, or may be interrupted by oxygen to form a heterocycl-c ring.

0 o Preferred values are 4

-(CH

2 and -(CH,),0(CH 2 0 7 0 0 Most preferably R 7 and R 9 are hydrogen.

00 0 0o The UV-absorbing compounds of this invention may be 0 0 oo used to provide protection to both biological and nonooooo biological materials from the damaging effects of o 0 environmental solar or artificial UV-radiation. One of the potentially more useful :pplications of these UV-agents is g 000 o their incorporation in sunscreen preparations for skin 0000 Soo 0 protection. For this purpose we prefer that the selected UV- 0 oooo agent, or combination of agents, have an absorption maximum 0 0 in the wavelength region 300 340 nm.

0o Therefore, in further aspects the invention 0 000 o provides; novel sunscreen compositions comprising as an active 000000 0 U ingredient one or more compounds of Formula I as hereinbefore defined; process for preparing such novel sunscreen compositions; and processes for the protection of

I~

8 sunscreen compositions; and processes for the protection of biological and non-biological materials from the damaging effects of environmental solar or artificial UV-radiation by incorporating into or applying to said material an effective amount of a compound or composition of the present invention.

The compounds of the invention may be readily compounded by the standard methods of the art into, for example, creams or lotions, making use of conventional emollients, emulsifiers, preservatives, anti-oxidants, perfumes and colouring agents approved for cosmetic use, o By way of illustration only, suitable emolliento may be selected from mineral oil, squalene, octyl palmitate, cocoa butter, sesame oil, and pristane, either singly or in Scombination. Typical emulsifiers include for example, O o polyoxyethylene(3)oleyl ether, polyglyceryl-4-oleate and a a? polysorbate 0 o The invention is now illustrated by but in no way 0 0'0 limited to the following examples: Example 1 N- 3-cclohexylamino-5,5-dimethylcyclohex-2-on-1 I ylidene) 0 00 l o -cyclohexyliminium chloride.

DCIO

c oH 7a N 9 a. Stoichiom etric amounts of triphenylphosphine (39,3g) and dimedone (14.0g) were suspended in CC14(59 mis) and heated at 50-55 degrees C with stirring. In about 30 min, the salt [(C6H 5 3

PH

2 C1)+ C1 began to separate in crystalline form. The reaction was complete in 4 hours, The phosphonium salt was removed by filtration and the SC0014 removed in vacuo, leaving a semicrystalline residue which was o triturated with n-pentane (3x100 ml).

0 000000 a Insoluble triphenylphosphine Oxide was removed by filtration and the solvent a 00 o evaporated to give crude product (7.9g, O oO 0 00o 99%) which distilled (120-122 degroes

C)

0000 o at water pump pressure to give 3-chloro- 5,5-dimethylcyclohx-2-enone as a pale ooo\ yellow liquid (7,0g, 88%) X iax 238nm, 0 00 26C. *14,000.

b. 3-chloro-5,5-dimethylcyclohex-2-einone 0.01 mole and cyclohexylamine 0,02 mole) were refluxed in benzene (20 mi) for 6 hours. Evaporation of the benzene provided crude product which crystallised from aqueous ethanol I to give N-(3-cyclohexylamino-5,5dimethyl-cyclohex-2-en- 1y2idene)cyclohexyliminium chloride as pale yellow crystals (2.9g, X max 312.8nmE 44,040, m~p, 269,9-271.4 degrees

C.

Example 2 3-cvclohexvlamino-5 5-dimethvlcylohex-2-en- 1-ylidene) cvclohexyimine.

;_A

o aN 3cyc1ohoxy I a n d i m h I a hox-2 I-yIi 00 f a. N- S-yc lhxy Lamno ,5 6,t~ dime thyiCy cloh x-2- on- y 1idnn cyclohexyliminium chlorio (E xanple 1; was dissolvod in boiling water (300 ml) and filtered into a solution of

Q"

KOH (250 ml), The oolid precipitate was colloctod and cry.tallied frzom aqueous ethanol to give the free base, N-(3- 5 -dimethylcyclohox-2en-1-yl4idenQ )cyclohexylimino as a pale yellow solid (0,48g, max 3 12 6 nm 11 E 42820. m.p. 166.7-168.6 degrees C.

Example 3 N-C 3-octylamino-5, 5-dimethylcyclohex-2-en- i-yJlidene) pipoeridinium iodide

C

0 -ItP

C

L

1Q~, 0 0 00 *0 00 000 0 00 0 0 d o 0 0 o o 2Q 0 0 0.) 1 g, 0. QC no :L1 n 1 n 0 re hoited 4- VQrr v,~rr~lu~wt over MONQ and evaPoiatrod t, 1 V Q t h c crado enaminokotonoc which c .yz t aI z-ed fr~omn benzene-light potrooeu (bp, 6Q-80 degrees C) to yield 5-dirnthylyclohex-2-enone cis orange needles (8.9g, A max 305nmk 28,500.

m~p, 57,8"60,3 degrees C.

/Q

r I w;L W -j- Qtoo o 2 a 2 o ~U a ;:a gr 12 3-(N-piperidinyi, enone (5.38 g, 0.026 mole) and iodomethane (25 ml) were heated under reflux for 18 hours. The product obtainea after evaporation of the iodomethane was triturated with ethylacetate (40 ml) and collected by filtration to give the crude methoxyiodide salt (8,6g, Crystallisation from methanolethylaCetate gave N-(3-methoxy-5,5d imethyoycl1ohe -2-e n-1-yliden e piperadinium iodide as pale yellow needles (8,4g; 931), max 287. m.p, 147.7-148,3 degrees 0.

N-Octylamine (1,55g, 0,012 mole) was added to a solution of N-(3-methoxy-~55d A m e t h y I c y c I o h a x 2 e n 1 ylidenq)piporidini~um iodide (3,47g; 0.01 mole) dissolved in methanol (25 ml) resulting in an exothermic reaction, The reaction mixture was ref luxed for minutes and the methanol evaporated. The crude product crystallised from methanolethylacetate to give N-(3-octylamino-515d i m e th y I o y cl o h e x 2 e n -I amine groups, quaternary ammonium salts, nitro, hydroxyl, alkoxyl, aryloxyl, oxo and carboxylic acid or ester groups; or /2 I~ yncill-urrp 13 ylidene)piperidinium iodide as pale yellow needles (3.2g, A max 322.6, E38510, m.p. 118.1-120.4 degrees C.

Examples 4-39 (3-ainocyclohex-2-en-1-ylidene)iines and N- (3-aminocyclohex-2-en-1-ylidene )iminium salts noa 100, 00e55' a 5i o '3o S3, 2~r.

The compound derivatives provided in Examples 4-39 of the invention were prepared by the procedures described in Examples 1-3 and are listed in Table I having the designated formula (II) of the general formula of the invention where (T NRg or NR R 9 X (YR 5 -CH 2

CRRCH

2 and (Rer,CH 3 R -7111" c, 1'

R

Compounds of formula (IT) where (R R 7

=R

8

R

9 may exist as resonance or tautomeric isomers (Ila) and (Ib) are defined as arbitrary. The structural geometry of the imino-nitrogen

(R

8

-N-R

9 or (R6-B-R 7 by resonance (or tautomeric isomerisation) are designated as arbitrary.

kX .7) R. 7- S p' P. R </I2 7 .7rr Y and R 5 are -CH 2

CRRCH

2 at least one R is not methyl.

r -~I~lrlICr i 14 Examples 1-39 TABLE T N- (3-aminocvclohex-2-en-l-vli'ene) imir.es and NI- (3-aminocclohex-2-en-1-,lidene) iminium salts.

3N 1

J"

n ~:cr 4 """r3

,I

oaf oanoS 1

R

R~ t- Example P, R xrnaX M. p.

N R 8 RX C) -g 4, >0 4o 4 44 44 cyc 1oheXy2 clclohexyi cynlohexy2 cy clohex y CH3 H Hi CHI 312.8 44040 269.9-271.4 312.6 42820 166.7-168.6 322.6 38510 118.1-120.4 R 6 R (CH 2 3 n-Qctl 14 fl-oc t~i n-ctl n-dodecyl n-dcdecyl n-octadecyl n-octadecyl CHu C3 310.0 32740 310.2 37450 gummy solid gummny solid 309.2 43570 87.4-89.0 Elir -r rY1 n~4~4t44r~ 7 pheny I phanyl H CH Cl 3 340.6 28040 300d Example R 6 R7 Z R A max mp.

No. R8 R9 C (nM) C)

S

er 4

C)I

o o.i no 9.

II

12.

13.

o, 14.

16.

17.

18.

19.

21.

phenyl H phenyl benzvl H banzyl H cyclohexyl H n-octyl H cyclohexyl H n-dodecyl H cyclohexyl H n-octadecyl H cyclohexyl H -benzyl 11 n-butyl n-butvl cvclohexvl H n-butyl n-butyl n-octyl H R 6=R 7--(CH 2 4 n-octyl H R =R cclhexyl 2 5

H

R

6 =R (CH 2) a-dodecyl H R6=R 2 n-ct~deyl R 6= R7=- 1) benzy!

H

R

6

-R

7

=-(CH

2 phenyl H

CH

CH3

CH

3 CUr CH3 CH3 CH3 CH 3 C1 3

C'

3 Cu 3 C" 3 340.0 313.4 311.6 310.0 311.8 312.2 323.6 317.6 319.4 324.8 322.2 32.14 325.0 334. 2 4.530 43570 32500 34250 36610 43320 31080 26740 33720 43320 317410 36900 44470 31440 194.2-195.3 226.0-226.9 heavy oil heavy oil 106.0-106.9 199.4-200.1 gummy slid gummuTy void heavy oil 173.3-174.9 guummy solid gummy solid 183.2-184.4 205.8-207.7 II -L -r-~~r-CI-L I i i Example R 6 Z R max m.p.

No. R 8

R

9 X (nM) C) 22.

23.

24.

R

6 7 5 R-R =-(CH n_.Ou n-b

R

6

=R

7 (CE 2 1 5-

R

8

R

9

=-R(CH

2 4

R

6

R

7 (CH 2

R

8

R

9

(CH

2 U (C 0 0 c,0, t o OC o o 0o o 0~ 0 1,5~ 0, 00 C) 0 0 0nn C C(.

Q 0(O 00 S0 0 L 26.

27.

28.

29.

30.

31.

32.

33.

34.

36.

benzyl benzyl cyclohexy).

benzy1

R

6 R 7

=-(CH

2 5 cyclohexyl cyclohexyl cyclohexy1 cyclohexy 1 benzyl n-buty n-I cyclohe xyl

R

6

=R

7

(CE

2 cyc1ohexyl cyclohexyl cyclohexyl cyclohexy].

cyclohexyl bu

H

I-

H

rtyl I-

H

I-

H

:1T2)- I- H ii H C1 H H

H

H I- H

CH

H c I H CE 3 H I Ity1 CH3 H I

HH

CE

3 H I H

CE

3 H I H CCH 3 H CJ.

H

OCH

3 H Cl- H OCH 3 H cl-

CH

3

CH

3

CH

3

CH

3

H

H

H

H

H

H

H

338.0 332.4 334.4 334.4 311.2 311.2 322.4 329,2 329.2 329,0 329.0 332.2 331.2 329.6 332.6 50320 53690 39000 25668 45350 44590 47850 40600 51110 55550 49020 45510 39680 42230 42360 164.8-165.4 166.6-167.2 124.6-126.9 211.8-213.1 184.7-187.3 249.8-251.6 213.3-215.7 269.3-270.5 261.8-262.5 265.8-267.5 268.4-269.5 250.4-252.6 227.8-228.0 114.6-117.3 170Gd n-octadecyl n-octadeciy benzyl benzyl i L.

Example R6 R7 Z R max M.P.

No. R 8 R 9X (M (C) 37. phenyl pheny! OCH 3H OCH H I -3 38. cyciche:<yl benz 'ii 348.6 43030 222.0-223.1 332.0 50720 200.2-203.4 331.6 54100 221.3-222.3 391. n-bouty. a-butyl cvc lcahexv 1 OCH 3 H 0 0 13 0 0 0 000 0 0 0 o00 0 Examcole NJ- (4-cvcrlohexvlarinopent-3-eri-2-ylidene) cyclohexylimninium iod ide

C.

C.

-o

H

-G

A

C A C i a. Acetylacetone cyclohexylamine heated under (25g, 0.4 mole) and (25g, 0,41 mole) were reflux with a Dean-Stark o Q 0 b o a 0 0 0 0 0 00 0 0 0 02 0 0 0 0C separator to remove water. The benzene solution was dried over MgSO 4 and evaporated to give the crude enaminoketone residue which was purified by distillation 104-106 degrees C/210 mTorr) to give 42.8g 4cyclohexylamino-3-pentene-2-one.

4-Cyclohexylamino-3-pentene-2-one (17.1g, 0.1 mole) and ethyliodide (30 ml) were heated neat under reflux on a steam bath.

After about 30 minutes a second liquid phase developed and the mixture was heated under reflux for an additional 4 hours to complete the reaction, Excess ethyliodide was removed by distillation on the steam bath. The resulting viscous oil was washed with diethyl ether and dissolved in the minimum volume of hot acetone. The precipitate formed on addition of ethyl acetate was removed by filtration and the crude ethoxy iodide was obtained as a viscous residue on evaporation of the organic

II

TW 19 solvents which solidified on standing (16g, The crude N-(4-ethoxypent-3en-2-ylidene) cyclohexyliminium iodide was used in the subsequent procedure without additional purification.

c. Cyclohexylamine (0,249g, 0.0024 mole) was added to a solution of N-(4-ethoxypent-3en-2-ylidene) cyclohexyliminium iodide aoa o(3,369g, 0.001 mole) in acetone (25 ml) rQQ with evolution of heat. The solution was 0 C warmed on the steam bath under ref lux 2 COO ~hours and ethyl acetate (50 ml) was added 0 a to the hot solution. The precipitate C (11 0 formed on cooling -va s collected by 0C' 0 filtration and the solid rocrystallised 0 0O from acetone-ethylacetate to give 1.2g

"COG

of N-(4-cyclohoxylaminopent-3-Cn-2ylidene) cyclohexyliminium iodide, mp G ,0 0 190,0-191.9 degrees C. N max 324.

4 nm, c3 7~ 100 Example 41 N-(4-anilinopent-3-en-2-ylidene) anilinium chloride D" O 0 a- 0 0 o a S a. Triphenylphosphine(55g) and acetylacetone 0 Q C o (10g) were stirred in CC1 4 at 50-55 O 0 degrees C for 4 hours. Insoluble phosphonium chloride was removed by co O filtration and the organic solvent was removed by evaporation in vacuo. The ac0. residue was -triturated with n-pentane (3 x 1 0 m 1) and insolu b le triphenylphosphine oxide was removed by 2Q filtration. Evaporation of the organic solvent and distillation 92-94 degrees C/760 mm) gave 4-chloro-3-penten- 2-one (42.8g, 94%).

b. 4-chloro-3-penten-2-one (i.19g, 0.01 mole) and cyglohexylamine (1.98g, 0.02 mole) were refluxed in benzene (20 ml) 21 fQr 6 hours. Evaporation of the benzene provided a crude residue which crystallised from aqueous ethanol to give N-(4-anilino-3-en-2-ylidene) anilinium chloride (1.9g, 66%) m.p. 208.6-209.7 degrees C.

Xmax 3 4 5 8 nm E24050.

Reference is made in J. Org, Chem. 29 794-7 (1964) to an article by Alt and Speziale which disclosed similar 1o compounds which are now excluded from the present invention.

Reference is also made to NJ. Leonard and JA. Adamcik, J.

S Am. Chem. Soc, 81 595 (1959) which refers to similar compounds which are also excluded from the present invention.

0 C-

Claims (9)

1. UV-absorbing enaminoketimine compounds having the general formula P R 7 Y- L C C N R6 I I g RS (I] wherein: T NR, or +NR 8 R, X- 00 00i00 Y Rif OR, SRI, or NRR 2 CZ It, R 3 1 OR 3 SR 3 or NR 3 R 4 in which: R 1 to R may be independently selected from hydrogen, alkyl, cycloalkyl, alkonyl, cycloalkenyl, aryl, arylalkyl, hoteroaryl or heotoroarylalkyl groups which groups may be further substituted by halogen, ammonia, primary or secondary amino groups, quaternary ammonium salts, nitro, hydroxyl, alkoxyl, aryloxyl, oxo and carboxylic acid or ester groups; or the groups R, to when present, may form a carbocyclic ring or 1% and R 7 or R 8 and R when taken together form a heterocyclic ring which may optionally be further oubstituted by halogen, ammonia, primary or secondary amin groups, quaternary ammonium sanlts, alkyl, nitro, hydroxyl, alkoxyl, oxo and carboxylic acid or ester groups; 3 7# S23 I 0- w 0 0 U U o 0) and the nitrogen group NRGR 7 or the substituents NR 3 R 4 and/or NR1R 2 when present, may have a structure of a primary, secondary or tertiary amine within the broad definition of R I to Rg and T NR 8 or +NR 8 R 9 X- may include imino derivatives of primary amino acids, which may be esterified; and the acid addition and quaternary salts thereof; and where the anion X- is present where T +NR g R 9 X- may be halogen, carbonate, carboxylate, perchlorate, sulfate or nitrate; with the following provisos: 1) when R, and R, are -(CH2)4- Rg and Rg are -(CH2)4- Y and Rg are -CH 2 CRRCHg- at least one R is not methyl 2) when RG and R 7 are -(CHZ)20(CH,) 2 Rg and Rg are -(CH2)e0(CH )g Y and Rg are -CH2CRRCH2- at least one R is not mothyl; and 3) when both R, and R 7 are othyl Rg and R, are -(CH) 4 Y and Rg aro -CH 2 CRRCHI at least one R is not mothyl. s a.~ 41 24

2. Compounds as claimed in claim 1 wherein in proviso both R groups are not methyl.

3. Compounds as claimed in claim 1 wherein in proviso both R groups are not methyl.

4. Compounds as claimed in claim 1 wherein in proviso both R groups are not methyl.

Compounds as claimed in claim I wherein T is NR 8 or +NRRX-, Y and R 5 are -CH 2 CRRCH- and R is hydrogen or methyl,

6. Compounds as claimed in claim 5 wherein R, and R, are selected from cycloalkyl, alkyl, phenyl and benzyl; R 7 and R9 S are selected from hydrogen or alkyl; Z represents hydrogen, o methyl or methoxyl and X- represents Cl- or I-.

7. Compounds as claimed in claim 5 wherein R and R taken together represent a methylene group to form a carbocyclic ring optionally interrupted by oxygen,

8, Compounds as claimed in claim 5 wherein R 8 and R, taken together represent a mothylene group to form a, carbocyclic ring optionally interrupted by oxygen,

9. Compounds as claimed in claim 6 wherein R and R 8 are selected from cyclohexyl, n-octyl, n-dodeoyl, n-octadecyl and n-butyl. Compounds as claimed in claJi 5 wherein both R 7 and R are hydrogen, 11, Compounds of examples 1 41 herein. QATED this 9th day of January, 1991 AUSTRALIAN INSTITUTE OF MARINE SCIENCE By their Patent Attorneys CULLEN CO.