NITROGEN CONTAINING HETEROCYCLIC COMPOUNDS

Abstract: Compounds of the formula (III): or salts or acyl derivatives thereof, for use as antifungal and antiprotozoal agents are disclosed. Compositions containing the compounds are also disclosed as are method for the preparation of the compounds and intermediates in their preparation.

Description: The present invention relates to a group of compounds which are useful in the treatment of certain microbial and fungal infections, and to compositions containing the compounds. British Patent No. 1181959 discloses that compounds of the formula (I): wherein R a and R b are hydrogen or chlorine and R c is hydrogen or methyl are effective in the prophylaxis of thrombosis. U.S. Patent No. 3823148 discloses inter alia compounds of the formula (II): wherein R d and R e are hydrogen, lower alkyl or benzyl or together form a methylene bridge and R f , R g and R h are each hydrogen or lower alkyl, as having hypotensive and CNS activity. Specifically disclosed is the compound of the formula (II) wherein R d -R h are each methyl. It has now been discovered that a group of vinylisoquinolines has activity against protozoa, particularly those of the genus Trichomonas, for example Trichomonas vaginalis , an organism responsible for causing irritation of the vaginal mucosa and consequent abnormal vaginal discharge. Accordingly the present invention provides a compound of the formula (III): or a salt or acyl derivative thereof, wherein the dotted line represents either a single or a double bond; m is 0 when the dotted line represents a double bond, or m is 1 when the dotted line represents a single bond; R o is hydrogen or a group CH₂R¹⁰; R¹ is hydrogen, or a substituent chosen from fluorine, chlorine, methoxy, methyl, trifluoromethyl or methylthio; R², R³ and R⁴ are the same or different and each is hydrogen or a substituent group of the formula R¹⁰-A- wherein R¹⁰ is hydrogen or C₁₋₁₆ hydrocarbyl optionally substituted by halogen, fluorosulphonyl, cyano, hydroxy, thio, nitro, C₁₋₃ alkoxy or C₁₋₃ alkylthio wherein the alkoxy and alkylthio groups are optionally further substituted by halogen, hydroxy, thio, C₁₋₂ alkoxy or C₁₋₂ alkylthio, and A is oxygen, sulphur or methylene; or any two adjacent substituents R¹-R⁴ together form a methylanedioxy or ethylenedioxy group; R 5a is hydrogen or C₁₋₁₂ hydrocarbyl and R 5b is hydrogen or R 5a and R 5b are each C₁₋₄ alkyl or R 5a and R 5b together with the carbon atom to which they are attached, form a C₃₋₈ spirocycloalkyl ring; R 6a and R 6b are the same or different and each is hydrogen or C₁₋₁₂ hydrocarbyl or, together with the carbon atom to which they are attached, form a C₃₋₈ spirocycloalkyl ring; or R 5a and R 6a together with the carbon atoms to which they are attached form a five or six membered carbocyclic ring optionally containing up to two double bonds; R⁷ is hydrogen or fluorine; R⁸ is hydrogen, halogen, cyano, nitro or C₁₋₂ alkyl optionally substituted by one or more halogen atoms; R⁹ is a group -(CH=CH) n R¹¹ wherein n is 0-2 and R¹¹ is hydrogen, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl or a monocyclic, bicyclic, tricyclic or tetracyclic ring system containing between three and sixteen ring members, optionally substituted by hydroxy, thio, halogen, fluorosulphonyl, nitro, cyano, C₁₋₁₂ hydrocarbyl, C₁₋₁₂ hydrocarbyloxy, C₁₋₁₂ hydrocarbylthio wherein the said hydrocarbyl, hydrocarbyloxy and hydrocarbylthio groups are each optionally further substituted by halogen, hydroxy, thio, C₁₋₂ alkylthio or C₁₋₂ alkoxy groups; the groups R⁸ and R⁹ optionally being linked through a C₁₋₄ alkylene bridge, with the proviso that i) when R² and R³ are the same or different and each is hydroxy, methoxy or ethoxy; or when R² and R³ together form a methylenedioxy or ethylenedioxy group; or when R² is benxyloxy and R³ is methoxy, R¹ must be a group R¹² wherein R¹² is fluorine, chlorine, methyl, trifluoromethyl or methylthio and/or R⁴ must be a substituent as hereinbefore defined, or ii) when R³ and R⁴ are each methoxy and R⁹ is a phenyl group bearing a 2-chloro and a 5-nitro substituent, the phenyl group is additionally substituted by a substituent as hereinbefore defined and/or at least one of R¹, R² and R 5a -R⁸ is a substituent as hereinbefore defined, or iii) when R¹-R⁴ are each hydrogen and R⁹ is hydrogen, methyl or unsubstituted phenyl, R 5a and/or R 5b are substituents as hereinbefore defined, or iv) when R¹-R⁴ are each hydrogen and R⁹ is a phenyl group bearing bromo, chloro, hydroxy, methyl, methoxy or nitro substituents, the phenyl ring is trisubstituted by substituents as hereinbefore defined, or v) when R⁹ is a phenyl group substituted at the 3-, 4- and 5-positions with hydroxy or C₁₋₆ alkoxy and R² and R³ are each hydroxy, C₁₋₄ alkoxy or benxyloxy, at least one of R¹, R⁴, R⁷ and R⁸ is a substituent as hereinbefore defined. The terms substituted and substituent used above and hereinafter are used in their conventional sense, i.e. to denote the attachment to a particular atom or molecule of an atom or group other than hydrogen. Other protozoa against which compounds of the present invention are active include Coccidia , Leishmania , Plasmodium , Trypanosoma , intestinal flagellates such as Giardia lamblia , amoeba such as Entamoeba histolytica and the protozoal organism responsible for the cattle disease Babesia . Many of the compounds of the present invention have also been found to possess broad spectrum antifungal activity. Fungi against which they are active include those pathogenic in man, animals and plants, for example: Candida albicans , Candida tropicalis , Cryptococcus neoformans , Saccharomyces cerevisiae , Aspergillus fumigatus , Aspergillus niger , Microsporum canis , Microsporum gypseum , Trichophyton equinum , Trichophyton mentagrophytes , Trichophyton rubrum , Epidermophyton floccosum , and Exophiala werneckii , Fusarium species such as Fusarium solani , Sporothrix schenckii , Penicillium species such as P.rubrum, Altermaria species, Ceratocystis pilifera, Chrysosporium pruinosum, Helminthsporium species and Paecilomyces variotti. Accordingly, the present invention also provides a compound of formula (III) for use against protozoal and fungal infections. The above mentioned compounds have been bound to be particularly useful in the treatment of infections caused by the yeast-like fungus Candida albicans and closely related organisms. Such infections are generically referred to as Candidiasis or Moniliasis and include, for example, vaginal candidiasis. In another aspect, therefore, the present invention provides a compound of the formula (III ), or salts or acyl derivatives thereof, for use against Candidal infections in mammals. In particular, there is provided a compound of the formula (III ) for use against Candidal infections in humans. The invention further provides a compound of the formula (III ) for use in the treatment or prevention of fungal infections in plants and plant products, for example timber. Preferred compounds of the present invention include those wherein R³ is a group R¹⁴-A-, and R¹, R², R⁴-R⁹ are as hereinbefore defined, R¹⁴-A-being C₃₋₁₆ hydrocarbyl optionally substituted as defined hereinabove in respect of R¹⁰. More preferred novel compounds of the present invention are those wherein R¹, R² and R⁴-R⁹ are preferred substituents as hereinbefore defined and R¹⁴-A-is C₃₋₆ alkoxy, benzyloxy, phenyloxy, C₃₋₇ cycloalkyloxy, C₄₋₈ cycloalkylalkyloxy and C₃₋₆ alkenyloxy, each optionally substituted as hereinbefore defined. Particularly preferred compounds are those wherein R¹⁴-A- is chosen from the preferred substituents described above and R² and R⁴ are each hydrogen, C₁₋₄ alkoxy or C₁₋₄ alkyl. A most preferred group of compounds is that wherein R² and R⁴ are hydrogen. A preferred group of compounds of the present invention is that of the formula (IV): or salts or acyl derivatives thereof, wherein the dotted line represents either a single or a double bond and m, R o , R¹, R², R⁴, R⁹ and R¹⁴-A- are as hereinbefore defined, except that when the group C(R⁸)= CR⁷ R⁹ is 3,4,5-trihydroxystyryl or a mono-, di- or tri-ether thereof, R² is other than hydroxy, C₁₋₄ alkoxy or benzyloxy and/or one or both of R¹ and R⁴ are substituents as hereinbefore defined. A further preferred group of compounds of the present invention is that of the formula (V): or salts or acyl derivatives thereof, wherein m, R o , R¹ and R⁵-R⁹ are as hereinbefore defined; R¹⁵ is hydrogen or a substituent group R¹⁸-A- wherein A is as hereinbefore defined and R¹⁸ is hydrogen, C₃₋₆ alkyl, C₃₋₇ cycloalkyl, C₄₋₈ cycloalkylalkyl, or phenyl each optionally substituted by one or more halogen, cyano, nitro, hydroxy, thio, C₁₋₂ alkoxy or C₁₋₂ alkylthio; R¹⁶ is a group R¹⁹-A wherein A is as hereinbefore defined and R¹⁹ is hydrogen, C₁₋₂ alkyl, ethenyl or ethynyl; R¹⁷ is hydrogen or a group R¹⁴-A- as hereinbefore defined. Preferred substituents R¹ and R⁵-R⁹ are those defined in respect of formula (III). Preferred groups of the formulae R¹⁸-A-, R¹⁹-A- and R¹⁴-A are those in which A is oxygen or methylene. A most preferred group of the formula R¹⁹-A-is that wherein A is oxygen. Another preferred group of compounds provided by the present invention is that of the formula (VI): or salts or acyl derivatives thereof, wherein m, R o , R¹, R¹⁶ and R⁵-R⁹ are as hereinabove defined and R²⁰ and R²¹ are the same or different and each is a group R¹⁰A- as hereinbefore defined. A still further preferred group of compounds are those of the formula (VII): or salts or acyl derivatives thereof, wherein R²² is methoxy or a group R¹² and R²³ is a group R¹⁰A- and (R o ), m, R¹⁰A, R¹² and R⁵-R⁸ are as hereinbefore defined. One preferred group of compounds of the formula (IV) is that of the formula (VIII): or a salt or acyl derivative thereof, wherein R²⁴ is C₃₋₁₀ alkyl, benzyl, phenyl, C₃₋₇ cycloalkyl, C₄₋₈ cycloalkylalkyl and C₃₋₁₀ alkenyl each optionally substituted by halogen, cyano, hydroxy, thio, nitro, C₁₋₃ alkoxy or C₁₋₃ alkylthio wherein the alkoxy and alkylthio groups are optionally further substituted by halogen, hydroxy, thio, C₁₋₂ alkoxy or C₁₋₂ alkylthio and R²⁵ is hydrogen or up to five substituents chosen from hydroxy, C₁₋₁₂ hydrocarbyloxy, thio, C₁₋₁₂ hydrocarbylthio, halogen, nitro, cyano or C₁₋₁₂ hydrocarbyl, the said hydrocarbyl, hydrocarbylthio or hydrocarbyloxy groups being each optionally further substituted by halogen, hydroxy, thio, C₁₋₂ alkylthio or C₁₋₂ alkoxy groups. Most preferably, R²⁵ is phenyl or up to two substituents chosen from halogen, nitro, cyano, hydroxy, C₁₋₂ alkoxy and C₁₋₄ alkyl. Another preferred group of compounds of the formula (IV) is that of the formula (IX): or a salt or acyl derivative thereof, wherein R²⁴ is as hereinbefore defined. Still another preferred group of compounds of the formula (IV) is that of the formula (X): or a salt or acyl derivative thereof, wherein E represents a five or six membered ring containing one heteroatomic ring member chosen from oxygen, sulphur and nitrogen, the ring being optionally susbstituted by one or two groups chosen from hydroxy, C₁₋₂ alkoxy, halogen, C₁₋₂ alkyl, nitro or cyano. Preferred heterocyclic rings are pyridyl, thienyl and furyl. An additional preferred group of compounds of the formula (IV) is that of the formula (XI): or salts or acyl derivatives thereof, wherein G is an optionally substituted bicyclic or tricyclic group as hereinbefore defined. Preferred bicyclic groups are naphthyl, anthryl, phenanthryl, indolyl, quinolyl and isoquinolyl or reduced or partially reduced derivatives thereof. Yet another preferred group of compounds of the formula (IV) is that of the general formula (XII): or a salt or acyl derivative thereof, wherein R²⁶ is chosen from fluorine, chlorine, bromine and methyl. Preferred compounds of the present invention include: 1. ( E )-6-Butyloxy-1-(2-cyclohexylvinyl)-3,4-dihydroisoquinoline 2. 6-Benzyloxy-1-[2-cyclohexylvinyl]-3,4-dihydroisoquinoline 3. 6-Butyloxy-3,4-dihydro-1-styrylisoquinoline 4. 1-(2-Chlorostyryl)-3,4-dihydro-6-propyloxyisoquinoline 5. ( E )-1-(2-Cyclohexylvinyl)-3,4-dihydro-6-(2-methylpropyloxy)-isoquinoline 6. (E)-1-(2-Cyclohexylvinyl)-3,4-dihydro-6-propyloxyisoquinoline 7. (E)-1-(Cyclohexylvinyl)-6-hexyloxy-3,4-dihydroisoquinoline 8. (E)-6-(4-Chlorobenzyloxy)-1-(2-cyclohexylvinyl)-3,4-dihydroisoquinoline 9. (E)-6-Benzyloxy-1-[2-(cyclohex-3-enyl)vinyl]-3,4-dihydroisoquinoline 10. 6-Butyloxy-3,4-dihydro-1-(2,5-dimethoxystyryl)-isoquinoline 11. 6-Butyloxy-3,4-dihydro-1-(3,4,5-trimethoxystyryl)-isoquinoline 12. 6-Butyloxy-1-(2-chlorostyryl)-3,4-dihydroisoquinoline 13. 6-Butyloxy-3,4-dihydro-1-(4-cyanostyryl)-isoquinoline 14. 6-Butyloxy-3,4-dihydro-1-(2,4-dimethoxystyryl)-isoquinoline 15. 6-Butyloxy-1-(4-t-butylstyryl)-3,4-dihydroisoquinoline 16. 6-Butyloxy-3,4-dihydro-1-(4-isopropylstyryl)-isoquinoline 17. 6-Butyloxy-3,4-dihydro-1-(4-methylstyryl)-isoquinoline 18. 6-Butyloxy-3,4-dihydro-1-(3,4-dimethoxystyryl)-isoquinoline 19. 6-Butyloxy-3,4-dihydro-1-(4-nitrostyryl)-isoquinoline 20. 6-Butyloxy-3,4-dihydro-1-(2,4-dimethylstyryl)-isoquinoline 21. 6-Butyloxy-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 22. 6-Butyloxy-1-(4-chlorostyryl)-3,4-dihydroisoquinoline 23. ( E )-6-Butyloxy-1-(2-pentafluorophenyl)vinyl-3,4-dihydroisoquinoline 24. 6-Butyloxy-3,4-dihydro-1-(4-phenylstyryl)-isoquinoline 25. 6-Butyloxy-1-(2,4-dichlorostyryl)-3,4-dihydro-7-methyl-isoquinoline 26. 3,4-Dihydro-1-(4-methylstyryl)-6-propyloxyisoquinoline 27. 1-(4-Cyanostyryl)-3,4-dihydro-6-propyloxyisoquinoline 28. 3,4-Dihydro-6-propyloxy-1-styrylisoquinoline 29. 3,4-Dihydro-1-(2,5-dimethoxystyryl)-6-propyloxyisoquinoline 30. 1-(4-Chlorostyryl)-3,4-dihydro-6-propyloxyisoquinoline 31. 1-(2,4-Dichlorostyryl)-3,4-dihydro-6-propyloxyisoquinoline 32. 3,4-Dihydro-1-(4-phenylstyryl)-6-propyloxyisoquinoline 33. 1-(2,4-Dichlorostyryl)-3,4-dihydro-6-(3,3-dimethylbutyloxy)-isoquinoline 34. 1-(2-Chlorostyryl)-3,4-dihydro-6-(3,3-dimethylbutyloxy)-isoquinoine 35. 1-(4-Chlorostyryl)-3,4-dihydro-6-(3,3-dimethylbutyloxy)-isoquinoline 36. 6-Cyclohexylmethoxy-3,4-dihydro-1-styrylisoquinoline 37. 1-(4-Cyanostyryl)-6-cyclohexylmethoxy-3,4-dihydroisoquinoline 38. 1-(4-Chlorostyryl)-6-cyclohexylmethoxy-3,4-dihydroisoquinoline 39. 1-(2-Chlorostyryl)-6-cyclohexylmethoxy-3,4-dihydroisoquinoline 40. 1-(2,4-Dichlorostyryl)-6-cyclohexylmethoxy-3,4-dihydroisoquinoline 41. ( E )-6-Cyclohexylmethoxy-1-(2-(pentafluorophenyl)vinyl)-3,4-dihydroisoquinoline 42. 1-(4-Chlorostyryl)-3,4-dihydro-6-(2-methylpropyloxy)-3-methylisoquinoline 43. 1-(2,4-Dichlorostyryl)-3,4-dihydro-3-methyl-6-(2-methylpropyloxy)-isoquinoline 44. 1-(2-Chlorostyryl)-3,4-dihydro-3-methyl-6-(2-methylpropyloxy)-isoquinoline 45. 6-(But-3-enyloxy)-1-(4-chlorostyryl)-3,4-dihydroisoquinoline 46. 6-(But-3-enyloxy)-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 47. 1-(2-Chlorostyryl)-3,4-dihydro-6-(2-methylpropyloxy)-isoquinoline 48. 1-(2,4-Dichlorostyryl)-3,4-dihydro-6-(2-methylpropyloxy)-isoquinoline 49. 1-(2,4-Dichlorostyryl)-3,4-dihydro-6-(3-methylbutyloxy)-isoquinoline 50. 1-(4-Chorostyryl)-3,4-dihydro-6-(3-methylbutyloxy)-isoquinoline 51. 1-(4-Chlorostyryl)-3,4-dihydro-6-(2-methylpropyloxy)-isoquinoline 52. 6-Benzyloxy-1-(4-cyanostyryl)-3,4-dihydroisoquinoline 53. 6-Benzyloxy-3,4-dihydro-1-styrylisoquinoline 54. 6-Benzyloxy-1-(2-chlorostyryl)-3,4-dihydroisoquinoline 55. 6-Benzyloxy-3,4-dihydro-1-(2,5-dimethoxystyryl)-isoquinoline 56. 6-Benzyloxy-3,4-dihydro-1-(2,4-dimethoxystyryl)-isoquinoline 57. 6-Benzyloxy-1-(4-chlorostyryl)-3,4-dihydroisoquinoline 58. 6-Benzyloxy-3,4-dihydro-1-(4-methylstyryl)-isoquinoline 59. 6-Benzyloxy-3,4-dihydro-1-(4-isopropylstyryl)-isoquinoline 60. 6-Benzyloxy-1-(4-t-butylstyryl)-3,4-dihydroisoquinoline 61. 6-Benzyloxy-3,4-dihydro-1-(2,4-dimethylstyryl)-isoquinoline 62. 6-Benzyloxy-3,4-dihydro-1-(4-nitrostyryl)-isoquinoline 63. 6-Benzyloxy-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 64. ( E )-6-Benzyloxy-1-[2-(pentafluorophenyl)vinyl]-3,4-dihydroisoquinoline 65. 1-(4-Chlorostyryl)-3,4-dihydro-6-phenoxy-isoquinoline 66. 1-(2,4-Dichlorostyryl)-3,4-dihydro-6-phenoxyisoquinoline 67. 6-(4-Chlorophenoxy)-1-(4-chlorostyryl)-3,4-dihydroisoquinoline 68. 6-(4-Chlorophenoxy)-3,4-dihydro-1-(4-nitrostyryl)-isoquinoline 69. 6-(4-Chlorophenoxy)-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 70. 6-(4-Chlorophenoxy)-3,4-dihydro-1-styrylisoquinoline 71. 6-(4-t-Butylphenoxy)-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 72. 6-(4-t-Butylphenoxy)-1-(4-chlorostyryl)-3,4-dihydroisoquinoline 73. 6-(4-t-Butylphenoxy)-3,4-dihydro-1-styrylisoquinoline 74. 6-Hexyloxy-3,4-dihydro-1-styrylisoquinoline 75. 1-(4-Cyanostyryl)-6-hexyloxy-3,4-dihydroisoquinoline 76. 1-(2-Chlorostyryl)-3,4-dihydro-6-hexyloxyisoquinoline 77. 1-(4-Chlorostyryl)-6-hexyloxy-3,4-dihydroisoquinoline 78. 1-(2,4-Dichlorostyryl)-6-hexyloxy-3,4-dihydroisoquinoline 79. 6-(4-t-Butylbenzyloxy)-1-(4-cyanostyryl)-3,4-dihydroisoquinoline 80. 6-(4-t-Butylbenzyloxy)-3,4-dihydro-1-styrylisoquinoline 81. 6-(4-t-Butylbenzyloxy)-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 82. 6-Benzyloxy-1-(4-phenylstyryl)-3,4-dihydroisoquinoline 83. 6-(4-Chlorobenzyloxy)-3,4-dihydro-1-styrylosoquinoline 84. 6-(4-Chlorobenzyloxy)-1-(4-chlorostyryl)-3,4-dihydroisoquinoline 85. 6-(4-Chlorobenzyloxy)-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 86. 6-(2-Chlorobenzyloxy)-1-(4-cyanostyryl)-3,4-dihydroisoquinoline 87. 6-(2-Chlorobenzyloxy)-1-(2-chlorostyryl)-3,4-dihydroisoquinoline 88. 6-(2-Chlorobenzyloxy)-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 89. 6-(2,4-Dichlorobenzyloxy)-1-(4-cyanostyryl)-3,4-dihydroisoquinoline 90. 1-(4-Chlorostyryl)-6-(2,4-dichlorobenzyloxy)-3,4-dihydroisoquinoline 91. 6-(2,4-Dichlorobenzyloxy)-3,4-dihydro-1-styrylisoquinoline 92. 6-(2,4-Dichlorobenzyloxy)-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 93. 6-Benzyloxy-3,4-dihydro-1-(3,4,5-trimethoxystyryl)-isoquinoline 94. 3,4-Dihydro-3-methyl-6- iso -propyloxy-1-styrylisoquinoline 95. 3,4-Dihydro-6-ethoxy-3-propyl-1-styrylisoquinoline 96. 3,4-Dihydro-3-ethyl-6-propyloxy-1-styrylisoquinoline 97. 1-(2-Chlorostyryl)-6-(3-trifluoromethyl benzyloxy)-3,4-dihydroisoquinoline 98. 1-(4-Cyanostyryl)-6-(3-trifluoromethyl benzyloxy)-3,4-dihydroisoquinoline 99. 3,4-Dihydro-1-styryl-6-(3-trifluoromethyl benzyloxy)-isoquinoline 100. 6-Butyloxy-1-(2-fluorostyryl)-3,4-dihydroisoquinoline 101. 6-Benzyloxy-1-(2-fluorostyryl)-3,4-dihydroisoquinoline 102. ( E )-6-Butyloxy-3,4-dihydro-1-[2-(4-bromo-2-thienyl)vinyl]-isoquinoline 103. ( E )-6-Butyloxy-3,4-dihydro-1-[2-(5-bromo-2-thienyl)vinyl]-isoquinoline 104. ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(2-thienyl)vinyl]-isoquinoline 105. ( E )-6-Butyloxy-3,4-dihydro-1-[2-(2-thienyl)vinyl]-isoquinoline 106. ( E )-6-Benzyloxy-3,4-dihydro-1-(3-thienyl)vinyl isoquinoline 107. ( E )-6-Butyloxy-3,4-dihydro-1-(3-thienyl)vinylisoquinoline 108. ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(4-bromo-2-thienyl)vinyl]-isoquinoline 109. ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(5-bromo-2-thienyl)vinyl]-isoquinoline 110. ( E )-6-Butyloxy-1-[2-(2-furyl)vinyl]-3,4-dihydroisoquinoline 111. ( E )-6-Benzyloxy-1-[2-(2-furyl)vinyl]-3,4-dihydroisoquinoline 112. ( E )-6-(4-Chlorobenzyloxy)-1-[2-(2-furyl)vinyl]-3,4-dihydroisoquinoline 113. ( E )-3,4-Dihydro-6-propyloxy-1-[2-(5-nitro-2-furyl)]vinyl isoquinoline 114. ( E )-6-Butyloxy-3,4-dihydro-1-[2-(5-nitro-2-furyl)]vinyl isoquinoline 115. ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(5-nitro-2-furyl)]vinyl isoquinoline 116. ( E )-6-Butyloxy-3,4-dihydro-1-[2-(3-methyl-2-thienyl)vinyl]-isoquinoline 117. ( E )-3,4-Dihydro-1-[2-(3-methyl-2-thienyl)vinyl]-6-propyloxyisoquinoline 118. ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(3-methyl-2-thenyl)vinyl]-isoquinoline 119. ( E )-3,4-Dihydro-1-[2-(5-methyl-2-furyl)vinyl]-6-propyloxy-isoquinoline 120. ( E )-6-Butyloxy-3,4-dihydro-1-[2-(5-methyl-2-furyl)vinyl]-isoquinoline 121. ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(5-methyl-2-furyl)vinyl]-isoquinoline 122. ( E )-3,4-Dihydro-1-[2-(5-nitro-2-thienyl)vinyl]-6-propyloxyisoquinoline 123. ( E )-6-Butyloxy-3,4-dihydro-1-[2-(5-nitro-2-thienyl)vinyl]-isoquinoline 124. ( E )-6-Butyloxy-3,4-dihydro-1-[2-(4-pyridyl)-vinyl]-isoquinoline 125. ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(4-pyridyl)-vinyl]-isoquinoline 126. ( E , E )-6-Benzyloxy-3,4-dihydro-1-(4-phenylbuta-1,3-dienyl)-isoquinoline 127. ( E , E )-3,4-Dihydro-1-(penta,-1,3-dienyl)-6-propyloxyisoquinoline 128. ( E , E )-6-Butyloxy-3,4-dihydro-1-(penta-1,3-dienyl)-isoquinoline 129. ( E , E )-6-Hexyloxy-3,4-dihydro-1-(penta-1,3-dienyl)-isoquinoline 130. ( E , E )-6-Benzyloxy-3,4-dihydro-1-(penta-1,3-dienyl)-isoquinoline 131. ( E )-3,4-Dihydro-1-[2-(2-naphthyl)vinyl]-6-propyloxyisoquinoline 132. ( E )-6-Butyloxy-3,4-dihydro-1-[2-(2-naphthyl)-vinyl]-isoquinoline 133. ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(2-naphthyl)-vinyl]-isoquinoline 134. ( E )-3,4-Dihydro-1-[2-(1-naphthyl)vinyl]-6-propyloxyisoquinoline 135. ( E )-6-Butyloxy-3,4-dihydro-1-[2-(1-naphthyl)vinyl]-isoquinoline 136. ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(1-naphthyl)vinyl]-isoquinoline 137. 3,4-Dihydro-1-prop-1-enyl-6-propyloxyisoquinoline 138. 6-Benzyloxy-3,4-dihydro-1-prop-1-enylisoquinoline 139. ( E )-6-Butyloxy-3,4-dihydro-1-(penta-1,3-dienyl)-isoquinoline 140. 6-Butyloxy-3,4-dihydro-1-(4-phenylbuta-1,3-dienyl)-isoquinoline 141. 1-[2-(9-Anthryl)vinyl]-6-benzyloxy-3,4-dihydroisoquinoline 142. 1-[2-(9-Anthryl)vinyl]-3,4-dihydro-6-propyloxy isoquinoline 143. 3,4-Dihydro-1-[2-(9-phenanthryl)vinyl]-6-propyloxyisoquinoline 144. 6-Butyloxy-3,4-dihydro-1-[2-(5-methyl-2-thienyl)vinyl]-isoquinoline, 145. 3,4-Dihydro-1-[2-(5-methyl-2-thienyl)vinyl]-6-propyloxyisoquinoline, 146. 6-Benzyloxy-3,4-dihydro-1-[2-(5-methyl-2-thienyl)vinyl]-isoquinoline, 147. ( Z )-6-Butyloxy-1-(1-bromo-2-phenylvinyl)-3,4-dihydroisoquinoline 148. ( Z )-6-Benzyloxy-1-(1-bromo-2-phenylvinyl)-3,4-dihydroisoquinoline 149. ( Z )-6-Butyloxy-1-(1-fluoro-2-phenylvinyl)-3,4-dihydrosioquinoline 150. ( Z )-6-Butyloxy-1-(1-chloro-2-phenylvinyl)-3,4-dihydroisoquinoline 151. ( Z )-6-Benzyloxy-1-(1-chloro-2-phenylvinyl)-3,4-dihydroisoquinoline 152. ( E )-6-Benzyloxy-3,4-dihydro-1-[(2-phenyl)-1-methylvinyl]-isoquinoline 153. ( E )-6-Butyloxy-3,4-dihydro-1-[(2-phenyl)-1-methylvinyl]-isoquinoline 154. ( Z )-6-Benzyloxy-1-(1-fluoro-2-phenylvinyl)-3,4-dihydroisoquinoline 155. 1-(2,4-Dichlorostyryl)-3,4-dihydro-6,7-dipropyloxyisoquinoline 156. 1-(4-Chlorostyryl)-3,4-dihydro-3-methyl-6,7-dipropyloxy isoquinoline 157. 6,7-Dibutyloxy-1-(4-chlorostyryl)-3,4-dihydroisoquinoline 158. 1-(2,4-Dichlorostyryl)-3,4-dihydro-3-methyl-6,7-dipropyloxyisoquinoline 159. 6,7-Dibutyloxy-1-(4-chlorostyryl)-3-methyl-isoquinoline 160. 6-Butyloxy-1-(2,4-dichlorostyryl)-7-ethoxy-3,4-dihydroisoquinoline 161. 7-Butyloxy-1-(2,4-dichlorostyryl)-6-ethoxy-3,4-dihydroisoquinoline 162. 7-Butyloxy-1-(4-chlorostyryl)-6-ethoxy-3,4-dihydroisoquinoline 163. 6-Butyloxy-1-(4-chlorostyryl)-7-ethoxy-3,4-dihydroisoquinoline 164. 1-(4-Chlorostyryl)-3,4-dihydro-6,7-dipentyloxyisoquinoline 165. 1-(4-Chlorostyryl)-6,7-dihexyloxy-3,4-dihydroisoquinoline 166. 3,4-Dihydro-1-(4-hydroxystyryl)-6,7-dipropyloxyisoquinoline 167. 3,4-Dihydro-1-(4-trifluoromethylstyryl)-6,7-dipropyloxyisoquinoline 168. 1-(4-Chlorostyryl)-3,4-dihydro-6,7-dipropyloxy isoquinoline 169. 6,7-Bisbenzyloxy-1-(2-Chlorostyryl)-3,4-dihydroisoquinoline 170. 6,7-Bisbenzyloxy-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 171. 5,6-Bis(benzyloxy)-3,4-dihydro-1-styrylisoquinoline 172. 5,6-Bis(benzyloxy)-1-(4-chlorostyryl)-3,4-dihydroisoquinoline 173. 5,6-Bis(benzyloxy)-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 174. 5-Benzyloxy-3,4-dihydro-8-methoxy-1-styryl-isoquinoline 175. 5-Benzyloxy-1-(4-cyanostyryl)-3,4-dihydro-8-methoxyisoquinoline 176. 6-Benzyloxy-1-(4-chlorostyryl)-3,4-dihydro-7-methoxy-5-propylisoquinoline 177. 6-Benzyloxy-1-(2-chlorostyryl)-3,4-dihydro-7-methoxy-5-propylisoquinoline 178. 6-Hydroxy-3,4-dihydro-7-methoxy-5-propyl-1-styrylisoquinoline 179. 1-(2,4-Dichlorostyryl)-3,4-dihydro-6-hydroxy-7-methoxy-5-propylisoquinoline 180. 1-(2-Chlorostyryl)-3,4-dihydro-6-hydroxy-7-methoxy-5-propylisoquinoline 181. 1-(4-Chlorostyryl)-3,4-dihydro-5-hydroxy-8-methoxyisoquinoline 182. 6-Butyloxy-1-(2,4-dichlorostyryl)-3,4-dihydro-7-methylisoquinoline 183. 1-(4-Acetoxystyryl)-3,4-dihydro-6,7-dipropyloxy isoquinoline 184. 1,2,3,4-Tetrahydro-6,7-dibutyloxy-1-(4-chlorostyryl)-isoquinoline 185. 1-(4-Chlorostyryl)-1,2,3,4-tetrahydro-6,7-dipropyloxy isoquinoline 186. 3,4-Dihydro-3,3-dimethyl-6-propyloxy-1-styrylisoquinoline 187. 3,4-Dihydro-3,3,4,4-tetramethyl-6-propyloxy-1-styrylisoquinoline 188. 6-Butyloxy-3,4-dihydro-3,3-dimethyl-1-styrylisoquinoline 189. 3,4-Dihydro-3,3-dimethyl-6-heptyloxy-1-styrylisoquinoline 190. 3,4-Dihydro-4,4-dimethyl-6-propyloxy-1-styrylisoquinoline 191. 4-Butyloxystyryl-3,4-dihydroisoquinoline 202. 6-Butyloxy-3,4-dihydro-1-[2-(3,4-dihydro-5,6,7-trimethoxynaphthyl)]-isoquinoline 203. 6-Benzyloxy-3,4-dihydro-1-[2-(3,4-dihydro-5,6,7-trimethoxynaphthyl]-isoquinoline or salts or acyl derivatives thereof. The most preferred compound of the present invention is ( E )-1-(2-Cyclohexylvinyl)-3,4-dihydro-6-propyloxyisoquinoline and its salts, particularly preferred salt being that formed with phosphoric acid. Compounds of the formula (III) to (XII) exist in a number of isomeric forms. The present invention provides mixtures of the isomeric forms as well as the individual isomers. Thus the compounds of the present invention may exist in either the E or Z isomeric forms with reference to the vinyl double bond. The E -isomers are generally preferred; the exceptions being those compounds wherein the vinyl double bond is trisubstituted and the third substituent is nitro, trifluoromethyl or halogen, in which cases the Z -isomers are preferred. When the compound is of the formula (III) to (VII) and is substituted at the 3-and/or 4-positions, it may exist in optical isomeric forms with respect to these positions, and when the compound is a tetrahydroisoquinoline, it may also exist in optical isomeric forms with respect to the 1-position of the isoquinoline ring. The substituents hereinbefore defined may also contain assymetric centres thereby imparting optical activity to the compound. All optical forms are within the scope of the present invention. Suitably the compounds of the formula (III to (XII) are present in the form of the free base or an acid addition salt thereof. Suitable acid addition salts of the compounds of the formulae (III) to (XII) include those formed with both organic and inorganic acids. Solvates, and particularly hydrates, are also within the scope of the present invention. Thus, suitable salts include those formed from hydrochloric, hydrobromic, nitric, perchloric, sulphuric, citric, tartaric, phosphoric, lactic, benzoic, glutamic, oxalic, aspartic, pyruvic, acetic, succinic, fumaric, maleic, oxaloacetic, isethionic, stearic, phthalic, methanesulphonic, p-toluenesulphonic, benzenesulphonic, lactobionic and glucuronic acids. Most preferably, the acid addition salts will be pharmaceutically acceptable. When the compounds of the formulae (III) to (XII) are substituted by hydroxy groups, alkali metal salts of these compounds may be formed and these salts also comprise part of the present invention. Particularly suitable alkali metal salts are those formed with sodium and potassium. Suitable acyl derivatives are those wherein a hydroxy group is substituted by a group -COM- wherein M is hydrogen or a group R²⁵ as hereinbefore defined. When the compounds of the formula (III) are 1, 2, 3, 4-tetrahydroisoquinolines, they form acyl derivatives wherein the group -COM is attached to the nitrogen atom in the 2-position of the isoquinoline ring. Whilst it is possible for a compound of the formula (III) to be administered alone as the raw chemical, it is preferable to present the compound of formula (III) as a pharmaceutical formulation. The exact method of administration to be used ultimately will be at the discretion of the physician treating the condition and will depend upon the particular nature of the infection being treated. However, it has been found most convenient to administer the compounds of the formulae (III) or (IIIA) topically. Accordingly in another aspect, the present invention provides a topical formulation, comprising a compound of the formula (III) or a salt or acyl derivative thereof in admixture with one or more pharmaceutically acceptable carriers or excipients. The formulation may take the form of an ointment, cream, suspension, lotion, powder, solution, paste, gel, spray, aerosol or oil. Alternatively, a formulation may comprise a pessary or a suppository or dressings such as bandages and adhesive plasters impregnated with active ingredients and optionally one or more excipients or diluents. Carriers which may be used include eg. polyhydric alcohols such as polyethylene glycols, propylene glycol or glycerol. Suitable excipients are those known in the art to be appropriate. The active ingredient is generally present in a concentration of between 0.1 and 95% w/w of the composition and preferably is present at a concentration of 0.1-5%. Formulations particularly suitable for rectal and vaginal administration suitably are presented as unit-dose suppositories or pessaries. These may be prepared by admixture of the active ingredient with one or more conventional solid carriers, for example coca butter, and shaping the resulting mixture. Alternatively, in the case of vaginal administration, the formulation may be presented as a tampon impregnated with the active ingredients and optionally one or more excipients or diluents. Other formulation suitable for rectal and vaginal administration include creams, gels, foams, pastes and sprays. The frequency of administration of the composition, the amount of compound administered and the duration of the treatment will of course all vary according to the severity of the infection or condition. Ultimately the treatment regimen will be at the discretion of the physician. Typically, pessaries will be inserted into the vagina singly or in twos or threes, generally once or twice daily. It is often convenient to administer pessaries nightly. Vaginal creams, gels, foams or ointments will generally be administered one to four times daily and, similarly, it may be found convenient to apply the medicament at night. Application of a cream is often assisted by means of an applicator. Often, a cream will be administered in conjunction with another form of the medicament, for example, a tampon or pessary. Combinations such as these are within the scope of the present invention. Tampons will usually be administered once daily although in certain cases it may prove necessary to increase the frequency of administration. The duration of treatment generally will be between one and fourteen days although longer periods may be required in some instances. As mentioned above, the quantity of active compound administered daily will depend upon the severity of the infection but typically it will vary between 10mg and 1g. Most conveniently the quantity of active compound administered will vary between 20mg and 500mg daily. Although topical formulations are preferred, compounds of the present invention may also be administered by other routes eg. orally or parenterally. Thus, in a further aspect, the present invention provides a pharmaceutical composition comprising a compound of the formula (III) in combination with a pharmaceutically acceptable carrier. By the terms "pharmaceutical composition" and "pharmaceutically acceptable carrier" are meant those compositions and carriers suitable for use in human and/or veterinary medicine.The pharmaceutically acceptable carriers present in the compositions of the present invention are materials recommended for the purpose of administering the medicament. These may be liquid, solid or gaseous materials, which are otherwise inert or medically acceptable and are compatible with the active ingredients. These pharmaceutical compositions may be given parenterally, used as a suppository or pessary or applied topically as an ointment, cream or powder. For oral administration, fine powders or granules will contain diluting, dispersing and/or surface active agents, and may be presented in a draught, in water or in a syrup, in capsules, cachets or tablets in the dry state or in a non-aqueous suspension in water or syrup. Where desirable or necessary, flavouring, preserving, suspending, thickening or emulsifying agents can be included. For parenteral administration, the compounds may be presented in sterile aqueous injection solutions which may contain antioxidants, buffers and other pharmaceutically acceptable additives where necessary. Other ingredients which may be included in compositions comprising compounds of the formula (III) include medically inert ingredients such a solid or liquid diluents eg. lactose, glucose, starch or calcium phosphate for tablets or capsules; olive oil or ethyl oleate for soft capsules; and water or vegetable oil for suspensions or emulsions; lubricating agents such as talc or magnesium stearate; gelling agents such as colloidal clays; thickening agents such a gum tragacanth or sodium alginate; and other therapeutically acceptable accessory ingredients such a humectants, preservatives, buffers and antioxidants which are useful as carriers in such formulations. For application to plants, or plant products such as timber, compounds of the formula (IIIa) typically are formulated as dusts or powders or as solutions or suspensions for spraying, dipping or painting on to the plant or plant product, the formulations being prepared according to methods well known in the art of plant and plant product protection. Where desired the formulations can be presented as concentrates, eg.powders and liquid concentrates, for dilution to the appropriate strength. The formulations optionally may contain other fungicides and/or preservatives, insecticides, dyes, solvents and diluents. For the treatment of timber, particularly suitable methods of administering the compounds of the formula (IIIa) include dipping, painting or vacuum impregnation of the timber. The antifungal activity of the compounds of the present invention may be evaluated by determining the minimum fungistatic (inhibition) concentration (m.i.c.). This test is usually performed by preparing a series of plates or tubes containing a suitable nutrient medium, each plate or tube also containing a different concentration of the test compound and then inoculating the medium with the fungal species. After an incubation period the plates are examined visually for the presence or absence of fungal growth. The m.i.c. is the minimum concentration required to prevent fungal growth. The antiprotozoal eg. antitrichomonal, activity of the compounds of the present invention may be assessed by conventional methods, for example by determining the minimum inhibition concentration (m.i.c.) or 50% inhibition level (IC₅₀). It follows from the above that many of the compounds of the present invention are active against both trichomonads and fungi and, indeed, those compounds exhibiting such dual activity represent a preferred embodiment of the present invention. In addition, many of the compounds are also active against other parasitic organisms, for example filarial worms such as Brugia pahange and Nippostrongylus brasiliensis . It has also been found that compounds of the formula (III) have activity against anaerobic or substantially anaerobic bacteria such as Gardnerella vaginalis , the species now known to be responsible for many of the conditions hitherto classified as non-specific vaginitis, B . fragilis , Cl . difficile and Fuso . nucleatum certain compounds of the formula (III) additionally have insecticidal activity, for example activity against mosquito larvae and clothes moth and carpet beetle larvae. The present invention also provides processes for the preparation of the compounds of the formula (III) which processes comprise: a) the cyclisation of a compound of the formula (XIII) wherein R¹-R⁷ are as hereinbefore defined, and either Z¹ is hydrogen and X¹-C-Y¹ is a group C=O, or X¹ is a leaving group and Y¹ and Z¹ together form a second bond between C a and N. b) when it is desired to prepare a compound of the formula (III) in which R⁷ is hydrogen and R⁸ is hydrogen, C₁₋₂alkyl, cyano or nitro, the condensation of a compound of the formula (XIV) wherein R¹-R⁶ are as hereinbefore defined and R 8a and R 8b are either both hydrogen or together form a group=P(O Alkyl)₂ or =PPh₃, with a compound of the formula (XV) wherein R⁷ and R⁹ are as hereinbefore defined. c) (i) When it is desired to prepare a compound of the formula (III) wherein both R 6a and R 6b are C₁₋₄ alkyl groups; the reaction of a compound of the formula (XVI) with a compound of the formula (XVII) wherein R¹-R⁵ and R⁷-R⁹ are as hereinbefore defined, R 6a and R 6b are the same or different and each is a C₁₋₄ alkyl group and X² is a leaving group. (ii) When it is desired to prepare a compound of the formula (III) wherein R 6b is a group CH₂R 6c and R 6c is hydrogen or C₁₋₃ alkyl, the reaction of compound of the formula (XVIa): with a compound of the formula (XVII). d) the cyclisation of a compound of the formula (XVIII) where in R¹-R⁹ are as hereinbefore defined. e) the conversion of a compound of the formula (III) into another compound of the formula (III) a) The cyclisation of a compound of the formula (XIII) wherein Z is hydrogen and X-C-Y is a group C=O, which is known to those skilled in the art as a Bischler-Napieralski reaction, is usually carried out by reacting the compound (XIII) with a dehydrating agent in the presence of an inert solvent, for example according to the conditions described in Organic Reactions , 1951, vol. VI, 74 or British Patent No. 1,181,959. Typically the solvent is a hydrocarbon such as benzene, toluene, xylene, cymene, decalin or tetralin, an inert polar aprotic solvent such as nitrobenzene or a halogenated hydrocarbon such as chloroform, carbon tetrachloride, 1,2-dichloroethane chlorobenzene, dichlorobenzene, trichlorobenzene or brominated alkenes. Preferably the solvent is chloroform or toluene. When the dehydrating agent is a liquid, e.g. phosphorus oxychloride, the reaction may, if so desired, be carried out in the neat reagent. The condensing or dehydrating agent is usually chosen from phosphorus pentoxide, phosphorus oxychloride, polyphosphoric acid, ethyl polyphosphate, phosphorus pentachloride, aluminium chloride, stannic chloride, thionyl chloride, zinc chloride, aluminium oxide, phosphorus oxybromide, trifluoroacetic acid, optionally in the presence of trifluoroacetic anhydride, and silicon tetrachloride. It has been found convenient to employ a phosphorus based reagent as the dehydrating agent; preferably the reagent is phosphorus oxychloride or phosphorus pentoxide or mixtures thereof. The cyclisation typically takes place at temperatures between 0 o C and 206 o C and conveniently is carried out between 55 o C and 120 o C. Compounds of the formula (XIII) wherein Z is hydrogen and X-C-Y is a group C=O are prepared by reacting amines of the formula (XIX) wherein R¹-R⁶ are as hereinbefore defined, with carboxylic acids of the formula (XX) or functional derivatives thereof such a acid halides, esters, amides or anhydrides, wherein R⁷-R⁹ are as hereinbefore defined. Acylation of the amines of the formula (XIX) will take place under a wide range of conditions well known to those skilled in the art, for example see U.S. Patent No. 3,823,148 Amines of the formula (XIX) may be synthesised according to methods well known to those skilled in the art. It was found particularly convenient to prepare amines of the formula (XIX) wherein R³ is R²⁴O and R²⁴ is as hereinbefore defined, according to the route described in schemes 1 and 2 below. b) The reaction of compounds of the formula (XIV), wherein R 8a and R 8b are hydrogen, with compounds of the formula (XV) takes place under conditions similar to those described in Izv. Akad. Nauk. Arm. SSR Khim. Nauki 17(5), 5 62-6(1964) (Russ) (C.A. 62 , 11778d) or C.R. Hebd. Seances Acad. Sci., Ser., C . 1978, 286(24), 675-7 (CA 89 : 163618j) Thus, for example, the reactants may simply be stirred together in the presence of an acylating agent such as acetic anhydride. Alternatively, the reaction may be carried out under basic conditions, for example, the 1-methyl group may be lithiated and the lithio-derivative subsequently treated with an aldehyde or ketone. Compounds of the formula (XIV) wherein R 8a and R 8b are hydrogen may be prepared by means of the Bischler-Napieralski reaction of a compound of the formula (XXI): wherein R¹-R⁶ and R⁸ are as hereinbefore defined. Compounds of the formula (XIV) wherein R 8a and R 8b together constitute a group: or =PPh₃ may be prepared and reacted with carbonyl compounds of the formula (XV) under conditions analogous to those well known to the man skilled in the art of Wittig end related reactions, see for example E. C. Taylor and S. F. Martin, J. Amer. Chem. Soc., 1972, 94 , 2874, A. Buzas and J. P. Finet, Tetrahedron Letters , 1976, 2433 and N. Whittaker, J. Chem. Soc. (C), 1969, 94. Thus the reactions are suitably carried out in an anhydrous solvent inert to the reaction conditions employed, for example toluene, benzene, tetrahydrofuran, dioxan, dimethylsulphoxide, glycol ethers and C₁₋₆alkyl ethers, in the temperature range -80 o C to 160 o C. The reaction is conveniently carried out between O o C and 50 o C and most conveniently is carried out at room temperature. Compounds of the formula (XIV) wherein R 8a and R 8b together form a group or =PPh₃ typically are prepared by reacting a compound of the formula (XXII) wherein R¹-R⁶ are as hereinbefore defined and X³ is chlorine, bromine or iodine, with triphenylphosphine or a trialkylphosphite, followed by treatment of the resulting phosphonium salt with a strong base such as dimsyl sodium ("dimsyl" refers to the carbanion of dimethylsulphoxide) or a C₁₋₄ alkyl or aryllithium compound such as butyl lithium, a metal hydride such a sodium hydride or an alkali metal amide such as sodamide in an anhydrous solvent as hereinbefore defined. Compounds of the formula (XXII) may be prepared by Bischler-Napieralski cyclisation of an α-halo acetyl derivative of a phenethylamine of the formula (XVI) as hereinbefore defined, for example under conditions analogous to those described by Buzas and Finet (idem) or by R. Child and F. L. Pyman, J. Chem. Soc., 1931, 41. c) The reaction of compounds of the formula (XVI), when X² is halogen, with compounds of the formula (XVII) are generally carried out in a suitable solvent and in the presence of a metal halide such as stannic chloride or aluminium chloride, for example according to conditions similar to those described in Chem. Ber., 1961, 94 , 199. When X² is hydroxy, the reaction will usually be carried out in the presence of a strong acid such as perchloric, phosphoric, polyphosphoric, formic or substituted sulphonic acid or boron trifluoride, and preferably the acid is sulphuric acid. If desired a co-solvent or diluent can be employed. Suitable co-solvents include glacial acetic acid, acetic anhydride, di- n -butyl ether, chloroform, carbon tetrechloride, nitrobenzene and hexane. The reaction generally will be carried out in the temperature range 0-100 o C, and preferably in the range 20-55 o C. In general the conditions employed in this reaction will be similar to those described for analogous processes in Organic Reactions Vol. 17, 213. It has additionally been found that when X² is hydroxy, the reaction can be carried out in the presence of trifluoroacetic acid/trifluoroacetic anhydride (TFA/TFAA) at approximately ambient temperature. Compounds of the formula (XVII) wherein X² is hydroxy can be prepared by reaction of the corresponding ester with two equivalents of an alkyl Grignard reagent, for example methyl magnesium iodide. The ester can be obtained via known hydrolysis/esterification procedures from compounds of the formula (X1Xe) or (X1Xg). d) The cyclisation of a compound of the formula (XVIII) will take place under conditions analogous to those disclosed in U.S. Patent No. 3,067,203 and U.K. Patent No. 862,052 for example by heating in the presence of an acidic reagent such as a mineral acid or phosphorus oxychloride, optionally in the presence of an organic solvent such as benzene, toluene or acetic acid. Preparation of compounds of the formula (XVIII) can be achieved by condensing an aldehyde of the formula (XV) as hereinbefore defined, with a compound of the formula (XXIII) wherein R¹-R⁶ and R⁸ are as hereinbefore defined and Y² is the acyl residue of a carboxylic acid e.g. acetyl. Condensation takes place in the presence of a base such as an alkali metal amide, alkoxide or hydroxide, in a solvent such as tetrahydrofuran, dioxan, or a C₁₋₄alcohol or aqueous mixtures thereof. The compounds of the formula (XXIII) are synthesised according to methods analogous to those described in U.S. Patent No. 3,067,203. (e) The conversion of a compound of the formula (III) into another compound of the formula (III) will be carried out according to methods well known to those skilled in the art. For example, when such a compound is substituted by a hydroxy or thio group, this may be acylated or alkylated according to known methods. When the compound of the formula (III) is substituted by acyloxy or benzyloxy, this may be transformed into hydroxy by hydrolysis or hydrogenolysis respectively. When a thio or hydrocarbylthio substituent is present, this may, if desired, be replaced by a hydrogen atom through hydrogenolysis. When a compound of the formula (III) is a tetrahydroisoquinoline, this may, if desired, be oxidised to the 3,4-dihydroisoquinoline according to known methods. It will be readily apparent to the skilled man that such methods will not be employed if the compound possesses additional groups which it is desired should be retained in the compound but which are sensitive to the aforementioned conditions. The compounds of the formula (XIII), (XV), (XVI), ( XVIa), (XVIII), (XIX), (XXI), (XXII) and (XXIII) are chemical intermediates. The following examples illustrate the invention. Example 1 (E)-6-Butyloxy-1-(2-cyclohexylvinyl)-3,4-dihydroisoquinoline nitrate 1A. 3-Butyloxybenzaldehyde 3-Hydroxybenzaldehyde (61g) was added over 40 minutes to a suspension of sodium hydride (13.0g) in dimethylformamide (700cm³), the temperature of the reaction mixture being kept below 10 o C by means of a CO₂/oxitol bath. After stirring for 35 minutes, 1-bromobutane (73g) was added dropwise over one hour and the mixture was then stirred at room temperature for 2.5 hours followed by heating at 85 o C for a further 2.5 hours. The resulting mixture was poured into ice water (1000cm³) and was allowed to stand overnight before extracting with 40-60 o petrol/ether (3:1) (5 x 200cm³). The combined organic layers were washed with 1M sodium hydroxide solution containing sodium chloride, dried over sodium sulphate, treated with activated charcoal, filtered and then evaporated down to give a golden brown mobile oil (79.7g). 1B. 3-Butyloxybenzylalcohol The product of Example 1A (79.7g) was dissolved in methanol (550cm⁵) and to the cooled stirred solution was added sodium borohydride (17.45g). After stirring at room temperature for 150 minutes the mixture was filtered and evaporated to dryness. The residue was partitioned between water (500cm⁵) and ether (200cm⁵) and the aqueous layer was separated and further extracted with ether (4 x 200cm⁵). The combined ether extracts were washed with water, dried, treated with activated charcoal, filtered and then evaporated down to give a golden oil (78.7g). 1C. 3-Butyloxybenzylchloride The product of Example 1B (78.7g) in ether (450cm⁵) was treated with thionyl chloride (85cm⁵) and pyridine (6 drops) in dry ether (4cm³) and following addition, the reaction mixture was heated at reflux for 3 hours. After allowing to cool the mixture was filtered and evaporated and the residue was partitioned between water (600cm³) and ether (200cm³). The aqueous phase was separated and further washed with ether (4 x 200cm³) and the combined ether extracts were washed with distilled water followed by 5% sodium bicarbonate solution before drying, filtering and evaporating down to a tan mobile oil (83.7g). 1D. 3-Butyloxybenzylcyanide The product of Example 1C (42.0g) in dimethylsulphoxide (200cm³) was added to a suspension of potassium cyanide (22.4.g) in dimethylsulphoxide (300cm³) and the mixture was stirred at room temperature for 3 days before being allowed to stand for a further 3 days. The mixture was then diluted with water and was extracted with ether (5 x 200cm³); the combined ether extracts were washed with distilled water, dried, treated with activated charcoal, filtered and evaporated down to give the title compound as a tan mobile oil (38.6g). 1E. 2-(3-Butyloxyophenyl)ethylamine The nitrile from Example 1D (38.64g) was dissolved in methanol (700cm³) saturated with ammonia and the resulting mixture was hydrogenated at 70 o C and 45 atmospheres of hydrogen over Raney nickel catalyst for 2 hours. After cooling the solution was filtered and evaporated to give a green oil (42.2.g). The green oil was distilled under reduced pressure and the product fraction was collected at 104-110 o /0.05mmHg (28.2g). 1F. N-[3-Cyclohexylpropenoyl]-m-butoxyphenethylamine Powdered potassium carbonate (4.5g) was added to a solution of 2-(3-butyloxyphenyl)ethylamine (4.12g) in acetonitrile (55cm³) A solution of 3-cyclohexylacryloyl chloride (3.66g) in acetonitrile (20 cm³) was added dropwise over fifteen minutes and the reaction mixture was then stirred at room temperature for 2 hours. Following treatment with distilled water (75cm³) and SVM (3cm³), a white precipitate was formed. This was filtered off and sucked dry to give the product (3.76g) m.p. 67-71 o C. 1G. 6-Butyloxy-1-[2-cyclohexylethenyl]-3,4-dihydroisoquinoline nitrate, one quarter hydrate To a solution of the product from Example 1F (4.6g) in dry ethanol-free chloroform (40cm³) was added phosphoryl chloride (5cm³). The resulting mixture was heated at reflux for 5.5 hours before evaporating the solvent to leave a pale tan mobile oil. The oil was treated with water (30cm³), stirred vigorously for 20 minutes and then cooled to 2 o C before running off the aqueous phase. The oil was then dissolved in acetone (10cm³), ether was added and the solution was extracted twice with saturated potassium bicarbonate solution (50cm³). The aqueous layer was then extracted once with ether (50cm³) and the combined ether extracts were dried over sodium sulphate, filtered and then added to a cold stirred solution of 70% nitric acid (1.25g) in ethyl acetate (20cm³). The title compound crystallised out as pale cream plates (2.06g) m.p. 160-161 o C. Analysis calculated for C₂₁H₂₉NO.HNO₃.0.25 H₂O: C, 66.58; H, 8.06; N, 7.39 %., Found; C, 66.65; H, 8.02; N, 7.30 %. Example 2 6-Benzyloxy-1-[2-cyclohexylethenyl]-3,4-dihydroisoquinoline nitrate 2A. N-[3-Cyclohexylpropenoyl]-2-[3-benzyloxyphenyl]ethylamine To a solution of 2-[3-benzyloxyphenyl]ethylamine (2.3g) (prepared in a manner analogous to that described in Example 1E) in acetonitrile (25cm³) was added powdered potassium carbonate (2.1g) followed by 3-cyclohexylpropenoyl chloride (1.72g) in acetonitrile (10cm³) which was added over ten minutes. The resulting mixture was stirred for one hour and was then treated with water (40cm³) and SVM (3cm³) thereby causing the precipitation of an oil which solidified to give a pale tan solid after several minutes. This solid was filtered off, washed with 5% SVM in water and sucked dry. Yield = 3.08g m.p. 98-100 o C. 2B. 6-Benzyloxy-1-[2-cyclohexylethenyl]-3,4-dihydroisoquinoline nitrate To a solution of the amide (1.0g), obtained from Example 2A, in sodium dried toluene (10cm³) at reflux was added phosphoryl chloride (1.2cm³), and the resulting reaction mixture was heated at reflux for fifteen minutes before evaporating to dryness. The residue was treated with distilled water (10cm³), stirred well and was then allowed to stand at 2 o C. The aqueous phase was decanted off, the residue was dissolved in a minimum quantity of SVM and the resulting solution was partitioned between ether and saturated potassium bicarbonate solution. The ether layer was separated, extracted a further two times with potassium bicarbonate solution, dried over sodium sulphate, filtered and was then added to a cold solution of nitric acid (0.26g) in ethyl acetate (6cm³) whereupon, with stirring, a gum separated out. Treatment of the gum with ethyl acetate, acetone and ether resulted in crystallisation of the title compound as beige prisms (0.25g) m.p. 151-152 o C. Analysis: Calculated for C₂₄H₂₇NO.HNO₃: C, 70.59; H, 6.86; N, 6.8%; Found: C, 70.46; H, 6.71; N, 6.92%. Example 3 6-Butyloxy-3,4-dihydro-1-styrylisoquinoline hydrochloride 3A. 2-[3-Butyloxyphenyl]-1-nitroethene The product of Example 1A (5.0g) was dissolved in glacial acetic acid (18cm³) and nitromethane (2.1g) and ammonium acetate (0.97g) were added. The reaction mixture was heated at reflux for 10 hours, further nitromethane (0.5g) being added after 4 hrs of refluxing. The reaction mixture was then treated with a methanol/water mixture (1:2) (40cm³) and extracted several times with ether. The combined ether extracts were washed successively with water and potassium bicarbonate solution, dried over sodium sulphate, treated with activated charcoal, filtered and then evaporated down to give a dark brown oil (5.4g). 3B. 2-[3-Butyloxyphenyl]ethylamine Lithium aluminium hydride (25.0g) was added carefully to sodium dried tetrahydrofuran (THF)(250cm³) at 0 o C. Sodium dried ether (250cm³) was then added via a pressure equalising dropping funnel and this was followed by the dropwise addition of a solution of the product of Example 38 (48.7g) in sodium dried ether (2500cm³) over 2 hours, the reaction mixture being maintained at approximately 10 o C throughout. The reaction mixture was allowed to warm to room temperature and was then stirred at this temperature for 1± hours before heating under reflux for a further 1.5 hours. After cooling the reaction mixture to 0 o C, ether (250cm³) was added followed by the careful addition of 5M sodium hydroxide. Following dilution of the mixture with water (200cm³), the organic phase was separated and the aqueous layer was further washed with ether (4 x 200cm³). The combined ether extracts were dried, treated with activated charcoal, filtered and evaporated down to give a brown oil which was distilled under high vacuum to give a colourless oil (22.2g) bp. 110-112 o /0.02mmHg. 3C. N-[3-phenylpropenoyl]-3-butyloxyphenethylamine To a solution of 2-(3-butyloxyphenyl)ethylamine (1.0g) in acetonitrile (40cm³) was added powdered potassium carbonate (0.80g). Cinnamoyl chloride (1.03g) was then added portionwise over a period of fifteen minutes and the reaction mixture was then stirred at room temperature for 6.5 hours after which distilled water (40cm³) was added. The mixture was left to stand overnight and was then filtered and extracted several times with ethyl acetate. The combined ethyl acetate extracts were washed successively with potassium bicarbonate solution, water and 0.5M hydrochloric acid before drying over sodium sulphate and then evaporating down to give the product a a tan coloured oil (1.60g). 3D. 6-Butyloxy-3,4-dihydro-1-styrylisoquinoline hydrochloride To a solution of the product from Example 3A (5.20g) in dry, ethanol free chloroform (50cm³) was added phosphoryl chloride (6.5cm³). The reaction mixture was heated under reflux for six hours and was then evaporated down to give a brown oil which was treated with water, warmed and stirred well. After allowing to cool, the aqueous phase was decanted off and the residual gummy solid was dissolved in boiling acetone. Addition of acetone and ether, followed by cooling resulted in the title compound crystallising from solution as pale yellow prisms (1.19g) m.p. 214-217 o C. Analysis: Calculated for C₂₁H₂₃NO.HCl: C, 73.79; H, 7.03; N, 4.10%; Found: C, 73.71; H, 7.17; N, 4.28%. 3E. 6-Butyloxy-3,4-dihydro-1-styrylisoquinoline hydrogen fumarate The product from Example 3A was treated with phosphoryl chloride in a manner analogous to that described in Example 3B except that the crude product was treated with 2N sodium hydroxide and ethylacetate. The organic phase was then dried over sodium sulphate and evaporated down to give a clear oil which was dissolved in ether, the solution then being added to a solution of fumaric acid in methanol and ether. The product was obtained as bright green/yellow crystals m.p. 179-182 o C. Analysis: Calculated for C₂₁H₂₃NO.C₄H₄O₄: C, 71.26; H, 6.41; N, 3.33%; Found: C, 71.04; H, 6.57; N, 3.16%. 3F. 6-Butyloxy-3,4-dihydro-1-styrylisoquinoline perchlorate The product of Example 3E was dissolved in dilute alkali and the free base was extracted into ether. The ethereal solution was dried, filtered and was then treated with perchloric acid in acetone to give lime yellow crystals. m.p. 228-230 o C. Analysis: Calculated for C₂₁H₂₃NO.HClO₄: C, 62.15; H, 5.92; N, 3.45%, Found: C, 62.44; H, 5.98; N, 3.41%. In a similar manner, by treatment of an ethereal solution of the free base with an appropriate acid, the following salts were formed: nitrate : m.p. 181-183 o C; Analysis, Calculated for C₂₁H₂₃NO.HNO₃: C, 68.48; H, 6.52; N, 7.61%: Found: C, 68.20: H, 6.58; N, 7.56%. hydrobromide : m.p. 243-246 o C; Analysis, Calculated for C₂₁H₂₃NO.HBr: C, 65.28; H, 6.22; N, 3.63%: Found: C, 65.55; H, 6.27; N, 3.62%. hydrogen sulphate m.p. 205-206 o C; Analysis, Calculated for C₂₁H₂₃NO.H₂SO₄: C, 62.53; H, 6.20; N, 3.47%: Found: C, 62.72; H, 6.21; N, 3.47%. p -toluenesulphonate m.p. 126-129 o C; Analysis, Calculated for C₂₁H₂₃NO.C₇H₈SO₃.0.25 H₂O: C, 69.78; H, 6.54; N, 2.91%: Found: C, 69.70; H, 6.46; N, 2.85%. D-hydrogen tartrate m.p. 158-160 o C; Analysis, Calculated for C₂₁H₂₃NO.D-(CHOH.CO₂H)₂: C, 65.93; H, 6.37; N, 3.08%; Found: C, 65.77; H, 6.42; N, 3.11%. di-hydrogen phosphate sesquihydrate m.p. 128-132 o C; Analysis, Calculated for C₂₁H₂₃NO.H₃PO₄.1.5H₂O; C, 58.60; H, 6.74; N, 3.26% Found: C, 58.48; H, 6.62; N, 3.22%. Example 4 1-(2-Chlorostyryl)-3,4-dihydro-6-propyloxyisoquinoline 4A. N-(2-Chlorocinnamoyl)-3-propyloxyphenethylamine To a solution of 2-(3-propyloxyphenyl)ethylamine prepared in a manner analogous to that described in Example 1E (2.69g) in acetonitrile (40cm³) was added triethylamine (3cm³). A solution of 2-chlorocinnamoyl chloride (3.6g) in acetonitrile (20cm³) was added slowly, the reaction mixture being cooled in an ice bath. When addition was complete, the mixture was stirred at room temperature for 40 minutes, treated with water (60cm³) and SVM (2cm³) and stirred well. The resulting precipitate was filtered off, washed and air-dried (5.49g)m.p. 96-99 o C. 4B. 1-(2-Chlorostyryl)-3,4-dihydro-6-propyloxyisoquinoline hydrochloride The amide (5.45g) produced in Example 4A was dissolved in dry, ethanol free chloroform (50cm³), phosphoryl chloride (6cm³) was added and the resulting mixture was heated under reflux for a period of four and a half hours. The mixture was then evaporated down and the residual oil was triturated to give a yellow solid which was dissolved in hot SVM (20cm³). A portion of the solution was treated with ether to cause the title compound to crystallise out as the hydrochloride salt which was filtered off, washed and dried (1.0g) m.p. 199-202 o C; Analysis, Calculated for C₂₀H₂₀ClNO.HCl.0.25H₂O; C, 65.48; H, 5.87; N, 3.82%; Found; C, 65.57; H, 5.95; H, 3.80%. The remaining portion (8cm³) was partitioned between saturated potassium bicarbonate and ether, the ether layer being separated and washed twice more with base before being dried, filtered and then added slowly to a solution of p-toluene sulphonic acid. The resulting precipitate of bright yellow crystals was filtered off, washed and dried (1.70g) m.p. 145-147 o C; Analysis; Calculated for C₂₀H₂₀ClNO.C₇H₈SO₃.0.33H₂O; C, 64.34; H, 5.69; N, 2.78%; H₂O 1.19%; Found; C, 64.38; H, 5.64; N, 2.74%; loss at 100 o C was 1.22%. Examples 5 - 94 According to methods analogous to those described in Examples 1 - 4, the following compounds were prepared. For all compounds listed, satisfactory elemental analyses were obtained, ie. the analytically obtained elemental compositions were within 0.4% of the calculated values. For each of the listed compounds, nuclear magnetic resonance (n.m.r.) spectra were in accordance with the structures described. The following abbreviations have been used: Me = methyl Et = ethyl Pr = propyl But = butyl Example 102 (E)-6-Butyloxy-3,4-dihydro-1-[2-(4-bromo-2-thienyl)vinyl)-isoquinoline hydrochloride 102A. (E)-4-Bromo-3-(2-thienyl)acrylic acid Malonic acid (16.2g) was added to a solution of 4-bromothiophen-2-aldehyde (25.1g) in pyridine (100cm³) and piperidine (3.2cm³) and the resulting mixture was heated at 100 o C for 6.5 hours, allowed to cool to room temperature overnight and was then evaporated down to give a beige semi-solid. The semi-solid was treated with aqueous potassium hydroxide solution and the resulting mixture was diluted with water (50cm³), acidified with concentrated hydrochloric acid (90cm³) and then cooled to yield a precipitate which was filtered off, washed with ether/40-60 petrol and was then sucked dry (26.1g) m.p. 167-169 o C (aqueous methanol); Analysis; Calculated; C, 36.05; H, 2.15%; Found; C, 36.30; H, 2.03%. 102B. N-[3-(3-Bromo-2-thienyl)prop-2-enoyl]-m-butyloxyphenethylamine The product from Example 102A (1g) was dissolved in dry benzene (5cm³) and heated at reflux in the presence of thionyl chloride (2cm³) for 4.5 hours before evaporating down to give the acid chloride as a fawn crystalline solid (1.07g) m.p. 89-91 o C. Powdered potassium carbonate (1.7g) was added to a solution of 2-(3-butyloxy phenyl)ethylamine (2.1g)(prepared by the method of Example 1) in acetonitrile (30cm³) and the acid chloride (3.24g), prepared as described above, in acetonitrile (30cm³) was added dropwise over ten minutes. The reaction mixture was stirred at room temperature for 4 hours, treated with water (60cm³) and then extracted with ether (3 x 60 cm³). The combined ether extracts were washed successively with 1M sodium hydroxide solution, water and 1M hydrochloric acid and were then dried over sodium sulphate, filtered and evaporated to give the title compound as a pale tan mobile oil (4.83g). 102C. (E)-6-Butyloxy-3,4-dihydro-1-[2-(4-bromo-2-thienyl)vinyl)-isoquinoline hydrochloride The product from 102B (4.4g) was dissolved in dry ethanol-free chloroform and was treated with phosphoryl chloride (5cm³) in a manner analogous to that described in Example 3. After recrystallisation from a mixture of ether, methanol and acetone, the product was obtained as yellow needles (2.76g) m.p. 196-198 o C; Analysis; Calculated for C₁₉H₂₀Br NOS.HCl; C, 53.46; H, 4.92; N, 3.28%; Found; C, 53.34; H, 4.94; N, 3.04%. Example 103 6-Butyloxy-3,4-dihydro-1-[2-(5-bromo-2-thienyl)vinyl]isoquinoline hydrochloride 96A. N-[3-(2-Bromo-2-thienyl)prop-2-enoyl]-m-butyloxyphenethylamine Malonic acid (6.47g) was reacted with 5-bromothiophen-2-aldehyde (10g) according to the method of Example 102A to give 3-[2-(5-bromothienyl)]prop-2-enoic acid (9.16g) m.p. 207-209 o C which was then converted to the acid chloride (m.p. 169-171 o C) according to the method described in Example 102B. The acid chloride was then used to acylate 2-(3-butyloxyphenyl)ethylamine by the method described in Example 102B affording the product as a dark tan oil. 103B. 6-Butyloxy-3,4-dihydro-1-[2-(5-bromo-2-thienyl)vinyl]isoquinoline The amide (4.6g) prepared in Example 103A was cyclised according to the procedure of Example 102C to give the title compound (2.89g) as bright yellow needles which were recrystallised from a mixture of acetone, methanol and ether m.p. 228-230 o C; Analysis Calculated for C₁₉H₂₀BrNOS.HCl.0.66H₂O; C, 51.99; H, 4.94; N, 3.19%; Found; C, 52.03; H, 4.82; N, 2.86%. Examples 104-146 The following compounds were made according to methods analogous to those described in Examples 102 and 103. Example 147 (Z)-1-(1-Bromo-2-phenylvinyl)-6-butyloxy-3,4-dihydroisoquinoline 147A. 2-(3-Butyloxyphenyl)ethylamine Raney nickel catalyst (approx 5g) was added to a solution of 3-butyloxybenzyl cyanide (38.64g, prepared according to example 1 D) in saturated ammoniacal methanol (700cm³). The resulting mixture was heated at 70 o C in the presence of hydrogen (45 Atmospheres) for two hours and was then allowed to cool to room temperature overnight. The cooled mixture was filtered to remove the catalyst and was then evaporated down to give a green oil (42.2g). 147B. N-(2-Bromo-3-phenylacryloyl)-2-(3-butyloxyphenyl)ethylamine A mixture of d-bromocinnamic acid (6.81g), dry chloroform (50cm³) and thionyl chloride (5cm³) was heated under reflux for 5.5 hours by which time evolution of HCl had ceased. The pale yellow solution was then evaporated to dryness to give the acid chloride as a pale yellow oil (7.35g). A portion of the acid chloride (3.6g) was dissolved in acetonitrile (10cm³) and was added to a mixture of 2-(3-butyloxyphenyl)ethylamine (2.9g) and powdered potassium carbonate (3g) in acetonitrile (30cm³). The resulting mixture was stirred at room temperature for one hour before partitioning between water and ether (50cm³). The organic phase was washed with water followed by 0.5 M hydrochloric acid, was dried over sodium sulphate, filtered and evaporated to give a pale tan oil which solidified to give cream waxy needles (5.00g) mp = 38-39 o C. 147C (Z)-1-(1-Bromo-2-phenylvinyl)-6-butyloxy-3,4-dihydroisoquinoline hydrogen oxalate The product of example 147B (4.9g) was treated with phosphoryl chloride (6 cm³) in dry ethanol-free chloroform according to the method described in Example 1G to give, after work-up and treatment with oxalic acid, the title compound as a cream crystalline solid (2.00g) mp 159-160 oo C. Analysis; Calculated for C₂₁H₂₂BrNo. C₂H₂O₄: C,58.22; H, 5.06; N, 2.95%. Found; C, 58.36; H, 5.09; N, 2.9%. T.l.c. (Silica gel), solvent methanol: chloroform (1:4), one spot R f 0.77. Examples 148-154 According to the method described in Example 147, the compounds listed below were prepared: Example 155 1-(2-,4-Dichlorostyryl)-3,4-dihydro-6,7-dipropyloxy isoquinoline 155A. 3,4-Dipropyloxy benzaldehyde A 50% suspension of sodium hydride (15.9) in mineral oil was washed with sodium dried ether (2 x 50cm³) under nitrogen before the addition of dimethylformamide (300 cm³). The mixture was cooled and 3,4-dihydroxybenzaldehyde (20.7g) was then added slowly. After a 15 minute stirring period propyliodide (56.1g) was added dropwise over 10 minutes and the resulting mixture was stirred at room temperature for 4 hours before allowing to stand overnight. The mixture was then poured into water and extracted with ether (200 cm³ followed by 3 x 150cm³). The combined ether extracts were washed with 2N sodium hydroxide (2 x 100 cm⁵) followed by water (2 x 100 cm³) and the washings were further extracted with ether (2 x 100 cm³). After drying over sodium carbonate, the ether phase was treated with activated charcoal, and was then filtered and evaporated down to give a dark brown oil (16.7 g)bp/0.05 mm Hg 110-115 o C. ν max 1690, 1510, 1270, 1135. 155B. 1-(3,4-Di-propyloxyphenyl)-2-nitroethene The product of Example 155A (4.44g) was reacted with nitromethane under conditions analogous to those described in Example 3A to afford the title compound as a yellow crystalline solid (3.3g) mp = 109-112 o C. 'H NMR (CDCl₃) 0.8-1.2 (6H, t) 1.5-2.1 (4H, sextet) 3.8-4.1 (4H, triplet of doublets), 6.7-7.2 (3H, m) 7.34 '1H, d (J=13Hz)) 7.84 (1 H, d (J=13 Hz)). 155C. 2-(3,4-Di-propyloxyphenyl)ethylamine The product of Example 155B (10.5g) was reduced with lithium aluminium hydride according to the procedure of Example 3B to give the title compound as a tan coloured oil (8.8g) bp/0.05 mm = 114-116 o C. IR max (cm⁻¹) 3380, 1515, 1265. 155D. N-[2,4-dichlorocinnamoyl]-2-[3,4-dipropyloxyphenyl]ethylamine The product of Example 155C (2.4g) was acylated with 2,4-dichlorocinnamoyl chloride in acetone solution in the presence of potassium carbonate in a manner similar to that described in Example 1F. The title compound was obtained as a light yellow crystalline solid. (4.5g) mp = 132-134 o C (methanol). 155E. 1-(2,4-Dichlorostyryl)-3,4-dihydro-6,7-dipropyloxyisoquinoline hydrochloride The product of Example 155D (2.6g) was treated with phosphoryl chloride (1.9g) according to the method of Example 1G. Following work-up and recrystallisation from acetone/ether, the title compound was obtained as fine yellow needles (2.0g) mp 171-173 o C. Analysis calculated for C₂₃ H₂₅ Cl₂ NO₂. HCl.2H₂O;C, 56.26; H 6.11; N, 2.85; H₂O 7.34%: Found; C, 55.94; H, 5.72; N, 2.83; loss at 105 o C 7.43%. T.l.c. (silica gel) n -butanol: water: ethyl acetate: acetic acid (1:1:1:1), one spot R f 0.74. IR ν max (cm⁻¹) 1595, 1580, 1370, 1335, 1275. monohydrate mp 179-181 o C. The free base was obtained by basifying an aqueous solution of the hydrochloride salt with potassium bicarbonate and extracting with ether. Drying of the ether layer, evaporation of the solvent and crystallisation of the residue from pentane/ether gave pale cream needles. mp 93.5-94.0 o C. Analysis calculated for C₂₃ H₂₅ Cl₂ NO₂; C, 66.08; H.5.99; N, 3.35%: Found; C, 66.46; H, 6.02; N, 3.14%. Example 156 1-(4-Chlorostyryl)-3,4-dihydro-3-methyl-6,7-di-propyloxyisoquinoline 156A. 1-(3,4-Dipropyloxyphenyl-2-nitroprop-1-ene A mixture of 3,4-di- n -propylbenzaldehyde (22.2g, obtained according to Example 155A), nitroethane (9.7g), n -butylamine (2.5 cm³) and toluene (50cm³) was heated under reflux in a Dean-Stark apparatus for three days by which time the theoretical amount of water had been azeotropically removed. The mixture was then evaporated down to give a brown oil. The oil was then treated with water (15 cm³), cooled to 0-3 o C and methanol added until crystallisation occurred. The dark golden solid was filtered off and sucked dry (21.0g) mp = 49-52 o C. 156B. 2-Amino-1-(3,4-dipropyloxyphenyl)propane The product of Example 156A was reduced with lithium aluminium hydride according to the method of Example 155B. Work-up and distillation under high vacuum gave a colourless oil (22.4g) bp/0.05 mm Hg 124-130 o C. 156C. N-[4-Chlorocinnamoyl]-3-[3,4-dipropylphenyl)prop-2-ylamine The product of 156B (4.0g), triethylamine (3.6g), and potassium carbonate (4.8g) in dry ethanol free chloroform (45 cm³) were stirred together at room temperature for 30 minutes and then 4-chlorocinnamoyl chloride (3.6g) was added portionwise, care being taken to ensure that the temperature remained between 15 o and 20 o C. The resulting mixture was then stirred at room temperature for 6 hours before extracting successively with water (45 cm³), 2M HCl (45cm³), 2M NaOH (45 cm³) and finally water (45 cm³). The organic phase was dried over anhydrous sodium carbonate, treated with hyflo/charcoal, filtered and evaporated to give a pale yellow solid (6.55 g) which was recrystallised from methanol to give an off-white solid (3.1 g) mp 142-144 o C. 156D. 1-(4-Chlorostyryl)-3,4-dihydro-3-methyl-6,7-dipropyloxyisoquinoline A solution of the product of Example 156C (3.1g) in dry ethanol free chloroform was treated with phosphoryl chloride according to the method of Example 1G. Following work-up and crystallisation from ethanol: ether: petrol (1 : 5 : 4) the product was obtained as yellow needles (1.7g) mp 117-119 o C. T.l.c. (Silica gel, n-BuOH: H₂O: H Ac: EtOAc (1:1:1:1), one spot R f = 0.72. T.l.c. (Silica gel, MeOH: CHCl₃ (1:4). one spot R f = 0.69. Dihydrate mp 109-111 o C. Analysis; Calculated for C₂₄H₂₈ClNO₂, HCl 2H₂O: C, 61.27; H, 7.02; N, 2.98; H₂O, 7.66%. Found; C, 61.09; H, 6.79; N, 2.78; loss at 100 o C=7.68%. Examples 157-183 By methods analogous to those described in Examples 141 and 142, the following compounds were prepared: Example 184 1.2.3.4-Tetrahydro-6,7-dibutyloxy-1-(4-chlorostyryl)isoquinoline hydrochloride hemihydrate The product of Example 157 (1.0g) in a water: methanol (1 : 1)mixture(80cm³) at 0⁰C was treated with sodium borohydride (0.1g) over a period of ten minutes. After stirring at room temperature for ninety minutes, benzene (50cm³) was added and the resulting mixture was extracted with ether (2 x 100cm³). The combined organic layers were washed with brine (2 x 50cm³), dried over sodium sulphate, filtered and were then evaporated to dryness to give a cream coloured solid (0.85g). The solid was dissolved in ether (25cm³) and the title compound was precipitated from solution by the addition of ethereal hydrogen chloride (2cm³). Yield = 0.76g, mp 189-190°C, Analysis Calculated for C₂₅H₃₂ Cl NO₂.HCl.0.5H₂O: C,65.35; H,7.40; N,3.05%. Found; C,65.50; H, 7.51; N,3.07%. Example 185 1-(4-Chlorostyryl)-1,2,3,4-tetrahydro-6,7-dipropyloxyisoquinoline hydrochloride By the method of Example 184, the product of Example 168 was reduced with sodium borohydride to give the title compound as colourless needles. mp229-231 o C, Analysis Calculated for C₂₃ H₂₈ Cl NO₂.HCl; C,65.40; H,6.87; N,3.32%; Found: C,65.11; H,6.94; N,3.22%. Example 186 186A Ethyl (3-propyloxy phenyl) acetate A mixture of ethanol (3.9g), water (0.2g), conc.sulphuric acid (3.9g) and 3-propyloxyphenylacetonitrile (3.5g; 20mmol) was heated under reflux during 6 hours. After cooling, ether (20ml) and water (20ml) were added and the mixture was stirred. The phases were separated and the ethereal extract washed with 10% potassium bicarbonate (2x20ml), dried over Na₂SO₄, filtered and evaporated to dryness to give a pale tan oil Y = 4.03g (90.8%) 186B 2-Methyl-3-(3-propyloxyphenyl)propan-2-ol A solution of methyl magnesium iodide in dry ether (100ml) was prepared from magnesium (1.9g; 77.3mmol) and iodomethane (11.0g; 77.5 mmol) using standard procedure. A solution of ethyl (3-propyloxyphenyl) acetate (7.8g; 35 mmol) in ether (20 ml) was added over 10 minutes to the methyl magnesium iodide. After stirring for 30 min. at 25°C, the mixture was heated under reflux during 2 hours, cooled to -5°C, treated cautiously with saturated ammonium chloride solution (50 mls) followed by conc. HCl (25 ml). The phases were separated and the organic layer washed with 10% brine (2x20ml), dried over Na₂SO₄, filtered and evaporated to dryness to give a pale tan oil Y = 7.1g (97.2%) 186C 3,4-Dihydro-3,3-dimethyl-6-propyloxy-1-styryl isoquinoline hydrogen oxalate, 1.25 hydrate To a solution of 2-methyl-3-(3-propyloxy)propan-2-ol (1.02g; 5.0 mmol) in trifluoroacetic acid (8 ml) at 20°C was added trifluoroacetic anhydride (0.94g; 5.5 mmol) followed by cinnamoyl nitrile (0.72g; 5.0 mmol). The temperature of the reaction mixture rose rapidly to 40°C. The reaction mixture was then stirred at 25-28°C for 2 hours, poured onto ice/water (75g), basified (pH 9-9.5) with 10M NaOH and the liberated basic material extracted into ether (3x20ml). The combined extracts were washed with 20% brine (2x20ml), dried over Na₂SO₄, filtered and the filtrate introduced into a stirred solution of oxalic acid (0.5g) in warm acetone (10 ml). On standing, yellow prisms were deposited Y = 1.85g (90.3%) mp 175-176°C (effervesc) Anal. Found: C, 66.66; H, 6.60; N, 2.98% Req.: C, 66.74; H, 6.83; N, 3.24 % Tlc (silica gel), solvent BuOH: H₂O: EtOAc: HOAc (1:1:1:1), one spot Rf 0.80 CHCl₃-MeOH (4:1), one spot Rf 0.60. Example 187 187A 2-Methyl-2-(3-propyloxyphenyl)propionitrile To a suspension of sodium hydride (0.5g; 21 mmol) in dry diglyme (20ml) was added 3-propyloxyphenyl acetonitrile 1.75g; 10 mmol) followed by iodomethane (3.12g; 22 mmol) which was added dropwise over 10 minutes. When the addition was complete, the reaction mixture was stirred at 20°C for 2 hours and then poured onto ice/water (100g). The precipitated oil was extracted into ether (3x20ml) and the combined extracts dried over Na₂SO₄, filtered and evaporated to dryness to give a tan oil which was distilled under reduced pressure to give a colourless oil Y = 1.96g (96.5%), bp 116-118°C/0.08 mm Hg 187B Ethyl-2-methyl-2-(3-propyloxyphenyl)propionate The title compound was prepared from 2-methyl-2-(3-propyloxyphenyl)propionitrile using a procedure similar to that described in Example 186A and obtained as a very pale oil in 84.8% yield 187C 2,3-Dimethyl-3-(3-propyloxyphenyl)butan-2-ol The title compound was prepared from ethyl-2-methyl-2(3-propyloxyphenyl)propionate using a procedure similar to that described for 186B above and obtained as a colourless oil in 95.6% yield. 187D 3,4-Dihydro-3,3,4,4-tetramethyl-6-propyloxy-1-styryl isoquinoline hydrogen fumarate,one quarter hydrate The title compound was prepared from 2,3-dimethyl-3-(3-propyloxy phenyl)butan-2-ol (7) using a procedure similar to that described for 186C. The hydrogen fumarate was obtained as bright yellow prisms by adding an ethereal solution of the base to a solution of fumaric acid in hot methanol and cooling. Y = 1.40g (39.8%) mp 218-220°C Anal. Found: C,71.87; H, 7.09; N, 3.00 % Req.: C,71.87; H, 7.16; N, 2.99 % Tlc (silica gel), solvent EtOAc-MeOH (4:1), one spot Rf 0.56 Examples 188-189 The following compounds were prepared in a manner analogous to that described in Example 186. 188 6-Butyloxy-3,4-dihydro-3,3-dimethyl-1-styrylisoquinoline hydrogen fumarate, mp 189-191°C. 189 3,4-Dihydro-3,3-dimethyl-6-heptyloxy-1-styrylisoquinoline hydrogen fumarate, mp 136-138°C. Example 190 190A 1-Amino-2-methyl-2-(3-propyloxyphenyl)propane (3) To a suspension of LiAlH₄ (1.0g) in dry THF (25ml) under dry N₂ was added a solution of 2-methyl-2-(3-propyloxyphenyl)propionitrile (1.02g) in dry THF (10ml) over 10 minutes. After stirring at 25°C for 20 minutes, the reaction mixture was heated under reflux for 5 hours, cooled to 0°C diluted with ether (50ml) and cautiously decomposed with ethyl acetate (2ml) followed by 5 M NaOH (5ml). The mixture was filtered and the residue triturated with ether (3x10ml). The combined filtrates were extracted with 20% HCl (4x10ml) and the combined extracts basified with 10M NaOH. The liberated oil was extracted into ether (3x15ml) and the combined extracts dried over Na₂SO₄, filtered and evaporated to dryness to give a colourless oil. Y = 0.93g (89.4%) 190B N-(Cinnamoyl-2-methyl-2-(3-propyloxyphenyl)propylamine A solution of 1-amino-2-methyl-2-(3-propyloxyphenyl)propane (2.07g; 10 mmol) in acetonitrile was treated with cinnamoyl chloride (1.87g; 11 mmol) according to the method described in Example 3C to give, after work up, the product as long colourless silky needles (2.72g, 81%). mp=86-88°C Anal. Found: C; 78.26, H;7.88, N; 4.06 % Required: C; 78.34, H; 8.01, N; 4.15 % 190C 3,4 Dihydro-4,4-dimethyl-6-propyloxy-1-styrylisoquinoline 1.5 hydrogen fumarate The product of Example 188B was reacted with phosphoryl chloride to give the title compound under conditions analogous to these described in Example 2B Yield = 43.6% mp = 156-158°C Anal. Found: C; 68.08, H; 6.10, N; 2.90 % Required: C; 68.15, H; 6.28, N; 2.84% T.l.c. (silica) CHCl₃-MeOH (4:1), one spot Rf 0.58 Example 191 4-Butyloxystyryl-3,4-dihydroisoquinoline A solution of 1-[2-(2-acetamidoethyl)phenyl)-3-(4-butyloxyphenyl)]propenone (3.06g, 8.38 mmol) in glacial acatic acid (5 cm³) and concentrated hydrochloric acid (30 cm³) was heated under reflux for a period of 3 hours. On cooling, a solid precipitated out. The crude hydrochloride was filtered off and washed with ether. The solid was recrystallised from acetone and ether to give bright yellow coloured prisms, which were filtered off, washed and sucked dry. Yield = 1.69g (59.1%) M.pt = 83-87°C. Analysis: Calc: C, 72.83; H, 7.08; N, 4.05% Found: C, 72.87; H, 7.29; N, 4.00% Biological Activity Example 192 Activity against Trichomonas vaginalis - IC₅₀ Determination Modified Diamonds Medium (MDM) was prepared according to the method described in J. Kulda et al ., American Journal of Obstetrics and Gynaecology 1970, 108 , 908-18 and 4cm³ of the medium were pipetted into each of a series of tubes (usually 16 tubes). To each tube was added 0.5 cm³ of varying concentration of a solution (usually in ethanol + MDM) or suspension of the test drug. Duplicate tubes for each drug concentration were prepared. Finally, to each tube was added T. vaginalis (0.5 cm³) at a concentration of 1x10⁵ cm⁻³,) to give a final trichomonas concentration of 1x10⁴ cm⁻³ in each tube. The tubes were then incubated (aerobically) at 37°C and the resulting trichomonad numbers were counted at 24 and 48 hours using a haemacytometer. The average count for each drug level was determined and compared with the untreated controls (which had received 0.5 cm³ control in place of drug concentrate), and from these results the % inhibitions were determined for each drug level. This information was then used to determine the 50% inhibition concentration (IC₅₀). The results are shown in Table 9. In vitro activity against T. vaginalis Compound of Ex. No. IC₅₀ (µg/cm³) Compound of Ex. No. IC₅₀ (µg/cm³) 24hr 48 hr 24 hr 48 hr. 1 1.3 1.8 113 0.7 1.2 2 1.0 1.8 115 0.4 1.0 3 3.7 8.8 5 6.1 6.4 135 1.3 1.6 12 1.2 2.0 104 7.4 7.3 13 1.5 2.5 105 2.0 6.7 14 5.5 8.0 106 1.4 3.7 15 1.5 2.8 108 2.7 6.1 19 10.0 13.5 130 3.6 5.4 23 1.1 2.3 129 2.9 3.1 24 1.2 128 128 1.5 1.6 33 0.7 1.0 126 1.5 1.7 45 2.2 2.8 137 1.0 1.7 46 1.1 1.3 147 0.2 0.3 47 1.1 1.7 150 0.2 0.2 74 3.3 0.9 151 0.3 0.3 75 0.3 0.8 153 0.3 0.5 52 2.9 3.2 155 1.2 2.2 53 3.2 5.5 157 1.8 2.1 56 8.0 8.0 158 0.8 1.1 60 5.6 10.5 160 0.6 1.0 65 1.2 1.6 161 0.7 1.4 68 5.0 5.3 165 9.0 10.0 71 0.8 1.4 170 1.0 3.2 73 0.4 1.1 171 0.8 1.8 80 2.5 2.4 172 0.7 2.0 81 1.1 1.6 174 1.4 2.0 82 0.6 2.0 175 0.4 1.0 85 1.1 1.5 176 1.7 3.1 92 0.5 1.0 6 0.4 0.4 180 1.0 1.6 FORMULATION EXAMPLES Example 193 2% Gel % w/w Compound 2.00 Hydroxypropyl Methyl cellulose (Methocel F4M) 2.50 Polyox WSR - 205 0.25 Propylene glycol 10.00 Methylparaben 0.15 Propylparaben 0.05 Purified Water to 100.00 Example 194 2% Cream % w/w Compound 2.0 Fractionated Coconut oil 11.0 (Miglyol 812) Dynaston 114 8.0 Tween 60 2.3 Tween 80 1.2 Propylene glycol 10.0 Phenylethyl alcohol 1.0 Purified Water to 100.0 Example 195 Tampon % w/w Compound 0.1 g Inwitor 742 0.1 g Hard Fat (Wite psol W35) to 2.0g Example 196 1% Gel % w/w Compound 1.00 Poloxamer 407 25.00 Ethanol 20.00 Methyl paraben 0.15 Propyl paraben 0.05 Purified water to 100.00 Example 197 Pessary g Compound 0.10 Glycerol 2.10 Gelatin 0.42 Purified water to 3.00 Example 198 1% Foam % w/w Compound 1.00 Polyoxyethylene cetyloleylalcohol 2.10 Polyoxyethylene oleylalcohol 0.28 Polyoxyethylene lanolin alcohol 0.19 2-methyl-pentane-2,4-diol 2.15 Dichlorodifluoromethane 2.00 Dichlorotetrafluoroethane 5.00 Purified water to 100.00 Example 199 1% Ointment % w/w Compound 1.00 Plastibase 50W to 100.00 Example 200 1% Insert Example 201 In vitro activity against Candida albicans Minimum Inhibition Concentrations (MICs) of compounds of the present invention vs . C.albicans were determined. The results are shown in table 11. Media: Yeast Nitrogen Base (YNB) Broth Difco YNB 6.7g D-glucose 10.0g L-asparagine 1.5g distillled water 100cm³ The solution was filter sterilised with a 0.45µm membrane filter unit and was then further diluted with sterile distilled water (SDW) - YNB solution: SDW (1:5). Minimum Inhibition Concentrations (MIC) vs. C. albicans. Compounds of Example Number Salt MIC (µg/cm³) 1 HNO₃ 1.6 2 HBr 1.6 3 H-fumarate 6.2 5 HCl 6.2 13 HCl 6.2 22 HCl 3.1 23 HCl 6.2 31 HCl 6.2 45 HCl 6.2 50 HCl 6.2 52 HCl 6.2 57 HCl 6.2 6 HBr 25 39 HNO₃ 1.6 107 HCl 25 128 HNO₃ 25 144 HCl 1.6

Claims: Claims for the following Contracting States : BE, CH, DE, FR, GB, IT, LI, LU, NL, SE Compound of the formula (III): or a salt or acyl derivative thereof, wherein the dotted line represents either a single or a double bond; m is 0 when the dotted line represents a double bond; or m is 1 when the dotted line represents a single bond; R o is hydrogen or a group CH₂R¹⁰; R¹ is hydrogen, or a substituent chosen from fluorine, chlorine, methoxy, methyl, trifluoromethyl or methylthio; R², R³ and R⁴ are the same or different and each is hydrogen or a substituent group of the formula R¹⁰-A- wherein R¹⁰ is hydrogen or C₁₋₁₆ hydrocarbyl optionally substituted by halogen, fluorosulphonyl, cyano, hydroxy, thio, nitro, C₁₋₃ alkoxy or C₁₋₃ alkylthio wherein the alkoxy and alkylthio groups are optionally further substituted by halogen, hydroxy, thio, C₁₋₂ alkoxy or C₁₋₂ alkylthio, and A is oxygen, sulphur or methylene; or any two adjacent substituents R¹-R⁴ together form a methylenedioxy or ethylenedioxy group; R 5a is hydrogen or C₁₋₁₂ hydrocarbyl and R 5b is hydrogen or R 5a and R 5b are each C₁₋₄ alkyl or R 5a and R 5b together with the carbon atom to which they are attached, form a C₃₋₈ spirocycloalkyl ring; R 6a and R 6b are the same or different and each is hydrogen or C₁₋₁₂ hydrocarbyl or, together with the carbon atom to which they are attached, form a C₃₋₈ spirocycloalkyl ring; or R 5a and R 6a together with the carbon atoms to which they are attached form a five or six membered carbocyclic ring optionally containing up to two double bonds; R⁷ is hydrogen or fluorine; R⁸ is hydrogen, halogen, cyano, nitro or C₁₋₂ alkyl optionally substituted by one or more halogen atoms; R⁹ is a group -(CH=CH) n R¹¹ wherein n is 0-2 and R¹¹ is hydrogen, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl or a monocyclic, bicyclic, tricyclic or tetracyclic ring system containing between three and sixteen ring members, optionally substituted by hydroxy, thio, halogen, fluorosulphonyl, nitro, cyano, C₁₋₁₂ hydrocarbyl, C₁₋₁₂ hydrocarbyloxy, C₁₋₁₂ hydrocarbylthio wherein the said hydrocarbyl, hydrocarbyloxy and hydrocarbylthio groups are each optionally further substituted by halogen, hydroxy, thio, C₁₋₂ alkylthio or C₁₋₂ alkoxy groups; the groups R⁸ and R⁹ optionally being linked through a C₁₋₄ alkylene bridge with the proviso that i) when R² and R³ are the same or different and each is hydroxy, methoxy or ethoxy; or when R² and R³ together form a methylenedioxy or ethylenedioxy group; or when R² is benzyloxy and R³ is methoxy, R¹ must be a group R¹² wherein R¹² is fluorine, chlorine, methyl, trifluoromethyl or methylthio and/or R⁴ must be a substituent as hereinbefore defined, or ii) when R³ and R⁴ are each methoxy and R⁹ is a phenyl group bearing a 2-chloro and a 5-nitro substituent, the phenyl group is additionally substituted by a substituent as hereinbefore defined and/or at least one of R¹, R² and R 5a -R⁸ is a substituent as hereinbefore defined, or iii) when R¹-R⁴ are each hydrogen and R⁹ is hydrogen, methyl or unsubstituted phenyl, R 5a and/or R 5b are substituents as hereinbefore defined,or iv) when R¹-R⁴ are each hydrogen and R⁹ is a phenyl group bearing bromo, chloro, hydroxy, methyl, methoxy or nitro substituents, the phenyl ring is trisubstituted by substituents as hereinbefore defined, or v) when R⁹ is a phenyl group substituted at the 3-, 4- and 5- positions with hydroxy or C₁₋₆ alkoxy and R² and R³ are each hydroxy, C₁₋₄ alkoxy or benzyloxy, at least one of R¹, R⁴, R⁷ and R⁸ is a substituent as hereinbefore defined. A compound of the formula (IV): or a salt or acyl derivative thereof, wherein the dotted line represents either a single or double bond; A, m, R⁰ and R¹, and R² and R⁴-R⁹ are as hereinbefore defined in claim 1, and R¹⁴ is C₃₋₁₆ hydrocarbyl optionally substituted as defined in clam 1 in respect of R¹⁰; except that when the group C(R⁸)=CR⁷R⁹ is 3,4,5-trihydroxystyryl or a mono-,di or tri-ether thereof, R² is other than hydroxy, C₁₋₄ alkoxy or benzyloxy and/or one or both of R¹ and R⁴ are substituents as hereinbefore defined in claim 1. A compound of the formula (V): or a salt or acyl derivative thereof, wherein the dotted line, R⁰, R¹, R 5a to R⁹ and m are as defined in any of the preceding claims; R¹⁵ is hydrogen or a group R¹⁸-A wherein R¹⁸ is hydrogen, C₃₋₆ alkyl, C₃₋₇ cycloalkyl, C₄₋₈ cycloalkylalkyl, or phenyl, each optionally substituted by one or more halogen, cyano, nitro, hydroxy, thio, C₁₋₂ alkoxy or C₁₋₂ alkylthio; R¹⁶ is a group R¹⁹-A and R¹⁹ is hydrogen, C₁₋₂ alkyl, ethenyl or ethynyl, R¹⁷ is hydrogen or a group R¹⁴-A, wherein R¹⁴ is as defined hereinabove in claim 2. A compound of the formula (VI): or a salt or acyl derivative thereof, wherein R²⁰ and R²¹ are the same or different and each is a group R¹⁰A and m, R⁰, R¹, R¹⁶, R⁵-R⁹ and R¹⁰A are as defined hereinabove. A compound of the formula (VII): or a salt or acyl derivative thereof, wherein R²² is methoxy or a group R¹², R²³ is a group R¹⁰A and m, R⁰, R¹⁰A, R¹² and R⁵-R⁸ are as defined in the preceding claims. A compound, according to claim 3, of the formula (VIII): or a salt or acyl derivative thereof, wherein R²⁴ is C₃₋₁₀ alkyl, benzyl, phenyl, C₃₋₇ cycloalkyl, C₄₋₈ cycloalkylalkyl and C₃₋₁₀ alkenyl each optionally substituted by halogen, cyano, hydroxy, thio, nitro, C₁₋₃ alkoxy or C₁₋₃ alkylthio wherein the alkoxy and alkylthio groups are optionally further substituted by halogen, hydroxy, thio, C₁₋₂ alkoxy or C₁₋₂ alkylthio and R²⁵ is hydrogen or up to five substituents chosen from hydroxy, C₁₋₁₂ hydrocarbyloxy, thio, C₁₋₁₂ hydrocarbylthio, halogen, nitro, cyano or C₁₋₁₂ hydrocarbyl, the said hydrocarbyl, hydrocarbylthio or hydrocarbyloxy groups being each optionally further substituted by halogen, hydroxy, thio, C₁₋₂ alkylthio or C₁₋₂ alkoxy groups. Most preferably, R²⁵ is phenyl or up to two substituents chosen from halogen, nitro, cyano, hydroxy, C₁₋₂ alkoxy and C₁₋₄ alkyl. A compound according to claim 3, of the formula (IX): or a salt or acyl derivative thereof, wherein R²⁴ is as hereinbefore defined. A compound, according to claim 3, of the formula (X): or a salt or acyl derivative thereof, wherein E represents a five or six membered ring containing one heteroatomic ring member chosen from oxygen, sulphur and nitrogen, the ring being optionally susbstituted by one or two groups chosen from hydroxy, C₁₋₂ alkoxy, halogen, C₁₋₂ alkyl, nitro or cyano. A compound, according to claim 1 of the formula (XI): or a salt or acyl derivative thereof, wherein G is an optionally substituted bicyclic or tricyclic group as hereinbefore defined in Claim 1. A compound according to claim 1 of the formula (XII): or a salt or acyl derivative thereof, wherein R²⁶ is chosen from fluorine, chlorine, bromine and methyl. A compound selected from: ( E )-6-Butyloxy-1-(2-cyclohexylvinyl)-3,4-dihydroisoquinoline 6-Benzyloxy-1-[2-cyclohexylvinyl]-3,4-dihydroisoquinoline 6-Butyloxy-3,4-dihydro-1-styrylisoquinoline 1-(2-Chlorostyryl)-3,4-dihydro-6-propyloxyisoquinoline ( E )-1-(2-Cyclohexylvinyl)-3,4-dihydro-6-(2-methylpropyloxy)-isoquinoline (E)-1-(2-Cyclohexylvinyl)-3,4-dihydro-6-propyloxyisoquinoline (E)-1-(Cyclohexylvinyl)-6-hexyloxy-3,4-dihydroisoquinoline (E)-6-(4-Chlorobenzyloxy)-1-(2-cyclohexylvinyl)-3,4-dihydroisoquinoline (E)-6-Benzyloxy-1-[2-(cyclohex-3-enyl)vinyl]-3,4-dihydroisoquinoline 6-Butyloxy-3,4-dihydro-1-(2,5-dimethoxystyryl)-isoquinoline 6-Butyloxy-3,4-dihydro-1-(3,4,5-trimethoxystyryl)-isoquinoline 6-Butyloxy-1-(2-chlorostyryl)-3,4-dihydroisoquinoline 6-Butyloxy-3,4-dihydro-1-(4-cyanostyryl)-isoquinoline 6-Butyloxy-3,4-dihydro-1-(2,4-dimethoxystyryl)-isoquinoline 6-Butyloxy-1-(4-t-butylstyryl)-3,4-dihydroisoquinoline 6-Butyloxy-3,4-dihydro-1-(4-isopropylstyryl)-isoquinoline 6-Butyloxy-3,4-dihydro-1-(4-methylstyryl)-isoquinoline 6-Butyloxy-3,4-dihydro-1-(3,4-dimethoxystyryl)-isoquinoline 6-Butyloxy-3,4-dihydro-1-(4-nitrostyryl)-isoquinoline 6-Butyloxy-3,4-dihydro-1-(2,4-dimethylstyryl)-isoquinoline 6-Butyloxy-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 6-Butyloxy-1-(4-chlorostyryl)-3,4-dihydroisoquinoline ( E )-6-Butyloxy-1-(2-pentafluorophenyl)vinyl-3,4-dihydroisoquinoline 6-Butyloxy-3,4-dihydro-1-(4-phenylstyryl)-isoquinoline 6-Butyloxy-1-(2,4-dichlorostyryl)-3,4-dihydro-7-methylisoquinoline 3,4-Dihydro-1-(4-methylstyryl)-6-propyloxyisoquinoline 1-(4-Cyanostyryl)-3,4-dihydro-6-propyloxyisoquinoline 3,4-Dihydro-6-propyloxy-1-styrylisoquinoline 3,4-Dihydro-1-(2,5-dimethoxystyryl)-6-propyloxyisoquinoline 1-(4-Chlorostyryl)-3,4-dihydro-6-propyloxyisoquinoline 1-(2,4-Dichlorostyryl)-3,4-dihydro-6-propyloxyisoquinoline 3,4-Dihydro-1-(4-phenylstyryl)-6-propyloxyisoquinoline 1-(2,4-Dichlorostyryl)-3,4-dihydro-6-(3,3-dimethylbutyloxy)-isoquinoline 1-(2-Chlorostyryl)-3,4-dihydro-6-(3,3-dimethylbutyloxy)-isoquinoline 1-(4-Chlorostyryl)-3,4-dihydro-6-(3,3-dimethylbutyloxy)-isoquinoline 6-Cyclohexylmethoxy-3,4-dihydro-1-styrylisoquinoline 1-(4-Cyanostyryl)-6-cyclohexylmethoxy-3,4-dihydroisoquinoline 1-(4-Chlorostyryl)-6-cyclohexylmethoxy-3,4-dihydroisoquinoline 1-(2-Chlorostyryl)-6-cyclohexylmethoxy-3,4-dihydroisoquinoline 1-(2,4-Dichlorostyryl)-6-cyclohexylmethoxy-3,4-dihydroisoquinoline ( E )-6-Cyclohexylmethoxy-1-(2-(pentafluorophenyl)vinyl)-3,4-dihydroisoquinoline 1-(4-Chlorostryryl)-3,4-dihydro-6-(2-methylpropyloxy)-3-methylisoquinoline 1-(2,4-Dichlorostyryl)-3,4-dihydro-3-methyl-6-(2-methylpropyloxy)-isoquinoline 1-(2-Chlorostyryl)-3,4-dihydro-3-methyl-6-(2-methylpropyloxy)-isoquinoline 6-(But-3-enyloxy)-1-(4-chlorostyryl)-3,4-dihydroisoquinoline 6-(But-3-enyloxy)-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 1-(2-Chlorostyryl)-3,4-dihydro-6-(2-methylpropyloxy)-isoquinoline 1-(2,4-Dichlorostyryl-3,4-dihydro-6-(2-methylpropyloxy)-isoquinoline 1-(2,4-Dichlorostytyl)-3,4-dihydro-6-(3-methylbutyloxy)-isoquinoline 1-(4-Chlorostyryl)-3,4-dihydro-6-(3-methylbutyloxy)-isoquinoline 1-(4-Chlorostyryl)-3,4-dihydro-6-(2-methylpropyloxy)-isoquinoline 6-Benzyloxy-1-(4-cyanostyryl)-3,4-dihydroisoquinoline 6-Benzyloxy-3,4-dihydro-1-styrylisoquinoline 6-Benzyloxy-1-(2-chlorostyryl)-3,4-dihydroisoquinoline 6-Benzyloxy-3,4-dihydro-1-(2,5-dimethoxystyryl)-isoquinoline 6-Benzyloxy-3,4-dihydro-1-(2,4-dimethoxystyryl)-isoquinoline 6-Benzyloxy-1-(4-chlorostyryl)-3,4-dihydroisoquinoline 6-Benzyloxy-3,4-dihydro-1-(4-methylstyryl)-isoquinoline 6-Benzyloxy-3,4-dihydro-1-(4-isopropylstyryl)-isoquinoline 6-Benzyloxy-1-(4-t-butylstyryl)-3,4-dihydroisoquinoline 6-Benzyloxy-3,4-dihydro-1-(2,4-dimethylstyryl)-isoquinoline 6-Benzyloxy-3,4-dihydro-1-(4-nitrostyryl)-isoquinoline 6-Benzyloxy-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline ( E )-6-Benzyloxy-1-[2-(pentafluorophenyl)vinyl]-3,4-dihydroisoquinoline 1-(4-Chlorostyryl)-3,4-dihydro-6-phenoxy-isoquinoline 1-(2,4-Dichlorostyryl)-3,4-dihydro-6-phenoxyisoquinoline 6-(4-Chlorophenoxy)-1-(4-chlorostyryl)-3,4-dihydroisoquinoline 6-(4-Chlorophenoxy)-3,4-dihydro-1-(4-nitrostyryl)-isoquinoline 6-(4-Chlorophenoxy)-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 6-(4-Chlorophenoxy)-3,4-dihydro-1-styrylisoquinoline 6-(4-t-Butylphenoxy)-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 6-(4-t-Butylphenoxy)-1-(4-chlorostyryl)-3,4-dihydroisoquinoline 6-(4-t-Butylphenoxy)-3,4-dihydro-1-styrylisoquinoline 6-Hexyloxy-3,4-dihydro-1-styrylisoquinoline 1-(4-Cyanostyryl)-6-hexyloxy-3,4-dihydroisoquinoline 1-(2-Chlorostyryl)-3,4-dihydro-6-hexyloxyisoquinoline 1-(4-Chlorostyryl)-6-hexyloxy-3,4-dihydroisoquinoline 1-(2,4-Dichlorostyryl)-6-hexyloxy-3,4-dihydroisoquinoline 6-(4-t-Butylbenzyloxy)-1-(4-cyanostyryl)-3,4-dihydroisoquinoline 6-(4-t-Butylbenzyloxy)-3,4-dihydro-1-styrylisoquinoline 6-(4-t-Butylbenzyloxy)-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 6-Benzyloxy-1-(4-phenylstyryl)-3,4-dihydroisoquinoline 6-(4-Chlorobenzyloxy)-3,4-dihydro-1-styrylisoquinoline 6-(4-Chlorobenzyloxy)-1-(4-chlorostyryl)-3,4-dihydroisoquinoline 6-(4-Chlorobenzyloxy)-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 6-(2-Chlorobenzyloxy)-1-(4-cyanostyryl)-3,4-dihydroisoquinoline 6-(2-Chlorobenzyloxy)-1-(2-chlorostyryl)-3,4-dihydroisoquinoline 6-(2-Chlorobenzyloxy)-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 6-(2,4-Dichlorobenzyloxy)-1-(4-cyanostyryl)-3,4-dihydroisoquinoline 1-(4-Chlorostyryl)-6-(2,4-dichlorobenzyloxy)-3,4-dihydroisoquinoline 6-(2,4-Dichlorobenzyloxy)-3,4-dihydro-1-styrylisoquinoline 6-(2,4-Dichlorobenzyloxy)-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 6-Benzyloxy-3,4-dihydro-1-(3,4,5-trimethoxystyryl)-isoquinoline 3,4-Dihydro-3-methyl-6- iso -propyloxy-1-styrylisoquinoline, 3,4-Dihydro-6-ethoxy-3-propyl-1-styrylisoquinoline, 3,4-Dihydro-3-ethyl-6-propyloxy-1-styrylisoquinoline, 1-(2-Chlorostyryl)-6-(3-trifluoromethyl benzyloxy)-3,4-dihydroisoquinoline 1-(4-Cyanostyryl)-6-(3-trifluoromethyl benzyloxy)-3,4-dihydroisoquinoline 3,4-Dihydro-1-styryl-6-(3-trifluoromethyl benzyloxy)-isoquinoline 6-Butyloxy-1-(2-fluorostyryl)-3,4-dihydroisoquinoline 6-Benzyloxy-1-(2-fluorostyryl)-3,4-dihydroisoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-[2-(4-bromo-2-thienyl)vinyl]-isoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-[2-(5-bromo-2-thienyl)vinyl]-isoquinoline ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(2-thienyl)vinyl]-isoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-[2-(2-thienyl)vinyl]-isoquinoline ( E )-6-Benzyloxy-3,4-dihydro-1-(3-thienyl)vinyl isoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-(3-thienyl)vinylisoquinoline ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(4-bromo-2-thienyl)vinyl]-isoquinoline ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(5-bromo-2-thienyl)vinyl]-isoquinoline ( E )-6-Butyloxy-1-[2-(2-furyl)vinyl]-3,4-dihydroisoquinoline ( E )-6-Benzyloxy-1-[2-(2-furyl)vinyl]-3,4-dihydroisoquinoline ( E )-6-(4-Chlorobenzyloxy)-1-[2-(2-furyl)vinyl]-3,4-dihydroisoquinoline ( E )-3,4-Dihydro-6-propyloxy-1-[2-(5-nitro-2-furyl)]vinyl isoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-[2-(5-nitro-2-furyl)]vinyl isoquinoline ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(5-nitro-2-furyl)]vinyl isoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-[2-(3-methyl-2-thienyl)vinyl]-isoquinoline ( E )-3,4-Dihydro-1-[2-(3-methyl-2-thienyl)vinyl]-6-propyloxyisoquinoline ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(3-methyl-2-thienyl)vinyl]-isoquinoline ( E )-3,4-Dihydro-1-[2-(5-methyl-2-furyl)vinyl]-6-propyloxyisoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-[2-(5-methyl-2-furyl)vinyl]-isoquinoline ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(5-methyl-2-furyl)vinyl]-isoquinoline ( E )-3,4-Dihydro-1-[2-(5-nitro-2-thienyl)vinyl]-6-propyloxyisoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-[2-(5-nitro-2-thienyl)vinyl]-isoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-[2-(4-pyridyl)-vinyl]-isoquinoline ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(4-pyridyl)-vinyl]-isoquinoline ( E , E )-6-Benzyloxy-3,4-dihydro-1-(4-phenylbuta-1,3-dienyl)-isoquinoline ( E , E )-3,4-Dihydro-1-(penta,-1,3-dienyl)-6-propyloxyisoquinoline ( E , E )-6-Butyloxy-3,4-dihydro-1-(penta-1,3-dienyl)-isoquinoline ( E , E )-6-Hexyloxy-3,4-dihydro-1-(penta-1,3-dienyl)-isoquinoline ( E , E )-6-Benzyloxy-3,4-dihydro-1-(penta-1,3-dienyl)-isoquinoline ( E )-3,4-Dihydro-1-[2-(2-naphthyl)vinyl]-6-propyloxyisoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-[2-(2-naphthyl)-vinyl]-isoquinoline (E)-6-Benzyloxy-3,4-dihydro-1-[2-(2-naphthyl)-vinyl]-isoquinoline ( E )-3,4-Dihydro-1-[2-(1-naphthyl)vinyl]-6-propyloxyisoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-[2-(1-naphthyl)vinyl]-isoquinoline ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(1-naphthyl)vinyl]-isoquinoline 3,4-Dihydro-1-prop-1-enyl-6-propyloxyisoquinoline 6-Benzyloxy-3,4-dihydro-1-prop-1-enylisoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-(penta-1,3-dienyl)-isoquinoline 6-Butyloxy-3,4-dihydro-1-(4-phenylbuta-1,3-dienyl)-isoquinoline 1-(2-(9-Anthryl)vinyl)-6-benzyloxy-3,4-dihydroisoquinoline, 1-[2-(9-Anthryl)vinyl]-3,4-dihydro-6-propyloxy isoquinoline, 3,4-Dihydro-1-[2-(9-phenanthryl)vinyl]-6-propyloxyisoquinoline, 6-Butyloxy-3,4-dihydro-1-[2-(5-methyl-2-thienyl)vinyl]-isoquinoline, 3,4-Dihydro-1-[2-(5-methyl-2-thienyl)vinyl]-6-propyloxyisoquinoline, 6-Benzyloxy-3,4-dihydro-1-[2-(5-methyl-2-thienyl)vinyl]-isoquinoline, ( Z )-6-Butyloxy-1-(1-bromo-2-phenylvinyl)-3,4-dihydroisoquinoline ( Z )-6-Benzyloxy-1-(1-bromo-2-phenylvinyl)-3,4-dihydroisoquinoline ( Z )-6-Butyloxy-1-(1-fluoro-2-phenylvinyl)-3,4-dihydroisoquinoline ( Z )-6-Butyloxy-1-(1-chloro-2-phenylvinyl-3,4-dihydroisoquinoline ( Z )-6-Benzyloxy-1-(1-chloro-2-phenylvinyl)-3,4-dihydroisoquinoline ( E )-6-Benzyloxy-3,4-dihydro-1-(2-phenyl)-1-methylvinyl)-isoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-(2-phenyl-1-methylvinyl)-isoquinoline ( Z )-6-Benzyloxy-1-(1-fluoro-2-phenylvinyl)-3,4-dihydroisoquinoline 1-(2,4-Dichlorostyryl)-3,4-dihydro-6,7-dipropyloxyisoquinoline 1-(4-Chlorostyryl)-3,4-dihydro-3-methyl-6,7-dipropyloxy isoquinoline 6,7-Dibutyloxy-1-(4-chlorostyryl)-3,4-dihydroisoquinoline 1-(2,4-Dichlorostyryl)-3,4-dihydro-3-methyl-5,6-dipropyloxyisoquinoline 6,7-Dibutyloxy-1-(4-chlorostyryl)-3-methyl-isoquinoline 6-Butyloxy-1-(2,4-dichlorostyryl)-7-ethoxy-3,4-dihydroisoquinoline 7-Butyloxy-1-(2,4-dichlorostyryl)-6-ethoxy-3,4-dihydroisoquinoline 7-Butyloxy-1-(4-chlorostyryl)-6-ethoxy-3,4-dihydroisoquinoline 6-Butyloxy-1-(4-chlorostyryl)-7-ethoxy-3,4-dihydroisoquinoline 1-(4-Chlorostyryl)-3,4-dihydro-6,7-dipentyloxyisoquinoline 1-(4-Chlorostyryl)-6,7-dihexyloxy-3,4-dihydroisoquinoline 3,4-Dihydro-1-(4-hydroxystyryl)-6,7-dipropyloxyisoquinoline 3,4-Dihydro-1-(4-trifluoromethylstyryl)-6,7-dipropyloxyisoquinoline 1-(4-Chlorostyryl)-3,4-dihydro-6,7-dipropyloxy isoquinoline 6,7-Bisbenzyloxy-1-(2-Chlorostyryl)-3,4-dihydroisoquinoline 6,7-Bisbenzyloxy-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 5,6-Bisbenzyloxy-3,4-dihydro-1-styrylisoquinoline 5,6-Bisbenzyloxy-1-(4-chlorostyryl)-3,4-dihydroisoquinoline 5,6-Bisbenzyloxy-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 5-Benzyloxy-3,4-dihydro-8-methoxy-1-styryl-isoquinoline 5-Benzyloxy-1-(4-cyanostyryl)-3,4-dihydro-8-methoxyisoquinoline 6-Benzyloxy-1-(4-chlorostyryl)-3,4-dihydro-7-methoxy-5-propylisoquinoline 6-Benzyloxy-1-(2-chlorostyryl)-3,4-dihydro-7-methoxy-5-propylisoquinoline 6-Hydroxy-3,4-dihydro-7-methoxy-5-propyl-1-styrylisoquinoline 1-(2,4-Dichlorostyryl)-3,4-dihydro-6-hydroxy-7-methoxy-5-propylisoquinoline 1-(2-Chlorostyryl)-3,4-dihydro-6-hydroxy-7-methoxy-5-propylisoquinoline 1-(4-Chlorostyryl)-3,4-dihydro-5-hydroxy-8-methoxyisoquinoline 6-Butyloxy-1-(2,4-dichlorostyryl)-3,4-dihydro-7-methylisoquinoline 1-(4-Acetoxystyryl)-3,4-dihydro-6,7-dipropyloxy isoquinoline 1,2,3,4-Tetrahydro-6,7-dibutyloxy-1-(4-chlorostyryl)-isoquinoline 1-(4-Chlorostyryl)-1,2,3,4-tetrahydro-6,7-dipropyloxy isoquinoline 3,4-Dihydro-3,3-dimethyl-6-propyloxy-1-styrylisoquinoline, 3,4-Dihydro-3,3,4,4-tetramethyl-6-propyloxy-1-styrylisoquinoline, 6-Butyloxy-3,4-dihydro-3,3-dimethyl-1-styrylisoquinoline, 3,4-Dihydro-3,3-dimethyl-6-heptyloxy-1-styrylisoquinoline, 3,4-Dihydro-4,4-dimethyl-6-propyloxy-1-styrylisoquinoline, 4-Butyloxystyryl-3,4-dihydroisoquinoline, or a salt or acyl derivative thereof. ( E )-1-(2-Cyclohexylvinyl)-3,4-dihydro-6-propyloxyisoquinoline or a salt thereof. A phosphoric acid salt of the compound of claim 12. A pharmaceutical formulation comprising a compound as defined in any of claims 1-13 together with one or more pharmaceutically acceptable carriers or excipients. A formulation, according to claim 14, for topical administration. A process for the preparation of a compound according to claim 1 which process comprises: a) the cyclisation of a compound of the formula (XIII) wherein R¹-R⁹ are as hereinbefore defined, and either Z¹ is hydrogen and X¹-C-Y¹ is a group C=O, or X¹ is a leaving group and Y¹ and Z¹ together form a second bond between C a and N; b) when it is desired to prepare a compound of the formula (III) in which R⁷ is hydrogen and R⁸ is hydrogen, C₁₋₂alkyl, cyano or nitro, the condensation of a compound of the formula (XIV) wherein R¹-R⁶ are as hereinbefore defined and R 8a and R 8b are either both hydrogen or together form a or =PPh₃, with a compound of the formula (XV) wherein R⁷ and R⁹ are as hereinbefore defined; c) (i) when it is desired to prepare a compound of the formula (III) wherein both R 6a and R 6b are C₁₋₄ alkyl groups; the reaction of a compound of the formula (XVI) with a compound of the formula (XVII) wherein R¹-R⁵ and R⁷-R⁹ are as hereinbefore defined, R 6a and R 6b are the same or different and each is a C₁₋₄ alkyl group and X² is a leaving group; (ii) when it is desired to prepare a compound of the formula (III) wherein R 6b is a group CH₂R 6c and R 6c is hydrogen or C₁₋₃ alkyl, the reaction of compound of the formula (XVIa); with a compound of the formula (XVII); d) the cyclisation of a compound of the formula (XVIII) where in R¹-R⁹ are as hereinbefore defined; e) the conversion of a compound of the formula (III) into another compound of the formula (III). Claims for the following Contracting State : AT A process for the preparation of a compound of the formula (III): or a salt or acyl derivative thereof, wherein the dotted line represents either a single or a double bond; m is 0 when the dotted line represents a double bond, or m is 1 when the dotted line represents a single bond; R o is hydrogen or a group CH₂R¹⁰; R¹ is hydrogen, or a substituent chosen from fluorine, chlorine, methoxy, methyl, trifluoromethyl or methylthio; R², R³ and R⁴ are the same or different and each is hydrogen or a substituent group of the formula R¹⁰-A- wherein R¹⁰ is hydrogen or C₁₋₁₆ hydrocarbyl optionally substituted by halogen, fluorosulphonyl, cyano, hydroxy, thio, nitro, C₁₋₃ alkoxy or C₁₋₃ alkylthio wherein the alkoxy and alkylthio groups are optionally further substituted by halogen, hydroxy, thio, C₁₋₂ alkoxy or C₁₋₂ alkylthio, and A is oxygen, sulphur or methylene; or any two adjacent substituents R¹-R⁴ together form a methylenedioxy or ethylenedioxy group; R 5a is hydrogen or C₁₋₁₂ hydrocarbyl and R 5b is hydrogen or R 5a and R 5b are each C₁₋₄ alkyl or R 5a and R 5b together with the carbon atom to which they are attached, form a C₃₋₈ spirocycloalkyl ring; R 6a and R 6b are the same or different and each is hydrogen or C₁₋₁₂ hydrocarbyl or, together with the carbon atom to which they are attached, form a C₃₋₈ spirocycloalkyl ring; or R 5a and R 6a together with the carbon atoms to which they are attached form a five or six membered carbocyclic ring optionally containing up to two double bonds; R⁷ is hydrogen or fluorine; R⁸ is hydrogen, halogen, cyano, nitro or C₁₋₂ alkyl optionally substituted by one or more halogen atoms; R⁹ is a group -(CH=CH) n R¹¹ wherein n is 0-2 and R¹¹ is hydrogen, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl or a monocyclic, bicyclic, tricyclic or tetracyclic ring system containing between three and sixteen ring members, optionally substituted by hydroxy, thio, halogen, fluorosulphonyl, nitro, cyano, C₁₋₁₂ hydrocarbyl, C₁₋₁₂ hydrocarbyloxy, C₁₋₁₂ hydrocarbylthio wherein the said hydrocarbyl, hydrocarbyloxy and hydrocarbylthio groups are each optionally further substituted by halogen, hydroxy, thio, C₁₋₂ alkylthlo or C₁₋₂ alkoxy groups; the groups R⁸ and R⁹ optionally being linked through a C₁₋₄ alkylene bridge, provided that i) when R² and R³ are the same or different and each is hydroxy, methoxy or ethoxy; or when R² and R³ together form a methylenedioxy or ethylenedioxy group; or when R² is benzyloxy and R³ is methoxy, R¹ must be a group R¹² wherein R¹² is fluorine, chlorine, methyl, trifluoromethyl or methylthio and/or R⁴ must be a substituent as hereinbefore defined, or ii) when R³ and R⁴ are each methoxy and R⁹ is a phenyl group bearing a 2-chloro and a 5-nitro substituent, the phenyl group is additionally substituted by a substituent as hereinbefore defined and/or at least one of R¹, R² and R 5a -R⁸ is a substituent as hereinbefore defined, or iii) when R¹-R⁴ are each hydrogen and R⁹ is hydrogen, methyl or unsubstituted phenyl, R 5a and/or R 5b are substituents as hereinbefore defined,or iv) when R¹-R⁴ are each hydrogen and R⁹ is a phenyl group bearing bromo, chloro, hydroxy, methyl, methoxy or nitro substituents, the phenyl ring is trisubstituted by substituents as hereinbefore defined, or v) when R⁹ is a phenyl group substituted at the 3-, 4- and 5- positions with hydroxy or C₁₋₆ alkoxy and R² and R³ are each hydroxy, C₁₋₄ alkoxy or benzyloxy, at least one of R¹, R⁴, R⁷ and R⁸ is a substituent as hereinbefore defined; which process comprises; a) the cyclisation of a compound of the formula (XII) wherein R¹-R⁷ are as hereinbefore defined, and either Z¹ is hydrogen and X¹-C-Y¹ is a group C=O, or X¹ is a leaving group and Y¹ and Z¹ together form a second bond between C a and N; b) when it is desired to prepare a compound of the formula (III) in which R⁷ is hydrogen and R⁸ is hydrogen, C₁₋₂alkyl, cyano or nitro, the condensation of a compound of the formula (XIV) wherein R¹-R⁶ are as hereinbefore defined and R 8a and R 8b are either both hydrogen or together form a or =PPh₃, with a compound of the formula (XV) wherein R⁷ and R⁹ are as hereinbefore defined; c) (i) When it is desired to prepare a compound of the formula (III) wherein both R 6a and R 6b are C₁₋₄ alkyl groups; the reaction of a compound of the formula (XVI) with a compound of the formula (XVII) wherein R¹-R⁵ and R⁷-R⁹ are as hereinbefore defined, R 6a and R 6b are the same or different and each is a C₁₋₄ alkyl group and X² is a leaving group; (ii) When it is desired to prepare a compound of the formula (III) wherein R 6b is a group CH₂R 6c and R 6c is hydrogen or C₁₋₃ alkyl, the reaction of compound of the formula (XVIa): with a compound of the formula (XVII); d) the cyclisation of a compound of the formula (XVIII) where in R¹-R⁹ are as hereinbefore defined; (e) the conversion of one compound of the formula (III) into another compound of the formula (III). A process according to claim 1 for the preparation of a compound of the formula (IV): or a salt or acyl derivative thereof, wherein A,m, R⁰, R¹ R² and R⁴-R⁹ are as defined in claim 1 and R¹⁴ is C₃₋₁₆ hydrocarbyl optionally substituted as defined in claim 1 in respect of R¹⁰. A process according to claim 1 for the preparation of a compound of the formula (V): or a salt or acyl derivative thereof, wherein R⁰, R¹, R 5a -R⁹, A and m are as defined in claim 1; R¹⁵ is hydrogen or a group R¹⁸-A wherein R¹⁸ is hydrogen, C₃₋₆ alkyl, C₃₋₇ cycloalkyl, C₄₋₈ cycloalkylalkyl or phenyl, each optionally substituted by one or more halogen, cyano, nitro, hydroxy, thio, C₁₋₂ alkoxy or C₁₋₂ alkylthio groups; R¹⁶ is a group R¹⁹A and R¹⁹ is hydrogen, C₁₋₂ alkyl, ethenyl or ethynyl; and R¹⁷ is hydrogen or a group R¹⁴A wherein R¹⁴ is as defined in claim 2. A process according to claim 1 for the preparation of a compound of the formula (VI): or a salt or acyl derivative thereof, wherein R²⁰ and R²¹ are the same or different and each is a group R¹⁰A and m,R⁰,R¹,R¹⁶, R⁵-R⁹ and R¹⁰A are as defined in claim 1. A process according to claim 1 for the preparation of a compound of the formula (VII): or a salt or acyl derivative thereof, wherein R²² is methoxy or a group R¹², R²³ is a group R¹⁰A and m, R⁰,R¹⁰A, R¹² and R⁵-R⁸ are as defined in the preceding claims. A process according to claim 1 for the preparation of a compound of the formula (VIII): or a salt or acyl derivative thereof, wherein R²⁴ is C₃₋₁₀ alkyl, benzyl, phenyl, C₃₋₇ cycloalkyl, C₄₋₈ cycloalkylalkyl and C₃₋₁₀ alkenyl each optionally substituted by halogen, cyano, hydroxy, thio, nitro, C₁₋₃ alkoxy or C₁₋₃ alkylthio wherein the alkoxy and alkylthio groups are optionally further substituted by halogen, hydroxy, thio, C₁₋₂ alkoxy or C₁₋₂ alkylthio and R²⁵ is hydrogen or up to five substituents chosen from hydroxy, C₁₋₁₂ hydrocarbyloxy, thio, C₁₋₁₂ hydrocarbylthio, halogen, nitro, cyano or C₁₋₁₂ hydrocarbyl, the said hydrocarbyl, hydrocarbylthio or hydrocarbyloxy groups being each optionally further substituted by halogen, hydroxy, thio, C₁₋₂ alkylthio or C₁₋₂ alkoxy groups. A process according to claim 1 for the preparation of a compound of the formula (IX): or a salt or acyl derivative thereof, wherein R²⁴ is as hereinbefore defined in claim 6. A process according to claim 1 for the preparation of a compound of the formula (X): or a salt or acyl derivative thereof, wherein E represents a five or six membered ring containing one heteroatomic ring member chosen from oxygen, sulphur and nitrogen, the ring being optionally susbstituted by one or two groups chosen from hydroxy, C₁₋₂ alkoxy, halogen, C₁₋₂ alkyl, nitro or cyano. A process according to claim 1 for the prepartion of a compound of the formula (XI): or a salt or acyl derivative thereof, wherein G is an optionally substituted bicyclic or tricyclic group as hereinbefore defined in claim 1. A process according to claim 1 for the preparation of a formula (XII): or a salt or acyl derivative thereof, wherein R²⁶ is chosen from fluorine, chlorine, bromine and methyl. A process according to claim 1 for the preparation of a compound selected from ( E )-6-Butyloxy-1-(2-cyclohexylvinyl)-3,4-dihydroisoquinoline 6-Benzyloxy-1-[2-cyclohexylvinyl]-3,4-dihydroisoquinoline 6-Butyloxy-3,4-dihydro-1-styrylisoquinoline 1-(2-Chlorostyryl)-3,4-dihydro-6-propyloxyisoquinoline ( E )-1-(2-Cyclohexylvinyl)-3,4-dihydro-6-(2-methylpropyloxy)-isoquinoline (E)-1-(2-Cyclohexylvinyl)-3,4-dihydro-6-propyloxyisoquinoline (E)-1-(Cyclohexylvinyl)-6-hexyloxy-3,4-dihydroisoquinoline (E)-6-(4-Chlorobenzyloxy)-1-(2-cyclohexylvinyl)-3,4-dihydroisoquinoline (E)-6-Benzyloxy-1-[2-(cyclohex-3-enyl)vinyl]-3,4-dihydroisoquinoline 6-Butyloxy-3,4-dihydro-1-(2,5-dimethoxystyryl)-isoquinoline 6-Butyloxy-3,4-dihydro-1-(3,4,5-trimethoxystyryl)-isoquinoline 6-Butyloxy-1-(2-chlorostyryl)-3,4-dihydroisoquinoline 6-Butyloxy-3,4-dihydro-1-(4-cyanostyryl)-isoquinoline 6-Butyloxy-3,4-dihydro-1-(2,4-dimethoxystyryl)-isoquinoline 6-Butyloxy-1-(4-t-butylstyryl)-3,4-dihydroisoquinoline 6-Butyloxy-3,4-dihydro-1-(4-isopropylstyryl)-isoquinoline 6-Butyloxy-3,4-dihydro-1-(4-methylstyryl)-isoquinoline 6-Butyloxy-3,4-dihydro-1-(3,4-dimethoxystyryl)-isoquinoline 6-Butyloxy-3,4-dihydro-1-(4-nitrostyryl)-isoquinoline 6-Butyloxy-3,4-dihydro-1-(2,4-dimethylstyryl)-isoquinoline 6-Butyloxy-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 6-Butyloxy-1-(4-chlorostyryl)-3,4-dihydroisoquinoline ( E )-6-Butyloxy-1-(2-pentaflourophenyl)vinyl-3,4-dihydroisoquinoline 6-Butyloxy-3,4-dihydro-1-(4-phenylstyryl)-isoquinoline 6-Butyloxy-1-(2,4-dichlorostyryl)-3,4-dihydro-7-methylisoquinoline 3,4-Dihydro-1-(4-methylstyryl)-6-propyloxyisoquinoline 1-(4-Cyanostyryl)-3,4-dihydro-6-propyloxyisoquinoline 3,4-Dihydro-6-propyloxy-1-styrylisoquinoline 3,4-Dihydro-1-(2,5-dimethoxystyryl)-6-propyloxyisoquinoline 1-(4-Chlorostyryl)-3,4-dihydro-6-propyloxyisoquinoline 1-(2,4-Dichlorostyryl)-3,4-dihydro-6-propyloxyisoquinoline 3,4-Dihydro-1-(4-phenylstyryl)-6-propyloxyisoquinoline 1-(2,4-Dichlorostyryl)-3,4-dihydro-6-(3,3-dimethylbutyloxy)-isoquinoline 1-(2-Chlorostyryl)-3,4-dihydro-6-(3,3-dimethylbutyloxy)-isoquinoline 1-(4-Chlorostyryl)-3,4-dihydro-6-(3,3-dimethylbutyloxy)-isoquinoline 6-Cyclohexylmethoxy-3,4-dihydro-1-styrylisoquinoline 1-(4-Cyanostyryl)-6-cyclohexylmethoxy-3,4-dihydroisoquinoline 1-(4-Chlorostyryl)-6-cyclohexylmethoxy-3,4-dihydroisoquinoline 1-(2-Chlorostyryl)-6-cyclohexylmethoxy-3,4-dihydroisoquinoline 1-(2,4-Dichlorostyryl)-6-cyclohexylmethoxy-3,4-dihydroisoquinoline ( E )-6-Cyclohexylmethoxy-1-(2-(pentafluorophenyl)vinyl)-3,4-dihydroisoquinoline 1-(4-Chlorostyryl)-3,4-dihydro-6-(2-methoxypropyloxy)-3-methylisoquinoline 1-(2,4-Dichlorostyryl)-3,4-dihydro-3-methyl-6-(2-methylpropyloxy)-isoquinoline 1-(2-Chlorostyryl)-3,4-dihydro-3-methyl-6-(2-methylpropyloxy)-isoquinoline 6-(But-3-enyloxy)-1-(4-chlorostyryl)-3,4-dihydroisoquinoline 6-(But-3-enyloxy)-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 1-(2-Chlorostyryl)-3,4-dihydro-6-(2-methylpropyloxy)-isoquinoline 1-(2,4-Dichlorostyryl-3,4-dihydro-6-(2-methylpropyloxy)-isoquinoline 1-(2,4-Dichlorostyryl)-3,4-dihydro-6-(3-methylbutyloxy)-isoquinoline 1-(4-Chlorostyryl)-3,4-dihydro-6-(3-methylbutyloxy)-isoquinoline 1-(4-Chlorostyryl)-3,4-dihydro-6-(2-methylpropyloxy)-isoquinoline 6-Benzyloxy-1-(4-cyanostyryl)-3,4-dihydroisoquinoline 6-Benzyloxy-3,4-dihydro-1-styrylisoquinoline 6-Benzyloxy-1-(2-chlorostyryl)-3,4-dihydroisoquinoline 6-Benzyloxy-3,4-dihydro-1-(2,5-dimethoxystyryl)-isoquinoline 6-Benzyloxy-3,4-dihydro-1-(2,4-dimethoxystyryl)-isoquinoline 6-Benzyloxy-1-(4-chlorostyryl)-3,4-dihydroisoquinoline 6-Benzyloxy-3,4-dihydro-1-(4-methylstyryl)-isoquinoline 6-Benzyloxy-3,4-dihydro-1-(4-isopropylstyryl)-isoquinoline 6-Benzyloxy-1-(4-t-butylstyryl)-3,4-dihydroisoquinoline 6-Benzyloxy-3,4-dihydro-1-(2,4-dimethylstyryl)-isoquinoline 6-Benzyloxy-3,4-dihydro-1-(4-nitrostyryl)-isoquinoline 6-Benzyloxy-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline ( E )-6-Benzyloxy-1-(2-(pentafluorophenyl)vinyl)-3,4-dihydroisoquinoline 1-(4-Chlorostyryl)-3,4-dihydro-6-phenoxyisoquinoline 1-(2,4-Dichlorostyryl)-3,4-dihydro-6-phenoxyisoquinoline 6-(4-Chlorophenoxy)-1-(4-chlorostyryl)-3,4-dihydroisoquinoline 6-(4-Chlorophenoxy)-3,4-dihydro-1-(4-nitrostyryl)-isoquinoline 6-(4-Chlorophenoxy)-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 6-(4-Chlorophenoxy)-3,4-dihydro-1-styrylisoquinoline 6-(4-t-Butylphenoxy)-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 6-(4-t-Butylphenoxy)-1-(4-chlorostyryl)-3,4-dihydroisoquinoline 6-(4-t-Butylphenoxy)-3,4-dihydro-1-styrylisoquinoline 6-Hexyloxy-3,4-dihydro-1-styrylisoquinoline 1-(4-Cyanostyryl)-6-hexyloxy-3,4-dihydroisoquinoline 1-(2-Chlorostyryl)-3,4-dihydro-6-hexyloxyisoquinoline 1-(4-Chlorostyryl)-6-hexyloxy-3,4-dihydroisoquinoline 1-(2,4-Dichlorostyryl)-6-hexyloxy-3,4-dihydroisoquinoline 6-(4-t-Butylbenzyloxy)-1-(4-cyanostyryl)-3,4-dihydroisoquinoline 6-(4-t-Butylbenzyloxy)-3,4-dihydro-1-styrylisoquinoline 6-(4-t-Butylbenzyloxy)-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 6-Benzyloxy-1-(4-phenylstyryl)-3,4-dihydroisoquinoline 6-(4-Chlorobenzyloxy)-3,4-dihydro-1-styrylisoquinoline 6-(4-Chlorobenzyloxy)-1-(4-chlorostyryl)-3,4-dihydroisoquinoline 6-(4-Chlorobenzyloxy)-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 6-(2-Chlorobenzyloxy)-1-(4-cyanostyryl)-3,4-dihydroisoquinoline 6-(2-Chlorobenzyloxy)-1-(2-chlorostyryl)-3,4-dihydroisoquinoline 6-(2-Chlorobenzyloxy)-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 6-(2,4-Dichlorobenzyloxy)-1-(4-cyanostyryl)-3,4-dihydroisoquinoline 1-(4-Chlorostyryl)-6-(2,4-dichlorobenzyloxy)-3,4-dihydroisoquinoline 6-(2,4-Dichlorobenzyloxy)-3,4-dihydro-1-styrylisoquinoline 6-(2,4-Dichlorobenzyloxy)-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 6-Benzyloxy-3,4-dihydro-1-(3,4,5-trimethoxystyryl)-isoquinoline 3,4-Dihydro-3-methyl-6- iso -propyloxy-1-styrylisoquinoline 3,4-Dihydro-6-ethoxy-3-propyl-1-styrylisoquinoline 3,4-Dihydro-3-ethyl-6-propyloxy-1-styrylisoquinoline 1-(2-Chlorostyryl)-6-(3-triflouoromethylbenzyloxy)-3,4-dihydroisoquinoline 1-(4-Cyanostyryl)-6-(3-trifluoromethylbenzyloxy)-3,4-dihydroisoquinoline 3,4-Dihydro-1-styryl-6-(3-trifluoromethylbenzyloxy)isoquinoline 6-Butyloxy-1-(2-flourostyryl)-3,4-dihydroisoquinoline 6-Benzyloxy-1-(2-fluorostyryl)-3,4-dihydroisoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-[2-(4-bromo-2-thienyl)vinyl)-isoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-[2-(5-bromo-2-thienyl)vinyl]-isoquinoline ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(2-thienyl)vinyl]-isoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-[2-(2-thienyl)vinyl]-isoquinoline ( E )-6-Benzyloxy-3,4-dihydro-1-(3-thienyl)vinylisoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-(3-thienyl)vinylisoquinoline ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(4-bromo-2-thienyl)vinyl]-isoquinoline ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(5-bromo-2-thienyl)vinyl]-isoquinoline ( E )-6-Butyloxy-1-[2-(2-furyl)vinyl]-3,4-dihydroisoquinoline ( E )-6-Benzyloxy-1-[2-(2-furyl)vinyl]-3,4-dihydroisoquinoline ( E )-6-(4-Chlorobenzyloxy)-1-[2-(2-furyl)vinyl]-3,4-dihydroisoquinoline ( E )-3,4-Dihydro-6-propyloxy-1-[2-(5-nitro-2-furyl)vinyl]-isoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-[2-(5-nitro-2-furyl)vinyl]-isoquinoline ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(5-nitro-2-furyl)vinyl]-isoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-[2-(3-methyl-2-thienyl)vinyl]-isoquinoline ( E )-3,4-Dihydro-1-[2-(3-methyl-2-thienyl)vinyl]-6-propyloxyisoquinoline ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(3-methyl-2-thienyl)vinyl]-isoquinoline ( E )-3,4-Dihydro-1-[2-(5-methyl-2-furyl)vinyl]-6-propyloxy-isoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-[2-(5-methyl-2-furyl)vinyl]-isoquinoline ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(5-methyl-2-furyl)vinyl]-isoquinoline ( E )-3,4-Dihydro-1-[2-(5-nitro-2-thienyl)vinyl]-6-propyloxyisoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-[2-(5-nitro-2-thienyl)vinyl]-isoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-[2-(4-pyridyl)-vinyl]-isoquinoline ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(4-pyridyl)-vinyl]-isoquinoline ( E , E )-6-Benzyloxy-3,4-dihydro-1-(4-phenylbuta-1,3-dienyl)-isoquinoline ( E , E )-3,4-Dihydro-1-(penta,-1,3-dienyl)-6-propyloxyisoquinoline ( E , E )-6-Butyloxy-3,4-dihydro-1-(penta-1,3-dienyl)-isoquinoline ( E , E )-6-Hexyloxy-3,4-dihydro-1-(penta-1,3-dienyl)-isoquinoline ( E , E )-6-Benzyloxy-3,4-dihydro-1-(penta-1,3-dienyl)-isoquinoline ( E )-3,4-Dihydro-1-[2-(2-naphthyl)vinyl]-6-propyloxyisoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-[2-(2-naphthyl)-vinyl]-isoquinoline ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(2-naphthyl)-vinyl]-isoquinoline ( E )-3,4-Dihydro-1-[2-(1-naphthyl)vinyl]-6-propyloxyisoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-[2-(1-naphthyl)vinyl]-isoquinoline ( E )-6-Benzyloxy-3,4-dihydro-1-[2-(1-naphthyl)vinyl]-isoquinoline 3,4-Dihydro-1-prop-1-enyl-6-propyloxyisoquinoline 6-Benzyloxy-3,4-dihydro-1-prop-1-enylisoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-(penta-1,3-dienyl)-isoquinoline 6-Butyloxy-3,4-dihydro-1-(4-phenylbuta-1,3-dienyl)-isoquinoline 1-(2-(9-Anthryl)vinyl)-6-benzyloxy-3,4-dihydroisoquinoline, 1-(2-(9-Anthryl)vinyl)-3,4-dihydro-6-propyloxyisoquinoline, 3,4-Dihydro-1-(2-(9-phenanthryl)vinyl)-6-propyloxyisoquinoline, 6-Butyloxy-3,4-dihydro-1-[2-(5-methyl-2-thienyl)vinyl]isoquinoline, 3,4-Dihydro-1-[2-(5-methyl-2-thienyl)vinyl]-6-propyloxyisoquinoline, 6-Benzyloxy-3,4-dihydro-1-[2-(5-methyl-2-thienyl)vinyl]-isoquinoline, ( Z )-6-Butyloxy-1-(1-bromo-2-phenylvinyl)-3,4-dihydroisoquinoline ( Z )-6-Benzyloxy-1-(1-bromo-2-phenylvinyl)-3,4-dihydroisoquinoline ( Z )-6-Butyloxy-1-(1-fluoro-2-phenylvinyl)-3,4-dihydroisoquinoline ( Z )-6-Butyloxy-1-(1-chloro-2-phenylvinyl)-3,4-dihydroisoquinoline ( Z )-6-Benzyloxy-1-(1-chloro-2-phenylvinyl)-3,4-dihydroisoquinoline ( E )-6-Benzyloxy-3,4-dihydro-1-[(2-phenyl)-1-methylvinyl]-isoquinoline ( E )-6-Butyloxy-3,4-dihydro-1-[(2-phenyl)-1-methylvinyl]-isoquinoline ( Z )-6-Benzyloxy-1-(1-fluoro-2-phenylvinyl)-3,4-dihydroisoquinoline 1-(2,4-Dichlorostyryl)-3,4-dihydro-6,7-dipropyloxyisoquinoline 1-(4-Chlorostyryl)-3,4-dihydro-3-methyl-6,7-dipropyloxy isoquinoline 6,7-Dibutyloxy-1-(4-chlorostyryl)-3,4-dihydroisoquinoline 1-(2,4-Dichlorostyryl)-3,4-dihydro-3-methyl-6,7-dipropyloxyisoquinoline 6,7-Dibutyloxy-1-(4-chlorostyryl)-3-methylisoquinoline 6-Butyloxy-1-(2,4-dichlorostyryl)-7-ethoxy-3,4-dihydroisoquinoline 7-Butyloxy-1-(2,4-dichlorostyryl)-6-ethoxy-3,4-dihydroisoquinoline 7-Butyloxy-1-(4-chlorostyryl)-6-ethoxy-3,4-dihydroisoquinoline 6-Butyloxy-1-(4-chlorostyryl)-7-ethoxy-3,4-dihydroisoquinoline 1-(4-Chlorostyryl)-3,4-dihydro-6,7-dipentyloxyisoquinoline 1-(4-Chlorostyryl)-6,7-dihexyloxy-3,4-dihydroisoquinoline 3,4-Dihydro-1-(4-hydroxystyryl)-6,7-dipropyloxy-isoquinoline 3,4-Dihydro-1-(4-trifluoromethylstyryl)-6,7-dipropyloxyisoquinoline 1-(4-Chlorostyryl)-3,4-dihydro-6,7-dipropyloxy isoquinoline 6,7-Bisbenzyloxy-1-(2-Chlorostyryl)-3,4-dihydroisoquinoline 6,7-Bis(benzyloxy)-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 5,6-Bis(benzyloxy)-3,4-dihydro-1-styrylisoquinoline 5,6-Bis(benzyloxy)-1-(4-chlorostyryl)-3,4-dihydroisoquinoline 5,6-Bis(benzyloxy)-1-(2,4-dichlorostyryl)-3,4-dihydroisoquinoline 5-Benzyloxy-3,4-dihydro-8-methoxy-1-styryl-isoquinoline 5-Benzyloxy-1-(4-cyanostyryl)-3,4-dihydro-8-methoxyisoquinoline 6-Benzyloxy-1-(4-chlorostyryl)-3,4-dihydro-7-methoxy-5-propylisoquinoline 6-Benzyloxy-1-(2-chlorostyryl)-3,4-dihydro-7-methoxy-5-propylisoquinoline 6-Hydroxy-3,4-dihydro-7-methoxy-5-propyl-1-styrylisoquinoline 1-(2,4-Dichlorostyryl)-3,4-dihydro-6-hydroxy-7-methoxy-5-propylisoquinoline 1-(2-Chlorostyryl)-3,4-dihydro-6-hydroxy-7-methoxy-5-propylisoquinoline 1-(4-Chlorostyryl)-3,4-dihydro-5-hydroxy-8-methoxyisoquinoline 6-Butyloxy-1-(2,4-dichlorostyryl)-3,4-dihydro-7-methylisoquinoline 1-(4-Acetoxystyryl)-3,4-dihydro-6,7-dipropyloxy isoquinoline 1,2,3,4-Tetrahydro-6,7-dibutyloxy-1-(4-chlorostyryl)isoquinoline 1-(4-Chlorostyryl)-1,2,3,4-tetrahydro-6,7-dipropyloxy isoquinoline 3,4-Dihydro-3,3-dimethyl-6-propyloxy-1-styrylisoquinoline 3,4-Dihydro-3,3,4,4-tetramethyl-6-propyloxy-1-styrylisoquinoline 6-Butyloxy-3,4-dihydro-3,3-dimethyl-1-styrylisoquinoline 3,4-Dihydro-3,3-dimethyl-6-heptyloxy-1-styrylisoquinoline 3,4-Dihydro-4,4-dimethyl-6-propyloxy-1-styrylisoquinoline 4-Butyloxystyryl-3,4-dihydroisoquinoline or salt or acyl derivative thereof. A process according to claim 1 for the preparation of (E)-1-(2-Cyclohexylvinyl)-3,4-dihydro-6-propyloxyisoquinoline and its salts. A process according to claim 12 wherein the salt is a phosphoric acid salt.

Inventors: FRANZMANN, KARL WITOLD
Applicants: THE WELLCOME FOUNDATION LIMITED
Application year: 1985
Main classification: A61K31
IPC codes: C07D491, A61P31, C07D217, A61K31, A61P33, A01N43, C07C45, C07D333, C07C47, C07D405, C07D401, C07D409