Claims for Patent: 7,807,708

Summary for Patent: 7,807,708

Title:	Ligands that modulate RAR receptors and pharmaceutical/cosmetic compositions comprised thereof
Abstract:	Novel ligand compounds having the general formula (I): ##STR00001## and pharmaceutical/cosmetic compositions comprised thereof are useful in human and veterinary medicine or, alternatively, in cosmetics.
Inventor(s):	Biadatti; Thibaud (Opio, FR), Dumais; Laurence (Le Rouret, FR), Soulet; Catherine (Antibes, FR), Talano; Sandrine (Vence, FR), Daver; Sebastien (Antibes, FR)
Assignee:	Galderma Research & Development (Biot, FR)
Application Number:	11/819,068
Patent Claims:	1. A ligand compound having the formula (I) below: ##STR00058## in which: R.sub.1 is a hydrogen atom, an alkyl radical of 1 to 4 carbon atoms or a --CF.sub.3 radical; R.sub.2 is a hydrogen atom, an alkyl or alkoxy radical of 1 to 4 carbon atoms or a chlorine atom; R.sub.3 is a hydrogen atom or a linear or branched alkyl or alkoxy radical of 1 to 10 carbon atoms optionally substituted with a methoxy group; R.sub.4 is a hydrogen atom or an alkyl radical of 1 to 3 carbon atoms; R.sub.5 is a hydrogen atom or an alkyl radical of 1 to 3 carbon atoms; or alternatively R.sub.4 and R.sub.5 form, together with the bond --N--C(.dbd.Y)--, a pyrrolidine, pyrrolidinone, piperidine or piperidinone ring; Y is two hydrogen atoms or a hetero atom; Ar is a 1,4-phenyl, 2,5-pyridyl, 5,2-pyridyl or 2,5-thiophenyl ring; X is an oxygen atom optionally substituted with an alkyl or alkylamine radical or a C--C single bond; A is a hydrogen atom or the following formula: ##STR00059## in which, Q is an oxygen atom or an --NH-- bond; R.sub.6 is a hydrogen atom, an alkyl radical of 1 to 6 carbon atoms, a cycloalkyl radical of 3 to 6 carbon atoms or a --C(O)CH.sub.3 or --C(O)CH.sub.2CH.sub.3 radical; R.sub.7 and R.sub.7' represent, independently of each other, a hydrogen atom or a hydroxyl group, with the provisio that R.sub.7 and R.sub.7' are not simultaneously a hydroxyl group; n is 0, 1, 2, 3, 4 or 5; and the salts of the compounds of formula (I) when R.sub.3 is a hydrogen atom and also the geometrical isomers of the said compounds of formula (I). 2. The ligand compound as defined by claim 1, wherein formula (I), R.sub.1 is a --CF.sub.3 radical. 3. The ligand compound as defined by claim 1, wherein formula (I), Ar is a 1,4-phenyl ring. 4. The ligand compound as defined by claim 1, wherein formula (I), Ar is a 2,5-pyridyl ring. 5. The ligand compound as defined by claim 1, wherein formula (I), Ar is a 5,2-pyridyl ring. 6. The ligand compound as defined by claim 1, wherein formula (I), Ar is a 2,5-thiophenyl ring. 7. The ligand compound as defined by claim 1, wherein formula (I), Y is oxygen. 8. The ligand compound as defined by claim 1, wherein formula (I), Y is sulfur. 9. The ligand compound as defined by claim 1, wherein formula (I), R.sub.4 and R.sub.5 together form, with the --N--C(.dbd.Y)-radical, a pyrrolidine, pyrrolidinone, piperidine or piperidinone ring. 10. The ligand compound as defined by claim 1, being an alkali metal or alkaline-earth metal salts, a zinc salt or a salt of an organic amine or of an acidic partner when the compound is itself basic. 11. The ligand compound as defined by claim 1, wherein the alkyl radical of 1 to 3 carbon atoms is selected from among methyl, ethyl, i-propyl and n-propyl radicals. 12. The ligand compound as defined by claim 1, wherein the alkyl radical of 1 to 4 carbon atoms is selected from among methyl, ethyl, i-propyl, i-butyl and t-butyl radicals. 13. The ligand compound as defined by claim 1, wherein the alkyl radical of 1 to 10 carbon atoms is selected from among methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, hexyl, heptyl, octyl, nonyl and dodecyl radicals. 14. The ligand compound as defined by claim 1, wherein the alkoxy radical having from 1 to 10 carbon atoms is selected from among methoxy, ethoxy, isopropyloxy, tert-butoxy and hexyloxy radicals. 15. The ligand compound as defined by claim 1, wherein the alkoxy radical having from 1 to 4 carbon atoms is selected from among methoxy, ethoxy, isopropyloxy and tert-butoxy radicals. 16. The ligand compound as defined by claim 1, wherein the cycloalkyl radical of 3 to 6 carbon atoms is selected from among cyclopropyl, cyclopentyl and cyclohexyl radicals. 17. The ligand compound as defined by claim 1, selected from the group consisting of: 1. ethyl 3''-tert-butyl-4''-diethylamino-4'-hydroxy[1,1';3',1'']terphenyl-4-carbox- ylate, 2. ethyl 3''-tert-butyl-4''-diethylamino-4'-(4-hydroxybutoxy)-[1,1';3',1'']terphen- yl-4-carboxylate, 3. 3''-tert-butyl-4''-diethylamino-4'-(4-hydroxybutoxy)-[1,1';3',1'']terphen- yl-4-carboxylic acid, 4. ethyl 4''-(acetylethylamino)-3''-tert-butyl-4'-(4-hydroxybutoxy)-[1,1',3',1'']t- erphenyl-4-carboxylate, 5. 4''-(acetylethylamino)-3''-tert-butyl-4'-(4-hydroxybutoxy)-[1,1';3',1'']t- erphenyl-4-carboxylic acid, 6. 3''-tert-butyl-4''-diethylamino-4'-(2-hydroxyethoxy)-[1,1';3',1'']terphen- yl-4-carboxylic acid, 7. ethyl 3''-tert-butyl-4''-diethylamino-4'-(3-hydroxypropoxy)-[1,1';3',1'']terphe- nyl-4-carboxylate, 8. 3''-tert-butyl-4''-diethylamino-4'-(3-hydroxypropoxy)-[1,1';3',1'']terphe- nyl-4-carboxylic acid, 9. ethyl 4''-diethylamino-4'-(3-hydroxypropoxy)-[1,1';3',1'']terphenyl-4-carboxyla- te, 10. 4''-diethylamino-4'-(3-hydroxypropoxy)-[1,1';3',1'']terphenyl-4-ca- rboxylic acid, 11. ethyl 4''-diethylamino-3''-ethyl-4'-(3-hydroxypropoxy)-[1,1',3',1'']terphenyl-4- -carboxylate, 12. 4''-diethylamino-3''-ethyl-4'-(3-hydroxypropoxy)-[1,1';3',1'']terphenyl-4- -carboxylic acid, 13. 4''-diethylamino-3''-ethyl-4'-(2-hydroxyethoxy)-[1,1';3',1'']terphenyl-4-- carboxylic acid, 14. ethyl 4''-diethylamino-3''-ethyl-4'-(2-hydroxyethoxy)-[1,1';3',1'']terphenyl-4-- carboxylate, 15. ethyl 3''-tert-butyl-4''-diethylamino-4'-(2-hydroxyethoxy)-[1,1';3',1'']terphen- yl-4-carboxylate, 16. ethyl 4''-diethylamino-4'-(3-hydroxypropoxy)-3''-methyl[1,1';3',1'']terphenyl-4- -carboxylate, 17. 4''-diethylamino-4'-(3-hydroxypropoxy)-3''-methyl[1,1';3',1'']terphenyl-4- -carboxylic acid, 18. ethyl 3''-tert-butyl-4'-(4-hydroxybutoxy)-4''-pyrrolidin-1-yl[1,1';3',1'']terph- enyl-4-carboxylate, 19. 3''-tert-butyl-4'-(4-hydroxybutoxy)-4''-pyrrolidin-1-yl[1,1';3',1'']terph- enyl-4-carboxylic acid, 20. ethyl 4'-(4-hydroxybutoxy)-4''-pyrrolidin-1-yl-3''-trifluoromethyl[1,1';3',1'']- terphenyl-4-carboxylate, 21. 4'-(4-hydroxybutoxy)-4''-pyrrolidin-1-yl-3''-trifluoromethyl[1,1';3',1'']- terphenyl-4-carboxylic acid, 22. ethyl 3''-tert-butyl-4'-(3-hydroxypropoxy)-4''-pyrrolidin-1-yl[1,1';3',1'']terp- henyl-4-carboxylate, 23. 3''-tert-butyl-4'-(3-hydroxypropoxy)-4''-pyrrolidin-1-yl[1,1';3',1'']terp- henyl-4-carboxylic acid, 24. ethyl 3''-tert-butyl-4'-(2-hydroxyethoxy)-4''-pyrrolidin-1-yl[1,1';3',1'']terph- enyl-4-carboxylate, 25. 3''-tert-butyl-4'-(2-hydroxyethoxy)-4''-pyrrolidin-1-yl[1,1';3',1'']terph- enyl-4-carboxylic acid, 26. 4'-(3-hydroxypropoxy)-4''-pyrrolidin-1-yl[1,1';3',1'']terphenyl-4-carboxy- lic acid, 27. 3''-tert-butyl-4''-diethylamino-4'-hydroxy[1,1';3',1'']terphenyl-4-carbox- ylic acid, 28. ethyl 4''-diethylamino-4'-hydroxy-3''-trifluoromethyl[1,1';3',1'']terphenyl-4-c- arboxylate, 29. 4''-diethylamino-4'-hydroxy-3''-trifluoromethyl[1,1';3',1'']terphenyl-4-c- arboxylic acid, 30. 3''-tert-butyl-4''-diethylamino-4'-(4-isopropylaminobutoxy)-[1,1';3',1'']- terphenyl-4-carboxylic acid, 31. 3''-tert-butyl-4'-(4-isopropylaminobutoxy)-4''-pyrrolidin-1-yl[1,1';3',1'- ']terphenyl-4-carboxylic acid, 32. ethyl 3''-tert-butyl-4''-diethylamino-4'-(3-hydroxypropyl)-[1,1';3',1'']terphen- yl-4-carboxylate, 33. 3''-tert-butyl-4''-diethylamino-4'-(3-hydroxypropyl)-[1,1';3',1'']terphen- yl-4-carboxylic acid, 34. ethyl 3''-tert-butyl-4''-diethylamino-4'-(2,3-dihydroxypropyl)-[1,1';3',1'']ter- phenyl-4-carboxylate, 35. 3''-tert-butyl-4''-diethylamino-4'-(2,3-dihydroxypropyl)-[1,1';3',1'']ter- phenyl-4-carboxylic acid, 36. ethyl 4''-(acetylethylamino)-3''-tert-butyl-4'-(3-hydroxypropyl)-[1,1';3',1'']t- erphenyl-4-carboxylate, 37. 4''-(acetylethylamino)-3''-tert-butyl-4'-(3-hydroxypropyl)-[1,1';3',1'']t- erphenyl-4-carboxylic acid, 38. ethyl 3''-tert-butyl-4'-(3-cyclopropylaminopropyl)-4''-diethylamino[1,1';3',1''- ]terphenyl-4-carboxylate, 39. 3''-tert-butyl-4'-(3-cyclopropylaminopropyl)-4''-diethylamino[1,1';3',1''- ]terphenyl-4-carboxylic acid, 40. ethyl 3''-tert-butyl-4'-(3-cyclopentylaminopropyl)-4''-diethylamino[1,1';3',1''- ]terphenyl-4-carboxylate, 41. 3''-tert-butyl-4'-(3-cyclopentylaminopropyl)-4''-diethylamino[1,1';3',1''- ]terphenyl-4-carboxylic acid, 42. ethyl 3''-tert-butyl-4'-(3-cyclohexylaminopropyl)-4''-diethylamino[1,1';3',1'']- terphenyl-4-carboxylate, 43. 3''-tert-butyl-4'-(3-cyclohexylaminopropyl)-4''-diethylamino[1,1';3',1'']- terphenyl-4-carboxylic acid, 44. ethyl 3''-tert-butyl-4'-(3-tert-butylaminopropyl)-4''-diethylamino[1,1';3',1'']- terphenyl-4-carboxylate, 45. 3''-tert-butyl-4'-(3-tert-butylaminopropyl)-4''-diethylamino[1,1';3',1'']- terphenyl-4-carboxylic acid, 46. ethyl 4''-(acetylethylamino)-3''-tert-butyl-4'-(3-cyclopropylaminopropyl)-[1,1'- ;3',1'']terphenyl-4-carboxylate, 47. 4''-(acetylethylamino)-3''-tert-butyl-4'-(3-cyclopropylaminopropyl)-[1,1'- ;3',1'']terphenyl-4-carboxylic acid, 48. ethyl 3''-tert-butyl-4''-diethylamino-4'-(3-isopropylaminopropyl)-[1,1';3',1'']- terphenyl-4-carboxylate, 49. 3''-tert-butyl-4''-diethylamino-4'-(3-isopropylaminopropyl)-[1,1';3',1'']- terphenyl-4-carboxylic acid, 50. ethyl 4'-(3-aminopropyl)-3''-tert-butyl-4''-diethylamino[1,1';3',1'']terphenyl-- 4-carboxylate, 51. 4'-(3-aminopropyl)-3''-tert-butyl-4''-diethylamino[1,1';3',1'']terphenyl-- 4-carboxylic acid, 52. [3''-tert-butyl-4-carboxy-4'-(3-hydroxypropyl)-[1,1';3',1'']terphenyl-4''- -yl]diethylamine hydrochloride, 53. 3''-tert-butyl-4'-(2-hydroxyethoxy)-4''-(2-oxopyrrolidin-1-yl)-[1,1';3',1- '']terphenyl-4-carboxylic acid, 54. 3''-tert-butyl-4''-ethylamino-4'-(3-hydroxypropoxy)-[1,1';3',1'']terpheny- l-4-carboxylic acid, 55. 4'-(3-acetoxypropoxy)-3''-tert-butyl-4''-diethylamino[1,1';3',1'']terphen- yl-4-carboxylic acid, 56. 3''-tert-butyl-4''-diethylamino-4'-(3-propionyloxypropoxy)-[1,1';3',1'']t- erphenyl-4-carboxylic acid, 57. methyl 3''-tert-butyl-4''-diethylamino-4'-(3-hydroxypropoxy)-[1,1';3',1'']terphe- nyl-4-carboxylate, 58. isopropyl 3''-tert-butyl-4''-diethylamino-4'-(3-hydroxypropoxy)-[1,1';3',1'']terphe- nyl-4-carboxylate, 59. isobutyl 3''-tert-butyl-4''-diethylamino-4'-(3-hydroxypropoxy)-[1,1';3',1'']terphe- nyl-4-carboxylate, 60. 3''-tert-butyl-4''-diethylamino-4'-(3-hydroxypropoxy)-5''-methyl[1,1';3',- 1'']terphenyl-4-carboxylic acid, 61. 4''-diethylamino-4'-(3-hydroxypropoxy)-3''-isopropyl-5''-methyl[1,1';3',1- '']terphenyl-4-carboxylic acid, 62. 3''-tert-butyl-5''-chloro-4''-diethylamino-4'-(3-hydroxypropoxy)-[1,1';3'- ,1'']terphenyl-4-carboxylic acid, 63. 4''-diethylamino-4'-(3-hydroxypropoxy)-3'',5''-diisopropyl[1,1';3',1'']te- rphenyl-4-carboxylic acid, 64. 3'',5''-di-tert-butyl-4''-diethylamino-4'-(3-hydroxypropoxy)-[1,1';3',1''- ]terphenyl-4-carboxylic acid, 65. 4''-diethylamino-4'-(3-hydroxypropoxy)-3''-trifluoromethyl[1,1';3',1'']te- rphenyl-4-carboxylic acid, 66. 3''-tert-butyl-4''-(ethylmethylamino)-4'-(2-hydroxyethoxy)-[1,1';3',1'']t- erphenyl-4-carboxylic acid, 67. 3''-tert-butyl-4''-dimethylamino-4'-(2-hydroxyethoxy)-[1,1';3',1'']terphe- nyl-4-carboxylic acid, 68. 3''-tert-butyl-4''-(ethylisopropylamino)-4'-(2-hydroxyethoxy)-[1,1';3',1'- ']terphenyl-4-carboxylic acid, 69. 3''-tert-butyl-4''-(ethylpropylamino)-4'-(2-hydroxyethoxy)-[1,1';3',1'']t- erphenyl-4-carboxylic acid, 70. 3''-tert-butyl-4''-dipropylamino-4'-(2-hydroxyethoxy)-[1,1';3',1'']terphe- nyl-4-carboxylic acid, 71. 3''-tert-butyl-4''-(ethylpropionylamino)-4'-(2-hydroxyethoxy)-[1,1';3',1'- ']terphenyl-4-carboxylic acid, 72. 6-[3'-tert-butyl-4'-diethylamino-6-(2-hydroxyethoxy)biphenyl-3-yl]nicotin- ic acid, 73. 5-[3'-tert-butyl-4'-diethylamino-6-(2-hydroxyethoxy)biphenyl-3-yl]pyridin- e-2-carboxylic acid, 74. 5-[3'-tert-butyl-4'-diethylamino-6-(2-hydroxyethoxy)biphenyl-3-yl]thiophe- ne-2-carboxylic acid, 75. 3''-tert-butyl-4'-(2-hydroxyethoxy)-5''-methyl-4''-pyrrolidin-1-yl[1,1';3- ',1'']terphenyl-4-carboxylic acid, 76. 3''-tert-butyl-5''-chloro-4'-(2-hydroxyethoxy)-4''-pyrrolidin-1-yl[1,1';3- ',1'']terphenyl-4-carboxylic acid, 77. 4'-(2-hydroxyethoxy)-3''-isopropyl-4''-pyrrolidin-1-yl[1,1';3',1'']terphe- nyl-4-carboxylic acid, 78. 3''-ethyl-4'-(2-hydroxyethoxy)-4''-pyrrolidin-1-yl[1,1';3',1'']terphenyl-- 4-carboxylic acid, 79. 4'-(2-hydroxyethoxy)-3'',5''-diisopropyl-4''-pyrrolidin-1-yl[1,1';3',1'']- terphenyl-4-carboxylic acid, 80. 3'',5''-diethyl-4'-(2-hydroxyethoxy)-4''-pyrrolidin-1-yl[1,1';3',1'']terp- henyl-4-carboxylic acid, 81. 3'',5''-dimethyl-4'-(2-hydroxyethoxy)-4''-pyrrolidin-1-yl[1,1';3',1'']ter- phenyl-4-carboxylic acid, 82. 4'-(2-acetoxyethoxy)-3''-tert-butyl-4''-pyrrolidin-1-yl[1,1';3',1'']terph- enyl-4-carboxylic acid, 83. 4'-(2-propionyloxyethoxy)-3''-tert-butyl-4''-pyrrolidin-1-yl[1,1';3',1'']- terphenyl-4-carboxylic acid, 84. methyl 3''-tert-butyl-4'-(2-hydroxyethoxy)-4''-pyrrolidin-1-yl[1,1';3',1'']terph- enyl-4-carboxylate, 85. isopropyl 3''-tert-butyl-4'-(2-hydroxyethoxy)-4''-pyrrolidin-1-yl[1,1';3',1'']terph- enyl-4-carboxylate, 86. isobutyl 3''-tert-butyl-4'-(2-hydroxyethoxy)-4''-pyrrolidin-1-yl[1,1';3',1'']terph- enyl-4-carboxylate, 87. ethyl 3''-tert-butyl-4'-(3-hydroxypropoxy)-4''-pyrrolidin-1-yl[1,1';3',1'']terp- henyl-4-carboxylate, 88. ethyl 3''-tert-butyl-5''-chloro-4'-(2-hydroxyethoxy)-4''-pyrrolidin-1-yl[1,1';3- ',1'']terphenyl-4-carboxylate, 89. 6-[3'-tert-butyl-6-(2-hydroxyethoxy)-4'-pyrrolidin-1-ylbiphenyl-3-yl]nico- tinic acid, 90. 5-[3'-tert-butyl-6-(2-hydroxyethoxy)-4'-pyrrolidin-1-ylbiphenyl-3-yl]pyri- dine-2-carboxylic acid, 91. ethyl 6-[3'-tert-butyl-6-(2-hydroxyethoxy)-4'-pyrrolidin-1-ylbiphenyl-3-yl]nico- tinate, 92. ethyl 3''-tert-butyl-4'-(3-hydroxypropyl)-4''-pyrrolidin-1-yl[1,1';3',1'']terph- enyl-4-carboxylate, 93. 3''-tert-butyl-4'-(3-hydroxypropyl)-4''-pyrrolidin-1-yl[1,1';3',1'']terph- enyl-4-carboxylic acid, 94. 3''-tert-butyl-4'-(2-hydroxyethoxy)-4''-(2-oxopyrrolidin-1-yl)-[1,1';3',1- '']terphenyl-4-carboxylic acid, 95. 3''-tert-butyl-4'-(2-hydroxyethoxy)-4''-(2-oxopiperid-1-yl)-[1,1';3',1]te- rphenyl-4-carboxylic acid, 96. 3''-tert-butyl-4'-(2-hydroxyethoxy)-4''-piperid-1-yl[1,1';3',1'']terpheny- l-4-carboxylic acid, 97. 5-[3'-tert-butyl-6-(2-hydroxyethoxy)-4'-pyrrolidin-1-ylbiphenyl-3-yl]thio- phene-2-carboxylic acid. 18. The ligand compound as defined by claim 1, wherein formula (I) at least one of the following conditions is satisfied: R.sub.1 is a hydrogen atom or a t-butyl or i-propyl radical; R.sub.2 is a hydrogen atom or a t-butyl or i-propyl radical; R.sub.3 is a hydrogen atom or an ethyl radical; R.sub.4 and R.sub.5 are, independently of each other, a methyl or ethyl radical or together form a pyrrolidine ring; A is as defined in which R.sub.6 is a hydrogen atom, an i-propyl or t-butyl radical, a cycloalkyl radical of 3 to 6 carbon atoms or a --C(O)CH.sub.3 or --C(O)CH.sub.2CH.sub.3 radical. 19. The ligand compound as defined by claim 18, wherein formula (I) all of the following conditions are satisfied: R.sub.1 is a hydrogen atom or a t-butyl or i-propyl radical; R.sub.2 is a hydrogen atom or a t-butyl or i-propyl radical; R.sub.3 is a hydrogen atom or an ethyl radical; R.sub.4 and R.sub.5 are, independently of each other, a methyl or ethyl radical or together form a pyrrolidine ring; A is as defined in which R.sub.6 is a hydrogen atom, an i-propyl or t-butyl radical, a cycloalkyl radical of 3 to 6 carbon atoms or a --C(O)CH.sub.3 or --C(O)CH.sub.2CH.sub.3 radical. 20. A cosmetic composition comprising a cosmetically effective amount of at least one ligand compound as defined by claim 1, formulated into a cosmetically and physiologically acceptable medium therefor. 21. The cosmetic composition as defined by claim 20, comprising from 0.001% to 3% by weight of said at least one ligand compound. 22. The cosmetic composition as defined by claim 20, formulated for body or hair hygiene. 23. A pharmaceutical composition comprising a pharmaceutically effective amount of at least one ligand compound as defined by claim 1, formulated into a pharmaceutically and physiologically acceptable medium therefor. 24. The pharmaceutical composition as defined by claim 23, comprising from 0.0001% to 10% by weight of said at least one ligand compound. 25. The cosmetic composition as defined by claim 20, formulated for preventing and/or treating the signs of aging and/or dry sun. 26. The ligand compound as defined by claim 1, selected from the group consisting of: 3''-tert-butyl-4''-diethylamino-4'-(4-hydroxybutoxy)-[1,1';3',1'']terphen- yl-4-carboxylic acid, 4''-(acetylethylamino)-3''-tert-butyl-4'-(4-hydroxybutoxy)-[1,1';3',1'']t- erphenyl-4-carboxylic acid, 3''-tert-butyl-4''-diethylamino-4'-(2-hydroxyethoxy)-[1,1';3',1'']terphen- yl-4-carboxylic acid, 3''-tert-butyl-4''-diethylamino-4'-(3-hydroxypropoxy)-[1,1';3',1'']terphe- nyl-4-carboxylic acid, 4''-diethylamino-3''-ethyl-4'-(3-hydroxypropoxy)-[1,1';3',1'']terphenyl-4- -carboxylic acid, 4''-diethylamino-3''-ethyl-4'-(2-hydroxyethoxy)-[1,1';3',1'']terphenyl-4-- carboxylic acid, 4''-diethylamino-4'-(3-hydroxypropoxy)-3''-methyl[1,1';3',1'']terphenyl-4- -carboxylic acid, 3''-tert-butyl-4'-(4-hydroxybutoxy)-4''-pyrrolidin-1-yl[1,1';3',1'']terph- enyl-4-carboxylic acid, 4'-(4-hydroxybutoxy)-4''-pyrrolidin-1-yl-3''-trifluoromethyl[1,1';3',1'']- terphenyl-4-carboxylic acid, 3''-tert-butyl-4'-(3-hydroxypropoxy)-4''-pyrrolidin-1-yl[1,1';3',1'']terp- henyl-4-carboxylic acid, 3''-tert-butyl-4'-(2-hydroxyethoxy)-4''-pyrrolidin-1-yl[1,1';3',1'']terph- enyl-4-carboxylic acid, 3''-tert-butyl-4''-diethylamino-4'-(3-hydroxypropyl)-[1,1';3',1'']terphen- yl-4-carboxylic acid, 3''-tert-butyl-4''-diethylamino-4'-(2,3-dihydroxypropyl)-[1,1';3',1'']ter- phenyl-4-carboxylic acid, 4''-(acetylethylamino)-3''-tert-butyl-4'-(3-hydroxypropyl)-[1,1';3',1'']t- erphenyl-4-carboxylic acid, 4''-(acetylethylamino)-3''-tert-butyl-4'-(3-cyclopropylaminopropyl)-[1,1'- ;3',1'']terphenyl-4-carboxylic acid, [3''-tert-butyl-4-carboxy-4'-(3-hydroxypropyl)-[1,1';3',1'']terphenyl-4''- -yl]diethylamine hydrochloride, 3''-tert-butyl-4'-(2-hydroxyethoxy)-4''-(2-oxopyrrolidin-1-yl)-[1,1';3',1- '']terphenyl-4-carboxylic acid, and 3''-tert-butyl-4''-ethylamino-4'-(3-hydroxypropoxy)-[1,1';3',1'']terpheny- l-4-carboxylic acid. 27. The ligand compound as defined by claim 1, which is 3''-tert-butyl-4'-(2-hydroxyethoxy)-4''-pyrrolidin-1-yl[1,1';3',1'']terph- enyl-4-carboxylic acid.