1-phenyl-3-dimethylaminopropane compounds with a pharmacological effects

• US RE39,593 E1
• Filed: 06/17/2003
• Issued: 04/24/2007
• Est. Priority Date: 07/23/1994
• Status: Expired due to Term

• Current Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Original Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Inventors: Buschmann, Helmut, Friderichs, Elmar, Strassburger, Wolfgang
• Primary Examiner(s): O SULLIVAN, PETER G
• Application Number:
  US10/462,844
• Time in Patent Office: 1,407 Days
• Field of Search: 544/86, 549/362, 549/348, 558/190, 558/273, 560/32, 560/37, 560/66, 560/250, 560/252, 514/231.8, 514/114, 514/452, 514/456, 514/488, 514/534, 514/546, 514/653, 514/654
• US Class Current: 514/238.2
• CPC Class Codes: C07C 215/30 containing hydroxy groups and carbon atoms of six-membered aromatic rings bound to the same carbon atom of the carbon skeleton
• CPC Class Codes: C07C 215/54 linked by carbon chains having at least three carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
• CPC Class Codes: C07C 215/62 the chain having at least three carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
• CPC Class Codes: C07C 217/62 linked by carbon chains having at least three carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
• CPC Class Codes: C07C 217/72 linked by carbon chains having at least three carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
• CPC Class Codes: C07C 217/74 with rings other than six-membered aromatic rings being part of the carbon skeleton
• CPC Class Codes: C07C 219/22 and containing six-membered aromatic rings
• CPC Class Codes: C07C 225/10 with doubly-bound oxygen atoms bound to carbon atoms not being part of rings
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07C 271/58 with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 323/36 the sulfur atom of the sulfide group being further bound to an acyclic carbon atom
• CPC Class Codes: C07D 307/79 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring

Abstract

1-phenyl-3-dimethylaminopropane compounds corresponding to the formula I
a method of preparing them, and the use of these substances as analgesic active ingredients in pharmaceutical compositions.

Claims

1. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer having a configuration corresponding to formula Ia′

;

X represents OH, F, Cl, H or an OCOR⁶ group in which R⁶ is a C_1-3-alkyl group;

R¹ is a C_1-4-alkyl group;

R² represents H or a C_1-4-alkyl group, and

R³ is different from R² and represents H or a straight chain C_1-4-alkyl group, and

R⁵ represents H, and R⁴ represents meta-O—

Z,

where Z is H, C_1-3-alkyl, PO(OC_1-4alkyl)₂, CO(OC_1-5-alkyl), CONH—

C₆H₄—

(C_1-3-alkyl) or CO—

C₆H₄—

R⁷, in which R⁷ is ortho-OCOC_1-3-alkyl or meta- or para-CH₂N(R⁸)₂, where R⁸ is C_1-4-alkyl or 4-morpholino,

or R⁴ represents meta-S-C_1-3-alkyl, meta-Cl, meta-F, meta-CR⁹R¹⁰R¹¹, ortho-OH, ortho-O—

C_2-3-alkyl, para-F or para-CR⁹R¹⁰R¹¹, where R⁹, R¹⁰ and R¹¹ independently represent H or F, or

R⁵ represents para-Cl, para-F, para-OH or para-O—

C_1-3-alkyl, and R⁴ represents meta-Cl, meta-F, meta-OH or meta-O—

C_1-3-alkyl, or

R⁴ and R⁵ together represent 3,4-OCH═

CH—

or 3,4-OCH═

CHO—

;

or a salt thereof with a physiologically acceptable acid.

2. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 1, wherein

X represents OH, F, Cl or H;

R¹ represents a C_1-4-alkyl group;

R² represents H or CH₃;

R³ is different from R² and represents H or CH₃, and

R⁵ represents H, and R⁴ represents meta-OC_1-3-alkyl, meta-OH, meta-S—

C_1-3-alkyl, meta-F, meta-Cl, meta-CH₃, meta-CF₂H, meta-CF₃ or para-CF₃, or

R⁵ represents para-Cl or para-F, and R⁴ represents meta-Cl or meta-F, or

R⁴ and R⁵ together represent 3,4-OCH═

CH—

.

3. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 1, wherein X represents OH, F, Cl or an OCOR⁴ group in which R⁶ is a C_1-3-alkyl group.

4. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 1, wherein R² is C_1-4-alkyl.

5. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 1, wherein R⁹, R¹⁰ and R¹¹ represent F.

6. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer having a configuration corresponding to the formula Ia,

wherein

X represents OH, F, Cl, H or an OCOR⁶ group in which R⁶ is a C_1-3-alkyl group;

R¹ is a C_1-4-alkyl group;

R² represents a C_1-4-alkyl group, and

R⁵ represents H, and R⁴ represents meta-O—

Z,

where Z is H, C_1-3-alkyl, PO(OC_1-4alkyl)₂, CO(OC_1-5-alkyl), CONH—

C₆H₄—

(C_1-3-alkyl) or CO—

C₆H₄—

R⁷, in which R⁷ is ortho-OCOC_1-3-alkyl or meta- or para-CH₂N(R⁸)₂, where R⁸ is C_1-4-alkyl or 4-morpholino, or R⁴ represents meta-S—

C_1-3-alkyl, meta-Cl, meta-F, meta-CR⁹R¹⁰R¹¹, ortho-OH, ortho-O—

C_2-3-alkyl, para-F or para-CR⁹R¹⁰R¹¹, where R⁹, R¹⁰ and R¹¹ independently represent H or F, or

R⁵ represents para-Cl, para-F, para-OH or para-O—

C_1-3-alkyl, and R⁴ represents meta-Cl, meta-F, meta-OH or meta-O—

C_1-3-alkyl, or

R⁴ and R⁵ together represent 3,4-OCH═

CH—

or 3,4-OCH═

CHO—

;

or a salt thereof with a physiologically acceptable acid.

19. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 6, wherein R⁵ is H and R⁴ is meta-OCH₃.

20. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 6, wherein R⁵ is H and R⁴ is meta-OH.

21. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 6, wherein X represents OH, F, Cl, or an OCOR⁶ group in which R⁶ is a C_1-3-alkyl group.

22. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 6, wherein R⁹, R¹⁰ and R¹¹ represent F.

23. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 6, wherein X represents OH.

24. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 6, wherein X represents F, Cl, H or an OCOR⁶ group in which R⁶ is a C_1-3-alkyl group.

124. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 6, wherein X is H.

7. An analgesic composition comprising at least one 1-phenyl-3-dimethylaminopropane diastereoisomer having a configuration corresponding to formula Ia′

;

wherein

X represents OH, F, Cl, H or an OCOR⁶ group in which R⁶ is a C_1-3-alkyl group;

R¹ is a C_1-4-alkyl group;

R² represents H or a C_1-4-alkyl group, and

R³ is different from R² and represents H or a straight chain C_1-4-alkyl group, and

R⁵ represents H, and R⁴ represents meta-O—

Z,

where Z is H, C_1-3-alkyl, PO(OC_1-4alkyl)₂, CO(OC_1-5-alkyl), CONH—

C₆H₄—

(C_1-3-alkyl) or CO—

C₆H₄—

R⁷, in which R⁷ is ortho-OCOC_1-3-alkyl or meta- or para-CH₂N(R⁸)₂, where R⁸ is C_1-4-alkyl or 4-morpholino,

or R⁴ represents meta-S—

C_2-3-alkyl, meta-Cl, meta-F, meta-CR⁹R¹⁰R¹¹, ortho-OH, ortho-O—

C_2-3-alkyl, para-F or para-CR⁹R¹⁰R¹¹, where R⁹, R¹⁰ and R¹¹ independently represent H or F, or

R⁵ represents para-Cl, para-F, para-OH or para-O—

C_1-3-alkyl, and R⁴ represents meta-Cl, meta-F, meta-OH or meta-O—

C_1-3-alkyl, or

R⁴ and R⁵ together represent 3,4-OCH═

CH—

or 3,4-OCH═

CHO—

;

or a salt thereof with a physiologically acceptable acid, and at least one conventional pharmaceutical carrier or adjuvant.

8. A method of treating a mammal suffering from pain, said method comprising administering to said mammal an effective analgesic amount of a 1-phenyl-3-dimethylaminopropane compound corresponding to formula I

wherein

X represents OH, F, Cl, H or an OCOR⁶ group in which R⁶ is a C_1-3-alkyl group;

R¹ is a C_1-4-alkyl group;

R² represents H or a C_1-4-alkyl group and R³ represents H or a straight chain C_1-4-alkyl group, or R² and R³ together form a C_4-7 cycloalkyl radical, and

R⁵ represents H, and R⁴ represents meta-O—

Z,

where Z is H, C_1-3-alkyl, PO(OC_1-4alkyl)₂, CO(OC_1-5-alkyl), CONH—

C₆H₄—

(C_1-3-alkyl) or CO—

C₆H₄—

R⁷, in which R⁷ is ortho-OCOC_1-3-alkyl or meta- or para-CH₂N(R⁸)₂, where R⁸ is C_1-4-alkyl or 4-morpholino,

or R⁴ represents meta-S—

C_1-3-alkyl, meta-Cl, meta-F, meta-CR⁹R¹⁰R¹¹, ortho-OH, ortho-O—

C_2-3-alkyl, para-F or para-CR⁹R¹⁰R¹¹, where R⁹, R¹⁰ and R¹¹ independently represent H or F, or

R⁵ represents para-Cl, para-F, para-OH or para-O—

C_1-3-alkyl, and R⁴ represents meta-Cl, meta-F, meta-OH or meta-O—

C_1-3-alkyl, or

R⁴ and R⁵ together represent 3,4-OCH═

CH—

or 3,4-OCH═

CHO—

, or a salt thereof with a physiologically acceptable acid.

86. A method according to claim 8, wherein

X represents OH, F, Cl, or H;

R¹ represents a C_1-4-alkyl group;

R² represents CH₈;

R³ represents H, and

R⁵ represents H, and R⁴ represents meta-OC_1-8-alkyl, meta-OH, meta-S—

C_1-3-alkyl, meta-F, meta-Cl, meta-CH₃, meta-CF₂H, meta-CF₃, or para-CF₃, or

R⁵ represents para-Cl, or para-F, and R⁴ represents meta-Cl, or meta-F, or

R⁴ and R⁵ together represent 3,4-OCH═

CH—

.

87. A method according to claim 8, wherein R⁵ is H and R⁴ is meta-OCH₈.

88. An method according to claim 8, wherein R⁵ is H and R⁴ is meta-OH.

89. A method according to claim 8, wherein X represents OH, F, Cl or an OCOR⁶ group in which R⁶ is a C_1-3-alkyl group.

90. A method according to claim 8, wherein R² is C_1-4-alkyl, and R³ is different from R² and is H or C_1-3 alkyl.

91. A method according to claim 8, wherein R⁹, R¹⁰ and R¹¹ represent F.

92. A method according to claim 8, wherein X represents OH.

93. A method according to claim 8, wherein X represents F, Cl, H or an OCOR⁶ group in which R⁶ is a C_1-3-alkyl group.

94. A method according to claim 8, wherein X represents H.

95. A method according to claim 8, wherein the compound of formula I has a configuration corresponding to at least one of formulae Ia′

and Ic′

;

96. A method according to claim 95, wherein

X represents OH, F, Cl, or H;

R¹ represents a C_1-4-alkyl group;

R² represents CH₃;

R³ represents H, and

R⁵ represents H, and R⁴ represents meta-OC_1-3-alkyl, meta-OH, meta-S—

C_1-3-alkyl, meta-F, meta-Cl, meta-CH₃, meta-CF₂H, meta-CF₃, or para-CF₃, or

R⁵ represents para-Cl, or para-F, and R⁴ represents meta-Cl, or meta-F, or

R⁴ and R⁵ together represent 3,4-OCH═

CH—

.

97. A method according to claim 95, wherein R⁵ is H and R⁴ is meta-OCH₃.

98. An method according to claim 95, wherein R⁵ is H and R⁴ is meta-OH.

99. A method according to claim 95, wherein X represents OH, F, Cl or an OCOR⁶ group in which R⁶ is a C_1-3-alkyl group.

100. A method according to claim 95, wherein R² is CH₃, and R³ is H.

101. A method according to claim 95, wherein R⁹, R¹⁰ and R¹¹ represent F.

102. A method according to claim 95, wherein X represents OH.

103. A method according to claim 95, wherein X represents F, Cl, H or an OCOR⁶ group in which R⁶ is a C_1-3-alkyl group.

104. A method according to claim 95, wherein the 1-phenyl-3-dimethylaminopropane diastereoisomer has a configuration corresponding to formula Ia′

.

105. A method according to claim 95, wherein the 1-phenyl-3-dimethylaminopropane diastereoisomer has a configuration corresponding to formula Ic′

.

106. A method according to claim 8, wherein the compound of formula I has a configuration corresponding to at least one of formulae Ia and Ic:

107. A method according to claim 106, wherein X represents OH, F, Cl or an OCOR⁶ group in which R⁶ is a C_1-3-alkyl group.

108. A method according to claim 106, wherein R⁹, R¹⁰ and R¹¹ represent F.

109. A method according to claim 106, wherein X represents OH.

110. A method according to claim 106, wherein X represents F, Cl, H or an OCOR⁶ group in which R⁶ is a C_1-3-alkyl group.

111. A method according to claim 106, wherein the compound is a 1-phenyl-3-dimethylaminopropane diastereoisomer having a configuration corresponding to formula Ia.

112. A method according to claim 106, wherein the compound is a 1-phenyl-3-dimethylaminopropane diastereoisomer having a configuration corresponding to formula Ic.

113. A method according to claim 106, wherein R⁵ is H and R⁴ is meta-OCH₃.

114. A method according to claim 106, wherein R⁵ is H and R⁴ is meta-OH.

115. A method according to claim 8, wherein the compound is (+)-(1RS,2RS)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride (+21).

116. A method according to claim 8, wherein the compound is (+)-(1S,2S)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride (+21).

117. A method according to claim 8, wherein the compound is (−

)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride (−

21).

118. A method according to claim 8, wherein the compound is (+)-(2RS,3RS)-[3-(3-methoxyphenyl)-2-methylpentyl]-dimethylamine hydrochloride (+23).

119. A method according to claim 8, wherein the compound is (+)-(2S,3S)-[3-(3-methoxyphenyl)-2-methylpentyl]-dimethylamine hydrochloride (+23).

120. A method according to claim 8, wherein the compound is (−

)-(2R,3R)-[3-(3-methoxyphenyl)-2-methylpentyl]-dimethylamine hydrochloride (−

23).

121. A method according to claim 8, wherein the compound is (+)-(2RS, 3RS)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol hydrochloride (+1).

122. A method according to claim 8, wherein the compound is (+)-(2R, 3R)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol hydrochloride (+1).

123. A method according to claim 8, wherein the compound is (−

)-(2S, 3S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol hydrochloride (−

1).

136. A method according to claim 86, wherein X is H.

137. A method according to claim 95, wherein X is H.

138. A method according to claim 106, wherein X is H.

139. A method according to claim 113, wherein X is H.

140. A method according to claim 114, wherein X is H.

9. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer having a configuration corresponding to at least one of formulae Ia′

and Ic′

;

10. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer having a configuration corresponding to formula Ia′

;

11. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 10, wherein R⁵ is H, and R⁴ is meta-OCH₃.

12. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 10, wherein R⁵ is H, and R⁴ is meta-OH.

13. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 10, wherein

X represents OH, F, Cl, or H;

R¹ is a C_1-4-alkyl group;

R² represents CH₃;

R³ is H; and

R⁵ represents H, and R⁴ represents meta-O—

C_1-3-alkyl, meta-OH, meta-S—

C_1-3-alkyl, meta-F, meta-Cl, meta-CH₃, meta-CF₂H, meta-CF₃, or para-CF₃, or

R⁵ represents para-Cl, or para-F, and R⁴ represents meta-Cl, or meta-F, or

R⁴ and R⁵ together represent 3,4-OCH═

CH—

.

14. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 10, wherein X represents OH, F, Cl, or an OCOR⁶group in which R⁶ is a C_1-3-alkyl group.

15. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 10, wherein R² is CH₃, and R³ is H.

16. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 10, wherein R⁹, R¹⁰ and R¹¹ represent F.

17. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 10, wherein X represents OH.

18. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 10, wherein X represents F, Cl, H or an OCOR⁶ group in which R⁶ is a C_1-3-alkyl group.

125. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 10, wherein X is H.

25. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer having a configuration corresponding to at least one of formulae Ia′

and Ic′

;

26. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 25, wherein

X represents OH, F, Cl, or H;

R¹ is a C_1-4-alkyl group;

R² represents CH₃;

R³ is H; and

R⁵ represents H, and R⁴ represents meta-OC_1-3-alkyl, meta-OH, meta-S—

C_1-3-alkyl, meta-F, meta-Cl, meta-CH₃, meta-CF₂H, meta-CF₃, or para-CF₃, or

R⁵ represents para-Cl, or para-F, and R⁴ represents meta-Cl, or meta-F, or

R⁴ and R⁵ together represent 3,4-OCH═

CH—

.

27. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 25, wherein R⁵ is H and R⁴ is meta-OCH₃.

28. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 25, wherein R⁵ is H and R⁴ is meta-OH.

29. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 25, wherein X represents OH, F, Cl or an OCOR⁶ group in which R⁶ is a C_1-3-alkyl group.

30. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 25, wherein R² is CH₃, and R³ is H.

31. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 25, wherein R⁹, R¹⁰ and R¹¹ represent F.

32. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 25, wherein X represents OH.

33. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 25, wherein X represents F, Cl, H or an OCOR⁶ group in which R⁶ is a C_1-3-alkyl group.

126. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 25, wherein X is H.

34. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer having a configuration corresponding to at least one of formulae Ia and Ic:

35. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 34, wherein R⁵ is H and R⁴ is meta-OCH₃.

36. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 34, wherein R⁵ is H and R⁴ is meta-OH.

37. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 34, wherein X represents OH, F, Cl or an OCOR⁶ group in which R⁶ is a C_1-3-alkyl group.

38. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 34, wherein R⁹, R¹⁰ and R¹¹ represent F.

39. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 34, wherein X represents OH.

40. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 34, wherein X represents F, Cl, H or an OCOR⁶ group in which R⁶ is a C_1-3-alkyl group.

57. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 34, wherein the compound is (2S, 3S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol hydrochloride (−

1).

58. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 34, wherein the compound is (+)-(2R, 3R)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol hydrochloride (+1).

59. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 34, wherein the compound is (+)-(2R, 3R)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol hydrochloride (+1).

60. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 34, wherein the compound is (+)-(1S,2S)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride (+21).

62. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 34, wherein the compound is (+)-(1RS,2RS)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride (+21).

63. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 34, wherein the compound is (+)-(2S,3S)-[3-(3-methoxyphenyl)-2-methylpentyl]-dimethylamine hydrochloride (+23).

64. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 34, wherein the compound is (−

)-(2R,3R)-[3-(3-methoxyphenyl)-2-methylpentyl]-dimethylamine hydrochloride (−

23).

65. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 34, wherein the compound is (+)-(2RS, 3RS)-[3-(3-methoxyphenyl)-2-methylpentyl]-dimethylamine hydrochloride (+23).

127. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 34, wherein X is H.

41. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer having a configuration corresponding to formula Ic′

;

42. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 41, wherein

X represents OH, F, Cl, or H;

R¹ is a C_1-4-alkyl group;

R² represents CH₃;

R⁸ is H; and

R⁵ represents H, and R⁴ represents meta-OC_1-3-alkyl, meta-OH, meta-S—

C_1-3-alkyl, meta-F, meta-Cl, meta-CH₃, meta-CF₂H, meta-CF₃, or para-CF₃, or

R⁵ represents para-Cl, or para-F, and R⁴ represents meta-Cl, or meta-F, or

R⁴ and R⁵ together represent 3,4-OCH═

CH—

.

43. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 41, wherein R⁵ is H and R⁴ is meta-OCH₃.

44. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 41, wherein R⁵ is H and R⁴ is meta-OH.

45. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 41, wherein X represents OH, F, Cl or an OCOR⁶ group in which R⁶ is a C_1-3-alkyl group.

46. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 41, wherein R² is CH₃, and R³ is H.

47. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 41, wherein R⁹, R¹⁰ and R¹¹ represent F.

48. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 41, wherein X represents OH.

49. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 41, wherein X represents F, Cl, H or an OCOR⁶ group in which R⁶ is a C_1-3-alkyl group.

128. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 41, wherein X is H.

50. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer having a configuration corresponding to formula Ic:

51. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 50, wherein R⁵ is H and R⁴ is meta-OCH₃.

52. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 50, wherein R⁵ is H and R⁴ is meta-OH.

53. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 50, wherein X represents OH, F, Cl or an OCOR⁶ group in which R⁶ is a C_1-3-alkyl group.

54. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 50, wherein R⁹, R¹⁰ and R¹¹ represent F.

55. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 50, wherein X represents OH.

56. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 50, wherein X represents F, Cl, H or an OCOR⁶ group in which R⁶ is a C_1-3-alkyl group.

129. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 50, wherein X is H.

61. (−

)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride (−

21).

66. An analgesic composition comprising at least one 1-phenyl-3-dimethylaminopropane diastereoisomer having a configuration corresponding to at least one of formulae Ia′

and Ic′

;

67. An analgesic composition according to claim 66, wherein

X represents OH, F, Cl, or H;

R¹ represents a C_1-4-alkyl group;

R² represents CH₃;

R³ is H; and

R⁵ represents H, and R⁴ represents meta-OC_1-3-alkyl, meta-OH, meta-S—

C_1-3-alkyl, meta-F, meta-Cl, meta-CH₃, meta-CF₂H, meta-CF₃, or

R⁵ represents para-Cl, or para-F, and R⁴ represents meta-Cl, or meta-F, or

R⁴ and R⁵ together represent 3,4-OCH═

CH—

.

68. An analgesic composition according to claim 66, wherein R⁵ is H and R⁴ is meta-OCH₃.

69. An analgesic composition according to claim 66, wherein R⁵ is H and R⁴ is meta-OH.

70. An analgesic composition according to claim 66, wherein X represents OH, F, Cl or an OCOR⁶ group in which R⁶ is a C_1-3-alkyl group.

71. An analgesic composition according to claim 66, wherein R² is CH₂, and R³ is H.

72. An analgesic composition according to claim 66, wherein R⁹, R¹⁰ and R¹¹ represent F.

73. An analgesic composition according to claim 66, wherein X represents OH.

74. An analgesic composition according to claim 66, wherein X represents F, Cl, H or an OCOR⁶ group in which R⁶ is a C_1-3-alkyl group.

75. An analgesic composition according to claim 66, wherein the 1-phenyl-3-dimethylaminopropane diastereoisomer has a configuration corresponding to formula Ia′

.

76. An analgesic composition according to claim 66, wherein the 1-phenyl-3-dimethylaminopropane diastereoisomer has a configuration corresponding to formula Ic′

.

130. An analgesic composition according to claim 66, wherein X is H.

131. An analgesic composition according to claim 75, wherein X is H.

132. An analgesic composition according to claim 76, wherein X is H.

77. An analgesic composition comprising at least one 1-phenyl-3-dimethylaminopropane diastereoisomer having a configuration corresponding to at least one of formulae Ia and Ic:

78. An analgesic composition according to claim 77, wherein R⁵ is H and R⁴ is meta-OCH₃.

79. An analgesic composition according to claim 77, wherein R⁵ is H and R⁴ is meta-OH.

80. An analgesic composition according to claim 77, wherein X represents OH, F, Cl or an OCOR⁶group in which R⁶ is a C_1-3-alkyl group.

81. An analgesic composition according to claim 77, wherein R⁹, R¹⁰ and R¹¹ represent F.

82. An analgesic composition according to claim 77, wherein X represents OH.

83. An analgesic composition according to claim 77, wherein X represents F, Cl, H or an OCOR⁶ group in which R⁶ is a C_1-3-alkyl group.

84. An analgesic composition according to claim 77, wherein the 1-phenyl-3-dimethylaminopropane diastereoisomer has a configuration corresponding to formula Ia.

85. An analgesic composition according to claim 77, wherein the 1-phenyl-3-dimethylaminopropane diastereoisomer has a configuration corresponding to formula Ic.

133. An analgesic composition according to claim 77, wherein X is H.

134. An analgesic composition according to claim 84, wherein X is H.

135. An analgesic composition according to claim 85, wherein X is H.

141. An isolated 1-phenyl-3-dimethylaminopropane diastereomer having a configuration corresponding to formula I:

142. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 141, wherein R⁵ is H, and R⁴ is meta-OCH₃.

143. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 141, wherein R⁵ is H, and R⁴ is meta-OH.

144. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 141, wherein

R² represents CH₃;

R³ is H; and

R⁵ represents H, and R⁴ represents meta-O—

C_1-3-alkyl, meta-OH, meta-S—

1-3-alkyl, meta-F, meta-Cl, meta-CH₃, meta-CF₂H, meta-CF₃, or para-CF₃, or

R⁵ represents para-Cl, or para-F, and R⁴ represents meta-Cl, or meta-F, or

R⁴ and R⁵ together represent 3,4-OCH═

CH—

.

145. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 141, wherein R² is CH₃, and R³ is H.

146. An isolated 1-phenyl-3-dimethylaminopropane diastereomer according to claim 141, wherein R⁹, R¹⁰ and R¹¹ represent F.

147. A pharmaceutically acceptable salt of (−

)-(1R,2R)-3R-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol.