1-phenyl-3-dimethylaminopropane compounds with a pharmacological effects
DC CAFCFirst Claim
Patent Images
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 C1-3-alkyl group;
R1 is a C1-4-alkyl group;
R2 represents H or a C1-4-alkyl group, and R3 is different from R2 and represents H or a straight chain C1-4-alkyl group, and R5 represents H, and R4 represents meta-O—
Z, where Z is H, C1-3-alkyl, PO(OC1-4alkyl)2, CO(OC1-5-alkyl), CONH—
C6H4—
(C1-3-alkyl) or CO—
C6H4—
R7, in which R7 is ortho-OCOC1-3-alkyl or meta- or para-CH2N(R8)2, where R8 is C1-4-alkyl or 4-morpholino, or R4 represents meta-S-C1-3-alkyl, meta-Cl, meta-F, meta-CR9R10R11, ortho-OH, ortho-O—
C2-3-alkyl, para-F or para-CR9R10R11, where R9, R10 and R11 independently represent H or F, orR5 represents para-Cl, para-F, para-OH or para-O—
C1-3-alkyl, and R4 represents meta-Cl, meta-F, meta-OH or meta-O—
C1-3-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.
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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.
41 Citations
147 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 C1-3-alkyl group;
R1 is a C1-4-alkyl group;
R2 represents H or a C1-4-alkyl group, and R3 is different from R2 and represents H or a straight chain C1-4-alkyl group, and R5 represents H, and R4 represents meta-O—
Z,where Z is H, C1-3-alkyl, PO(OC1-4alkyl)2, CO(OC1-5-alkyl), CONH—
C6H4—
(C1-3-alkyl) or CO—
C6H4—
R7, in which R7 is ortho-OCOC1-3-alkyl or meta- or para-CH2N(R8)2, where R8 is C1-4-alkyl or 4-morpholino,or R4 represents meta-S-C1-3-alkyl, meta-Cl, meta-F, meta-CR9R10R11, ortho-OH, ortho-O—
C2-3-alkyl, para-F or para-CR9R10R11, where R9, R10 and R11 independently represent H or F, orR5 represents para-Cl, para-F, para-OH or para-O—
C1-3-alkyl, and R4 represents meta-Cl, meta-F, meta-OH or meta-O—
C1-3-alkyl, orR4 and R5 together represent 3,4-OCH═
CH—
or 3,4-OCH═
CHO—
;
or a salt thereof with a physiologically acceptable acid.- View Dependent Claims (2, 3, 4, 5)
R1 represents a C1-4-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-OC1-3-alkyl, meta-OH, meta-S—
C1-3-alkyl, meta-F, meta-Cl, meta-CH3, meta-CF2H, meta-CF3 or para-CF3, orR5 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 C1-3-alkyl group.
-
4. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer according to claim 1, wherein R2 is C1-4-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 C1-3-alkyl group; -
R1 is a C1-4-alkyl group;
R2 represents a C1-4-alkyl group, and R5 represents H, and R4 represents meta-O—
Z,where Z is H, C1-3-alkyl, PO(OC1-4alkyl)2, CO(OC1-5-alkyl), CONH—
C6H4—
(C1-3-alkyl) or CO—
C6H4—
R7, in which R7 is ortho-OCOC1-3-alkyl or meta- or para-CH2N(R8)2, where R8 is C1-4-alkyl or 4-morpholino, or R4 represents meta-S—
C1-3-alkyl, meta-Cl, meta-F, meta-CR9R10R11, ortho-OH, ortho-O—
C2-3-alkyl, para-F or para-CR9R10R11, where R9, R10 and R11 independently represent H or F, orR5 represents para-Cl, para-F, para-OH or para-O—
C1-3-alkyl, and R4 represents meta-Cl, meta-F, meta-OH or meta-O—
C1-3-alkyl, orR4 and R5 together represent 3,4-OCH═
CH—
or 3,4-OCH═
CHO—
;
or a salt thereof with a physiologically acceptable acid. - View Dependent Claims (19, 20, 21, 22, 23, 24, 124)
-
-
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 C1-3-alkyl group;
R1 is a C1-4-alkyl group;
R2 represents H or a C1-4-alkyl group, and R3 is different from R2 and represents H or a straight chain C1-4-alkyl group, and R5 represents H, and R4 represents meta-O—
Z,where Z is H, C1-3-alkyl, PO(OC1-4alkyl)2, CO(OC1-5-alkyl), CONH—
C6H4—
(C1-3-alkyl) or CO—
C6H4—
R7, in which R7 is ortho-OCOC1-3-alkyl or meta- or para-CH2N(R8)2, where R8 is C1-4-alkyl or 4-morpholino,or R4 represents meta-S—
C2-3-alkyl, meta-Cl, meta-F, meta-CR9R10R11, ortho-OH, ortho-O—
C2-3-alkyl, para-F or para-CR9R10R11, where R9, R10 and R11 independently represent H or F, orR5 represents para-Cl, para-F, para-OH or para-O—
C1-3-alkyl, and R4 represents meta-Cl, meta-F, meta-OH or meta-O—
C1-3-alkyl, orR4 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 C1-3-alkyl group; -
R1 is a C1-4-alkyl group;
R2 represents H or a C1-4-alkyl group and R3 represents H or a straight chain C1-4-alkyl group, or R2 and R3 together form a C4-7 cycloalkyl radical, and R5 represents H, and R4 represents meta-O—
Z,where Z is H, C1-3-alkyl, PO(OC1-4alkyl)2, CO(OC1-5-alkyl), CONH—
C6H4—
(C1-3-alkyl) or CO—
C6H4—
R7, in which R7 is ortho-OCOC1-3-alkyl or meta- or para-CH2N(R8)2, where R8 is C1-4-alkyl or 4-morpholino,or R4 represents meta-S—
C1-3-alkyl, meta-Cl, meta-F, meta-CR9R10R11, ortho-OH, ortho-O—
C2-3-alkyl, para-F or para-CR9R10R11, where R9, R10 and R11 independently represent H or F, orR5 represents para-Cl, para-F, para-OH or para-O—
C1-3-alkyl, and R4 represents meta-Cl, meta-F, meta-OH or meta-O—
C1-3-alkyl, orR4 and R5 together represent 3,4-OCH═
CH—
or 3,4-OCH═
CHO—
, or a salt thereof with a physiologically acceptable acid.- View Dependent Claims (86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 136, 137, 138, 139, 140)
R1 represents a C1-4-alkyl group;
R2 represents CH8;
R3 represents H, and R5 represents H, and R4 represents meta-OC1-8-alkyl, meta-OH, meta-S—
C1-3-alkyl, meta-F, meta-Cl, meta-CH3, meta-CF2H, meta-CF3, or para-CF3, orR5 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 C1-3-alkyl group.
-
90. A method according to claim 8, wherein R2 is C1-4-alkyl, and R3 is different from R2 and is H or C1-3 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 C1-3-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′
;
- and Ic′
-
96. A method according to claim 95, wherein
X represents OH, F, Cl, or H; -
R1 represents a C1-4-alkyl group;
R2 represents CH3;
R3 represents H, and R5 represents H, and R4 represents meta-OC1-3-alkyl, meta-OH, meta-S—
C1-3-alkyl, meta-F, meta-Cl, meta-CH3, meta-CF2H, meta-CF3, or para-CF3, orR5 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 C1-3-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 C1-3-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 C1-3-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 C1-3-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).
- )-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride (−
-
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).
- )-(2R,3R)-[3-(3-methoxyphenyl)-2-methylpentyl]-dimethylamine hydrochloride (−
-
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).
- )-(2S, 3S)-1-dimethylamino-3-(3-methoxyphenyl)-2-methylpentan-3-ol hydrochloride (−
-
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′
;
- and Ic′
- 10. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer having a configuration corresponding to formula Ia′
- 25. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer having a configuration corresponding to at least one of formulae Ia′
- 34. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer having a configuration corresponding to at least one of formulae Ia and Ic:
- 41. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer having a configuration corresponding to formula Ic′
- 50. An isolated 1-phenyl-3-dimethylaminopropane diastereoisomer having a configuration corresponding to formula Ic:
-
61. (−
- )-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride (−
21).
- )-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride (−
- 66. An analgesic composition comprising at least one 1-phenyl-3-dimethylaminopropane diastereoisomer having a configuration corresponding to at least one of formulae Ia′
- 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:
- 141. An isolated 1-phenyl-3-dimethylaminopropane diastereomer having a configuration corresponding to formula I:
-
147. A pharmaceutically acceptable salt of (−
- )-(1R,2R)-3R-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol.
Specification