- 2-aminoethylamine derivatives, compositions of the same and use of said compounds in medicine
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A compound of formula (I): STR1 or a salt and/or solvate thereof, wherein R represents an acyl group containing a substituted or unsubstituted carbocyclic aromatic or heterocyclic aromatic group; R1 and R2 each independently represents an alkyl, alkenyl or alkynyl group or R1 together with R2 represents a C3-6 polymethylene or alkenylene group; R3 represents hydrogen or alkyl; R4 represents hydrogen, halogen, alkyl, hydroxy, alkoxy, nitrile, nitro, amino or mono or disubstituted amino; and n represents O or an integer 1, is useful in the treatment of pain.
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- 2-(3,4-Dichlorophenyl)-N-methyl-N-acetamides: The Use of Conformational Analysis in the Development of a Novel Series of Potent Opioid κ Agonists
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This paper describes the synthesis of a series of N-acetamides (1), methylated at C1 and/or C2 of the ethyl linking group, and their biological evaluation as opioid κ agonists.Conformational analysis of corresponding desaryl analogues 2 suggested that only those compounds capable of occupying an energy minimum close to that of the known κ agonist N-acetamide U-50488 might possess κ agonist properties.Starting from chiral amino acids, other alkyl and aryl substituents were introduced at C1 of the ethyl-linking moiety, giving compounds capable of adopting the same conformation as U-50488.The most potent of these, 2-(3,4-dichlorophenyl)-N-methyl-N-acetamide (8), was 146-fold more active than U-50488 in vitro in the mouse vas deferens model and exhibited potent naloxone-reversible analgesic effects (ED50 = 0.004 mg/kg sc) in an abdominal constriction model.
- Costello, Gerard F.,James, Roger,Shaw, John S.,Slater, Anthony M.,Stutchbury, Neil C. J.
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p. 181 - 189
(2007/10/02)
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