Potential GABAB Receptor Antagonists. X The Synthesis of Further Analogues of Baclofen, Phaclofen and Saclofen

1997 ◽  
Vol 50 (8) ◽  
pp. 813 ◽  
Author(s):  
Rolf H. Prager ◽  
Karl Schafer
Keyword(s):  
Hydroxamic Acid ◽  
Gabab Receptor ◽  
Receptor Site ◽  
Binding Activity ◽  
Pentanoic Acid ◽  
Receptor Antagonists ◽  
New Compounds ◽  
Gabab Receptor Antagonists

In an attempt to obtain new compounds with binding activity at the GABAB receptor site, we report the synthesis of 3-amino-2-arylpropanoic acids, and the sulfonic, phosphonic and hydroxamic acid analogues. In addition, we report the synthesis of the isomer of phaclofen, 3-amino-1-(4-chlorophenyl)-propylphosphonic acid, and the higher homologue of baclofen, 5-amino-2-(4-chlorophenyl)pentanoic acid.

Potential GABAB Receptor Antagonists. V. The Application of Radical Additions to Styrenes to Produce 2-Hydroxysaclofen

1992 ◽  
Vol 45 (11) ◽  
pp. 1791 ◽  
Author(s):  
G Abbenante ◽  
RH Prager
Keyword(s):  
Free Radical ◽  
Gabab Receptor ◽  
Receptor Site ◽  
Radical Addition ◽  
Receptor Antagonists ◽  
The Third ◽  
Potent Antagonist ◽  
Gabab Receptor Antagonists ◽  
Free Radical Addition

3-Amino-2-(4-chlorophenyl)-2-hydroxypropanesulfonic acid (2-hydroxysaclofen), and its 2- phenyl analogue have been synthesized by three methods. Two involve the oxygen- catalysed free radical addition of bisulfite to the corresponding 3-aminopropene or 3-phthalimidopropene, and the third involves the sulfite opening of the epoxide of the phthalimidopropene. 2-Hydroxysaclofen is a potent antagonist of GABA and baclofen at the GABAB receptor site.

GABAB receptor antagonists: from synthesis to therapeutic applications

1993 ◽  
Vol 14 (11) ◽  
pp. 391-394 ◽  
Author(s):  
Helmut Bittiger ◽  
Wolfgang Froestl ◽  
Stuart J. Mickel ◽  
Hans-Rudolf Olpe
Keyword(s):  
Gabab Receptor ◽  
Receptor Antagonists ◽  
Therapeutic Applications ◽  
Gabab Receptor Antagonists

Potential GABAB Receptor Antagonists. III. Folded Baclofen Analogs Based on Phthalide

1989 ◽  
Vol 42 (6) ◽  
pp. 787 ◽  
Author(s):  
C Donati ◽  
RH Prager ◽  
B Weber
Keyword(s):  
Ethyl Acetoacetate ◽  
Gabab Receptor ◽  
Hydrazoic Acid ◽  
Receptor Antagonists ◽  
Keto Ester ◽  
Acidic Conditions ◽  
Gabab Receptor Antagonists ◽  
Hydrolysis Of ◽  
Parallel Series

Possible analogues of baclofen, 3-aminomethyl-5-chloro-, 3-aminomethyl-6-chloro- and 3-aminomethyl-5,6-dichloro-isobenzofuran-1(3H)-one, have been prepared for evaluation as antispasticity agents. The corresponding 3-hydroxyisobenzofuran-l(3H)-one was reacted with ethyl acetoacetate under acidic conditions, and the keto ester hydrolysed and decarboxylated to give the 3-(2-oxopropyl)isobenzofuran-l(3H)-one; this was treated with hydrazoic acid, and the product was hydrolysed. A parallel series of (3-oxo-1,3-dihydroisobenzofuran-1-y1)glycines was obtained by treating the keto ester first with hydrazoic acid, and hydrolysis of the resulting acetamides.

Potential GABAB Receptor Antagonists. VIII. The Synthesis of 3-Amino-N-aryl-2-hydroxy- propane-1-sulfonamides and Analogues of Baclofen Containing Nitro Groups

1997 ◽  
Vol 50 (1) ◽  
pp. 19 ◽  
Author(s):  
Robert Hughes ◽  
Rolf H. Prager
Keyword(s):  
Sodium Azide ◽  
Gabab Receptor ◽  
Amino Group ◽  
Receptor Antagonists ◽  
Gabab Receptor Antagonists

3-Amino-N-aryl-2-hydroxypropane-1-sulfonamides were synthesized by the reaction of the corresponding epoxy sulfonamide with sodium azide, followed by reduction to the corresponding amine. The synthesis of 3-nitropropan-1-amine and two 2-thienyl derivatives is also reported. 3-Amino-2-hydroxy-N-(4-nitrophenyl)propane-1-sulfonamide and 3-nitropropan-1-amine were found to be specific antagonists of GABA at the GABAB receptor. Substitution of the amino group by alkyl or aryl groups reduced the activity.

Morpholin-2-yl-phosphinic acids are potent GABAB receptor antagonists in rat brain

1998 ◽  
Vol 362 (1) ◽  
pp. 27-34 ◽  
Author(s):  
Jennifer Ong ◽  
David I.B. Kerr ◽  
Helmut Bittiger ◽  
Peter C. Waldmeier ◽  
Peter A. Baumann ◽  
...  
Keyword(s):  
Rat Brain ◽  
Gabab Receptor ◽  
Receptor Antagonists ◽  
Phosphinic Acids ◽  
Gabab Receptor Antagonists

AMPA and GABAB receptor antagonists and their interaction in rats with a genetic form of absence epilepsy

2001 ◽  
Vol 430 (2-3) ◽  
pp. 251-259 ◽  
Author(s):  
Rafał M Kamiński ◽  
Clementina M Van Rijn ◽  
Waldemar A Turski ◽  
Stanisław J Czuczwar ◽  
Gilles Van Luijtelaar
Keyword(s):  
Gabab Receptor ◽  
Absence Epilepsy ◽  
Receptor Antagonists ◽  
Gabab Receptor Antagonists ◽  
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