Potential GABAB Receptor Antagonists. VI. The Synthesis of Saclofen and Other Sulfonic Acid Derivatives

1992 ◽  
Vol 45 (11) ◽  
pp. 1801 ◽  
Author(s):  
G Abbenante ◽  
RH Prager
Keyword(s):  
Sulfonic Acid ◽  
Gabab Receptor ◽  
Sulfonyl Chloride ◽  
Radical Addition ◽  
Hydroxy Derivative ◽  
Thioacetic Acid ◽  
Receptor Antagonists ◽  
Specific Antagonist ◽  
Gabab Receptor Antagonists

Saclofen, 3-amino-2-(4chlorophenyl) propanesulfonic acid (3), has been synthesized by two routes. Attempts to hydrogenolyse or dehydrate the 2-hydroxy derivative were unsuccessful, however. Radical sulfonation of 3-amino-1-bromo-2-(4-chlorophenyl) propene gave 3-amino-2- (4-chlorophenyl)propene-1-sulfonic acid (6) which was readily reduced to (3). Alternatively, 2-(4-chlorophenyl)-3-phthalimidopropene underwent radical addition of thioacetic acid, and oxidation of the product to the sulfonyl chloride and hydrolysis gave (3). The corresponding sulfonamide (4) was also prepared. The acid (3) is a powerful specific antagonist of GABA at the GABAB receptor, while (4) and (6) are only weak antagonists.

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
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