Cartazolate (SQ-65,396) is a
drug of the
pyrazolopyridine class. It acts as a
GABAA receptor positive allosteric modulator
In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimulus. Some of them, like benzodiazepines, are drugs. The site that an allosteric modulator binds to ...
at the
barbiturate binding site
In biochemistry and molecular biology, a binding site is a region on a macromolecule such as a protein that binds to another molecule with specificity. The binding partner of the macromolecule is often referred to as a ligand. Ligands may includ ...
of the complex and has
anxiolytic
An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiet ...
effects in animals.
It is also known to act as an
adenosine antagonist at the
A1 and
A2 subtypes and as a
phosphodiesterase inhibitor
A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase (PDE), thereby preventing the inactivation of the intracellular second messengers, cyclic adenosine monophosphate (cAMP) and cyc ...
.
Cartazolate was tested in human
clinical trial
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...
s and was found to be efficacious for
anxiety
Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
but was never marketed.
It was developed by a team at E.R. Squibb and Sons in the 1970s.
Synthesis
Condensation of aminopyrazole (1) with diethyl ethoxymethylenemalonate (2) gives the product of the addition-elimination (3). The product tautomerizes spontaneously to the hydroxypyridine (4). The hydroxyl group is then converted to the chloro-derivative by means of
phosphorus oxychloride
Phosphoryl chloride (commonly called phosphorus oxychloride) is a colourless liquid with the formula . It hydrolyses in moist air releasing phosphoric acid and fumes of hydrogen chloride. It is manufactured industrially on a large scale from pho ...
(5). Displacement of halogen by
''n''-butylamine gives the antidepressant compound cartazolate. Displacement of halogen by the basic nitrogen of
acetone hydrazone affords the antidepressant etazolate.
See also
*
Etazolate
*
ICI-190,622
*
Tracazolate
References
{{Phosphodiesterase inhibitors
Adenosine receptor antagonists
Amines
Ethyl esters
Carboxylate esters
GABAA receptor positive allosteric modulators
Phosphodiesterase inhibitors
Pyrazolopyridines
Butyl compounds