Aptiganel (Cerestat; CNS-1102) is an unsuccessful drug candidate which acts as a noncompetitive
NMDA antagonist, and that was under development by Cambridge Neuroscience, Inc as a treatment for stroke.[1] It has
neuroprotective effects and was researched for potential use in the treatment of
stroke,[2] but despite positive results in animal studies,[3] human trials showed limited efficacy,[4] as well as undesirable side effects such as
sedation and
hallucinations,[5][6] and clinical development was ultimately not continued.[7]
The drug's failure led to the collapse of Cambridge Neuroscience in 1998[8] and its eventual sale to CeNeS Pharmaceuticals in 2000.[9]
Other guanidine substances that the company had been bowling on was Cns-1145 & CNS1237.
Synthesis
1-Naphthylamine is reacted with
cyanogen bromide to give 2. Treatment of this intermediate with 3-ethyl-N-methylaniline leads to addition to the cyano group and formation of the corresponding diaryl guanidine, aptiganel, 3.
^Hoyte L, Barber PA, Buchan AM, Hill MD (March 2004). "The rise and fall of NMDA antagonists for ischemic stroke". Current Molecular Medicine. 4 (2): 131–6.
doi:
10.2174/1566524043479248.
PMID15032709.