Aptiganel (Cerestat; CNS-1102) is an unsuccessful drug candidate which acts as a noncompetitive

NMDA antagonist NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the ''N''-Methyl-D-aspartate receptor (NMDAR). They are commonly used as anesthetics for animals and humans; the state of anesthesia they induce ...

, and that was under development by Cambridge Neuroscience, Inc as a treatment for stroke. It has

neuroprotective Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult (a neurodegenerative insult) the relative preservation of neuronal integrity implies a reduction in the rate of neuronal los ...

effects and was researched for potential use in the treatment of

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

, but despite positive results in animal studies, human trials showed limited efficacy, as well as undesirable side effects such as

sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...

and

hallucinations A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinatio ...

, and clinical development was ultimately not continued. The drug's failure led to the collapse of Cambridge Neuroscience in 1998 and its eventual sale to CeNeS Pharmaceuticals in 2000.Staff, ICIS. 23 May 200
CeNeS to buy US neuroscience firm CNSI for $44m
/ref> Other guanidine substances that the company had been bowling on was Cns-1145 & CNS1237.

Synthesis

1-Naphthylamine is reacted with

cyanogen bromide Cyanogen bromide is the inorganic compound with the formula (CN)Br or BrCN. It is a colorless solid that is widely used to modify biopolymers, fragment proteins and peptides (cuts the C-terminus of methionine), and synthesize other compounds. ...

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.

References

{{Ionotropic glutamate receptor modulators NMDA receptor antagonists Guanidines Naphthylamines Anilines

Synthesis

See also

References