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 humans and animals; the state of anesthesia they ind ...

, and that was under development by Cambridge Neuroscience, Inc as a treatment for stroke. It has neuroprotective effects and was researched for potential use in the treatment of

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

, 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 compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...

, 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 1-Naphthylamine is an aromatic amine derived from naphthalene. It can cause bladder cancer (transitional cell carcinoma). It crystallizes in colorless needles which melt at 50 °C. It possesses a disagreeable odor, sublimes readily, and tur ...

is reacted with

cyanogen bromide Cyanogen bromide is the inorganic compound with the chemical formula, formula 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 compo ...

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 Dissociative drugs

Synthesis

See also

References