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Aptiganel

Clinical data
ATC code	none
Legal status
Legal status	In general: uncontrolled
Identifiers
IUPAC name 1-(3-ethylphenyl)-1-methyl-2-naphthalen-1-ylguanidine
CAS Number	137159-92-3
PubChem CID	60840
ChemSpider	54827
UNII	46475LV84I
ChEMBL	ChEMBL92484
CompTox Dashboard (EPA)	DTXSID4048432
Chemical and physical data
Formula	C20H21N3
Molar mass	303.409 g·mol
3D model (JSmol)	Interactive image
SMILES CCC1=CC(=CC=C1)N(C)C(=NC2=CC=CC3=CC=CC=C32)N
InChI InChI=1S/C20H21N3/c1-3-15-8-6-11-17(14-15)23(2)20(21)22-19-13-7-10-16-9-4-5-12-18(16)19/h4-14H,3H2,1-2H3,(H2,21,22) Key:BFNCJMURTMZBTE-UHFFFAOYSA-N
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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. It has neuroprotective effects and was researched for potential use in the treatment of stroke, but despite positive results in animal studies, human trials showed limited efficacy, as well as undesirable side effects such as sedation and hallucinations, 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.

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.

See also

• Ditolylguanidine
• CNS1237 shares predominantly most of the same structural entities.

References

1. Reddy NL, Hu LY, Cotter RE, Fischer JB, Wong WJ, McBurney RN, et al. (January 1994). "Synthesis and structure-activity studies of N,N'-diarylguanidine derivatives. N-(1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine: a new, selective noncompetitive NMDA receptor antagonist". Journal of Medicinal Chemistry. 37 (2): 260–7. doi:10.1021/jm00028a009. PMID 8295213.
2. Muir KW, Grosset DG, Gamzu E, Lees KR (July 1994). "Pharmacological effects of the non-competitive NMDA antagonist CNS 1102 in normal volunteers". British Journal of Clinical Pharmacology. 38 (1): 33–8. doi:10.1111/j.1365-2125.1994.tb04318.x. PMC 1364834. PMID 7946934.
3. Schäbitz WR, Li F, Fisher M (July 2000). "The N-methyl-D-aspartate antagonist CNS 1102 protects cerebral gray and white matter from ischemic injury following temporary focal ischemia in rats". Stroke. 31 (7): 1709–14. doi:10.1161/01.str.31.7.1709. PMID 10884477.
4. Albers GW, Goldstein LB, Hall D, Lesko LM (December 2001). "Aptiganel hydrochloride in acute ischemic stroke: a randomized controlled trial". JAMA. 286 (21): 2673–82. doi:10.1001/jama.286.21.2673. PMID 11730442.
5. Muir KW, Grosset DG, Lees KR (August 1997). "Effects of prolonged infusions of the NMDA antagonist aptiganel hydrochloride (CNS 1102) in normal volunteers". Clinical Neuropharmacology. 20 (4): 311–21. doi:10.1097/00002826-199708000-00003. PMID 9260729.
6. Lees KR (November 1997). "Cerestat and other NMDA antagonists in ischemic stroke". Neurology. 49 (5 Suppl 4): S66-9. doi:10.1212/wnl.49.5_suppl_4.s66. PMID 9371155. S2CID 45771202.
7. 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. PMID 15032709.
8. Staff, Boston Business Journal. May 7, 1998. CNSI appoints new president, CEO
9. Staff, ICIS. 23 May 2000 CeNeS to buy US neuroscience firm CNSI for $44m
10. Reddy NL, Hu LY, Cotter RE, Fischer JB, Wong WJ, McBurney RN, et al. (January 1994). "Synthesis and structure-activity studies of N,N'-diarylguanidine derivatives. N-(1-naphthyl)-N'-(3-ethylphenyl)-N'-methylguanidine: a new, selective noncompetitive NMDA receptor antagonist". Journal of Medicinal Chemistry. 37 (2): 260–7. doi:10.1021/jm00028a009. PMID 8295213.
11. WO 9112797, Weber, Eckard & Keana, John F. W., "Tri- and tetra-substituted guanidines and their use as excitatory amino acid antagonists", published 1991-09-05, assigned to University of Oregon and Oregon Health Sciences University ; E. Weber, J. F. W. Keana, U.S. patent 5,262,568 (1993 to State of Oregon)

• Drugs not assigned an ATC code
• NMDA receptor antagonists
• Guanidines
• Naphthylamines
• Anilines
• Dissociative drugs