Aptiganel
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| Formula | C20H21N3 |
| Molar mass | 303.401 g/mol g·mol−1 |
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Aptiganel (Cerestat; CNS-1102) was a drug candidate that acted 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 eventually sale to CeNeS Pharmaceuticals in 2000.[9]
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
References
- ^ Reddy NL, Hu LY, Cotter RE, Fischer JB, Wong WJ, McBurney RN, Weber E, Holmes DL, Wong ST, Prasad R, et al. 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. 1994 Jan 21;37(2):260-7. PMID 8295213
- ^ Muir KW, Grosset DG, Gamzu E, Lees KR. Pharmacological effects of the non-competitive NMDA antagonist CNS 1102 in normal volunteers. British Journal of Clinical Pharmacology. 1994 Jul;38(1):33-8. PMID 7946934
- ^ Schäbitz WR, Li F, Fisher M. The N-methyl-D-aspartate antagonist CNS 1102 protects cerebral gray and white matter from ischemic injury following temporary focal ischemia in rats. Stroke. 2000 Jul;31(7):1709-14. PMID 10884477
- ^ Albers GW, Goldstein LB, Hall D, Lesko LM; Aptiganel Acute Stroke Investigators. Aptiganel hydrochloride in acute ischemic stroke: a randomized controlled trial. Journal of the American Medical Association. 2001 Dec 5;286(21):2673-82. PMID 11730442
- ^ Muir KW, Grosset DG, Lees KR. Effects of prolonged infusions of the NMDA antagonist aptiganel hydrochloride (CNS 1102) in normal volunteers. Clinical Neuropharmacology. 1997 Aug;20(4):311-21. PMID 9260729
- ^ Lees KR. Cerestat and other NMDA antagonists in ischemic stroke. Neurology. 1997 Nov;49(5 Suppl 4):S66-9. PMID 9371155
- ^ Hoyte L, Barber PA, Buchan AM, Hill MD. The rise and fall of NMDA antagonists for ischemic stroke. Current Molecular Medicine. 2004 Mar;4(2):131-6. PMID 15032709
- ^ Staff, Boston Business Journal. May 7, 1998. CNSI appoints new president, CEO
- ^ Staff, ICIS. 23 May 2000 CeNeS to buy US neuroscience firm CNSI for $44m
- ^ Reddy, N. L.; Hu, Lain-Yen; Cotter, R. E.; Fischer, J. B.; Wong, W. J.; McBurney, R. N.; Weber, E.; Holmes, D. L.; Wong, S. T. (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. doi:10.1021/jm00028a009. PMID 8295213.
- ^ E. Weber, J. F. W. Keana, WO 9112797; eidem, U.S. patent 5,262,568 (1991, 1993 both to State of Oregon)