Aptiganel

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Aptiganel
Aptiganel.svg
Systematic (IUPAC) name
1-(3-ethylphenyl)-1-methyl-2-naphthalen-1-ylguanidine
Clinical data
Legal status
  • Uncontrolled
Identifiers
CAS Number 137159-92-3 N
ATC code none
PubChem CID: 60840
ChemSpider 54827 YesY
UNII 46475LV84I YesY
ChEMBL CHEMBL92484 YesY
Chemical data
Formula C20H21N3
Molecular mass 303.401 g/mol
 NYesY (what is this?)  (verify)

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

Aptiganel synthesis:[10][11]

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

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. Lees KR. Cerestat and other NMDA antagonists in ischemic stroke. Neurology. 1997 Nov;49(5 Suppl 4):S66-9. PMID 9371155
  7. 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
  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. Lua error in Module:Citation/CS1/Identifiers at line 47: attempt to index field 'wikibase' (a nil value).
  11. E. Weber, J. F. W. Keana, WO 9112797 ; eidem, U.S. Patent 5,262,568 (1991, 1993 both to State of Oregon)