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
  • CCC1=CC(=CC=C1)N(C)C(=NC2=CC=CC3=CC=CC=C32)N
  • 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) YesY
  • Key:BFNCJMURTMZBTE-UHFFFAOYSA-N YesY
 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 package.lua at line 80: module 'strict' not found.
  11. ↑ E. Weber, J. F. W. Keana, WO 9112797 ; eidem, U.S. Patent 5,262,568 (1991, 1993 both to State of Oregon)
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