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Aptiganel

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(Redirected fromARL-16247)
Chemical compound
Pharmaceutical compound
Aptiganel
Clinical data
ATC code
  • none
Legal status
Legal status
  • In general: uncontrolled
Identifiers
  • 1-(3-ethylphenyl)-1-methyl-2-naphthalen-1-ylguanidine
CAS Number
PubChemCID
ChemSpider
UNII
ChEMBL
CompTox Dashboard(EPA)
Chemical and physical data
FormulaC20H21N3
Molar mass303.409 g·mol−1
3D model (JSmol)
  • 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) checkY
  • Key:BFNCJMURTMZBTE-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Aptiganel (Cerestat;CNS-1102) is an unsuccessful drug candidate which acts as a noncompetitiveNMDA antagonist, and that was under development by Cambridge Neuroscience, Inc as a treatment for stroke.[1] It hasneuroprotective effects and was researched for potential use in the treatment ofstroke,[2] but despite positive results in animal studies,[3] human trials showed limited efficacy,[4] as well as undesirable side effects such assedation andhallucinations,[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 eventual sale to CeNeS Pharmaceuticals in 2000.[9]

Other guanidine substances that the company had been bowling on was Cns-1145 & CNS1237.

Synthesis

[edit]
Aptiganel synthesis:[10][11]

1-Naphthylamine is reacted withcyanogen bromide to give2. 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

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

References

[edit]
  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 2000CeNeS 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 toUniversity of Oregon andOregon Health Sciences University ; E. Weber, J. F. W. Keana,U.S. patent 5,262,568 (1993 to State of Oregon)
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