| 词条 | Aptiganel |
| 释义 |
| Verifiedfields = changed | verifiedrevid = 477350281 | IUPAC_name = 1-(3-ethylphenyl)-1-methyl-2-naphthalen-1-ylguanidine | image = Aptiganel.svg | tradename = | pregnancy_category = | legal_status = Uncontrolled | bioavailability = | metabolism = | excretion = | CAS_number_Ref = {{cascite|changed|??}} | CAS_number = 137159-92-3 | ATC_prefix = none | ATC_suffix = | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 92484 | PubChem = 60840 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 46475LV84I | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 54827 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 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) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = BFNCJMURTMZBTE-UHFFFAOYSA-N | C=20 | H=21 | N=3 | molecular_weight = 303.401 g/mol | smiles = CCC1=CC(=CC=C1)N(C)C(=NC2=CC=CC3=CC=CC=C32)N }}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.[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 eventual sale to CeNeS Pharmaceuticals in 2000.[9] Synthesis1-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
References1. ^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}} {{Hallucinogens}}{{Ionotropic glutamate receptor modulators}}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. ^{{Cite journal|doi=10.1021/jm00028a009|pmid=8295213|title=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=Journal of Medicinal Chemistry|volume=37|issue=2|pages=260|year=1994|last1=Reddy|first1=N. L.|last2=Hu|first2=Lain-Yen|last3=Cotter|first3=R. E.|last4=Fischer|first4=J. B.|last5=Wong|first5=W. J.|last6=McBurney|first6=R. N.|last7=Weber|first7=E.|last8=Holmes|first8=D. L.|last9=Wong|first9=S. T.}} 11. ^E. Weber, J. F. W. Keana, {{Cite patent|WO|9112797}}; eidem, {{US patent|5262568}} (1991, 1993 both to State of Oregon) 4 : NMDA receptor antagonists|Guanidines|Naphthylamines|Anilines |
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