137160-25-9Relevant academic research and scientific papers
Synthesis and in vitro evaluation of N,N'-diphenyl and N-naphthyl-N'-phenylguanidines as N-methyl-D-aspartate receptor ion-channel ligands.
Dumont, Filip,Sultana, Abida,Waterhouse, Rikki N
, p. 1583 - 1586 (2007/10/03)
A series of N,N'-diphenyl and N-naphthyl-N'-phenyl guanidine derivatives was synthesized as potential N-methyl-D-aspartate (NMDA) receptor positron emission tomography (PET) ligands. The affinity of the different compounds was determined using in vitro receptor binding assays, and their log P values were estimated using HPLC analysis. The effect of N'-3 and N'-3,5 substitution on affinity and lipophilicity was examined. The K(i) values ranged from 1.87 to 839nM, while log P values between 1.22 and 2.88 were observed.
Synthesis and pharmacological evaluation of N-(2,5-disubstituted phenyl)-N'-(3-substituted phenyl)-N'-methylguanidines as N-methyl-D-aspartate receptor ion-channel blockers
Hu, Lain-Yen,Quo, Junqing,Magar, Sharad S.,Fischer, James B.,Burke-Howie, Kathleen J.,Durant, Graham J.
, p. 4281 - 4289 (2007/10/03)
In the mammalian central nervous system, the N-methyl-D-aspartate (NMDA) subclass of glutamate receptors may play an important role in brain diseases such as stroke, brain or spinal cord trauma, epilepsy, and certain neurodegenerative diseases. Compounds which specifically antagonize the actions of the neurotransmitter glutamate at the NMDA receptor ion-channel site offer a novel approach to treating these disorders. CERESTAT (4, aptiganel CNS 1102) is currently undergoing clinical trial for the treatment of traumatic brain injury and stroke. Previously, we reported that analogues of N-1-naphthyl-N'-(3-ethylphenyl)-N'-methylguanidine (4) bound to the NMDA receptor ion-channel site with high potency and selectivity. Recently, molecules active at both σ receptors and NMDA receptor sites were investigated. A series of substituted diphenylguanidines 6 which are structurally related to N-1-naphthyl-N'-(3-ethylphenyl)-N'-methylguanidine was prepared. Compounds containing appropriate substitution/pattern in one of the phenyl rings of diphenylguanidines displayed high affinity. For example, N-(2,5-dibromophenyl)-N'-(3-ethylphenyl)-N'-methylguanidine (27b, R2 = R5 = Br, R3 = C2H5) exhibited potency at both 5 receptors and NMDA receptor sites; 27b also showed high efficacy in vivo in a neonatal rat excitotoxicity model. Further studies indicated that substituent effects were important in this compound series, and 2,5-disubstituted phenyl was the preferred substitution pattern for high-affinity binding at NMDA receptor sites. Bromo and methylthio were the optimal substituents for the R2 and R5 positions of the 2,5-disubstituted phenyl group, respectively. N-(2-Bromo-5- (methylthio)phenyl)-N'-(3-ethylphenyl)-N'-methylguanidine (34b, R2 = Br, R5 = SMe, R3 = C2H5) was highly active at NMDA receptor sites. We found that the binding affinity of guanidines of type 6 could be further enhanced with the appropriate substitution at R3. Optimal activity in this series are afforded by 43b and 44b (R2 = Cl or Br, R5 = R3 = SCH3). Both 43b and 44b bound to NMDA receptor sites with high potency and selectivity (K(i) vs [3H]MK-801: 1.87 and 1.65 nM, respectively); these compounds are active in vivo in various animal models of neuroprotection. The structure-activity relationships for these compounds at the NMDA receptor ion-channel site are discussed.
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
Reddy, N. Laxma,Hu, Lain-Yen,Cotter, Ronald E.,Fischer, James B.,Wong, Wen Jee,et al.
, p. 260 - 267 (2007/10/02)
Diarylguanidines, acting as NMDA receptor ion channel site ligands, represent a new class of potential neuroprotective drugs.Several diarylguanidines structurally related to N,N'-di-o-tolylguanidine (DTG), a known selective ? receptor ligand, were synthes
TRI- AND TETRA-SUBSTITUTED GUANIDINES AND THEIR USE AS EXCITATORY AMINO ACID ANTAGONISTS
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, (2008/06/13)
Tri-and tetra-substituted guanidines which exhibit a high binding affinity to phencyclidine (PCP) receptors and, more preferably, low affinity to the brain sigma receptors. These guanidine derivatives act as non-competitive inhibitorsSTATEMENT AS TO RIGHT
