5634-21-9Relevant academic research and scientific papers
Efficacious N-protection of O-aryl sulfamates with 2,4-dimethoxybenzyl groups
Reuillon, Tristan,Bertoli, Annalisa,Griffin, Roger J.,Miller, Duncan C.,Golding, Bernard T.
, p. 7610 - 7617 (2012/10/29)
Sulfamates are important functional groups in certain areas of current medicinal chemistry and drug development. Alcohols and phenols are generally converted into the corresponding primary sulfamates (ROSO2NH 2 and ArOSO2NH2, respectively) by reaction with sulfamoyl chloride (H2NSO2Cl). The lability of the O-sulfamate group, especially to basic conditions, usually restricts this method to a later stage of a synthesis. To enable a more flexible approach to the synthesis of phenolic O-sulfamates, a protecting group strategy for sulfamates has been developed. Both sulfamate NH protons were replaced with either 4-methoxybenzyl or 2,4-dimethoxybenzyl. These N-protected sulfamates were stable to oxidising and reducing agents, as well as bases and nucleophiles, thus rendering such masked sulfamates suitable for multi-step synthesis. The protected sulfamates were synthesised by microwave heating of 1,1′-sulfonylbis(2-methyl-1H-imidazole) with a substituted phenol to give an aryl 2-methyl-1H-imidazole-1-sulfonate. This imidazole-sulfonate was N-methylated by reaction with trimethyloxonium tetrafluoroborate, which enabled subsequent displacement of 1,2-dimethylimidazole by a dibenzylamine (e.g. bis-2,4-dimethoxybenzylamine). The resulting N-diprotected, ring-substituted phenol O-sulfamates were further manipulated through reactions at the aryl substituent and finally deprotected with trifluoroacetic acid to afford a phenol O-sulfamate. The use of 2,4-dimethoxybenzyl was particularly attractive because deprotection occurred quantitatively within 2 h at room temperature with 10% trifluoroacetic acid in dichloromethane. The four key steps in the protocol described [reaction of 1,1′-sulfonylbis(2-methyl-1H-imidazole) with a phenol, methylation, displacement with a dibenzylamine and deprotection] all proceeded in very high yields.
Resistance-modifying agents. 11. Pyrimido[5,4-d]pyrimidine modulators of antitumor drug activity. Synthesis and structure-activity relationships for nucleoside transport inhibition and binding to α1-acid glycoprotein
Curtin, Nicola J.,Barlow, Hannah C.,Bowman, Karen J.,Calvert, A. Hilary,Davison, Richard,Golding, Bernard T.,Huang, Bing,Loughlin, Peter J.,Newell, David R.,Smith, Peter G.,Griffin, Roger J.
, p. 4905 - 4922 (2007/10/03)
The cardiovascular and antithrombotic agent dipyridamole (DP) has potential therapeutic utility as a modulator of the activity of antimetabolite antitumor agents by virtue of its inhibition of nucleoside transport. However, the activity of DP can be compromised by binding to the acute phase serum protein, α1-acid glycoprotein (AGP). Analogues of DP were synthesized and evaluated as inhibitors of 3H-thymidine uptake into L1210 leukamia cells in the presence and absence of 5 mg/mL AGP. Compounds with potency similar to that of DP were identified where the piperidino substituents at the 4,8-positions were replaced by 4?-methoxybenzylamino, 3?,4?-dimethoxybenzylamino, or piperonylamino groups. Replacement of the diethanolamino groups at the 2,6-positions of DP by alkylamino or alkoxy substituents was tolerated, although at least one oxygen-bearing function (hydroxyl or alkoxy) was required in the side chain for activity comparable to that of DP. Whereas AGP completely ablated the activity of DP, the majority of the newer compounds synthesized retained significant activity in the presence of excess AGP, although replacement of the piperidino groups at the 4,8-positions by N-methylbenzylamino substituents did, in some cases, restore susceptibility to AGP. Selected compounds have been demonstrated to prevent rescue from antifolate cytotoxicity, mediated by nucleoside salvage.
COMPOUNDS, COMPOSITIONS AND METHODS FOR THE TREATMENT OF AMYLOID DISEASES AND SYNUCLEINOPATHIES SUCH AS ALZHEIMER'S DISEASE, TYPE 2 DIABETES, AND PARKINSON'S DISEASE
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Page 50, (2008/06/13)
Bis- and tris-dihydroxyaryl compounds and their methylenedioxy analogs and pharmaceutically acceptable esters, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of amyloid diseases, especially A? amyloidosis, such as observed in Alzheimer's disease, IAPP amyloidosis, such as observed in type 2 diabetes, and synucleinophathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment.
Rapid reduction of nitriles to primary amines with nickel boride at ambient temperature
Khurana, Jitender M.,Kukreja, Gagan
, p. 1265 - 1269 (2007/10/03)
Reduction of a variety of nitriles to their corresponding primary amines can be achieved with nickel boride generated in situ in dry ethanol at ambient temperature. The reductions are very rapid and chemoselective.
Resistance-modifying agents. Part 7: 2,6-Disubstituted-4,8-dibenzylaminopyrimido[5,4-d]pyrimidines that inhibit nucleoside transport in the presence of α1-acid glycoprotein (AGP)
Barlow, Hannah C.,Bowman, Karen J.,Curtin, Nicola J.,Calvert, A. Hilary,Golding, Bernard T.,Huang, Bing,Loughlin, Peter J.,Newell, David R.,Smith, Peter G.,Griffin, Roger J.
, p. 585 - 589 (2007/10/03)
The synthesis and biological evaluation of potent 4,8-dibenzylaminopyrimidopyrimidine nucleoside transport inhibitors, with reduced binding to α1-acid glycoprotein, is reported. (C) 2000 Elsevier Science Ltd. All rights reserved.
Synthesis of 7,12-dihydro-12-phenyl-5H-6,12-methanodibenz[cf]azocines via N,N-dibenzylphenacylamines
Coskun, Necdet,Bueyuekuysal, Levent
, p. 53 - 59 (2007/10/03)
N,N-DibenzyIphenacylamines (1) were prepared in high yields by a onepot reaction and cyclized at room temperature to give 7,12-dihydro-12-phenyl-5H-6,12-methanodibenz[cf]azocines in high yields. 95% H2SO4 or 70% HClO4 was used as cyclization catalysts. The double-cyclization proceeds smoothly in the cases where electron-donating groups are present in both benzene ring. N-2,3-dimethoxybenzyl-N-benzylphenacylamine (If) gave the corresponding N-benzyl-1,2-dihydro-4-phenylisoquinoline on treatment with 95% H2SO4 while N-3,4-Dimethoxybenzyl-N-benzylphenacylamine (1a) at the same reaction conditions and reaction time cyclized to the corresponding dibenzazocine. However la gave the corresponding dihydroisoquinoline which disproportionates to give N-benzyl-1,2,3,4-tetrahydro-4-phenylisoquinoline and N-benzyl-4-phenylisoquinolinium when treated with 70% perchloric acid at room temperature.
