197644-83-0Relevant academic research and scientific papers
Triazolophostins: A library of novel and potent agonists of IP3 receptors
Vibhute, Amol M.,Konieczny, Vera,Taylor, Colin W.,Sureshan, Kana M.
, p. 6698 - 6710 (2015)
IP3 receptors are channels that mediate the release of Ca2+ from the intracellular stores of cells stimulated by hormones or neurotransmitters. Adenophostin A (AdA) is the most potent agonist of IP3 receptors, with the β-anomeric adenine contributing to the increased potency. The potency of AdA and its stability towards the enzymes that degrade IP3 have aroused interest in AdA analogs for biological studies. The complex structure of AdA poses problems that have necessitated optimization of synthetic conditions for each analog. Such lengthy one-at-a-time syntheses limit access to AdA analogs. We have addressed this problem by synthesizing a library of triazole-based AdA analogs, triazolophostins, by employing click chemistry. An advanced intermediate having all the necessary phosphates and a β-azide at the anomeric position was reacted with various alkynes under Cu(i) catalysis to yield triazoles, which upon deprotection gave triazolophostins. All eleven triazolophostins synthesized are more potent than IP3 and some are equipotent with AdA in functional analyses of IP3 receptors. We show that a triazole ring can replace adenine without compromising the potency of AdA and provide facile routes to novel AdA analogs. This journal is
Total synthesis of nucleobase-modified adenophostin A mimics
Shuto, Satoshi,Horne, Graeme,Marwood, Rachel D.,Potter, Barry V. L.
, p. 4937 - 4946 (2007/10/03)
The adenophostins exhibit approximately 10-100 times higher receptor binding and Ca2+ mobilising potencies in comparison with the natural second messenger D-myo-inositol 1,4,5-trisphosphate [InS(1,4,5)P3]. Despite many synthetic atte
Convergent synthesis of adenophostin A analogues via a base replacement strategy
Marwood, Rachel D.,Shuto, Satoshi,Jenkins, David J.,Potter, Barry V. L.
, p. 219 - 220 (2007/10/03)
The first totally synthetic base-modified analogues of the natural product and potent D-myo-inositol 1,4,5-trisphosphate receptor agonist adenophostin A were efficiently synthesised from D-xylose and D-glucose using methodology employing base and surrogate base addition to a common disaccharide intermediate.
Contribution of the adenine base to the activity of adenophostin A investigated using a base replacement strategy
Marwood,Jenkins,Correa,Taylor,Potter
, p. 4278 - 4287 (2007/10/03)
Syntheses of 3'-O-α-D-glucopyranosyl-1-β-D-ribofuranosidoimidazole 2',3',4'-trisphosphate (7) and 3'-O-α-D-glucopyranosyl-9-β-D-ribofuranosidopurine 2',3',4'-trisphosphate (8), two analogues of the superpotent 1D-myo-inositol 1,4,5-trisphosphate receptor agonist adenophostin A (2), are described. 5-O-Benzyl-1,2-O-isopropylidene-α-D-ribofuranose was prepared by an improved route from 1,2-O-isopropylidene-α-D-xylofuranose and was coupled with 3,4-di-O-acetyl-2,6-di-O-benzyl-D-glucopyranosyl dimethyl phosphite to give 3',4'-di-O-acetyl-2',5,6'-tri-O-benzyl-3-O-α-D-glucopyranosyl-1,2-O-isopropy lidene-α-D-ribofuranose. Removal of the isopropylidene acetal and subsequent acetylation gave the central disaccharide 1,2,3',4'-tetra-O-acetyl-2',5,6'-tri-O-benzyl-3-O-α-D-glucopyranosyl-D-ribof uranose. Vorbruggen condensation with activated imidazole or purine gave the required β-substituted derivatives which were further elaborated to 7 and 8, respectively. Radioligand binding assays to hepatic InsP3 receptors and functional assays of Ca2+ release from permeabilized hepatocytes gave a rank order of potency of the ligands 2 ? 8 > 7 ? Ins(1,4,5)P3 indicating that the N6-amino group of 2 is of little importance for activity and that a minimum of a two-fused-ring nucleobase is required for activity to exceed that of Ins(1,4,5)P3. The role of the adenine base in the activity of the adenophostins is discussed. This general method should facilitate ready access to nucleobase-modified adenophostin analogues for SAR studies.
Synthesis of photoaffinity derivatives of adenophostin A
De Kort, Martin,Luijendijk, Jaco,Van Der Marel, Gijs A.,Van Boom, Jacques H.
, p. 3085 - 3092 (2007/10/03)
Photoaffinity derivatives 7 and 8 of adenophostin A, modified at the 5'- and 1'-positions, were prepared by a chemoselective reaction of the aminophostins 15 and 30 with N-succini-midyl p-benzoyl-2,3-dihydrocinnamate (p-benzoyldihydrocinnamoyl-N-hydroxysu
Synthesis of potent agonists of the D-myo-inositol 1,4,5-trisphosphate receptor based on clustered disaccharide polyphosphate analogues of adenophostin A
De Kort,Correa,Valentijn,Van der Marel,Potter,Taylor,Van Boom
, p. 3295 - 3303 (2007/10/03)
Clustered disaccharide analogues of adenophostin A (2), i.e. mono-, di-, and tetravalent derivatives 6-8, respectively, were synthesized and evaluated as novel ligands for the tetrameric D-myo-inositol 1,4,5-trisphosphate receptor (IP3R). The s
