The Experts below are selected from a list of 20121 Experts worldwide ranked by ideXlab platform
Leroy B Townsend - One of the best experts on this subject based on the ideXlab platform.
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synthesis and antiviral activity of novel erythrofuranosyl imidazo 1 2 a pyridine c nucleosides constructed via Palladium Coupling of iodoimidazo 1 2 a pyridines and dihydrofuran
Journal of Medicinal Chemistry, 2003Co-Authors: Kristjan Gudmundsson, John D Williams, John C Drach, Leroy B TownsendAbstract:2,5,6-Trichloro-1-(β-d-ribofuranosyl)benzimidazole (TCRB) and certain analogues have shown significant activity against human cytomegalovirus. The metabolic instability of the glycosidic linkage in TCRB prompted us to synthesize the structurally similar imidazo[1,2-a]pyridine erythrofuranosyl C-nucleosides. As an approach to the synthesis of polychlorinated imidazo[1,2-a]pyridine C-3-erythrofuranosides, a Palladium-based methodology for Coupling 2,3-dihydrofuran with chlorinated 3-iodoimidazo[1,2-a]pyridines was developed and optimized to give 80−90% yields of 2,6-dichloro- and 2,6,7-trichloro-3-(2,3-dideoxy-2,3-didehydro-d/l-erythrofuranosyl)imidazo[1,2-a]pyridine. Dihydroxylation of these didehydro derivatives with osmium tetroxide or with AD-mix α gave a mixture of erythrofuranosyl C-nucleosides that were separated by standard and then chiral chromatography. When screened for anti-HCMV and HSV-1 activity, the α-d anomer of 2,6,7-trichloro-3-(erythrofuranosyl)imidazo[1,2-a]pyridine proved to be the most...
Kristjan Gudmundsson - One of the best experts on this subject based on the ideXlab platform.
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synthesis and antiviral activity of novel erythrofuranosyl imidazo 1 2 a pyridine c nucleosides constructed via Palladium Coupling of iodoimidazo 1 2 a pyridines and dihydrofuran
Journal of Medicinal Chemistry, 2003Co-Authors: Kristjan Gudmundsson, John D Williams, John C Drach, Leroy B TownsendAbstract:2,5,6-Trichloro-1-(β-d-ribofuranosyl)benzimidazole (TCRB) and certain analogues have shown significant activity against human cytomegalovirus. The metabolic instability of the glycosidic linkage in TCRB prompted us to synthesize the structurally similar imidazo[1,2-a]pyridine erythrofuranosyl C-nucleosides. As an approach to the synthesis of polychlorinated imidazo[1,2-a]pyridine C-3-erythrofuranosides, a Palladium-based methodology for Coupling 2,3-dihydrofuran with chlorinated 3-iodoimidazo[1,2-a]pyridines was developed and optimized to give 80−90% yields of 2,6-dichloro- and 2,6,7-trichloro-3-(2,3-dideoxy-2,3-didehydro-d/l-erythrofuranosyl)imidazo[1,2-a]pyridine. Dihydroxylation of these didehydro derivatives with osmium tetroxide or with AD-mix α gave a mixture of erythrofuranosyl C-nucleosides that were separated by standard and then chiral chromatography. When screened for anti-HCMV and HSV-1 activity, the α-d anomer of 2,6,7-trichloro-3-(erythrofuranosyl)imidazo[1,2-a]pyridine proved to be the most...
John C Drach - One of the best experts on this subject based on the ideXlab platform.
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synthesis and antiviral activity of novel erythrofuranosyl imidazo 1 2 a pyridine c nucleosides constructed via Palladium Coupling of iodoimidazo 1 2 a pyridines and dihydrofuran
Journal of Medicinal Chemistry, 2003Co-Authors: Kristjan Gudmundsson, John D Williams, John C Drach, Leroy B TownsendAbstract:2,5,6-Trichloro-1-(β-d-ribofuranosyl)benzimidazole (TCRB) and certain analogues have shown significant activity against human cytomegalovirus. The metabolic instability of the glycosidic linkage in TCRB prompted us to synthesize the structurally similar imidazo[1,2-a]pyridine erythrofuranosyl C-nucleosides. As an approach to the synthesis of polychlorinated imidazo[1,2-a]pyridine C-3-erythrofuranosides, a Palladium-based methodology for Coupling 2,3-dihydrofuran with chlorinated 3-iodoimidazo[1,2-a]pyridines was developed and optimized to give 80−90% yields of 2,6-dichloro- and 2,6,7-trichloro-3-(2,3-dideoxy-2,3-didehydro-d/l-erythrofuranosyl)imidazo[1,2-a]pyridine. Dihydroxylation of these didehydro derivatives with osmium tetroxide or with AD-mix α gave a mixture of erythrofuranosyl C-nucleosides that were separated by standard and then chiral chromatography. When screened for anti-HCMV and HSV-1 activity, the α-d anomer of 2,6,7-trichloro-3-(erythrofuranosyl)imidazo[1,2-a]pyridine proved to be the most...
John D Williams - One of the best experts on this subject based on the ideXlab platform.
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synthesis and antiviral activity of novel erythrofuranosyl imidazo 1 2 a pyridine c nucleosides constructed via Palladium Coupling of iodoimidazo 1 2 a pyridines and dihydrofuran
Journal of Medicinal Chemistry, 2003Co-Authors: Kristjan Gudmundsson, John D Williams, John C Drach, Leroy B TownsendAbstract:2,5,6-Trichloro-1-(β-d-ribofuranosyl)benzimidazole (TCRB) and certain analogues have shown significant activity against human cytomegalovirus. The metabolic instability of the glycosidic linkage in TCRB prompted us to synthesize the structurally similar imidazo[1,2-a]pyridine erythrofuranosyl C-nucleosides. As an approach to the synthesis of polychlorinated imidazo[1,2-a]pyridine C-3-erythrofuranosides, a Palladium-based methodology for Coupling 2,3-dihydrofuran with chlorinated 3-iodoimidazo[1,2-a]pyridines was developed and optimized to give 80−90% yields of 2,6-dichloro- and 2,6,7-trichloro-3-(2,3-dideoxy-2,3-didehydro-d/l-erythrofuranosyl)imidazo[1,2-a]pyridine. Dihydroxylation of these didehydro derivatives with osmium tetroxide or with AD-mix α gave a mixture of erythrofuranosyl C-nucleosides that were separated by standard and then chiral chromatography. When screened for anti-HCMV and HSV-1 activity, the α-d anomer of 2,6,7-trichloro-3-(erythrofuranosyl)imidazo[1,2-a]pyridine proved to be the most...
Jo Klaveness - One of the best experts on this subject based on the ideXlab platform.
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brain penetrant small molecule 18f gnrh receptor gnrh r antagonists synthesis and preliminary positron emission tomography imaging in rats
Nuclear Medicine and Biology, 2016Co-Authors: Dag Erlend Olberg, Nadine Bauer, Kjetil Wessel Andressen, Trine Hjornevik, Paul Cumming, Finn Olav Levy, Jo KlavenessAbstract:Abstract Introduction The gonadotropin releasing hormone receptor (GnRH-R) has a well-described neuroendocrine function in the anterior pituitary. However, little is known about its function in the central nervous system (CNS), where it is most abundantly expressed in hippocampus and amygdala. Since peptide ligands based upon the endogenous decapetide GnRH do not pass the blood–brain-barrier, we are seeking a high-affinity small molecule GnRH-R ligand suitable for brain imaging by positron emission tomography. We have previously reported the radiosynthesis and in vitro evaluation of two novel [ 18 F]fluorinated GnRH-R ligands belonging to the furamide class of antagonists, with molecular weight less than 500 Da. We now extend this work using Palladium Coupling for the synthesis of four novel radioligands, with putatively reduced polar surface area and hydrophilicity relative to the two previously described compounds, and report the uptake of these 18 F-labeled compounds in brain of living rats. Methods We synthesized reference standards of the small molecule GnRH-R antagonists as well as mesylate precursors for 18 F-labeling. The antagonists were tested for binding affinity for both human and rat GnRH-R. Serum and blood stability in vitro and in vivo were studied. Biodistribution and PET imaging studies were performed in male rats in order to assess brain penetration in vivo . Results A Palladium Coupling methodology served for the synthesis of four novel fluorinated furamide GnRH receptor antagonists with reduced heteroatomic count. Radioligand binding assays in vitro revealed subnanomolar affinity of the new fluorinated compounds for both human and rat GnRH-R. The 18 F-GnRH antagonists were synthesized from the corresponding mesylate precursors in 5–15% overall radiochemical yield. The radiolabeled compounds demonstrated good in vivo stability. PET imaging with the 18 F-radiotracers in naive rats showed good permeability into brain and rapid washout, but absence of discernible specific binding in vivo . Conclusions The novel small molecule 18 F-fluorinated GnRH-R antagonist compounds show high receptor affinity in vitro , and may prove useful for quantitative autoradiographic studies in vitro . The compounds were permeable to the blood–brain barrier, but nonetheless failed to reveal significant specific binding in brain of living rats. Nonetheless, our approach may serve as a foundation for designing PET ligands suitable to image the GnRH-R distribution in brain.