This work describes the development of a highly enantioselective asymmetric catalysis on the intramolecular cyclopropanation of alpha-diazo-beta-keto sulfones. We have found that the catalytic asymmetric intramolecular reactions of alpha-diazo-beta-keto sulfones generally proceed with high enantioselectivity when the alpha-diazo-beta-keto mesityl sulfone is used with the newly prepared ligand 2e. The absolute configuration of products has been determined by X-ray crystallographic analysis, and the outcome of the enantioselectivities is explained well by our proposed models A and B. The products possess great potential for natural product synthesis because (1) many different chemistries of cyclopropane, ketone, and sulfone are available, and (2) the products are generally highly crystalline, facilitating the supplies of enantiomerically pure synthetic intermediates.

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15-in. XGA TFT-LCD with fast response time is developed. The response time between grayscale transitions is reduced to less than 20ms by adopting newly developed Feedforward Driving (FFD) technology. High brightness, high color saturation, and wide viewing angle characteristics are also achieved, which are significant for multimedia applications.

Purpose Phosphodiesterase (PDE) 7 is a potential therapeutic target for neurological and inflammatory diseases, although in vivo visualization of PDE7 has not been successful. In this study, we aimed to develop [11C]MTP38 as a novel positron emission tomography (PET) ligand for PDE7. Methods [11C]MTP38 was radiosynthesized by 11C-cyanation of a bromo precursor with [11C]HCN. PET scans of rat and rhesus monkey brains and in vitro autoradiography of brain sections derived from these species were conducted with [11C]MTP38. In monkeys, dynamic PET data were analyzed with an arterial input function to calculate the total distribution volume (VT). The non-displaceable binding potential (BPND) in the striatum was also determined by a reference tissue model with cerebellar reference. Finally, striatal occupancy of PDE7 by an inhibitor was calculated in monkeys according to changes in BPND. Results [11C]MTP38 was synthesized with radiochemical purity ≥99.4% and molar activity of 38.6 ± 12.6 GBq/μmol. Autoradiography revealed high radioactivity in the striatum and its reduction by non-radiolabeled ligands, in contrast with unaltered autoradiographic signals in other regions. In vivo PET after radioligand injection to rats and monkeys demonstrated that radioactivity was rapidly distributed to the brain and intensely accumulated in the striatum relative to the cerebellum. Correspondingly, estimated VT values in the monkey striatum and cerebellum were 3.59 and 2.69 mL/cm3, respectively. The cerebellar VT value was unchanged by pretreatment with unlabeled MTP38. Striatal BPND was reduced in a dose-dependent manner after pretreatment with MTP-X, a PDE7 inhibitor. Relationships between PDE7 occupancy by MTP-X and plasma MTP-X concentration could be described by Hill’s sigmoidal function. Conclusion We have provided the first successful preclinical demonstration of in vivo PDE7 imaging with a specific PET radioligand. [11C]MTP38 is a feasible radioligand for evaluating PDE7 in the brain and is currently being applied to a first-in-human PET study.

Purpose: Phosphodiesterase (PDE) 7 is a potential therapeutic target for neurological and inflammatory diseases, while in-vivo visualization of PDE7 has not been successful. In this study, we aimed to develop [11C]MTP38 as a novel positron emission tomography (PET) ligand for PDE7. Methods: [11C]MTP38 was radiosynthesized by 11C-cyanation of a bromo precursor with [11C]HCN. PET scans of rat and rhesus monkey brains and in-vitro autoradiography of brain sections derived from these species were conducted with [11C]MTP38. In monkeys, dynamic PET data were analyzed with an arterial input function to calculate the total distribution volume (VT). The non-displaceable binding potential (BPND) in the striatum was also determined by a reference tissue model with the cerebellar reference. Finally, striatal occupancy of PDE7 by an inhibitor was calculated in monkeys according to changes in BPND. Results: [11C]MTP38 was synthesized with radiochemical purity ≥ 99.4% and molar activity of 38.6 ± 12.6 GBq/μmol. Autoradiography revealed high radioactivity in the striatum and its reduction by non-radiolabeled ligands, in contrast with unaltered autoradiographic signals in other regions. In-vivo PET after radioligand injection to rats and monkeys demonstrated that radioactivity was rapidly distributed to the brain and intensely accumulated in the striatum relative to the cerebellum. Correspondingly, VT values estimated in the monkey striatum and cerebellum were 3.59 and 2.69 mL/cm3, respectively. The cerebellar VT value was unchanged by pretreatment with unlabeled MTP38. Striatal BPND was reduced in a dose-dependent manner after pretreatment with MTP-X, a PDE7 inhibitor. Relationships between the PDE7 occupancy by MTP-X and plasma MTP-X concentration could be described by Hill′s sigmoidal function. Conclusion: We have provided the first successful preclinical demonstration of in-vivo PDE7 imaging with a specific PET radioligand. [11C]MTP38 is a feasible radioligand to evaluate PDE7 in the brain and is currently applied to a first-in-human PET study.

Genomic DNA extracted from peripheral blood mononuclear cells of monozygotic twin patients with urticaria pigmentosa was investigated for mutations of proto-oncogene c-kit. Neither the patients nor their families had genomic mutations in exon 11 or exon 17 of c-kit. The patients did not have any systemic involvement or bone marrow abnormalities. There are indications that some genetic factors may participate in the pathogenesis of urticaria pigmentosa in monozygotic twins. In the present patients, factors other than genomic faults in exon 11 and exon 17 of c-kit may be responsible for the pathogenesis.

The above findings demonstrate that patients with suspected ovarian cancer experience a high level of anxiety. Physicians should be aware of the risk of adjustment disorder in these patients. Additionally, ovarian cancer patients need psychological assessment during the course of treatment.