Abstract The monosubstituted ferrocene derivatives, ω-[4-(4-methoxyphenoxycarbonyl) phenoxy]alkoxycarbonyl ferrocene, were synthesized in order to compare the liquid crystallinity to that of disubstituted ferrocene derivatives, 1,1′-bis[ω-[4-(4-methoxy-phenoxycarbonyl)phenoxy]alkoxycarbonyl]ferrocene. Some of the monosubstituted ferrocene derivatives containing relatively longer flexible spacer showed the liquid crystalline phase, nematic and/or smectic phases. The crystal structure of 2-[4-(4-methoxyphenoxycarbonyl)phenoxy]ethoxycarbonyl ferrocene was determined by X-ray diffraction method using a single crystal. The molecular structure revealed a bent structure that is almost a half of “Z” shaped molecular structure of 1,1′-bis[2-[4-(4-methoxyphenoxycarbonyl)phenoxy]ethoxycarbonyl]ferrocene. Keywords: Crystal structureferroceneliquid crystalmetallomesogenmonosubstituted ferrocene derivative A High-Tech Research Center Project for Private Universities matching fund subsidy from Ministry of Education, Culture, Sports, Science and Technology, 2006–2010 is gratefully acknowledged for partial financial support of the present work. We are grateful to Assoc. Prof. T. Hanasaki, Ritsumeikan University for his useful discussion on the molecular design, and Mr. T. Takamatsu, Ritsumeikan University for his support of structure analysis. Notes CCDC 707627 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_requestccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033. ∗Present address: TOYOBO Co., Ltd. 2-8, Dojima Hama 2-chome, Kita-ku, Osaka 530-8230, Japan. ∗∗Present address: Molex Japan Co., Ltd. 1-5-4, Fukami-higashi, Yamato, Kanagawa 242–8585, Japan. ∗∗∗Present address: Unitika LTD, 31-3, Uji-hinojiri, Uji-city, Kyoto 611-0021, Japan.
Background The treatment landscape for men with metastatic hormone-naïve prostate cancer (mHNPC) has dramatically changed with the approval of next-generation anti-androgen drugs. We compared the treatment efficacy of abiraterone with that of combined androgen blockade (CAB) therapy and androgen deprivation therapy (ADT) alone in men with high-risk mHNPC. Methods In total, 146 Japanese men with high-risk mHNPC were retrospectively analyzed. As initial hormonal therapy, 30, 83, and 33 men were treated with ADT plus abiraterone (ABI group), ADT plus bicalutamide (CAB group), and ADT alone (ADT group), respectively. Treatment efficacy was compared using time to castration resistance (TTCR) and prostate-specific antigen (PSA) response among the groups. Propensity score matching analysis was also performed to adjust for baseline differences. Results The median (95% confidence interval [CI]) TTCR in the ABI, CAB, and ADT groups were not reached, 10.7 (7.6–13.8) months and 11.0 (7.9–12.4) months, respectively, and it was significantly longer in the ABI group than in the other groups (p = 0.0012, p = 0.0008). In propensity score matching analysis, the median TTCR was also significantly longer in the ABI group than in the other groups (hazard ratio [HR], 0.47; 95% CI, 0.22–0.98; p = 0.010; HR, 0.32; 95% CI, 0.12–0.85; p = 0.004). The number of men who achieved PSA levels ≤0.2 ng/mL after propensity score matching were significantly higher in the ABI group than in the other groups. Conclusions Our results provide important evidence regarding the superiority of abiraterone over CAB therapy and ADT alone for initial treatment for men with newly diagnosed mHNPC.
The molecular and crystal structures of the title compound, which exhibited smectic C and nematic phases, have been determined by direct methods using single-crystal X-ray diffraction data. The structure was orthorhombic with the space group Pbca and Z = 8. The two cyclopentadienyl rings were an eclipsed conformation, and the flexible spacer was an all-trans conformation, but the molecule was slightly bow-shaped. Additionally, the molecules were packed in an antiparallel fashion, and two molecules had become a pair except for a ferrocenyl moiety. The molecules were in a head-to-head arrangement between contiguity layers and formed a layer structure similar to that of a smectic one. Also, dipole–dipole interaction of carbonyl groups was seen between neighboring molecules.
Abstract The circadian system has endowed animals with the ability to anticipate recurring food availability at particular times of day. As daily food anticipation (FA) is independent of the suprachiasmatic nuclei, the central pacemaker of the circadian system, questions arise of where FA signals originate and what role components of the circadian clock might play. Here we show that liver-specific deletion of Per2 in mice abolishes FA, an effect that is rescued by viral overexpression of Per2 in the liver. RNA sequencing indicates that Per2 regulates β-hydroxybutyrate (βOHB) production to induce FA leading to the conclusion that liver Per2 is important for this process. Unexpectedly, we show that FA originates in the liver and not in the brain. However, manifestation of FA involves processing of the liver-derived βOHB signal in the brain, indicating that the food-entrainable oscillator is not located in a single tissue but is of systemic nature.
ABSTRACT The molecular and crystal structures of 1,1′-disubstituted ferrocene derivative, 1,1′-bis[5-[4-(4-methoxyphenoxycarbonyl)phenoxy]pentyloxycarbonyl]ferrocene (bMAF-5) were determined by X-ray diffraction method using a single crystal. This compound is a liquid crystalline one. As generally expected, the molecular feature is “S” shape in which the two substituents are present in the opposite directions. The ‒C5H10 − chain introduced into the molecule as a flexible spacer includes two gauche conformations. The gauche conformation plays an important role to make a rod-like shape, which is favorable to show liquid crystallinity.
In mammals, the circadian rhythm central generator consists of interactions among clock genes, including Per1/2/3, Cry1/2, Bmal1, and Clock. Circadian rhythm disruption may lead to increased risk of cancer in humans, and deregulation of clock genes has been implicated in many types of cancers. Among these genes, Per2 is reported to have tumor suppressor properties, but little is known about the correlation between Per2 and HIF, which is the main target of renal cell carcinoma (RCC) therapy. In this study, the rhythmic expression of the Per2 gene was not detectable in renal cancer cell lines, with the exception of Caki-2 cells. In Caki-2 cells, HIF1α increased the amplitude of Per2 oscillation by directly binding to the HIF-binding site located on the Per2 promoter. These results indicate that HIF1α may enhance the amplitude of the Per2 circadian rhythm.
Abstract The molecular and crystal structures of a metallomesogen, 9-[4-(4-methoxyphenoxycarbonyl) phenoxycarbonyl]nonyl 4-ferrocenylbenzoate, have been determined. The space group was monoclinic with the P21/a, and Z = 4. An eclipsed conformation of two cyclopentadienyl rings was observed in the ferrocenyl moiety. The flexible spacer was an almost all-trans conformation. The largest value of the dihedral angle between the two phenyl groups in the mesogenic group was observed throughout all the homologues. This result shows that even if the dihedral angle in the mesogenic group is large, the mesophase can be exhibited by elongating the molecular length. The molecular packing arrangement was similar to those of liquid-crystalline homologues. Keywords: crystal structureferroceneliquid crystalmetallomesogenmonosubstituted ferrocene derivative ACKNOWLEDGMENT A High-Tech Research Center Project for Private Universities matching fund subsidy from the Ministry of Education, Culture, Sports, Science and Technology, 2002–2005, is gratefully acknowledged for partial support of the present work. We are grateful to T. Hanasaki and K. Uno, Ritsumeikan University, Japan, for helpful suggestions.
