- 著者
- Yoshiaki Kato Kenji Niiyama Hideki Jona Shigemitsu Okada Atsushi Akao Shouichi Hiraga Yoshimi Tsuchiya Koji Tomimoto Toshiaki Mase
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.50, no.8, pp.1066-1072, 2002 (Released:2002-08-01)
- 参考文献数
- 16
- 被引用文献数
- 6 8
An asymmetric synthesis of a selective endothelin A receptor antagonist 1b is described. Asymmetric conjugate addition of aryllithium derived from 18 to the chiral oxazoline 17 followed by hydrolysis afforded 15 in 96% ee via purification as (S)-(−)-1-phenylethylamine salt. Pd(OAc)2/dppf (1,1′-bis(diphenylphosphino)ferrocene) catalyzed carbonylation followed by chemoselective addition of aryllithium derived from 23 which gave ketone 24. Diastereoselective reduction of the ketone with catecholborane followed by concomitant activation of the resulting alcohol and cyclization gave the late intermediate 26. Introduction of amino moiety on the pyridine ring by imidoyl rearrangement followed by deprotection and purification by crystallization furnished the enantiomerically pure target molecule 1b in 8% overall yield from 16.
- 著者
- Masao Yoshinaga Yoshiaki Kato Yuichi Nomura Daisuke Hazeki Toshiaki Yasuda Kazuhiro Takahashi Takashi Higaki Yuji Tanaka Akihiro Wada Hitoshi Horigome Hideto Takahashi Kentaro Ueno Hiroshi Suzuki Masami Nagashima
- 出版者
- 日本不整脈学会
- 雑誌
- Journal of Arrhythmia (ISSN:18804276)
- 巻号頁・発行日
- vol.27, no.3, pp.193-201, 2011-07-25 (Released:2011-08-26)
- 参考文献数
- 27
Background: Electrocardiographic and molecular studies have clarified an association between sudden infant death syndrome (SIDS) and long QT syndrome (LQTS), and few data are available for the QT interval in infancy from birth to 1 year of age. Appropriate time of electrocardiographic screening is not clarified. Medical examinations during infancy are mandatory in Japan.Methods and Results: The study population included 1,058 infants. Electrocardiograms were collected with information of infants at birth and at examination. The QT intervals of three consecutive beats were measured in lead V5. Statistical analysis revealed that the following formula was appropriate to minimize the effect of heart rate for infants: corrected QT interval; QTc = QT interval/RR interval0.43. Subjects were divided into four groups as follows: 0–2, 3–6, 6–11, and 12–52 weeks of age. Tukey’s multiple comparison showed that the QTc intervals were longest (p<0.0001) in subjects who were 6–11 weeks of age.Conclusions: The QTc interval showed the highest peak at 6–11 weeks of age in infancy. The peak period of occurrence of SIDS is at approximately 2 months of age. An appropriate time of electrocardiographic screening for QT prolongation will be one month of age, and follow-up studies are needed.