Katsumi Kubota

Synthesis and structure―activity relationships of phenothiazine carboxylic acids having pyrimidine-dione as novel histamine H1 antagonists

A series of phenothiazine carboxylic acid derivatives, having 6-amino-pyrimidine-2,4(1H,3H)-dione moiety via a appropriate linker, were synthesized and evaluated for their affinity toward human histamine H(1) receptor and Caco-2 cell permeability. Selected compounds were further evaluated for their oral anti-histaminic activity in mice and bioavailability in rats. Finally, promising compounds were examined for their anti-inflammatory potential in mice OVA-induced biphasic cutaneous reaction model. Among the compounds tested, phenothiazineacetic acid compound 27 showed both histamine H(1)-receptor antagonistic activity and anti-inflammatory activity in vivo model.

Synthesis and structure–activity relationship of tricyclic carboxylic acids as novel anti-histamines

A series of tricyclic carboxylic acids having 6-amino-pyrimidine-2,4(1H,3H)-dione with piperazino or homopiperazino moiety linked by propylene, were synthesized and evaluated for their affinity toward human histamine H(1) receptor and Caco-2 cell permeability. Selected compounds were further evaluated for their oral anti-histaminic activity in mice, bioavailability in rats, and their anti-inflammatory activity in mice OVA-induced biphasic cutaneous reaction model. Among the compounds tested, dibenzoxazepine carboxylic acid 13b showed both histamine H(1) receptor antagonistic activity and anti-inflammatory activity in vivo. In addition, 13b exhibited low affinity toward α(1) receptor and low occupancy of H(1) receptor in the brain. It is therefore, believed that 13b is a potential candidate for development as 3rd generation anti-histamine.

Synthesis and biological evaluations of A-ring isomers of 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3

The activated vitamin D3 derivative 26,27-F6-1alpha,25(OH)2D3 (2a), its three A-ring diastereomers (2b, 2c, 2d), and 5,6-trans isomer (2e) were prepared. Two analogues (2b, 2c) of these isomers were synthesized by a palladium catalyzed coupling reaction using vinyl bromide 5 and enynes (6a, 6b), which were derived from readily commercially available 2S-(+)-glycidyl p-toluenesulfonate 7, as a common starting material. Competitive vitamin D receptor (VDR) binding affinities of these diastereomers of 2a were evaluated. Interestingly, the stereochemical effects at C-1,3 of 2a were considerably more moderate than those of 1alpha,25(OH)2D3 (1). In particular, isomerization at the 5,6-double bond of 2a only slightly reduced VDR affinity, whereas 5,6-trans-1alpha,25(OH)2D3 had a significantly lower binding affinity than 1.

Suzaku observations of SS 433 in the 2006 April multi-wavelength campaign

K. Kubota,a Y. Ueda,a T. Kotani,b N. Kawai,c M. Namiki,d K. Kinugasa,e S. Ozaki, f T. Iijimag and S. Fabrikah a Kyoto University, Japan b Aoyama Gakuin University, Japan c Tokyo Institute of Technology, Japan d Osaka University, Japan e Gunma Astronomical Observatory, Japan f Okayama Astrophysical Observatory, Japan g Astronomical Observatory of Padova, Italy h Special Astrophysical Observatory, Russia