The Experts below are selected from a list of 141 Experts worldwide ranked by ideXlab platform
Tatsuo Tsuri - One of the best experts on this subject based on the ideXlab platform.
-
Short synthesis of tert-butyl-hydroxylated 3,5-di-tert-butyl-4-hydroxybenzaldehyde: Synthesis of tert-butyl-hydroxylated S-2474.
Journal of Organic Chemistry, 2003Co-Authors: Masanao Inagaki, Saichi Matsumoto, Tatsuo TsuriAbstract:We have developed a very short synthesis of tert-butyl-hydroxylated di-tert-butyl-4-hydroxybenzaldehyde in which the HBr-DMSO system is used as an effective oxidant (overall yield of 45% for the entire four-step process from 2-tert-butyl-p-cresol). We also accomplished the synthesis of a major metabolite of the Antiarthritic Drug candidate S-2474.
-
highly e selective and effective synthesis of Antiarthritic Drug candidate s 2474 using quinone methide derivatives
Journal of Organic Chemistry, 2002Co-Authors: Masanao Inagaki, Nobuhiro Haga, Makoto Kobayashi, Naoki Ohta, Susumu Kamata, Tatsuo TsuriAbstract:We have developed an efficient and E-selective synthesis of an Antiarthritic Drug candidate (E)−(5)−(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-ethyl-1,2-isothiazolidine-1,1-dioxide (S-2474; 1), in which α-methoxy-p-quinone methide is used as a key intermediate. α-Methoxy-p-quinone methide was revealed to be an equivalent to a p-hydroxy protected benzaldehyde. It reacts smoothly with α-sulfonyl carbanion to give 1,6-addition intermediates, which can be further processed to provide S-2474 directly in the presence of a base. This procedure gives S-2474 as an almost single isomer on the benzylidene double bond in excellent yield and thus is a very practical method adaptable to large-scale synthesis. The detailed mechanistic aspects are studied and discussed.
-
Novel Antiarthritic Agents with 1,2-Isothiazolidine-1,1-dioxide (γ-Sultam) Skeleton: Cytokine Suppressive Dual Inhibitors of Cyclooxygenase-2 and 5-Lipoxygenase
Journal of Medicinal Chemistry, 2000Co-Authors: Masanao Inagaki, Tatsuo Tsuri, Hirokuni Jyoyama, Katsutoshi Yamada, Mika Kobayashi, Yozo Hori, Akinori Arimura, Kiyoshi Yasui, Kouji OhnoAbstract:Various 1,2-isothiazolidine-1,1-dioxide (γ-sultam) derivatives containing an antioxidant moiety, 2,6-di-tert-butylphenol substituent, were prepared. Some compounds, which have a lower alkyl group at the 2-position of the γ-sultam skeleton, showed potent inhibitory effects on both cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LO), as well as production of interleukin (IL)-1 in in vitro assays. They also proved to be effective in several animal arthritic models without any ulcerogenic activities. Among these compounds, (E)-(5)-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-ethyl-1,2-isothiazolidine-1,1-dioxide (S-2474) was selected as an Antiarthritic Drug candidate and is now under clinical trials. The structure−activity relationships (SAR) examined and some pharmacological evaluations are described.
Inchan Youn - One of the best experts on this subject based on the ideXlab platform.
-
prediction of Antiarthritic Drug efficacies by monitoring active matrix metalloproteinase 3 mmp 3 levels in collagen induced arthritic mice using the mmp 3 probe
Molecular Pharmaceutics, 2014Co-Authors: Kyeongsoon Park, Sung Jae Choi, Kuiwon Choi, Ick Chan Kwon, Soo Young Yoon, Inchan YounAbstract:Active matrix metalloproteinase-3 (MMP-3) is a prognostic marker of rheumatoid arthritis (RA). We recently developed an MMP-3 probe that can specifically detect the active form of MMP-3. The aim of this study was to investigate whether detection and monitoring of active MMP-3 could be useful to predict therapeutic Drug responses in a collagen-induced arthritis (CIA) model. During the period of treatment with Drugs such as methotrexate (MTX) or infliximab (IFX), MMP-3 mRNA and protein levels were correlated with fluorescence signals in arthritic joint tissues and in the serum of CIA mice. Also, bone volume density and erosion in the knee joints and the paws of CIA mice were measured with microcomputed tomography (micro-CT), X-ray, and histology to confirm Drug responses. In joint tissues and serum of CIA mice, strong fluorescence signals induced by the action of active MMP-3 were significantly decreased when Drugs were applied. The decrease in RA scores in Drug-treated CIA mice led to fluorescence reductio...
Masanao Inagaki - One of the best experts on this subject based on the ideXlab platform.
-
studies on the new Antiarthritic Drug candidate s 2474
Yakugaku Zasshi-journal of The Pharmaceutical Society of Japan, 2003Co-Authors: Masanao InagakiAbstract:: Various 1,2-isothiazolidine-1,1-dioxide (gamma-sultam) derivatives containing an antioxidant moiety, 2,6-di-tert-butyl-phenol substituent, were prepared. Some compounds that have a lower alkyl group at the 2-position of the gamma-sultam skeleton showed potent inhibitory effects on both cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LO), as well as production of interleukin-1 (IL-1) in in vitro assays. They also proved to be effective in several animal arthritic models without any ulcerogenic activities. Among these compounds, (E)-(5)-(3,5-di-tert-butyl-4-hydroxybenzylidence)-2-ethyl-1,2- isothiazolidine-1,1-dioxide (S-2474) was selected as an Antiarthritic Drug candidate. The structure-activity relationships examined and some pharmacological evaluations are described. Furthermore, we have developed an efficient and E-selective synthesis of S-2474, in which alpha-methoxy-p-quinone methide is used as a key intermediate. alpha-Methoxy-p-quinone methide was revealed to be equivalent to a p-hydroxy-protected benzaldehyde. It reacts smoothly with alpha-sulfonyl carbanion to give 1,6-addition intermediates, which can be further processed to provide S-2474 directly in the presence of a base. This procedure gives S-2474 as an almost single isomer on the benzylidene double bond in excellent yield and thus is a very practical method adaptable to large-scale synthesis. The detailed mechanistic aspects are studied and discussed.
-
Short synthesis of tert-butyl-hydroxylated 3,5-di-tert-butyl-4-hydroxybenzaldehyde: Synthesis of tert-butyl-hydroxylated S-2474.
Journal of Organic Chemistry, 2003Co-Authors: Masanao Inagaki, Saichi Matsumoto, Tatsuo TsuriAbstract:We have developed a very short synthesis of tert-butyl-hydroxylated di-tert-butyl-4-hydroxybenzaldehyde in which the HBr-DMSO system is used as an effective oxidant (overall yield of 45% for the entire four-step process from 2-tert-butyl-p-cresol). We also accomplished the synthesis of a major metabolite of the Antiarthritic Drug candidate S-2474.
-
highly e selective and effective synthesis of Antiarthritic Drug candidate s 2474 using quinone methide derivatives
Journal of Organic Chemistry, 2002Co-Authors: Masanao Inagaki, Nobuhiro Haga, Makoto Kobayashi, Naoki Ohta, Susumu Kamata, Tatsuo TsuriAbstract:We have developed an efficient and E-selective synthesis of an Antiarthritic Drug candidate (E)−(5)−(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-ethyl-1,2-isothiazolidine-1,1-dioxide (S-2474; 1), in which α-methoxy-p-quinone methide is used as a key intermediate. α-Methoxy-p-quinone methide was revealed to be an equivalent to a p-hydroxy protected benzaldehyde. It reacts smoothly with α-sulfonyl carbanion to give 1,6-addition intermediates, which can be further processed to provide S-2474 directly in the presence of a base. This procedure gives S-2474 as an almost single isomer on the benzylidene double bond in excellent yield and thus is a very practical method adaptable to large-scale synthesis. The detailed mechanistic aspects are studied and discussed.
-
Novel Antiarthritic Agents with 1,2-Isothiazolidine-1,1-dioxide (γ-Sultam) Skeleton: Cytokine Suppressive Dual Inhibitors of Cyclooxygenase-2 and 5-Lipoxygenase
Journal of Medicinal Chemistry, 2000Co-Authors: Masanao Inagaki, Tatsuo Tsuri, Hirokuni Jyoyama, Katsutoshi Yamada, Mika Kobayashi, Yozo Hori, Akinori Arimura, Kiyoshi Yasui, Kouji OhnoAbstract:Various 1,2-isothiazolidine-1,1-dioxide (γ-sultam) derivatives containing an antioxidant moiety, 2,6-di-tert-butylphenol substituent, were prepared. Some compounds, which have a lower alkyl group at the 2-position of the γ-sultam skeleton, showed potent inhibitory effects on both cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LO), as well as production of interleukin (IL)-1 in in vitro assays. They also proved to be effective in several animal arthritic models without any ulcerogenic activities. Among these compounds, (E)-(5)-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-ethyl-1,2-isothiazolidine-1,1-dioxide (S-2474) was selected as an Antiarthritic Drug candidate and is now under clinical trials. The structure−activity relationships (SAR) examined and some pharmacological evaluations are described.
Alvito P Alvares - One of the best experts on this subject based on the ideXlab platform.
-
species differences in the renal toxicity of the Antiarthritic Drug gold sodium thiomalate
Journal of Biochemical Toxicology, 1996Co-Authors: Elizabeth Cheriathundam, Alvito P AlvaresAbstract:Two gold compounds, gold sodium thiomalate (AuTM) and auranofin, are presently in clinical use in therapy of rheumatoid arthritis. In these studies, AuTM administered to Sprague-Dawley rats and three strains of mice, Swiss-Webster, C3H/HeJ, and DBA/2J, were studied with regard to its effect on liver and renal monooxygenases, metallothionein contents, and serum levels of alanine aminotransferase and urea nitrogen. These effects of AuTM were compared to those of cadmium, since the latter metal has exhibited tissue and species differences in the induction of metallothionein. Benzo(a)pyrene hydroxylase and benzphetamine N-demethylase activities were not altered by AuTM in livers of rats and the three strains of mice. Benzo(a)pyrene hydroxylase activity was significantly decreased in rat kidney, whereas this enzyme activity was not affected in the kidneys of mice. In rats, AuTM caused a sevenfold induction in liver metallothionein, while in mice, liver metallothionein was induced twofold in Swiss-Webster mice and about fivefold in the inbred strains. AuTM caused minimal changes in renal metallothionein contents in the three strains of mice studied. Serum alanine amino-transferase, an indicator of hepatotoxicity, was not altered by AuTM in rats and mice studied. Blood urea nitrogen, an indicator of kidney dysfunction, was increased threefold in rats, but not in AuTM-treated mice. These data demonstrate that AuTM, a nephrotoxic agent in rats and humans, showed no nephrotoxic effects in the mouse strains studied here. © 1997 John Wiley & Sons, Inc.
Kyeongsoon Park - One of the best experts on this subject based on the ideXlab platform.
-
prediction of Antiarthritic Drug efficacies by monitoring active matrix metalloproteinase 3 mmp 3 levels in collagen induced arthritic mice using the mmp 3 probe
Molecular Pharmaceutics, 2014Co-Authors: Kyeongsoon Park, Sung Jae Choi, Kuiwon Choi, Ick Chan Kwon, Soo Young Yoon, Inchan YounAbstract:Active matrix metalloproteinase-3 (MMP-3) is a prognostic marker of rheumatoid arthritis (RA). We recently developed an MMP-3 probe that can specifically detect the active form of MMP-3. The aim of this study was to investigate whether detection and monitoring of active MMP-3 could be useful to predict therapeutic Drug responses in a collagen-induced arthritis (CIA) model. During the period of treatment with Drugs such as methotrexate (MTX) or infliximab (IFX), MMP-3 mRNA and protein levels were correlated with fluorescence signals in arthritic joint tissues and in the serum of CIA mice. Also, bone volume density and erosion in the knee joints and the paws of CIA mice were measured with microcomputed tomography (micro-CT), X-ray, and histology to confirm Drug responses. In joint tissues and serum of CIA mice, strong fluorescence signals induced by the action of active MMP-3 were significantly decreased when Drugs were applied. The decrease in RA scores in Drug-treated CIA mice led to fluorescence reductio...
