Showing papers by "Kazuo Nagasawa published in 2003"
TL;DR: The prepared anti- androgens exhibited full antagonistic activity toward human prostate tumor LNCaP cells with T877A point-mutated nuclear androgen receptor, towards which other known anti-androgens, including hydroxyflutamide, are inactive or act as androgen agonists.
82 citations
TL;DR: These potent and specific PSA inhibitors showed dose-dependent cell invasion-inhibitory activity in a Matrigel assay using mouse melanoma B16F10/L5 cells, in spite of their low cell toxicity.
Abstract: Potent, specific, chemically stable and non-peptide/small-molecular inhibitors of puromycin-sensitive aminopeptidase, such as 3-(2,6-diethylphenyl)-2,4(1H,3H)-quinazolinedione (PAQ-22, 5), were prepared by the structural development of a potent PSA inhibitor, 2-(2,6-diethylphenyl)-1,2,3,4-tetrahydroisoquinoline-1,3-dione (PIQ-22, 4). The design was carried out partly by applying electrostatic potential field information obtained from PIQ-22 (4) and its derivatives based on thalidomide (2). This information revealed that a positive electrostatic potential field around the benzylic methylene in the tetrahydroisoquinoline ring is necessary for potent activity. Lineweaver-Burk plot analysis showed that PAQ-22 (5) and its derivatives inhibit puromycin-sensitive aminopeptidase (PSA) in a non-competitive manner. These potent and specific PSA inhibitors showed dose-dependent cell invasion-inhibitory activity in a Matrigel assay using mouse melanoma B16F10/L5 cells, in spite of their low cell toxicity.
56 citations
TL;DR: The first method developed for the synthesis of the pentacyclic guanidine core structure involved successive 1,3-dipolar cycloaddition reactions and resulted in the first total synthesis of crambescidin 359.
Abstract: Ptilomycalin A and crambescidins, novel marine guanidine alkaloids, have a unique pentacyclic guanidine structure, and exhibit a considerable array of biological activities. The first method developed for the synthesis of the pentacyclic guanidine core structure involved successive 1,3-dipolar cycloaddition reactions and resulted in the first total synthesis of crambescidin 359. The synthesis of other pentacyclic guanidine derivatives has been based on this methodology and applied as tools for studying biological activities, and as chemical reaction catalysts. © 2003 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 3: 201–211; 2003: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.10064
30 citations
TL;DR: Non-peptide, small-molecular, non-competitive inhibitors of puromycin-sensitive aminopeptidase (PSA), that is, 3-(2,6-diethylphenyl)-2,4(1H,3H)-quinazolinedione and its 1N-methyl analogue (MPAQ-22 4), were structurally modified to afford fluorescent bioprobes.
17 citations
TL;DR: Several N-3,5-dimethylphenylphthalimide analogs possessing more potent cyclooxygenase-inhibiting activity than that of aspirin were prepared during structural development studies based on thalidomide.
Abstract: Several N-3,5-dimethylphenylphthalimide analogs possessing more potent cyclooxygenase-inhibiting activity than that of aspirin were prepared during structural development studies based on thalidomide. Substituent effects on the activity were investigated.
16 citations
TL;DR: In this paper, the synthesis of novel vitamin D3 analogs containing heteroatoms in their side chains via 1,3-dipolar cycloaddition reaction was described as a key step.
Abstract: Vitamin D3 and its synthetic analogs are promising compounds for controlling various types of cell differentiation. In this article, we describe the synthesis of novel vitamin D3 analogs containing heteroatoms in their side chains – so-called vitamin D3 lactam analogs – via 1,3-dipolar cycloaddition reaction as a key step.
15 citations
TL;DR: During synthetic studies of crambescidins and batzelladines, the absolute stereochemistry was revealed and the novel C2-symmetric pentacyclic guanidine compounds 69a-d were designed and synthesized as Guanidine organocatalysts.
Abstract: Crambescidins and batzelladines, novel marine guanidine alkaloids, have unique pentacyclic and tricyclic guanidine core structures, respectively. They display a considerable array of biological activity and not surprisingly have attracted considerable synthetic interest. The first total synthesis of crambescidin 359 (7) and stereoselective total synthesis of batzelladine D (11) were accomplished based on a successive 1,3-dipolar cycloaddition reaction strategy. During synthetic studies of 7, the absolute stereochemistry was revealed. Based on the structure of 7, the novel C2-symmetric pentacyclic guanidine compounds 69a-d were designed and synthesized as guanidine organocatalysts. The catalyst 69b works efficiently as an asymmetric catalyst of the alkylation reaction of the glycynate-benzophenone Schiff base 73, which gives 74 with 80-90% ee.
3 citations
TL;DR: The FAB mass spectrum of the Ca(2+) salt of RK-682 (1, MW 368), a potent protein tyrosine phosphatase inhibitor, shows a complex pattern due to Ca( 2+) adduct ions with multimers of 1 and their decomposition ions.
Abstract: The FAB mass spectrum of the Ca(2+) salt of RK-682 (1, MW 368), a potent protein tyrosine phosphatase inhibitor, shows a complex pattern due to Ca(2+) adduct ions with multimers of 1 and their decomposition ions. Addition of LiCl greatly simplified the FAB mass spectrum, providing a prominent Li(+) adduct ion of 1 at m/z 381 [M+2Li-H](+). The addition of LiCl also greatly simplified the FAB mass spectrum of calcium pantothenate. This approach may be generally useful for molecular weight determination of multivalent metal salts of organic compounds, or organic compounds that can form Li salts, by FAB mass spectrometry.
3 citations
TL;DR: In this article, a deterministic total synthesis of batzelladine D was achieved in 15 steps, which features successive 1,3-dipolar cycloaddition reactions to form the 2,5-disubstituted pyrrolidine ring system, esterification of the side chain to the bicyclic guanidine carboxylate, a common synthetic intermediate of biclomerate alkaloids, and tricyclic ganidine formation under the Mitsunobu reaction conditions.
Abstract: [structure: see text] Stereoselective total synthesis of batzelladine D was accomplished in 15 steps. This synthesis features (i) successive 1,3-dipolar cycloaddition reactions to form the 2,5-disubstituted pyrrolidine ring system, (ii) esterification of the side chain to the bicyclic guanidine carboxylate, a common synthetic intermediate of batzelladine alkaloids, and (iii) tricyclic guanidine formation under the Mitsunobu reaction conditions.
2 citations
TL;DR: The pentacyclic guanidine compounds 4 and 5 were stereoselectively synthesized as novel ptilomycalin A and crambescidin analogs, and exhibited significant inhibitory activity against Ca 2 + -ATPase.
Abstract: The pentacyclic guanidine compounds 4 and 5 were stereoselectively synthesized as novel ptilomycalin A and crambescidin analogs. The synthetic method involves successive 1,3-dipolar cycloaddition reactions which effectively access the key intermediates, trans- and cis-2,5-disubstituted pyrrolidine 8 having hydroxyl groups at the p-positions on their side chains. Among the analogs synthesized, 4b and 5b exhibited significant inhibitory activity against Ca 2 + -ATPase.
1 citations
TL;DR: The first total synthesis of crambescidin 359 (7) and stereoselective complete synthesis of batzelladine D (11) were accomplished based on a successive 1,3-dipolar cycloaddition reaction strategy as discussed by the authors.
Abstract: Crambescidins and batzelladines, novel marine guanidine alkaloids, have unique pentacyclic and tricyclic guanidine core structures, respectively. They display a considerable array of biological activity and not surprisingly have attracted considerable synthetic interest. The first total synthesis of crambescidin 359 (7) and stereoselective total synthesis of batzelladine D (11) were accomplished based on a successive 1,3-dipolar cycloaddition reaction strategy. During synthetic studies of 7, the absolute stereochemistry was revealed. Based on the structure of 7, the novel C2-symmetric pentacyclic guanidine compounds 69a-d were designed and synthesized as guanidine organocatalysts. The catalyst 69b works efficiently as an asymmetric catalyst of the alkylation reaction of the glycynate-benzophenone Schiff base 73, which gives 74 with 80-90% ee.