Showing papers by "Kazuo Nagasawa published in 2004"
TL;DR: A chiral bis-thiourea-type organocatalyst 2 developed for the Baylis-Hillman reaction provided a drastic rate enhancement in the case of cyclohexanecarboxaldehyde as discussed by the authors.
212 citations
51 citations
TL;DR: In this paper, 1α,25-dihydroxyvitamin D3-26,23-lactams (DLAMs) were designed based on the principle of regulation of the folding of helix-12 in the vitamin D nuclear receptor (VDR), and they were synthesized via 1,3-dipolar cycloaddition reaction and subsequent reduction of the isoxazolidine as key steps.
45 citations
TL;DR: Chiral urea compounds 10a-g were synthesized as catalysts for conjugate addition of pyrrolidine to gamma-crotonolactone in the presence of a catalytic amount of the chiral ureas and this hetero-Michael reaction was greatly accelerated.
Abstract: Chiral urea compounds 10a—g were synthesized as catalysts for conjugate addition of pyrrolidine (2) to γ-crotonolactone (3). In the presence of a catalytic amount of the chiral ureas, this hetero-Michael reaction was greatly accelerated. Asymmetric induction was observed with the catalysts 10e, 10f, and 10g.
36 citations
TL;DR: Specific and potent compounds acting on each of these target phenomena/molecules have been prepared by appropriate modification of the thalidomide structure and are expected to be superior lead compounds for novel immunomodulators, antiangiogenic agents and antitumor-promoting agents.
Abstract: Thalidomide is a hyprotic/sedative drug which was withdrawn from the market because of teratogenicity. However, it has been established to be useful for the treatment of various diseases, including Hansen's disease and various cancers. Thalidomide elicits a wide range of pharmacological effects, including anti-cachexia, antitumor-promoting, antiangiogenic, immunosuppressing, antiviral, hypoglycemic, cell differentiation-inducing and antimetastatic activities. It appears to be a multitarget drug and hypothetical target events/molecules of thalidomide include TNF-α production, nuclear androgen receptor, cyclooxygenases, nuclear retinoic acid receptor, aminopeptidases and α-glucesidase. Specific and potent compounds acting on each of these target phenomena/molecules have been prepared by appropriate modification of the thalidomide structure and are expected to be superior lead compounds for novel immunomodulators, antiangiogenic agents and antitumor-promoting agents.
32 citations
TL;DR: Design and developed chemically stable PSA specific inhibitors, 3-(2,6-diethylphenyl)-2,4(1H,3H)-quinazolinedione (5: PAQ-22) and N-amino4H-3,1-benzoxazin-4-one (6: PAZOX-22), which can be used as biological/biochemical probes is important.
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.
11 citations
TL;DR: A chiral bis-thiourea-type organocatalyst 2 developed for the Baylis-Hillman reaction provided a drastic rate enhancement in the case of cyclohexanecarboxaldehyde.
Abstract: A new chiral bis-thiourea-type organocatalyst 2 developed for the Baylis–Hillman reaction provided a drastic rate enhancement. Allylic alcohols were obtained with up to 90% ee in the case of cyclohexanecarboxaldehyde ( 4i ).
4 citations
TL;DR: In this paper, 1α,25-dihydroxyvitamin D3-26,23-lactams (DLAMs) were designed based on the principle of regulation of the folding of helix-12 in the vitamin D nuclear receptor (VDR), and they were synthesized via 1,3-dipolar cycloaddition reaction and subsequent reduction of the isoxazolidine as key steps.
Abstract: Novel vitamin D3 analogs having a lactam structure in their side chains, 1α,25-dihydroxyvitamin D3-26,23-lactams (DLAMs), were designed based on the principle of regulation of the folding of helix-12 in the vitamin D nuclear receptor (VDR). The new analogs were synthesized via 1,3-dipolar cycloaddition reaction and subsequent reduction of the isoxazolidine as key steps. Among the analogs, (23S,25S)-DLAM-01 (4a) and (23S,25S)-DLAM-1P (5a) bind strongly to VDR. Moreover, these analogs were found to inhibit the differentiation of HL-60 cells induced by 1α,25-dihydroxyvitamin D3.
4 citations
TL;DR: Chiral urea compounds 10a-g were synthesized as catalysts for conjugate addition of pyrrolidine (2) to γ-crotonolactone (3).
Abstract: Chiral urea compounds 10a—g were synthesized as catalysts for conjugate addition of pyrrolidine (2) to γ-crotonolactone (3). In the presence of a catalytic amount of the chiral ureas, this hetero-Michael reaction was greatly accelerated. Asymmetric induction was observed with the catalysts 10e, 10f, and 10g.
2 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 as mentioned in this paper.
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.
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