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Aya Tanatani

Publications and source records attributed to Aya Tanatani.

At least 19 recordsLinked to original sources
PubMed2006

Spontaneous resolution of aromatic sulfonamides: effective screening method and discrimination of absolute structure.

An effective screening method combining parallel synthesis and solid-state CD measurements was established to identify achiral aromatic sulfonamides that show spontaneous resolution with rapidity. We found that 4 of the 12 achiral sulfonamides crystallized as chiral crystals through this method. The chirality of each sulfonamide was discriminated by solid-state CD spectra and Flack parameter in an X-ray analysis. Correspondence between the observed Cotton effect and the absolute configuration could be confirmed by time-dependent DFT calculations. [structure: see text]

Chemistry, Organic↗
PubMed2006

Ligands with a 3,3-diphenylpentane skeleton for nuclear vitamin D and androgen receptors: Dual activities and metabolic activation.

Ligands possessing dual vitamin D(3) (VD(3))-agonistic and androgen-antagonistic activities with various activity spectra were prepared based on a substituted 3,3-diphenylpentane (DPP) skeleton. Among the compounds, (R,S)-DPP-1023 [(R,S)-7b] and (S,S)-DPP-0123 [(S,S)-7c] showed the most potent vitamin D(3)-agonistic activity [with potency comparable to that of 1alpha,25-dihydroxyvitamin D(3) (1,25-VD(3))] and nuclear androgen receptor (AR)-binding activity (with higher affinity than that of hydroxyflutamide), respectively. Metabolic activation (reduction of the carbonyl group) of pivaloyl analogs [DPP-1113 (3a), DPP-1013 (3b), DPP-0113 (3c), and DPP-0013 (3d)] in HL-60 cells was found to be necessary for binding to nuclear vitamin D(3) receptor (VDR).

Androgen Receptor Antagonists↗
PubMed2006

Practical synthesis and evaluation of the biological activities of 1alpha,25-dihydroxyvitamin D3 antagonists, 1alpha,25-dihydroxyvitamin D3-26,23-lactams. Designed on the basis of the helix 12-folding inhibition hypothesis.

A practical synthetic route to novel vitamin D antagonists of DLAM (1alpha,25-dihydroxyvitamin D(3)-26,23-lactam) was developed from vitamin D(2) via the 1,3-dipolar cycloaddition reaction as a key step. Six DLAM derivatives (24 compounds) with a variety of nitrogen substituents and stereochemistries at C23 and C25 were synthesized. Among these new derivatives, (23S,25S)-DLAM isomers bound effectively to VDRs and showed antagonistic activity in the HL-60 cell differentiation inhibition assay. The importance of the substituent on the nitrogen of DLAMs for antagonistic activity was also suggested by computational docking studies.

Animals↗
PubMed2005

Total synthesis of (+)-batzelladine A and (-)-batzelladine D, and identification of their target protein.

Asymmetric total synthesis of batzelladine A (1) and batzelladine D (2) has been achieved. Our synthesis of batzelladines features 1) stereoselective construction of the cyclic guanidine system by means of successive 1,3-dipolar cycloaddition reaction and subsequent cyclization, 2) direct esterification of the bicyclic carboxylic acid 35 with the guanidine alcohol 8 or 59 to construct the whole carbon skeleton of batzelladines, and 3) one-step formation of the alpha,beta-unsaturated aldehyde 53 from the primary alcohol 47 with tetra-n-propylammoniumperruthenate (TPAP), providing an efficient route to the left-hand bicyclic guanidine alcohol of batzelladine A (1). With the synthetic compounds 1 and 2 in hand, their target protein was examined by using immobilized CD4 and gp120 affinity gels. The results indicated that batzelladines A (1) and D (2) bind specifically to CD4.

Alkaloids↗
PubMed2005

Ligands with dual vitamin D3-agonistic and androgen-antagonistic activities.

Ligands possessing dual vitamin D3-agonistic (estimated as HL-60 monocytic cell differentiation induction) and androgen-antagonistic (estimated as testosterone-induced SC-3 cell growth inhibition) activities with various activity spectra were prepared based on a substituted bis-phenylmethane skeleton. Some of them were revealed to be potent androgen antagonists with a nonsecosteroidal vitamin D3 skeleton.

Androgen Antagonists↗
PubMed2005

Helical structures of N-alkylated poly(p-benzamide)s.

Poly(p-benzamide)s 1 bearing a chiral side chain on the nitrogen atom were synthesized by chain-growth polycondensation methodology. The polyamides exhibited well-defined molecular weights with narrow polydispersities. Solutions of the polyamides in several organic solvents (CH(3)CN, CHCl(3), and CH(3)OH) showed dispersion type CD signals characteristic of coupled-oscillator and much larger as compared with the corresponding monomer. The CD signals were dependent on the temperature and molecular weight of the polyamides but independent of the solvent, as far as examined. An exciton model analysis of the absorption and CD spectra provided a clear-cut picture for the secondary structure of these polyamides in solution that the N-alkylated poly(p-benzamide)s possess a right-handed helical conformation ((P)-helix). In the solid states, the results of X-ray crystallographic analysis of 4-(methylamino)benzoic acid oligomers substantiated that they have a helical conformation with three monomer units per turn.

Journal Article↗
PubMed2005

Design and synthesis of subtype-selective cyclooxygenase (COX) inhibitors derived from thalidomide.

A series of substituted indoline and indole derivatives with cyclooxygenase (COX)-inhibitory activity was prepared during our structural development studies based on thalidomide as a multi-template lead compound. Structure-activity relationship studies indicated that the nature of the substituent introduced at the benzene ring of the indoline (indole) backbone, and the length and type of the linking group between the nitrogen atom of indoline (indole) and the N-substituent are important for the activity. This study has led to the identification of COX-1-selective inhibitors, and these should be useful not only as pharmacological tools to investigate the physiology and pathophysiology of COX, but also as sophisticated leads for the development of novel drugs to treat COX-associated diseases, such as inflammatory diseases, and cancer.

Cyclooxygenase 1↗
PubMed2005

Novel non-steroidal/non-anilide type androgen antagonists: discovery of 4-substituted pyrrole-2-carboxamides as a new scaffold for androgen receptor ligands.

We designed and synthesized novel pyrrole-2-carboxamide derivatives as androgen antagonists. Compounds 10 and 13 bearing benzylamine or aniline at the 4-position of the pyrrole ring showed moderate androgen antagonistic activity, and inhibited the androgen-dependent growth of Shionogi carcinoma cells (SC-3). Study of the structure-activity relationships of compound 13 led to a potent androgen antagonist 36, which has higher affinity than flutamide (4) for androgen nuclear receptor (AR). Thus, pyrrole-2-carboxamide is a new scaffold for developing AR antagonists.

Amides↗
PubMed2004

Phenylhomophthalimide-type NOS inhibitors derived from thalidomide.

Thalidomide shows moderate inhibitory activity toward neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS), but not toward endothelial NOS (eNOS). Structural development studies of thalidomide yielded novel phenylhomophthalimide-type NOS inhibitors with enhanced activity and different subtype selectivity.

Enzyme Inhibitors↗
PubMed2004

Synthesis of 1alpha,25-dihydroxyvitamin D3-26,23-lactams (DLAMs), a novel series of 1 alpha,25-dihydroxyvitamin D3 antagonist.

Novel vitamin D(3) analogs having a lactam structure in their side chains, 1 alpha,25-dihydroxyvitamin D(3)-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 1 alpha,25-dihydroxyvitamin D(3).

Cell Differentiation↗
PubMed2004

Development of novel chiral urea catalysts for the hetero-Michael reaction.

Chiral urea compounds 10a-g were synthesized as catalysts for conjugate addition of pyrrolidine (2) to gamma-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.

4-Butyrolactone↗
PubMed2003

Absolute helical arrangement of sulfonamide in the crystal.

[reaction: see text] 1,2-Bis(N-benzenesulfonyl-N-methylamino)benzene (2), which has no fixed asymmetric element, was crystallized from ethyl acetate as chiral crystals belonging to space group P4(1)2(1)2 (No. 92) or P4(3)2(1)2 (No. 96). The array of molecules built by the CH-pi interaction along the c-axis forms an enantiomeric helical superstructure in each individual crystal. The absolute configurations of the chiral crystals of 2 were determined by X-ray crystal structure analysis using the Flack parameter method. The solid-state CD spectra of the chiral crystals in KBr were mirror images. The equilibrium between the two enantiomers in solution is fast during crystallization at ambient temperature, and the energy barrier (DeltaG()) is estimated to be 11.7 +/- 0.3 kcal/mol (233 K).

Journal Article↗
PubMed2003

Anti-androgens with full antagonistic activity toward human prostate tumor LNCaP cells with mutated androgen receptor.

Anti-androgens were designed based on the principle of inhibiting the folding of helix 12 of the nuclear androgen receptor. The prepared anti-androgens exhibited full antagonistic activity toward human prostate tumor LNCaP cells with T877A point-mutated nuclear androgen receptor, as far as examined, towards which other known anti-androgens, including hydroxyflutamide, are inactive or act as androgen agonists.

Androgen Antagonists↗