bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preparation and Properties of Mixed Ligand Dinuclear Copper(II) Complexes Bridged by Deprotonated Oximato and Hydroxo or Acetato
Authors: Mori Wasuke , Suzuki Shinnichiro , Nakao Yasuo , Nishimura Tsukasa , Ichimura Akio 
Published: August 2006

Abstract
Mixed ligand dinuclear copper(II) complexes bridged by one deprotonated oximato and one hydroxo or two acetato were prepared and characterized according to their magnetic susceptibilities, electric conductivities, visible absorption spectra, and cyclic voltammograms. A very strong antiferromagnetic interaction between two copper(II) ions in hydroxo-bridged complexes has been observed (coupling constants J = −520 – −530 cm−1, H = −2JS1·S2). Two acetato-containing complexes comprise triply (one deprotonated oximato and two acetato) bridged coppers, which are characterized by J = −130 – −235 cm−1.
Sonolysis Studies of Alcohols in Aqueous Solutions by Gaseous Products Analysis
Authors: Koike Tohru 
Published: August 2006

Abstract
Sonolysis studies of alcohol–water mixtures were carried out for CH3OH, C2H5OH, n-C3H7OH, and i-C3H7OH by analyzing the gaseous products of CH4, C2H6, C2H4, C2H2, and C3H6. By comparing the product distributions which depended on the four alcohol–water mixtures it was found that alcohols decay in a similar manner as in the pyrolysis of alcohols at high temperatures and that sonolysis progresses through radical reactions.
Study of the Charge Transfer Band Observed in Dialkoxo-Bridged Binuclear Copper(II) Complexes
Authors: Handa Makoto , Idehara Tsutomu , Nakano Kenji , Kasuga Kuninobu , Mikuriya Masahiro , Matsumoto Naohide , Kodera Masahito , Kida Sigeo 
Published: August 2006

Abstract
The near-ultraviolet absorption band characteristic of dialkoxo-bridged binuclear copper(II) complexes was reinvestigated by using a series of binuclear copper(II) complexes with N,N-dialkyldiaminoalcohols, Cu2{R2N(CH2)mNH(CH2)nO}2X′2 (abbreviated as Cu(R-m-n)X′, X′ = ClO4, BF4). In this study eighteen complexes including ten new compounds were prepared and classified into two types, i.e., type-A and B according to Kida’s classification, based on their temperature dependencies of magnetic susceptibilities (80–300 K) and reflectance spectra. The crystal structures of Cu(n-Bu-3-2)ClO4 (10), Cu(H-3-3)BF4·EtOH (11b), and Cu(Me-3-3)ClO4 (12a) were determined by the single-crystal X-ray diffraction method. The detailed analysis of the structures and reflectance spectra led to the same conclusion as Kida’s one in assigning the near-ultraviolet absorption band. That is, the absorption was ascribed to the charge transfer (CT) from the bridging oxygen’s nonbonding orbital to vacant copper d-orbital. On the other hand, in assigning the origin of the appearance of the CT band in the near-ultraviolet region, the conclusion different from Kida’s one was presented. The origin was interpreted in terms of the red-shift of the band owing to the electrostatic repulsion between the bridging oxygen atoms. Moreover, the unusually low frequency and low intensity of the CT band of 12a were also reasonably explained.
Pressure Effects on the Aquation Reactions of Tris(2,2′-bipyridine)chromium(III) Ion and Tris(1,10-phenanthroline)chromium(III) Ion
Authors: Kita Shouichi , Shibata Masayasu , Uchida Kengo 
Published: August 2006

Abstract
The effects of high pressure on the rates of aquation reactions of Cr(bpy)33+ and Cr(phen)33+ have been measured. The activation volumes of aquation were derived as −0.9 ± 0.5 and +5.2 ± 0.4 cm3 mol−1 for Cr(bpy)33+ and Cr(phen)33+, respectively. These values are consistent with those expected from an interchange mechanism involving water penetration to the coordination sphere and an extension of one or both of the Cr-polypyridine bonds.
Synthesis of a Polycyclic π-Conjugated System Containing an Azulene Unit by the Flash Vacuum Pyrolytic Method. III. Synthesis and Properties of 4-Hydroxy-3H-cyclopent[a]azulen-3-one
Authors: Kitamori Yoichiro , Yasunami Masafumi , Hioki Takanori , Takase Kahei , Yoshifuji Masaaki 
Published: August 2006

Abstract
4-Hydroxy-3H-cyclopent[a]azulen-3-one, a new tricyclic π-conjugated system containing a hydroxyazulene unit and a cyclopentadienone moiety, was synthesized by the application of flash vacuum pyrolysis in the final step. All the proton magnetic resonances of the compound shifted up-field compared with those of the referenced 1,2-dihydro compound in terms of an induced paramagnetic ring current in the periphery of this molecule. The characteristic prototropic tautomerization of 4-hydroxyazulenes was not observed in this system.
Optical Resolution by Preferential Crystallization of 2-(3,4-Carbonyldioxyphenyl)-2-(phthalimidooxy)acetic Acid, a Key Intermediate of Cephalosporin Antibiotic M-14659
Authors: Murakami Kimihiro , Ohashi Masayuki , Matsunaga Atsuo , Yamamoto Ichiro , Tomiguchi Akira , Nohira Hiroyuki 
Published: August 2006

Abstract
(±)-2-(3,4-Carbonyldioxyphenyl)-2-(phthalimidooxy)acetic acid [(±)-1] was efficiently resolved into a pair of optically active forms by preferential crystallization. Successive preferential crystallization of (±)-1 was experimented at 15 °C under stirring in acetone, and (+)- and (−)-1 with optical purity of 68–85% were obtained. The racemization of (−)-1 proceeded smoothly in the presence of triethylamine to give (±)-1 which was reusable for the preferential crystallization procedure. A potent antipseudomonal cephalosporin M-14659 (2) was prepared from (+)-1.
Highly Regioselective Allylation of α-Enones and Epoxides with Lithium Tetraallyllanthanoid Ate Complex
Authors: Fukuzawa Shin-ichi , Sakai Shizuyoshi 
Published: August 2006

Abstract
Tetraallyllanthanoid ate complex (1), which was readily prepared in situ from tetraallyltin, lanthanoid trichloride, and butyllithium in tetrahydrofuran (THF), reacts smoothly with α-enones (3–11) with a high degree of 1,2-regioselectivity (1,2 : 1,4 = &gt;99 : 1) to give 1,5-diene-3-ols in good to excellent yields. The mechanistic study with 4,4-(ethylenedioxy)-2,6-dimethyl-2,5-cyclohexadienone (29) as a probe suggests that single electron transfer (SET) may be involved in this carbonyl allylation reaction with 1. Allylative ring opening of styrene oxide with 1 occurs at the more subsituted carbon (α-attack) in higher selectivity (α : β = 85 : 15) than with allyllithium and allylmagnesium bromide in diethyl ether. The complex 1 reacts with 3,4-epoxy-1-butene (35) in diethyl ether predominantly at the most substituted carbon of the oxirane to give 3-hydroxymethyl-1,5-hexadiene (36) together with 1,6-heptadien-3-ol (37), (E) and (Z)-2,6-heptadienols (38) (36 : 37 : 38 = 87 : 9 : 4)
Abnormal Diels-Alder Reaction of 5-Alkoxythiazoles with Highly Reactive Dienophiles; 4-Phenyl-3H-1,2,4-triazole-3,5(4H)-dione, Diethyl Azodicarboxylate, and Diethyl Oxomalonate
Authors: Shi Xiaolan , Ibata Toshikazu , Suga Hiroyuki , Matsumoto Kiyoshi 
Published: August 2006

Abstract
The reaction of 5-alkoxythiazoles with equimolar amount of 4-phenyl-3H-1,2,4-triazole-3,5(4H)-dione (PTAD) in an acetonitrile solution at room temperature gave the corresponding O-alkyl 6,7-dihydro-5,7-dioxo-6-phenyl-1H,5H-[1,2,4]triazolo[1,2-a] [1,2,4]triazole-1-carbothioate in high yields. The reaction was assumed to proceed through stepwise addition of PTAD toward thiazole accompanying thiazole ring opening. Diethyl azodicarboxylate also gave 2,3-dihydro-1H-1,2,4-triazole derivatives in moderate yields. High pressure improved the yields a little. On the other hand, the reaction of diethyl oxomalonate in the presence of tin tetrachloride with 4-unsubstituted thiazoles did not give an adduct of similar type but gave diethyl 2-hydroxy-2-(4-thiazolyl)malonate through the usual electrophilic substitution reaction of thiazole at C-4.
Oxidation of 2,2,3,3-Tetramethyl-1,4-diphenyl-5,6-dithiabicyclo[2.1.1]hexane and Its Oxidation Products: An Important Role of 1,3-Transannular Interaction in the 1,3-Dithietane Part
Authors: Ishii Akihiko , Ding Meng-Xin , Maeda Kiyoto , Nakayama Juzo , Hoshino Masamatsu 
Published: August 2006

Abstract
Oxidation of 2,2,3,3-tetramethyl-1,4-diphenyl-5,6-dithiabicyclo[2.1.1]hexane with m-chloroperbenzoic acid gives two isomeric endo- (4a) and exo-sulfoxides (4b), three S,S′-dioxides (endo, exo-5a, exo, exo-5b, and endo, endo-5c), and an S,S,S′-trioxide (6). The relative reactivity to further oxidation is 4b &gt;&gt; 4a and 5b &gt; 5a, which suggests that the attractive 1,3-transannular interaction operative in 1,3-dithietane part of 4a and 5a decreases the reactivity of 4a and 5a. 4b isomerizes to 4a on standing over silica gel at room temperature and also 5b is converted to 5a on heating. Heating 6 in refluxing toluene yields 3,3,4,4-tetramethyl-1,2-diphenylcyclobutene, 2,5-dimethyl-3,4-diphenyl-2,4-hexadiene, and the isomeric trioxide.
Crystal Structures of Metallic and Insulating Molecular Complexes between Naphthaceno[5,6-cd: 11,12-c′d′]bis[1,2]diselenole and 4,8-Bis(dicyanomethylene)-4H,8H-benzo[1,2-c: 4,5-c′]bis[1,2,5]thiadiazole: (TSeN)(BTDA-TCNQ) and (TSeN)(BTDA-TCNQ)(C6H5Cl)
Authors: Iwasaki Kentaro , Ugawa Akito , Kawamoto Atsushi , Yamashita Yoshiro , Yakushi Kyuya , Suzuki Takanori , Miyashi Tsutomu 
Published: August 2006

Abstract
The charge-transfer complex between naphthaceno[5,6-cd:11,12-c′d′]bis[1,2]diselenole (TSeN) and 4,8-bis(dicyanomethylene)-4H,8H-benzo[1,2-c:4,5-c′]bis[1,2,5]thiadiazole (BTDA-TCNQ) is found to show at least three different types of crystal modifications; insulating Type-I has a (1 : 1 : 1) ratio containing solvent molecules (chlorobenzene), metallic Type-II has a (1 : 1) stoichiometry, and semiconductive Type-III is conjectured to have a (1 : 2) or (2 : 1) stoichiometry. The crystal structures of Type-I and Type-II were determined by a single-crystal X-ray diffraction method. Type-I comprises mixed-stack molecular columns, and Type-II segregated-stack molecular columns. In both types the neighboring columns are linked along short molecular axes by two Se···N contacts that are shorter than the corresponding van der Waals contact. In the Type-II crystal, there are other short distances between TSeN and BTDA-TCNQ in the direction of the long molecular axes. From the C=C bond length in the C=C(CN)2 group of BTDA-TCNQ, the degrees of charge transfer of these molecular complexes were estimated as 0.2 ± 0.3 in Type-I and 0.9 ± 0.2 in Type-II.
Equilibrium and X-Ray Structural Studies on Dimeric and Trimeric Species Formed in the Extraction of Nickel(II) with 2-Methyl-8-quinolinol
Authors: Yuchi Akio , Murakami Hiroshi , Shiro Motoo , Wada Hiroko , Nakagawa Genkichi 
Published: August 2006

Abstract
Nickel(II) has been extracted with 2-methyl-8-quinolinol (Hmq) into chloroform under the following conditions: CNi = 2 × 10−5–4 × 10−3; CHmq = 7.5 × 10−3–4.8 × 10−1 mol dm−3; supporting electrolyte: 0.1 mol dm−3 NaClO4 or Na2SO4; −log [H+] = 4.5–9. An equilibrium analysis has demonstrated that neutral species, (Ni2(mq)4)o and (Ni3(mq)6)o, are responsible for extraction from sulfate solutions, whereas ion-pair species, ([Ni3H(mq)6]ClO4)o and ([Ni2H3(mq)6]ClO4)o, are predominant from perchlorate solutions. The dimeric structure of (Ni2(mq)4)o is cleaved stoichiometrically along with adduct formation upon adding 1,10-phenanthroline, while being converted to (NiH(mq)3)o and/or (Ni2H2(mq)6)o at high concentrations of Hmq. X-ray crystallographic studies show that the complexes, [Ni3(mq)6]·2C2H5OH and [Ni3H(mq)6]ClO4·C2H5OH, have discrete bent-trimeric structures, and maintain all the nickel atoms octahedral by two μ- and two μ3-bridgings at the phenolate oxygen atoms. In the [Ni2H3(mq)6]ClO4 complex, each nickel atom is surrounded by three ligands in a fac configuration and two octahedrons are connected by three hydrogen bondings. All the three structures in solids are discrete and possibly the same as those in organic solvents. Compared with 8-quinolinol, the methyl group of Hmq makes the coordination of the third ligand unfavorable for both neutral and ion-pair species. Bridging at the phenolate oxygen atoms yields extractable oligomeric species.
The Crystal Water Affecting the 2Eg→4A2g Relaxation in Tris(oxalato)chromate(III) Complexes
Authors: Otsuka Takuhiro , Sekine Akiko , Ohashi Yuji , Kaizu Youkoh 
Published: August 2006

Abstract
The measurements of absorption and luminescence spectra and luminescence decay are carried out on pure crystals of Na3[Cr(ox)3]·xH2O (ox2− = C2O42−) (x = 5 or 4) and Li3 [Cr(ox)3]·yH2O (y = 6 or 5). In sodium salt, dehydration of one crystal water (x = 4) causes the luminescence intensity to be about thirty times larger and the lifetime to be about thirty times longer than those of the most hydrated crystal (x = 5) while the opposite trend is obtained in lithium salt. However, in both salts, no change of the position of luminescence maximum is observed by the dehydration of one crystal water from the most hydrated crystals. Comparing these results with X-ray crystallographic analyses shows that a crystal water located near the oxalato-oxygen atom, which is coordinated to Cr3+ ion, affects the 2Eg→4A2g (all in Oh notation) relaxation of [Cr(ox)3]3− complexes in the pure crystal.
Stability and Reactivity of Dihydroxobis(trimethylphosphine)platinum(II), an Intermediate Species for the Synthesis of a Variety of Water-Soluble Phosphine Complexes
Authors: Miyamoto T Ken , Suzuki Yoshitsugu , Ichida Hikaru 
Published: August 2006

Abstract
A dihydroxoplatinum(II) compound, cis-[Pt(OH)2(PMe3)2]·nH2O (Me = methyl, n = 2–3; 1), has been characterized by 31P, 195Pt, 13C, and 1H NMR spectroscopy. The thermal stability of 1 was examined. The presence of several water molecules is required for the stabilization of 1. The solution equilibria and the reaction of 1 with aqueous hydrogen peroxide were observed by 31P NMR spectroscopy. The neutralization of 1 with several dicarboxylic acids afforded water-soluble phosphine complexes in quantitative yields. Exposure of 1 toward air gives the carbonatoplatinum(II), cis-[Pt(CO3)(PMe3)2]·2H2O. Its crystal structure determination has revealed that the carbonate anion forms four-membered ring with a platinum atom.
Synthesis and Biological Evaluation of Dehydrophenylalanine Containing Substance P Fragments
Authors: Kaur Paramjeet , Patnaik Gyanedra Kumar , Raghubir Ram , Chauhan Virander Singh 
Published: August 2006

Abstract
Peptide fragments of Substance P corresponding to the C-terminal segments (6-11) and (4-11), which contain a putative β-turn, were synthesised using solution phase methodology. Analogs of Substance P were synthesised where the phenylalanine residue at position 8 was replaced by dehydrophenylalanine (ΔPhe) and the glycine residue in position 9 was replaced by alanine, valine, sarcosine (N–Me–Gly) and α-aminoisobutyric acid. In two of the analogs [8-ΔPhe, 9-Sar]–SP (4-11) (5) and [5,8-ΔPhe, 9-Aib]–SP (4-11) (7) glutamine residue at position 5 was also substituted by ΔPhe. These analogs were evaluated for their ability to cause smooth muscle contraction in guinea pig ileum preparation (in vitro) and for hypotensive activity (in vivo) in female rats anesthetized with urethane. In the hexapeptide series [8-ΔPhe]–SP (6-11) (1) and [8-ΔPhe, 9-Sar]–SP (6-11) (4) showed significant activity in both the assays. Octapeptide [5,8-ΔPhe, 9-Sar]–SP (4-11) (5) with ΔPhe residue in positions 5 and 8 and sarcosine in position 9 was found to be the most potent analog both in vitro and in vivo systems.
Chiral Stationary Phases Derived from (−)-anti Head-to-Head Coumarin Dimer: Preparation, Characterization, and Chiral Recognition Ability
Authors: Chen Yun , Shiao Ming-Tang 
Published: August 2006

Abstract
A monoamide derived from (−)-anti head-to-head coumarin dimer [(−)-CD] with propylamine has been successfully bonded to silica gel (Lichrospher 100 NH2: Merck) through amide linkage to prepare CSP-1. Another monoamide derivative CSP-2 was prepared by direct nucleophilic opening of one lactone ring of (−)-CD by Lichospher 100 NH2, followed by hydrolysis of the other lactone. CSP-1 and CSP-2 showed high enantioselectivity to trans-stilbene oxide with separation factors (α) at 2.42 and 2.46, respectively, and the (−)-isomer eluted first. The capacity factor (k′) and α decrease with increasing polarity of the eluent (hexane/2-propanol), indicating that hydrogen bonding plays important role in chiral recognition. CSP-3, obtained by ligand exchange of CSP-2 with CuSO4(aq), resolved Dl-tryptophan, Dl-tyrosine, and Dl-phenylalanine (α = kD′/kL′ = 1.14–1.33), which all contain aromatic chromophore. The stability difference of the ternary complexes formed with d-isomer and l-isomer is explained by steric hindrance and aromatic π-π interactions.
The Effect of the Coexistent Gases on the Thermal Reaction of Toluene or Methane in a Clusius-Dickel Type Thermal Diffusion Column
Authors: Kawakami Shigenobu , Kanaguchi Takeshi , Tagami Hiroshi , Nakada Masahiro , Yamaguchi Tatsuaki 
Published: August 2006

Abstract
The thermal reactions of toluene or methane in a Clusius–Dickel type thermal diffusion column was investigated in the temperature range from 1300 K to 1470 K under atmospheric pressure from the viewpoint of the effect of coexistent gases to clarify the effect of thermal diffusion on the reactions. The addition of hydrogen accelerated the hydrogenolysis of toluene resulting in the high selectivity of benzene. Contrarily, by the addition of either helium or nitrogen, the reactions were retarded. On the other hand, the reactions of methane were promoted by the addition of nitrogen, and retarded by the addition of helium. This difference of the effect of coexistent gases of helium and nitrogen shows that the partial separation of reaction mixture due to thermal diffusion and convection actually occurs and has a great influence on the reaction results in a Clusius–Dickel type thermal diffusion column.
Diastereoselective Construction of 2,2,6-Trisubstituted Tetrahydropyrans by Intramolecular Alkylation Reaction of Lithium Enolates Generated from α-Alkoxy Carboxylates
Authors: Fujisawa Tamotsu , Okumura Yoshiyuki , Morita Kazuhisa , Ukaji Yutaka 
Published: August 2006

Abstract
The intramolecular alkylation reaction of enolates of t-butyl α-alkoxy carboxylates in THF–HMPA proceeded stereoselectively to afford 2,2,6-trisubstituted tetrahydropyrans with high cis-selectivity.
Syntheses of Aryltetralin Lignans: Concise Syntheses of (±)-Isopodophyllotoxone, (±)-Picropodophyllone and Their Related Compounds
Authors: Ogiku Tsuyoshi , Yoshida Shin-ichi , Kuroda Tooru , Takahashi Masami , Ohmizu Hiroshi , Iwasaki Tameo 
Published: August 2006

Abstract
(±)-Isopodophyllotoxone and (±)-picropodophyllone were synthesized stereoselectively from the O-(t-butyldimethylsilyl) cyanohydrins (3a) in good yields. This new method was successfully applied to the syntheses of a variety of lignans of the aryltetralin series.
Asymmetric Diels–Alder Reaction of Cyclopentadiene and Methyl Acrylate Catalyzed by Chiral Organoaluminum Reagents
Authors: Maruoka Keiji , Concepcion Arnel B , Yamamoto Hisashi 
Published: August 2006

Abstract
The asymmetric Diels–Alder reaction of cyclopentadiene and methyl acrylate has been effected with high enantioselectivity under the influences of catalytic amounts of chiral organoaluminum reagents.
General and Convenient Approach to Flavan-3-ols: Stereoselective Synthesis of (−)-Gallocatechin
Authors: Higuchi Takashi , Ohmori Ken , Suzuki Keisuke 
Published: August 2006

Abstract
General synthetic route to flavan-3-ols was developed. Union of two fragments was accomplished by an efficient three-step protocol, enabling the stereoselective synthesis of (−)-gallocatechin.
Polymerization of a Butadiyne Derivative in Crystalline State Stimulated by Radical Initiators
Authors: Arai Makoto , Okada Shuji 
Published: August 2006

Abstract
Solid-state polymerization of a butadiyne derivative initiated by radical species was investigated for the first time. In the nanocrystals, monomers were fully converted to the polydiacetylenes as the case of conventional photopolymerization. In bulk crystals, polymerization occurred only the parts near the specific crystal surfaces.
Polymorphisms of the inflammatory system and risk of ischemic cerebrovascular events
Authors: Lalouschek Wolfgang , Schillinger Martin , Hsieh Kety , Endler Georg , Greisenegger Stefan , Marculescu Rodrig , Lang Wilfried , Wagner Oswald , Cheng Suzanne , Mannhalter Christine 
Published: August 2006

AbstractClin Chem Lab Med 2006;44:918–23.
Association of aminothiols with the clinical outcome in hemodialysis patients: comparison of chromatography and immunoassay for homocysteine determination
Authors: Badiou Stéphanie , Terrier Nathalie , Jaussent Isabelle , Naudin Estelle , Maurice François , Dupuy Anne-Marie , Leray-Moragues Hélène , Rivory Jean-Pierre , Delcourt Cécile , Canaud Bernard , Cristol Jean-Paul 
Published: August 2006

AbstractClin Chem Lab Med 2006;44:949–54.
Unchanged androgen-binding properties of sex hormone-binding globulin in male patients with liver cirrhosis
Authors: Luppa Peter B. , Thaler Markus , Schulte-Frohlinde Ewert , Schreiegg Anita , Huber Ursula , Metzger Jochen 
Published: August 2006

AbstractClin Chem Lab Med 2006;44:967–73.
Biologic Basis of Sequential and Combination Therapies for Hormone-Responsive Breast Cancer
Authors: Pietras Richard J. 
Published: August 2006

Abstract

Learning Objectives
After completing this course, the reader will be able to: Explain the possible role of alternate growth factor signaling pathways in the development of resistance to endocrine therapies in estrogen receptor (ER)-positive breast cancer.Describe how the proposed mechanisms of action of tamoxifen, fulvestrant, aromatase inhibitors, and estrogens differ from one another.Summarize the rationale for use of sequential endocrine therapy in postmenopausal women with ER-positive breast cancer.
Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Although pharmacologic therapies that reduce or block estrogen signaling are effective treatments of estrogen receptor (ER)-positive breast cancer, acquired resistance to individual drugs can develop. Furthermore, this approach is ineffective as initial therapy for a subgroup of receptor-positive patients. The mechanisms of drug resistance are not completely understood, but the presence of alternative signaling pathways for activating ER response appears to play a significant role. Cross-talk between signaling pathways can activate ERs when conventional ER pathways are blocked or inactivated. For example, signaling via epidermal growth factor or HER-2 receptors, mitogen-activated protein kinases, phosphatidylinositol 3′ kinase/protein kinase B, and vascular endothelial growth factor receptor can lead to estrogen-independent stimulation of ERs and tumor growth. The discovery that alternative pathways are involved in estrogen signaling has prompted development of newer endocrine therapies, such as aromatase inhibitors and pure estrogen antagonists, with distinct mechanisms for interrupting signal transduction. The existence of multiple pathways may explain the effectiveness of follow-up therapy with a different class of endocrine agents after failure of prior endocrine treatment. Because they do not have the partial agonist activity of tamoxifen that is enhanced by the adaptive hypersensitivity process, these alternative endocrine agents may play an increasingly important role in the treatment of ER-positive breast cancer. Although optimal sequencing of these agents has not been determined and is continuing to evolve, current evidence allows rational recommendations to be made. The multiple pathways involved in activating ERs also provide a rationale for combining endocrine and non-endocrine therapies that block different signaling pathways, which may have synergistic and overlapping interactions.