83647-29-4Relevant articles and documents
Identification of photodegradants of droloxifene by combined HPLC-MS, NMR spectroscopy and computational chemistry
Campeta, Anthony M.,Lombardo, Franco,Sharp, Thomas R.,Horan, George J.,Rescek, Diane M.
, p. 881 - 889 (1999)
A combination of high-performance liquid chromatograpny (HPLC)-mass spectrometry and 1H and 13C NMR spectroscopy was utilized to charactorize the photodecay products of droloxifene, a potent new estrogen receptor agonist. Structurally similar to tamoxifen, droloxifene demonstrates a complex and unique decay scheme, including the formation of two naphthalene derivatives which were unexpected decay products and previously unreported for this class of compound. Elucidation of the decay products was assisted by the use of computational chemistry, namely by correlating simulated UV spectra and aqueous solvation free energies with actual UV spectra and HPLC retention data. In addition to describing the photodecay scheme of droloxifene, the present work demonstrates the utility of computational chemistry in providing support for the identification of unknown compounds. Copyright
Short-step synthesis of droloxifene via the three-component coupling reaction among aromatic aldehyde, cinnamyltrimethylsilane, and β-chlorophenetole
Sano, Yoshiyuki,Shiina, Isamu
, p. 1631 - 1635 (2007/10/03)
A short-step route for the preparation of droloxifene has been established via the novel three-component coupling reaction among 3-pivaloyloxybenzaldehyde, cinnamyltrimethylsilane, and β-chlorophenetole, the successive installation of the side-chain part, and the base-induced migration of the double bond. The present synthesis of tetra-substituted ethylene moieties is a widely applicable strategy for producing a variety of SERMs (selective estrogen receptor modulators) and SARMs (selective androgen receptor modulators), such as tamoxifen, raloxifene, and other compounds that can lead to new drugs.
Hydroxy derivatives of tamoxifen
Foster,Jarman,Leung,McCague,Leclercq,Devleeschouwer
, p. 1491 - 1497 (2007/10/02)
In the exploration of the structural features that affect the RBA (binding affinity for the estrogen receptor of rat uterus relative to that of estradiol) in the tamoxifen [trans-(Z)-1-[4-(dimethylamino)ethoxy]-1,2-diphenyl-1-butene] series, several derivatives variously substituted in the 1-phenyl group have been synthesized. In the tamoxifen series, the descriptors E and Z, which define the configuration of the geometrical isomers and depend on the location and nature of substituents in the aromatic moieties and the ethyl group, may vary, although the relative configuration (cis or trans) does not. In order to avoid confusion the terms cis and trans will be used in this paper to refer to the relative positions of the 4-[2-(dimethylamino)ethoxy]phenyl and ethyl (or hydroxyethyl, hydroxypropyl, or bromo) substituents attached to the ethene moiety]. The final stage of each synthesis involved acid-catalyzed dehydration of a tertiary alcohol, and, in contrast to the known 3- and 4-hydroxy derivatives which were obtained as near-equimolar cis,trans mixtures, only the trans forms of the 2-hydroxy, 2-methyl, 2,4-dihydroxy, and 4-hydroxy-2-methyl derivatives were obtained. Also, in contrast to the trans forms of the 3- and 4-hydroxy derivatives, which are readily equilibrated to cis,trans mixtures, the trans 2-hydroxy derivative could not be isomerized. Tamoxifen and 2-methyltamoxifen had similar RBA's (~1% of that of E2), but that of 2-hydroxytamoxifen was much lower (0.1%). Introduction of a second hydroxyl group (2,4-dihydroxy derivative) enhanced the RBA, and for the 4-hydroxy-2-methyl derivative, the RBA and growth inhibitory activity against the MCF-7 mammary tumor cell line in vitro were high and comparable to those of 4-hydroxytamoxifen, a metabolite of the parent drug. Tamoxifen derivatives hydroxylated at positions 3 or 4 of the 1-butene moiety and the 5-hydroxy-1-pentene analogue were also synthesized, but they had very low RBA values.
