134414-14-5Relevant academic research and scientific papers
Design and synthesis of fluorescently labeled steroidal antiestrogens
Hanson, Robert N.,Gajadeera, Nisal
, p. 39 - 46 (2019/02/28)
A set of derivatives of 11β-(4-oxyphenyl)estradiol were prepared as potential fluorescent imaging agents for the evaluation of the estrogen receptor. The compounds were designed based on the established affinity and selectivity of 11β-[4-(dimethylethoxy)p
ESTROGEN RECEPTOR IMAGING AGENTS
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Page/Page column 16, (2014/07/07)
Compounds useful for molecular imaging of cells expressing estrogen receptors are provided. Also provided are intermediates for making the compounds and methods of making the compounds using a modular convergent strategy. Further, methods of making the intermediates are described, as well as methods of diagnosing disease in a subject by using the compounds as imaging agents.
Synthesis and preliminary evaluation steroidal antiestrogen-geldanamycin conjugates
Adam Hendricks,Hanson, Robert N.,Amolins, Michael,Mihelcic, John M.,Blagg, Brian S.
, p. 3635 - 3639 (2013/07/19)
Three novel steroidal antiestrogen-geldanamycin conjugates were prepared using a convergent strategy. The antiestrogenic component utilized the 11β-(4-functionalized-oxyphenyl) estradiol scaffold, while the geldanamycin component was derived by replacement of the 17-methoxy group with an appropriately functionalized amine. Ligation was achieved in high yield using azide alkyne cyclization reactions. Evaluation of the products against two breast cancer cell lines indicated that the conjugates retained significant antiproliferative activity.
Design, synthesis, and initial biological evaluation of a steroidal anti-estrogen - Doxorubicin bioconjugate for targeting estrogen receptor-positive breast cancer cells
Dao, Kinh-Luan,Sawant, Rupa R.,Hendricks, J. Adam,Ronga, Victoria,Torchilin, Vladimir P.,Hanson, Robert N.
experimental part, p. 785 - 795 (2012/07/28)
As part of our program to develop breast cancer specific therapeutic agents, we have synthesized a conjugate agent that is a conjugate of the steroidal anti-estrogen and the potent cytotoxin doxorubicin. In this effort, we employed a modular assembly appr
Convergent synthesis of a steroidal antiestrogen-mitomycin C hybrid using "click" chemistry
Hanson, Robert N.,Hua, Edward,Labaree, David,Hochberg, Richard B.,Proffitt, Kyle,Essigmann, John M.,Croy, Robert G.
, p. 8501 - 8508 (2012/11/14)
A convergent synthesis of a novel estrogen receptor-targeted drug hybrid was developed based on structures of the potent anti-proliferative mitomycin C and the steroidal anti-estrogen RU 39411. The steroidal antiestrogen was prepared with an azido-triethylene glycoloxy linker while the mitomycin C derivative (porfirimycin) incorporated a complementary 7-N-terminal alkyne. The two components were ligated using the Huisgen [3 + 2] cycloaddition ("click") reaction. Preliminary biological assays demonstrated that the final hybrid compound retained both potent anti-estrogenic and anti-proliferative activities.
Synthesis of a spin-labeled anti-estrogen as a dynamic motion probe for the estrogen receptor ligand binding domain
Hendricks, J. Adam,Gullà, Stefano V.,Budil, David E.,Hanson, Robert N.
supporting information; experimental part, p. 1743 - 1746 (2012/04/10)
The preparation and characterization of a novel nitroxide spin probe based on a steroidal anti-estrogen is described. The probe 5 demonstrated very high binding affinity for both the alpha and beta isoforms of the estrogen receptor-ligand binding domain. EPR spectrometric studies demonstrate conformational constraints for the ligand, consistent with the nitroxyl moiety occupying a position just beyond the receptor-solvent interface.
Synthesis and evaluation of 11β-(4-Substituted phenyl) estradiol analogs: Transition from estrogen receptor agonists to antagonists
Hanson, Robert N.,Hua, Edward,Adam Hendricks,Labaree, David,Hochberg, Richard B.
experimental part, p. 3768 - 3780 (2012/08/28)
Introduction: As part of our program to develop estrogen receptor (ER) targeted imaging and therapeutic agents we chose to evaluate 11β-substituted estradiol analogs as a representative scaffold. Previous synthetic studies provided an entry into this class of compounds and other work indicated that 11β-(substituted aryl) estradiol analogs were potent antagonists of the ER. Little information existed about the specific structural features involved in the transition from agonism to antagonism for the 11β-aryl estradiol analogs or their potential as scaffolds for drug conjugation. Methods: We prepared and characterized a series of 11β-(4-Substituted phenyl) estradiol analogs using modifications of existing synthetic methods. The new compounds, as well as standard steroidal agonists and antagonists, were evaluated as competitive ligands for the ERβ-LBD. Functional assays used the induction of alkaline phosphatase in Ishikawa cells to determine potency of the compounds as ER agonists or antagonists. Results: The synthetic strategy successfully generated a series of compounds in which the 4-substituent was sequentially modified from hydroxyl to methoxy to azidoethoxy/N,N-dimethylaminoethoxy and eventually to a prototypical 1,4-naphthoquinone-containing moiety. The new compounds all retained high relative binding affinity (RBA) for the ERα-LBD, ranging from 13-83% that of estradiol. No subtype selectivity was observed. More importantly, the transition from agonist to antagonist activity occurs at the 4-methoxy stage where the compound is a mixed antagonist. More notably, antagonism appeared to be more dependent upon the size of the 11β-substituent than upon the nature of the terminal group Conclusions: We have developed a synthetic strategy that provides facile access to potent 11β-(4-substituted phenyl) estradiol analogs. The resultant compounds retain high affinity for the ERα-LBD and, more importantly, demonstrate potent antagonist activity in cells. Large functionalities distal to the 11β-phenyl ring had little additional effect on either affinity or efficacy, suggesting the incorporation of diverse imaging or biologically active groups can be attached without significantly compromising the ER-binding capacity. Future studies are in progress to exploit the 11β-aryl estradiol analogs as potential drug delivery systems and imaging agents.
STEROIDAL ANTI-HORMONE HYBRIDS
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Page/Page column 47-48, (2010/08/08)
Disclosed are novel compounds and compositions for inhibition of androgen and estrogen receptor signaling, methods for inhibiting androgen signaling, methods for inhibiting estrogen signaling, methods for inhibiting the interaction between a co-regulatory protein and an androgen or estrogen receptor, and methods for treating cancer.
11-PHOSPHOROUS STEROID DERIVATIVES USEFUL AS PROGESTERONE RECEPTOR MODULATORS
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Page/Page column 19, (2010/11/28)
The present invention is directed to novel 11-phosphorous steroid derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by a progesterone or glucocorticoid receptor.
19-nor steroids having a thiocarbonated chain in position 11beta, their preparation process and the intermediates of this process, and the intermediates of this process, their use as medicaments and compositions
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, (2008/06/13)
Compounds of formula (I), wherein R17and R′17are such that: either R17and R′17together form ketone, hydrazono, oxime or methylene, or R17is hydroxyl, hydroxymethyl or acyloxy and R′17is hydrogen, alkyl or optionally substitued alkenyl or alkynyl; R3is hydrogen or alkyl; R16is hydrogen, halogen or alkyl; m is 0, 1 or 2; X, Y and Z are such that: X is methylene, arylene or arylenoxy bonded to the steroid by a carbon atom; Y is a saturated or unsaturated straight or branched aliphatic chain which is optionally interrupted by oxygen; and Z is aryl, arylalkyl or straight or branched alkyl; addition salts thereof, a preparation method therefor, medicinal uses thereof, compositions containing said compounds, and resulting novel intermediates.
