Boron clusters for medicinal drug design: Selective estrogen receptor modulators bearing carborane

@article{Endo2003BoronCF,
  title={Boron clusters for medicinal drug design: Selective estrogen receptor modulators bearing carborane},
  author={Yasuyuki Endo and Tomohiro Yoshimi and Chisato Miyaura},
  journal={Pure and Applied Chemistry},
  year={2003},
  volume={75},
  pages={1197 - 1205}
}
The molecular shape and hydrophobicity of dicarba-closo -dodecaboranes may allow a new medical application as biologically active molecules. Recently, we have developed potent estrogen receptor (ER) agonists bearing carborane cage. The most potent compound (BE120) exhibited activity at least several times greater than that of 17 beta-estradiol in luciferase reporter gene assay and ER alpha binding. We also designed and synthesized estrogen antagonists on the basis of the structure of BE120, and… 

Figures from this paper

Synthesis and biological evaluation of novel m-carborane-containing estrogen receptor partial agonists as SERM candidates.
TLDR
Novel m-carborane-containing selective estrogen receptor modulator (SERM) candidates are designed and synthesized using previously reported m- carborane -containing ER partial agonist 1 as the lead compound and showed the highest relative binding affinity and lowest maximal efficacy in MCF-7 cell proliferation assay.
Novel estrogen receptor (ER) modulators containing various hydrophobic bent-core structures.
TLDR
Compound 9 showed greater binding affinity than 4 in ER-binding assay using [6,7-(3)H]-17β-estradiol and was a more effective partial agonist than4 in MCF-7 cell proliferation assay, and appears to be a promising candidate as a selective ER modulator (SERM).
Facile Docking and Scoring Studies of Carborane Ligands with Estrogen Receptor
Closo-carborane has been considered as an efficient boron-carrier for boron neutron capture therapy (BNCT) and an attractive surrogate of lipophilic phenyl or cyclohexyl ring in drug design. Despite
Design and Synthesis of Novel Breast Cancer Therapeutic Drug Candidates Based upon the Hydrophobic Feedback Approach of Antiestrogens
TLDR
Based upon hydrophobic feedback approaches, novel sulfur-containing ERα modulators (4 and 5) as breast cancer therapeutic drug candidates and docking simulation studies of compound 5d with the ERα BD revealed that the largeHydrophobic moiety of compounds 5d fit well into the hydrophilic pocket of the ER α LBD and that the sulfur atom of compound5d formed a sulfur–π interaction with the amino acid residue His524 of theERα LBD.
Design and synthesis of carborane-containing estrogen receptor-beta (ERβ)-selective ligands.
TLDR
The p-carborane cage in 8a and 8b appears to play a crucial role in the increased ERβ selectivity, as well as key amino acid residues that influence ER-subtype selectivity.
Preparation and evaluation of carborane analogues of tamoxifen.
TLDR
A stereoselective synthesis of closo carborane analogues of tamoxifen was developed where the products represent a new approach to developing metabolically robust SERMs, and the Z isomer was able to inhibit cell proliferation better than tamoxIFen in an E2 free environment.
Enhanced estrogen receptor beta (ERβ) selectivity of fluorinated carborane-containing ER modulators.
TLDR
A series of fluorinated carborane-containing selective estrogen receptor modulator compounds are designed and synthesized as candidate ERβ-selective ligands to alter the agonist/antagonist activity balance and the estrogen receptor (ER) α/β subtype selectivity.
Novel estrogen receptor (ER) modulators: carbamate and thiocarbamate derivatives with m-carborane bisphenol structure.
TLDR
Novel carborane-containing estrogen receptor (ER) modulators, carbamate and thiocarbamate derivatives 5 and 6, were designed and synthesized based upon the m-carborane bisphenol skeleton, and the (thio)carbamates can be classified as an agonist group.
Synthesis and biological evaluation of p-carborane bisphenols and their derivatives: structure-activity relationship for estrogenic activity.
TLDR
1, 12-Bis(4-hydroxyphenyl)-1,12-dicarba-closo-dodecaborane 4a showed potent estrogenic activity, approaching that of 17beta-estradiol, in transactivation assay and MCF-7 cell proliferation-enhancing activity.
The Use of Carboranes in Cancer Drug Development
TLDR
A review of applications of carboranes to the medicinal chemistry of cancer to highlight some important examples in the literature where carborane containing pharmacophores were successfully translated into small animal models.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 14 REFERENCES
Advances in Drug Research
TLDR
The concept of emergence dissolvence in drug research, B. Testa, S. Batra and A.P. Bhaduri.
Pure and Applied Chemistry
The proceedings of the Eleventh International Congress of Pure and Applied Chemistry, held in London from July 17 to 24, covered a wide variety of topics of medical interest. Joint meetings between
Advances in Drug Research
Advances in Drug ResearchVol. 1. Edited by N. J. Harper and Alma B. Simmonds. Pp. x + 209. (London: Academic Press, Inc. (London), Ltd.; New York: Academic Press, Inc., 1964.) 50s.
Chem. Biol
  • Chem. Biol
  • 2001
Application of boron clusters for medicinal drug design
  • BioMed. Chem. Lett
  • 1999
BioMed. Chem. Lett
  • BioMed. Chem. Lett
  • 1999
BioMed. Chem. Lett
  • BioMed. Chem. Lett
  • 1999
J. Med. Chem
  • J. Med. Chem
  • 1999
Effects of 1 and 12 on the uterine weight (A) and BMD of femurs (B) in OVX mice
  • Drug Research”,
  • 1997
Proc. Natl. Acad. Sci. USA 93
  • Proc. Natl. Acad. Sci. USA 93
  • 1996
...
1
2
...