PMID- 26298498
OWN - NLM
STAT- MEDLINE
DCOM- 20160524
LR  - 20150910
IS  - 1464-3405 (Electronic)
IS  - 0960-894X (Linking)
VI  - 25
IP  - 19
DP  - 2015 Oct 1
TI  - Design and synthesis of carborane-containing estrogen receptor-beta 
      (ERbeta)-selective ligands.
PG  - 4174-8
LID - S0960-894X(15)00831-8 [pii]
LID - 10.1016/j.bmcl.2015.08.007 [doi]
AB  - Candidates for highly selective estrogen receptor-beta (ERbeta) ligands (6a-c, 7a-c, 
      8a and 8b) were designed and synthesized based on carborane-containing ER ligands 
      1 and 2 as lead compounds. Among them, p-carboranylcyclohexanol derivatives 8a 
      and 8b exhibited high ERbeta selectivity in competitive binding assay: for example, 
      8a showed 56-fold selectivity for ERbeta over ERalpha. Docking studies of 8a and 8b with 
      the ERalpha and ERbeta ligand-binding domains (LBDs) suggested that the p-carborane cage 
      of the ligands is located close to key amino acid residues that influence 
      ER-subtype selectivity, that is, Leu384 in the ERalpha LBD and Met336 in the ERbeta LBD. 
      The p-carborane cage in 8a and 8b appears to play a crucial role in the increased 
      ERbeta selectivity.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Ohta, Kiminori
AU  - Ohta K
AD  - Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 
      Komatsushima, Aoba-ku, Sendai 981-8558, Japan. Electronic address: 
      k-ohta@tohoku-pharm.ac.jp.
FAU - Ogawa, Takumi
AU  - Ogawa T
AD  - Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 
      Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
FAU - Oda, Akifumi
AU  - Oda A
AD  - Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, 
      Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.
FAU - Kaise, Asako
AU  - Kaise A
AD  - Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 
      Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
FAU - Endo, Yasuyuki
AU  - Endo Y
AD  - Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 
      Komatsushima, Aoba-ku, Sendai 981-8558, Japan. Electronic address: 
      yendo@tohoku-pharm.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150807
PL  - England
TA  - Bioorg Med Chem Lett
JT  - Bioorganic & medicinal chemistry letters
JID - 9107377
RN  - 0 (Boranes)
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Ligands)
SB  - IM
MH  - Boranes/chemical synthesis/chemistry/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - *Drug Design
MH  - Estrogen Receptor beta/*antagonists & inhibitors
MH  - Humans
MH  - Ligands
MH  - Molecular Dynamics Simulation
MH  - Molecular Structure
MH  - Structure-Activity Relationship
OTO - NOTNLM
OT  - Carborane
OT  - Docking study
OT  - Estrogen receptor
OT  - Subtype selectivity
EDAT- 2015/08/25 06:00
MHDA- 2016/05/25 06:00
CRDT- 2015/08/24 06:00
PHST- 2015/07/09 00:00 [received]
PHST- 2015/08/01 00:00 [revised]
PHST- 2015/08/04 00:00 [accepted]
PHST- 2015/08/24 06:00 [entrez]
PHST- 2015/08/25 06:00 [pubmed]
PHST- 2016/05/25 06:00 [medline]
AID - S0960-894X(15)00831-8 [pii]
AID - 10.1016/j.bmcl.2015.08.007 [doi]
PST - ppublish
SO  - Bioorg Med Chem Lett. 2015 Oct 1;25(19):4174-8. doi: 10.1016/j.bmcl.2015.08.007. 
      Epub 2015 Aug 7.