PMID- 23735831
OWN - NLM
STAT- MEDLINE
DCOM- 20140121
LR  - 20240514
IS  - 1464-3391 (Electronic)
IS  - 0968-0896 (Print)
IS  - 0968-0896 (Linking)
VI  - 21
IP  - 14
DP  - 2013 Jul 15
TI  - Recent syntheses of PI3K/Akt/mTOR signaling pathway inhibitors.
PG  - 4063-91
LID - S0968-0896(13)00422-7 [pii]
LID - 10.1016/j.bmc.2013.04.083 [doi]
AB  - This review focuses on the syntheses of PI3K/Akt/mTOR inhibitors that have been 
      reported outside of the patent literature in the last 5years but is largely 
      centered on synthetic work reported in 2011 and 2012. While focused on syntheses 
      of inhibitors, some information on in vitro and in vivo testing of compounds is 
      also included. Many of these reported compounds are reversible, competitive 
      adenosine triphosphate (ATP) binding inhibitors, so given the structural 
      similarities of many of these compounds to the adenine core, this review presents 
      recent work on inhibitors based on where the synthetic chemistry was started, 
      that is, inhibitor syntheses which started with purines/pyrimidines are followed 
      by inhibitor syntheses which began with pyridines, pyrazines, azoles, and 
      triazines then moves to inhibitors which bear no structural resemblance to 
      adenine: liphagal, wortmannin and quercetin analogs. The review then finishes 
      with a short section on recent syntheses of phosphotidyl inositol (PI) analogs 
      since competitive PI binding inhibitors represent an alternative to the 
      competitive ATP binding inhibitors which have received the most attention.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Welker, Mark E
AU  - Welker ME
AD  - Department of Chemistry, Wake Forest University, PO Box 7486, Winston-Salem, NC 
      27109, USA. welker@wfu.edu
FAU - Kulik, George
AU  - Kulik G
LA  - eng
GR  - R01 CA118329/CA/NCI NIH HHS/United States
GR  - R01CA118329/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20130509
PL  - England
TA  - Bioorg Med Chem
JT  - Bioorganic & medicinal chemistry
JID - 9413298
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Humans
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Kinase Inhibitors/*chemical synthesis/chemistry/*pharmacology
MH  - Proto-Oncogene Proteins c-akt/*antagonists & inhibitors
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
PMC - PMC3711139
MID - NIHMS478764
EDAT- 2013/06/06 06:00
MHDA- 2014/01/22 06:00
PMCR- 2014/07/15
CRDT- 2013/06/06 06:00
PHST- 2013/04/23 00:00 [received]
PHST- 2013/04/30 00:00 [accepted]
PHST- 2013/06/06 06:00 [entrez]
PHST- 2013/06/06 06:00 [pubmed]
PHST- 2014/01/22 06:00 [medline]
PHST- 2014/07/15 00:00 [pmc-release]
AID - S0968-0896(13)00422-7 [pii]
AID - 10.1016/j.bmc.2013.04.083 [doi]
PST - ppublish
SO  - Bioorg Med Chem. 2013 Jul 15;21(14):4063-91. doi: 10.1016/j.bmc.2013.04.083. Epub 
      2013 May 9.