PMID- 20303263
OWN - NLM
STAT- MEDLINE
DCOM- 20100812
LR  - 20211203
IS  - 1464-3405 (Electronic)
IS  - 0960-894X (Linking)
VI  - 20
IP  - 8
DP  - 2010 Apr 15
TI  - Novel benzofuran-3-one indole inhibitors of PI3 kinase-alpha and the mammalian 
      target of rapamycin: hit to lead studies.
PG  - 2586-90
LID - 10.1016/j.bmcl.2010.02.082 [doi]
AB  - A series of benzofuran-3-one indole phosphatidylinositol-3-kinases (PI3K) 
      inhibitors identified via HTS has been prepared. The optimized inhibitors possess 
      single digit nanomolar activity against p110alpha (PI3K-alpha), good 
      pharmaceutical properties, selectivity versus p110gamma (PI3K-gamma), and tunable 
      selectivity versus the mammalian target of rapamycin (mTOR). Modeling of 
      compounds 9 and 32 in homology models of PI3K-alpha and mTOR supports the 
      proposed rationale for selectivity. Compounds show activity in multiple cellular 
      proliferation assays with signaling through the PI3K pathway confirmed via 
      phospho-Akt inhibition in PC-3 cells.
CI  - Copyright 2010 Elsevier Ltd. All rights reserved.
FAU - Bursavich, Matthew G
AU  - Bursavich MG
AD  - Medicinal Chemistry, Chemical Sciences, Wyeth Research, Pearl River, NY 10965, 
      USA.
FAU - Brooijmans, Natasja
AU  - Brooijmans N
FAU - Feldberg, Lawrence
AU  - Feldberg L
FAU - Hollander, Irwin
AU  - Hollander I
FAU - Kim, Stephen
AU  - Kim S
FAU - Lombardi, Sabrina
AU  - Lombardi S
FAU - Park, Kaapjoo
AU  - Park K
FAU - Mallon, Robert
AU  - Mallon R
FAU - Gilbert, Adam M
AU  - Gilbert AM
LA  - eng
PT  - Journal Article
DEP - 20100223
PL  - England
TA  - Bioorg Med Chem Lett
JT  - Bioorganic & medicinal chemistry letters
JID - 9107377
RN  - 0 (Benzofurans)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
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 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Benzofurans/chemistry/*pharmacology
MH  - Cell Line, Tumor
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*antagonists & inhibitors
MH  - Models, Molecular
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Kinase Inhibitors/chemistry/*pharmacology
MH  - Protein Serine-Threonine Kinases/*antagonists & inhibitors
MH  - Structure-Activity Relationship
MH  - TOR Serine-Threonine Kinases
EDAT- 2010/03/23 06:00
MHDA- 2010/08/13 06:00
CRDT- 2010/03/23 06:00
PHST- 2010/01/17 00:00 [received]
PHST- 2010/02/18 00:00 [revised]
PHST- 2010/02/19 00:00 [accepted]
PHST- 2010/03/23 06:00 [entrez]
PHST- 2010/03/23 06:00 [pubmed]
PHST- 2010/08/13 06:00 [medline]
AID - S0960-894X(10)00282-9 [pii]
AID - 10.1016/j.bmcl.2010.02.082 [doi]
PST - ppublish
SO  - Bioorg Med Chem Lett. 2010 Apr 15;20(8):2586-90. doi: 10.1016/j.bmcl.2010.02.082. 
      Epub 2010 Feb 23.