PMID- 20797855
OWN - NLM
STAT- MEDLINE
DCOM- 20110224
LR  - 20211203
IS  - 1464-3405 (Electronic)
IS  - 0960-894X (Linking)
VI  - 20
IP  - 19
DP  - 2010 Oct 1
TI  - PKI-179: an orally efficacious dual phosphatidylinositol-3-kinase 
      (PI3K)/mammalian target of rapamycin (mTOR) inhibitor.
PG  - 5869-73
LID - 10.1016/j.bmcl.2010.07.104 [doi]
AB  - A series of mono-morpholino 1,3,5-triazine derivatives (8a-8q) bearing a 
      3-oxa-8-azabicyclo[3.2.1]octane were prepared and evaluated for PI3-kinase/mTOR 
      activity. Replacement of one of the bis-morpholines in lead compound 1 (PKI-587) 
      with 3-oxa-8-azabicyclo[3.2.1]octane and reduction of the molecular weight 
      yielded 8m (PKI-179), an orally efficacious dual PI3-kinase/mTOR inhibitor. The 
      in vitro activity, in vivo efficacy, and PK properties of 8m are discussed.
CI  - Copyright (c) 2010. Published by Elsevier Ltd.
FAU - Venkatesan, Aranapakam M
AU  - Venkatesan AM
AD  - Chemical Sciences, PGRD, Pfizer Inc, Legacy Wyeth Research, 401 N. Middletown Rd, 
      Pearl River, NY 10965, USA. venkata699@gmail.com
FAU - Chen, Zecheng
AU  - Chen Z
FAU - dos Santos, Osvaldo
AU  - dos Santos O
FAU - Dehnhardt, Christoph
AU  - Dehnhardt C
FAU - Santos, Efren Delos
AU  - Santos ED
FAU - Ayral-Kaloustian, Semiramis
AU  - Ayral-Kaloustian S
FAU - Mallon, Robert
AU  - Mallon R
FAU - Hollander, Irwin
AU  - Hollander I
FAU - Feldberg, Larry
AU  - Feldberg L
FAU - Lucas, Judy
AU  - Lucas J
FAU - Yu, Ker
AU  - Yu K
FAU - Chaudhary, Inder
AU  - Chaudhary I
FAU - Mansour, Tarek S
AU  - Mansour TS
LA  - eng
PT  - Journal Article
DEP - 20100730
PL  - England
TA  - Bioorg Med Chem Lett
JT  - Bioorganic & medicinal chemistry letters
JID - 9107377
RN  - 0 (Morpholines)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Triazines)
RN  - 0 (Tropanes)
RN  - 8W8T17847W (Urea)
RN  - CNN7Y60164 
      (1-(4-(4-(3-oxa-8-azabicyclo(3.2.1)octan-8-yl)-6-morpholino-1,3,5-triazin-2-yl)phenyl)-3-(pyridin-4-yl)urea)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Cell Line, Tumor
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - Morpholines/chemical synthesis/*chemistry/pharmacokinetics
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Kinase Inhibitors/chemical synthesis/*chemistry/pharmacokinetics
MH  - Structure-Activity Relationship
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
MH  - Triazines/chemical synthesis/*chemistry/pharmacokinetics
MH  - Tropanes/chemistry
MH  - Urea/*analogs & derivatives/chemical synthesis/chemistry/pharmacokinetics
MH  - Xenograft Model Antitumor Assays
EDAT- 2010/08/28 06:00
MHDA- 2011/02/25 06:00
CRDT- 2010/08/28 06:00
PHST- 2010/05/18 00:00 [received]
PHST- 2010/07/21 00:00 [revised]
PHST- 2010/07/26 00:00 [accepted]
PHST- 2010/08/28 06:00 [entrez]
PHST- 2010/08/28 06:00 [pubmed]
PHST- 2011/02/25 06:00 [medline]
AID - S0960-894X(10)01073-5 [pii]
AID - 10.1016/j.bmcl.2010.07.104 [doi]
PST - ppublish
SO  - Bioorg Med Chem Lett. 2010 Oct 1;20(19):5869-73. doi: 10.1016/j.bmcl.2010.07.104. 
      Epub 2010 Jul 30.