PMID- 25893045
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150420
LR  - 20200929
IS  - 1948-5875 (Print)
IS  - 1948-5875 (Electronic)
IS  - 1948-5875 (Linking)
VI  - 6
IP  - 4
DP  - 2015 Apr 9
TI  - Discovery of a Novel Series of Thienopyrimidine as Highly Potent and Selective 
      PI3K Inhibitors.
PG  - 434-8
LID - 10.1021/ml5005014 [doi]
AB  - Inhibition of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of 
      rapamycin (mTOR) signaling pathway provides a promising new approach for cancer 
      therapy. Through a rational design, a novel series of thienopyrimidine was 
      discovered as highly potent and selective PI3K inhibitors. These thienopyrimidine 
      derivatives were demonstrated to bear nanomolar PI3Kalpha inhibitory potency with 
      over 100-fold selectivity against mTOR kinase. The lead compounds 6g and 6k 
      showed good developability profiles in cell-based proliferation and ADME assays. 
      In this communication, their design, synthesis, structure-activity relationship, 
      selectivity, and some developability properties are described.
FAU - Han, Fangbin
AU  - Han F
AD  - PKUCare Pharmaceutical R&D Center, A106-109, Biotech Innovation Works , No. 29 
      Life Science Park Road, Changping District, Beijing 102206, P. R. China.
FAU - Lin, Songwen
AU  - Lin S
AD  - PKUCare Pharmaceutical R&D Center, A106-109, Biotech Innovation Works , No. 29 
      Life Science Park Road, Changping District, Beijing 102206, P. R. China.
FAU - Liu, Peng
AU  - Liu P
AD  - PKUCare Pharmaceutical R&D Center, A106-109, Biotech Innovation Works , No. 29 
      Life Science Park Road, Changping District, Beijing 102206, P. R. China.
FAU - Liu, Xiujie
AU  - Liu X
AD  - PKUCare Pharmaceutical R&D Center, A106-109, Biotech Innovation Works , No. 29 
      Life Science Park Road, Changping District, Beijing 102206, P. R. China.
FAU - Tao, Jing
AU  - Tao J
AD  - PKUCare Pharmaceutical R&D Center, A106-109, Biotech Innovation Works , No. 29 
      Life Science Park Road, Changping District, Beijing 102206, P. R. China.
FAU - Deng, Xiaobing
AU  - Deng X
AD  - PKUCare Pharmaceutical R&D Center, A106-109, Biotech Innovation Works , No. 29 
      Life Science Park Road, Changping District, Beijing 102206, P. R. China.
FAU - Yi, Chongqin
AU  - Yi C
AD  - PKUCare Pharmaceutical R&D Center, A106-109, Biotech Innovation Works , No. 29 
      Life Science Park Road, Changping District, Beijing 102206, P. R. China.
FAU - Xu, Heng
AU  - Xu H
AD  - PKUCare Pharmaceutical R&D Center, A106-109, Biotech Innovation Works , No. 29 
      Life Science Park Road, Changping District, Beijing 102206, P. R. China.
LA  - eng
PT  - Journal Article
DEP - 20150311
PL  - United States
TA  - ACS Med Chem Lett
JT  - ACS medicinal chemistry letters
JID - 101521073
PMC - PMC4394348
OTO - NOTNLM
OT  - dual inhibitors
OT  - mammalian target of rapamycin
OT  - phosphoinositide 3-kinase
OT  - selective PI3K inhibitors
OT  - thienopyrimidines
COIS- The authors declare no competing financial interest.
EDAT- 2015/04/22 06:00
MHDA- 2015/04/22 06:01
PMCR- 2016/04/09
CRDT- 2015/04/21 06:00
PHST- 2014/12/05 00:00 [received]
PHST- 2015/03/11 00:00 [accepted]
PHST- 2015/04/21 06:00 [entrez]
PHST- 2015/04/22 06:00 [pubmed]
PHST- 2015/04/22 06:01 [medline]
PHST- 2016/04/09 00:00 [pmc-release]
AID - 10.1021/ml5005014 [doi]
PST - epublish
SO  - ACS Med Chem Lett. 2015 Mar 11;6(4):434-8. doi: 10.1021/ml5005014. eCollection 
      2015 Apr 9.