- Inhibitor of heat shock factor 1, and preparation method and application of inhibitor
-
The invention provides an inhibitor of a heat shock factor 1 (HSF1) and an application of the inhibitor, particularly a compound as shown in a formula I or pharmaceutically-acceptable salt of the compound. The compound has excellent HSF1 restraining activity and tumor resisting effects. The invention further provides a medical composition containing the compound and an application of the medical composition in the respect of restraining HSF1.
- -
-
-
- Design and synthesis of minimalist terminal alkyne-containing diazirine photo-crosslinkers and their incorporation into kinase inhibitors for cell- and tissue-based proteome profiling
-
Less is more: A minimalist "clickable" photo-crosslinker (see scheme) was incorporated with numerous small-molecule kinase inhibitors. The resulting probes were used for both in vitro (cell lysates) and in situ (live cells) proteome profiling, for large-scale identification of their potential cellular kinase targets and shows improved outcomes over previous probes. Copyright
- Li, Zhengqiu,Hao, Piliang,Li, Lin,Tan, Chelsea Y. J.,Cheng, Xiamin,Chen, Grace Y. J.,Sze, Siu Kwan,Shen, Han-Ming,Yao, Shao Q.
-
p. 8551 - 8556
(2013/09/12)
-
- INHIBITORS OF THE BMP SIGNALING PATHWAY
-
The present invention provides small molecule inhibitors of BMP signaling. These compounds may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation.
- -
-
-
- Microwave-assisted protocols for the expedited synthesis of pyrazolo[1,5-a] and [3,4-d]pyrimidines
-
General, high-yielding MAOS protocols for the expedited synthesis of functionalized pyrazolo[1,5-a]pyrimidines and pyrazolo[3,4-b]pyrimidines, as well as their pyrazole precursors, are described amenable to an iterative analogue library synthesis strategy for lead optimization.
- Daniels, R. Nathan,Kim, Kwangho,Lebois, Evan P.,Muchalski, Hubert,Hughes, Mary,Lindsley, Craig W.
-
p. 305 - 310
(2008/09/17)
-
- Structure-activity relationship study of bone morphogenetic protein (BMP) signaling inhibitors
-
A structure-activity relationship study of dorsomorphin, a previously identified inhibitor of SMAD 1/5/8 phosphorylation by bone morphogenetic protein (BMP) type 1 receptors ALK2, 3, and 6, revealed that increased inhibitory activity could be accomplished by replacing the pendent 4-pyridine ring with 4-quinoline. The activity contributions of various nitrogen atoms in the core pyrazolo[1,5-a]pyrimidine ring were also examined by preparing and evaluating pyrrolo[1,2-a]pyrimidine and pyrazolo[1,5-a]pyridine derivatives. In addition, increased mouse liver microsome stability was achieved by replacing the ether substituent on the pendent phenyl ring with piperazine. Finally, an optimized compound 13 (LDN-193189 or DM-3189) demonstrated moderate pharmacokinetic characteristics (e.g., plasma t1/2 = 1.6 h) following intraperitoneal administration in mice. These studies provide useful molecular probes for examining the in vivo pharmacology of BMP signaling inhibition.
- Cuny, Gregory D.,Yu, Paul B.,Laha, Joydev K.,Xing, Xuechao,Liu, Ji-Feng,Lai, Carol S.,Deng, Donna Y.,Sachidanandan, Chetana,Bloch, Kenneth D.,Peterson, Randall T.
-
supporting information; scheme or table
p. 4388 - 4392
(2009/04/06)
-
- Optimization of a pyrazolo[1,5-a]pyrimidine class of KDR kinase inhibitors: improvements in physical properties enhance cellular activity and pharmacokinetics.
-
We have introduced solubilizing functionality to a 3,6-disubstituted pyrazolo[1,5-a]pyrimidine series of KDR kinase inhibitors to improve the physical properties of these compounds. The addition of a basic side-chain to the 6-aryl ring, introduction of 3-pyridyl groups, and most significantly, incorporation of a 4-pyridinonyl substituent at the 6-position of the core are modifications that maintain and often enhance the intrinsic potency of this class of inhibitors. Moreover, the improvements in physical properties result in marked increases in cellular activity and more favorable pharmacokinetics in rats. The synthesis and SAR of these compounds are described.
- Fraley, Mark E,Rubino, Robert S,Hoffman, William F,Hambaugh, Scott R,Arrington, Kenneth L,Hungate, Randall W,Bilodeau, Mark T,Tebben, Andrew J,Rutledge, Ruth Z,Kendall, Richard L,McFall, Rosemary C,Huckle, William R,Coll, Kathleen E,Thomas, Kenneth A
-
p. 3537 - 3541
(2007/10/03)
-