- SERINE/THREONINE PAK1 INHIBITORS
-
Compounds having the formula I wherein A, Z, R1a, R1b, R2, R3, R4, R5, R6, R7, R9, R10, Ra, Rb and n are as defined herein are inhibitors of PAK1. Also disclosed are compositions and methods for treating cancer and hyperproliferative disorders.
- -
-
-
- Orthogonal aerobic conversion of N-benzyl amidoximes to 1,2,4-oxadiazoles or quinazolinones
-
Concise synthesis of 1,2,4-oxadiazoles was achieved by heating N-benzyl amidoximes with K3PO4 in DMF at 60°C under an O 2 atmosphere via benzylic C-H oxygenation. On the other hand, aerobic treatment of N-benzyl amidoximes
- Zhang, Feng-Lian,Wang, Yi-Feng,Chiba, Shunsuke
-
supporting information
p. 6003 - 6007
(2013/09/12)
-
- In vitro structure-activity relationship and in vivo characterization of 1-(aryl)-3-(4-(amino)benzyl)urea transient receptor potential vanilloid 1 antagonists
-
The synthesis and structure-activity relationship of 1-(aryl)-3-(4-(amino) benzyl)urea transient receptor potential vanilloid 1 (TRPV1) antagonists are described. A variety of cyclic amine substituents are well tolerated at the 4-position of the benzyl group on compounds containing either an isoquinoline or indazole heterocyclic core. These compounds are potent antagonists of capsaicin activation of the TRPV1 receptor in vitro. Analogues, such as compound 45, have been identified that have good in vivo activity in animal models of pain. Further optimization of 45 resulted in compound 58 with substantially improved microsome stability and oral bioavailability, as well as in vivo activity.
- Perner, Richard J.,DiDomenico, Stanley,Koenig, John R.,Gomtsyan, Arthur,Bayburt, Erol K.,Schmidt, Robert G.,Drizin, Irene,Guo, Zhu Zheng,Turner, Sean C.,Jinkerson, Tammie,Brown, Brian S.,Keddy, Ryan G.,Lukin, Kurill,McDonald, Heath A.,Honore, Prisca,Mikusa, Joe,Marsh, Kennan C.,Wetter, Jill M.,St. George, Karen,Jarvis, Michael F.,Faltynek, Connie R.,Lee, Chih-Hung
-
p. 3651 - 3660
(2008/02/12)
-