96227-40-6Relevant academic research and scientific papers
Crystal structures of PI3Kα complexed with PI103 and its derivatives: New directions for inhibitors design
Zhao, Yanlong,Zhang, Xi,Chen, Yingyi,Lu, Shaoyong,Peng, Yuefeng,Wang, Xiang,Guo, Chengliang,Zhou, Aiwu,Zhang, Jingmiao,Luo, Yu,Shen, Qiancheng,Ding, Jian,Meng, Linghua,Zhang, Jian
supporting information, p. 138 - 142 (2014/03/21)
The phosphatidylinositol 3-kinase (PI3K) signaling pathway plays important roles in cell proliferation, growth, and survival. Hyperactivated PI3K is frequently found in a wide variety of human cancers, validating it as a promising target for cancer therapy. We determined the crystal structure of the human PI3Kα-PI103 complex to unravel molecular interactions. Based on the structure, substitution at the R1 position of the phenol portion of PI103 was demonstrated to improve binding affinity via forming a new H-bond with Lys802 at the bottom of the ATP catalytic site. Interestingly, the crystal structure of the PI3Kα-9d complex revealed that the flexibility of Lys802 can also induce additional space at the catalytic site for further modification. Thus, these crystal structures provide a molecular basis for the strong and specific interactions and demonstrate the important role of Lys802 in the design of novel PI3Kα inhibitors.
Synthesis of antibiotics WS 5995 A and C and related compounds by palladium-catalyzed coupling of 2-bromonaphthoquinones with organostannanes
Echavarren,Tamayo,Cardenas
, p. 6075 - 6083 (2007/10/02)
The synthesis of arylnaphthoquinones can be performed simply by using as the key reaction the Pd(0)- and Cu(I)-catalyzed coupling of arylstannanes with 2-bromonaphthoquinones as the electrophiles. The palladium-catalyzed coupling reaction is general and allows for the functionalization of the unprotected quinone nucleus with alkyl, alkenyl, and aryl substituents. The coupling process tolerates the presence of a chelated peri hydroxyl and steric crowding of a 2,6-disubstituted arylstannane, although the preparation of a 2,6,2',6'-tetrasubstituted biaryl by coupling of 2-bromo-3,5-bis(acetyloxy)-1,4-naphthoquinone as the electrophile with 2,6-disubstituted arylstannanes was unsuccessful. The syntheses of quinonoid antibiotics WS 5995 A and C was accomplished by using this method as the key step. Benz[b]phenanthridinone 1, hypothetical intermediate in the biosynthesis of benz[b]phenanthridine alkaloids, was also prepared from antibiotic WS 5995 C or by addition of ammonia to the 2-aryl-1,4-naphthoquinone 41 followed by heterocyclization.
A New Synthesis of Defucogilvocarcin M
Hart, David J.,Merriman, Gregory H.
, p. 5093 - 5096 (2007/10/02)
A convergent synthesis of the title compound is described.The synthesis revolves around a MAD-mediated coupling of oxazoline 11 and naphthoquinone ketal 16 and requires eight steps via the longest linear sequence.
Synthesis of Antibiotic SS-228R. Strong Base Induced Cycloaddition of Homophthalic Anhydrides
Tamura, Yasumitsu,Fukata, Fumio,Sasho, Manabu,Tsugoshi, Teruhisa,Kita, Yasuyuki
, p. 2273 - 2277 (2007/10/02)
Two types of naphthacenediones, 1,6,7-trihydroxy-9-methyl- (2) and 1,6,10-trihydroxy-8-methyl-naphthacene-5,12-diones (4), were prepared by the cycloaddition of 8-methoxy-6-methyl- (9) and 5-methoxy-7-methylhomophthalic anhydrides (10) with 2-bromojuglone
