The work in this paper describes the optimization of the 3-(3-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine chemical series as potent, selective allosteric inhibitors of AKT kinases, leading to the discovery of ARQ 092 (21a). The cocrystal structure of compound 21a bound to full-length AKT1 confirmed the allosteric mode of inhibition of this chemical class and the role of the cyclobutylamine moiety. Compound 21a demonstrated high enzymatic potency against AKT1, AKT2, and AKT3, as well as potent cellular inhibition of AKT activation and the phosphorylation of the downstream target PRAS40. Compound 21a also served as a potent inhibitor of the AKT1-E17K mutant protein and inhibited tumor growth in a human xenograft mouse model of endometrial adenocarcinoma.

A convergent, enantioselective total synthesis of (+)-guanacastepene N was developed that features a 7-endo Heck cyclization as the key step. In the course of this synthesis, short syntheses of the enantiomerically pure cyclopentenone and cyclohexene building blocks 5 and 6, which constitute A and C ring fragments of guanacastepene N, were developed. These fragments were linked by a challenging conjugate addition reaction that also generated the C11 quaternary carbon stereocenter. Regioselective 7-endo Heck cyclization gave rise to a tricyclic intermediate, which was elaborated to complete the first total synthesis of guanacastepene N and the second enantioselective total synthesis of a guanacastepene natural product.

To investigate the role of the 2'-hydroxy group at the C-13 side chain of docetaxel in the antitumor activity, we prepared several 2',2'-difluoro derivatives of docetaxel and evaluated their cytotoxicity against mouse leukemia and human tumor cell lines and their microtubule disassembly-inhibitory activity. These analogues were prepared by esterification of protected 10-deacetylbaccatin III (21) with appropriate alpha, alpha-difluorinated carboxylic acids (Charts 1 and 2). Among these 2',2'-difluorodocetaxel derivatives, 2',2'-difluorodocetaxel (23b) was approximately 3-10 times as active as 2'-fluorodocetaxel (29a) in terms of cytotoxicity. In addition, the 3'-(2-furyl) (23h) and 3'-(2-pyrrolyl) (23p) analogues showed activity comparable or superior to that of docetaxel (2).

Metal halide perovskites (MHPs) are plausible candidates for practical p-type semiconductors. However, in thin film transistor (TFT) applications, both 2D PEA 2 SnI 4 and 3D FASnI 3 MHPs have different drawbacks. In 2D MHP, the TFT mobility is seriously reduced by grain-boundary issues, whereas 3D MHP has an uncontrollably high hole density, which results in quite a large threshold voltage (V th ). To overcome these problems, a new concept based on a 2D-3D core-shell structure is herein proposed. In the proposed structure, a 3D MHP core is fully isolated by a 2D MHP, providing two desirable effects as follows. (i) V th can be independently controlled by the 2D component, and (ii) the grain-boundary resistance is significantly improved by the 2D/3D interface. Moreover, SnF 2 additives are used, and they facilitate the formation of the 2D/3D core-shell structure. Consequently, a high-performance p-type Sn-based MHP TFT with a field-effect mobility of ≈25 cm 2 V −1 s −1 is obtained. The voltage gain of a complementary metal oxide semiconductor (CMOS) inverter comprising an n-channel InGaZnO x TFT and a p-channel Sn-MHP TFT is ≈200 V/V at V DD = 20 V. Overall, the proposed 2D/3D core-shell structure is expected to provide a new route for obtaining high-performance MHP TFTs.

The hydride ion (H–) is a unique anionic species that exhibits high reactivity and chemical energy. H– conductors are key materials to utilize advantages of H– for applications, such as chemical reactors and energy storage systems. However, low H– conductivity at room temperature (RT) in current H– conductors limit their applications. In this study, we report a H– conductivity of ∼1 mS cm–1 at RT, which is higher by 3 orders of magnitude than that of the best conductor, in lightly oxygen-doped lanthanum hydride, LaH3–2x O x with x < 0.25. The oxygen concentration (x) is crucial in achieving fast H– conduction near RT; the low activation barrier of 0.3–0.4 eV is attained for x < 0.25, above which it increases to 1.2–1.3 eV. Molecular dynamics simulations using neural-network potential successfully reproduced the observed activation energy, revealing the presence of mobile and immobile H–.