Next-generation epidermal growth factor receptor (EGFR) inhibitors against the d746-750/T790M/C797S mutation were discovered through two-track virtual screening and de novo design. A number of nanomolar inhibitors were identified using 2-aryl-4-aminoquinazoline as the molecular core and the modified binding energy function involving a proper dehydration term, which provides important structural insight into the key principles for high inhibitory activities against the d746-750/T790M/C797S mutant. Furthermore, some of these EGFR inhibitors showed a greater than 1000-fold selectivity for the d746-750/T790M/C797S mutant over the wild type, as well as nanomolar activity against the mutant.

A strategy for visible-light-induced site-selective C–H acylation of pyridinium salts was developed by employing N-methoxy- or N-aminopyridinium salts, offering a powerful synthetic tool for accessing highly valuable C2- and C4-acylated pyridines. The methoxy or amidyl radicals photocatalytically generated from the pyridinium salts can undergo hydrogen atom abstraction from readily available aldehydes to form acyl radicals, which can engage in addition to pyridinium substrates. Remarkably, the use of N-methoxypyridinium salts preferentially gives the C2-acylated pyridines, and the site selectivity can be switched from C2 to C4 by using N-aminopyridinium salts. The utility of this transformation was further demonstrated by the late-stage functionalization of complex biorelevant molecules and by application of acyl radicals to photocatalytic radical cascades.

In this paper, our aim is finding the term of generalized Euler polynomials. We also obtain some identities and relations involving the Bernoulli numbers, the Euler numbers and the Stirling numbers.

A new approach has elaborated on the conversion of γ-lactones to the corresponding NH γ-lactams that can serve as γ-lactone bioisosteres. This approach consists of reductive C–O cleavage and an Ir-catalyzed C–H amidation, offering a powerful synthetic tool for accessing a wide range of valuable NH γ-lactam building blocks starting from γ-lactones. The synthetic utility was further demonstrated by the late-stage transformation of complex bioactive molecules and the asymmetric transformation.

Let K be an imaginary quadratic field of discriminant less than or equal to −7 and K (N) be its ray class field modulo N for an integer N greater than 1. We prove that the singular values of certain Siegel functions generate K (N) over K by extending the idea of our previous work. These generators are not only the simplest ones conjectured by Schertz, but also quite useful in the matter of computation of class polynomials. We indeed give an algorithm to find all conjugates of such generators by virtue of the works of Gee and Stevenhagen.

Intravitreal injection (IVI) is a common technology which is used to treat ophthalmic diseases inside eyeballs by delivering various drugs into the vitreous cavity using hypodermic needles. However, in some cases, there are possible side effects such as ocular tissue damage due to repeated injection or eyeball infection through the hole created during the needle retraction process. The best scenario of IVI is a one-time injection of drugs without needle retraction, keeping the system of the eyeball closed. Microneedles (MNs) have been applied to ocular tissues over 10 years, and no serious side effects on ocular tissue due to MN injection have been reported. Therefore, a self-plugging MN (SPM) is developed to perform intraocular drug delivery and to seal the scleral puncture simultaneously. The SPMs are fabricated by a thermal drawing process and then coated with a polymeric carrier of drugs and a hydrogel-based scleral plugging component. Each coated functional layer is characterized and demonstrated by in vitro and ex vivo experiments. Finally, in vivo tests using a porcine model confirms prompt sealing of SPM and sustained intraocular drug delivery.

Many mathematicians have studied various relations beweenEuler number En, Bernoulli number Bn and Genocchi number Gn (see [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]). They have found numerous important applications in number theory. Howard, T.Agoh, S.-H.Rim have studied Genocchi numbers, Bernoulli numbers, Euler numbers and polynomials of these numbers [1,5,9,15]. T.Kim, M.Cenkci, C.S.Ryoo, L. Jang have studied the q-extension of Euler and Genocchi numbers and polynomials [6,8,10,11,14,17]. In this paper, our aim is introducing and investigating an extension term of generalized Euler polynomials. We also obtain some identities and relations involving the Euler numbers and the Euler polynomials, the Genocchi numbers and Genocchi polynomials.

We investigate two kinds of Fricke families, those consisting of Fricke functions and those consisting of Siegel functions. In terms of their special values we then generate ray class fields of imaginary quadratic fields over the Hilbert class fields, which are related to the Lang–Schertz conjecture.