Predicting key example compounds in competitors' patent applications using structural information alone

In drug discovery programs, predicting key example compounds in competitors' patent applications is important work for scientists working in the same or in related research areas. In general, medicinal chemists are responsible for this work, and they attempt to guess the identity of key compounds based on information provided in patent applications, such as biological data, scale of reaction, and/or optimization of the salt form for a particular compound. However, this is sometimes made difficult by the lack of such information. This paper describes a method for predicting key compounds in competitors' patent applications by using only structural information of example compounds. Based on the assumption that medicinal chemists usually carry out extensive structure--activity relationship (SAR) studies around key compounds, the method identifies compounds located at the centers of densely populated regions in the patent examples' chemical space, as represented by Extended Connectivity Fingerprints (ECFPs). For the validation of the method, a total of 30 patents containing structures of launched drugs were selected to test whether or not the method is able to predict key compounds (the launched drugs). In 17 out of the 30 patents (57%), the method was able to successfully predict the key compounds. The result indicates that our method could provide an alternative approach to predicting key compounds in cases where the conventional medicinal chemist's approach does not work well. This method could also be used as a complement to the traditional medicinal chemist's approach.     

Tandem migration-carboalkoxylation of o-isocyanophenyl acetals leading to benzoxazoles

An efficient approach to benzoxazoles via tandem migration-carboalkoxylation of o-isocyanophenyl acetals has been developed. Both a Lewis acid and base are essential for this reaction, and the BF(3)·OEt(2)/2,4,6-collidine combination is the best choice for cooperative transformation.     

Palladium doping of magic gold cluster Au38(SC2H4Ph)24: formation of Pd2Au36(SC2H4Ph)24 with higher stability than Au38(SC2H4Ph)24

A phenylethanethiolate-protected Pd(2)Au(36)(SC(2)H(4)Ph)(24) cluster, which is a two-Pd atom-doped cluster of the well studied magic gold cluster Au(38)(SC(2)H(4)Ph)(24), was synthesized in high purity and its stability was investigated. The results demonstrate that Pd(2)Au(36)(SC(2)H(4)Ph)(24) is more stable than Au(38)(SC(2)H(4)Ph)(24) against degradation in solution and core etching by thiols.     

A novel photocatalytic microreactor bundle that does not require an electric power source

A new type of photocatalytic reactor was developed. Capillaries coated on the inside with photocatalytic materials induced an effective photocatalytic reaction by pulling up a solution under the action of capillary forces; no electric pump was required for the replacement of the chemicals, due to the concentration gradient generated in the capillaries.     

Rhodium-catalyzed enantioselective hydrogenation of unsaturated phosphonates by ClickFerrophos ligands

Newly developed ClickFerrophos II ligands were applied in the hydrogenation of α,β-unsaturated phosphonates. The use of a rhodium/ClickFerrophos II catalyst was examined in the hydrogenation of functionalized α,β-unsaturated phosphonates and was revealed to be effective for β-alkyl-β-aryl or β-dialkyl phosphonates, (Z)-β-enolester phosphonates, and α-phenylethenyl phosphonates, producing the corresponding chiral phosphonates in good yields with high enantioselectivities (up to 96% ee).     

Polycationic gramicidin s analogues with both high antibiotic activity and very low hemolytic activity

The substitution of each constituent amino acid residue of gramicidin S (GS), cyclo(-Val(1,1')-Orn(2,2')-Leu(3,3')-D-Phe(4,4')-Pro(5,5')-)(2) with Lys residue indicated that each side chain structure of the constituent amino acid residues affect largely the antibiotic activity and hemolytic activity of GS. Further, the substitution of D-Phe(4,4') and Pro(5,5') residues with basic amino acid residues as a Lys residue results the high antibiotic activity and the very low hemolytic activity. Thus, we have found novel positions on the scaffold of GS at D-Phe(4,4') and Pro(5,5') residues whose modification will significantly increase the therapeutic index.     

Theoretical study of absorption and fluorescence spectra of firefly luciferin in aqueous solutions

The absorption and fluorescence spectra of firefly luciferin, which is an analog of oxyluciferin, are investigated by performing the density functional theory (DFT) calculations, especially focusing on the experimentally unassigned peaks. Time-dependent DFT calculations are performed for the excited states of firefly luciferin and its conjugate acids and bases. We find that (1) the peaks in the experimental absorption spectra correspond to the excited states of not only (6'O(-), 4COO(-)) and (6'OH, 4COO(-)), but also (6'OH, 4COOH) and (6'OH, 3H(+), 4COOH); (2) the peaks in the experimental fluorescence spectra correspond to the excited states of not only (6'O(-), 4COO(-)), but also (6'OH, 4COO(-)), (6'O(-), 4COOH), (6'OH, 4COOH) and (6'OH, 3H(+), 4COOH); (3) the unassigned peak near 400 nm in the experimental absorption spectra at pH 1 is assigned to the absorption from the equilibrium ground state to the first excited state of (6'OH, 3H(+), 4COOH); and (4) the unassigned peak at 610 nm in the experimental fluorescence spectra corresponds to the transition from the equilibrium first excited state to the ground state of (6'OH, 4COO(-)).