A new chemical series was identified via high-throughput screening as having antiproliferative activity on DU-145 human prostate carcinoma cell line (hit compound potency - 2.9 microM). Medicinal chemistry optimization of two peripheral diversity vectors of the hit molecule, independently, led to SAR generalizations and identification of the 'best' moieties. The latter were merged in a single compound that exhibited an over 100-fold better potency than the hit compound. For the most potent compounds it was confirmed that the observed antiproliferative potency was not associated with the compounds' non-specific cytotoxicity.

Spirocyclic 1-oxa-9-azaspiro[5.5]undecan-4-amine scaffold was explored as a basis for the design of potential inhibitors of soluble epoxide hydrolase (sEH). Synthesis and testing of the initial SAR-probing library followed by biochemical testing against sEH allowed nominating a racemic lead compound (±)-22. The latter showed remarkable (> 0.5 mM) solubility in aqueous phosphate buffer solution, unusually low (for sEH inhibitors) lipophilicity as confirmed by experimentally determined logD of 0.99, and an excellent oral bioavailability in mice (as well as other pharmacokinetic characteristics). Individual enantiomer profiling revealed that the inhibitory potency primarily resided with the dextrorotatory eutomer (+)-22 (IC 4.99 ± 0.18 nM). For the latter, a crystal structure of its complex with a C-terminal domain of sEH was obtained and resolved. These data fully validate (+)-22 as a new non-racemic advanced lead compound for further development as a potential therapeutic agent for use in such areas as cardiovascular disease, inflammation and pain.

A four-center, three-component Ugi-type reaction of a variety of keto acids, Boc-or Cbz-protected hydrazine, and isocyanides offers a simple and high-yielding access to cyclic products containing an N-aminolactam unit. The latter are shown to form consistently an intramolecular hydrogen bond leading to a -turn-like secondary structure. The possibility of integrating such N-aminolactam units (without disruption of the folded structure) into pseudotripeptide fragments is demonstrated.The successful use of keto (as well as aldehydo) carboxylic acids as bifunctional inputs for isocyanide-based multicomponent reactions (IMCR) was demonstrated by Harrimann 1 and Ugi. 2 This four-center, three-component process was found to provide a simple and efficient (as well as atom-economical) entry into novel dipeptoid lactam structures. The strategy has been aggressively exploited to give rise to a wide variety of novel small-and medium-size lactamtype heterocyclic scaffolds 3 and validated, in general, the use of bifunctional reagents in IMCR as a source of significant product diversity. 4

The overall power conversion efficiency of the polymer solar cell based on P13 (DPP/BTQx ratio is 1/1) showed the highest value of 9.20% with a Voc of 0.86 V, Jsc of 15.74 mA cm−2, and FF of 0.68.

We synthesized two novel ultra low bandgap donor-acceptor (D-A) copolymers (E(g) ≤ 1.2 eV), containing the thiadiazoloquinoxaline unit as the main electron accepting unit (A) and benzodithiophene (BDT) and dithienosilole (DTS) as different donor units (D), denoted as P1 and P2, respectively, using the cross-coupling Stille reaction. The copolymers possess light absorption ranging from UV (350 nm) to near-IR (1300 nm) with optical bandgaps of 1.16 eV and 1.08 eV, respectively. Quantum-chemical calculations and experimental data were compared for proposing a more detailed concept for the optical and electronic properties of these copolymers which can be used as donors for polymer solar cells (PSCs). The PSCs based on optimized P1:PC71BM and P2:PC71BM showed overall power conversion efficiencies (PCEs) of 4.32% and 3.48%, respectively. Although P2 possesses a broad absorption coverage of up to 1300 nm, the lower PCE may be attributed to the low J(sc), due to the poor driving force for exciton dissociation, since the LUMO offset with PC71BM is less than 0.3 eV. The PCE has been significantly increased to 7.27% and 6.68% for solvent vapor annealing (SVA) treated P1:PC71BM and P2:PC71BM active layers, respectively. This improvement arises from the appropriate nanoscale morphology and an increase in hole mobility, induced by the SVA treatment of the active layers.