No abstract

The strain-promoted click 1,3-dipolar cycloaddition reactions involving azides and cyclooctynes for the synthesis of triazoles offer the advantage of being able to be performed in biological settings via copper-free chemistries. While strained reagents conjugated to optical dyes and radiometal conjugates have been reported, cyclooctyne reagents labeled with fluorine-18 ( 18 F) and radiochemically evaluated in a copper-free click reaction have yet to be explored. This report describes the conversion of a bifunctional azadibenzocyclooctyne (ADIBO) amine to the 18 Flabeled cyclooctyne 4, the subsequent fast copper-free 1,3-dipolar cycloaddition reaction with alkyl azides at 37°C (>70% radiochemical conversion in 30 min), and biological evaluations (serum stability of >95% at 2 h). These findings demonstrate the excellent reactivity of the 18 F-labeled cyclooctyne 4 with readily available azides that will allow future work focusing on rapid copper-free in vitro and in vivo click chemistries for PET imaging using 18 F-labeled cyclooctyne derivatives of ADIBO.

An effective route to benzimidazo[2,1-b]quinazolin-12(5H)-ones from commercially available o-aryl isothiocyanate esters and o-phenylenediamines is reported. This method accommodates a variety of substituents on either starting material and proceeds under microwave irradiation in the presence of barium hydroxide, conditions that do not hydrolyze methyl ester substituents. The pharmacologically pertinent benzimidazoquinazolinone heterocycle is delivered in excellent yield and purity via both solution- and solid-phase protocols, the latter involving traceless release from the resin.

An efficient synthesis is reported that delivers in 5 steps in 52% overall yield a new structurally simplified fluorescent K+ sensor with improved K+ sensitivity and selectivity over existing K+ sensors. The synthesis procedure utilizes a new template-directed oxidative C-N bond forming macrocyclization reaction, and reports new approaches to Pd(0), Sandmeyer-like and metal-free aminoarylations, as well as organotitanium additions to vinylogous sulfonates.

The cell surface receptor alpha 4 beta 1 integrin, activated constitutively in lymphoma, can be targeted with the bisaryl urea peptidomimetic antagonist 1 (LLP2A). However, concerns on its preliminary pharmacokinetic (PK) profile provided an impetus to change the pharmacophore from a bisaryl urea to a 2-arylaminobenzimidazole moiety, resulting in improved solubility while maintaining picomolar potency [5 (KLCA4); IC50 = 305 pM]. With exceptional solubility, this finding has the potential for improving PK to help diagnose and treat lymphomas.