Antibody-drug conjugates (ADCs) represent an important class of emerging cancer therapeutics. Recent ADC development efforts highlighted the use of pyrrolobenzodiazepine (PBD) dimer payload for the treatment of several cancers. We identified the isoquinolidinobenzodiazepine (IQB) payload (D211), a new class of PBD dimer family of DNA damaging payloads.
View Article and Find Full Text PDFA series of novel 2-piperidinopiperidine thiadiazoles were synthesized and evaluated as new leads of histamine H3 receptor antagonists. The 4-(5-([1,4'-bipiperidin]-1'-yl)-1,3,4-thiadiazol-2-yl)-2-(pyridin-2-yl)morpholine (5u) displayed excellent potency and ex vivo receptor occupancy. Compound 5u was also evaluated in vivo for antidiabetic efficacy in STZ diet-induced obesity type 2 diabetic mice for 2 or 12 days.
View Article and Find Full Text PDFThe first examples of efficient catalytic asymmetric conjugate addition (ACA) of alkylzincs to trisubstituted cyclic enones is disclosed. These Cu-catalyzed reactions proceed efficiently with five- and seven-membered ring substrates to afford the desired products in >/=95% ee. Intermediate enolates can be trapped with alkyl halides to generate a quaternary stereogenic center.
View Article and Find Full Text PDFCu-catalyzed enantioselective conjugate additions to acyclic aliphatic enones are reported. The resulting enolates may be functionalized intra- and intermolecularly, leading to the formation of an additional C-C bond. The utility of the present method is not limited to reactions involving Et2Zn; a variety of alkylzincs may be used.
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