Anti-tumor activity of novel biisoquinoline derivatives against breast cancers.

Breast cancer is classified into three groups according to its expression of hormone/growth factor receptors: (i) estrogen receptor (ER) and progesterone receptor (PR)-positive; (ii) human epidermal growth factor receptor 2 (HER2)-positive; and (iii) ER, PR, and HER2-negative (triple-negative). A series of methoxy-substituted biisoquinoline compounds have been synthesized as a potential chemotherapeutic agent for the triple-negative breast cancers which are especially challenging to manage. Structure activity relationship study revealed that rigid 6,6'-dimethoxy biisoquinoline imidazolium compound (1c, DH20931) exhibited the significant growth inhibitory effects on both triple-positive and triple-negative human breast cancer cell lines with IC50 in the range of 0.

Isoquinoline-based chiral monodentate N-heterocyclic carbenes.

C(1)-symmetric isoquinoline-based chiral diaminocarbene ligands (MIQ) have been developed to block three quadrants of the metal coordination sphere, complementing C(2)-symmetric biisoquinoline-based ligands (BIQ). MIQ-Cu complexes catalyzed conjugate borylation of various α,β-unsaturated amides in good yields (82-99%) and enantioselectivities (75-87% ee).

In situ generation of novel acyclic diaminocarbene-copper complex.

A novel acyclic diaminocarbene-copper complex appears to be generated from a chloroamidinium salt and Cu(I)-thiophenecarboxylate in the presence of Grignard reagent based on (13)C NMR studies and is a highly efficient catalyst for S(N)2'-allylic alkylation.

Development of biisoquinoline-based chiral diaminocarbene ligands: enantioselective SN2' allylic alkylation catalyzed by copper-carbene complexes.

Chiral biisoquinoline-based diaminocarbene ligands (BIQ) were designed to create a chiral environment extended toward the metal center, which was confirmed by an X-ray structure. The concise ligand synthesis is highlighted by a modified Bischler-Napieralski cyclization of bisamides prepared from readily available chiral phenethylamines, and allows easy variation of the stereodifferentiating groups. The cyclohexyl-BIQ-copper complex is an efficient catalyst for enantioselective SN2' allylic alkylation with Grignard reagents showing SN2' regioselectivity higher than 5:1 and enantioselectivity in the range of 68-77% ee.