A simple, straightforward, and highly efficient multicomponent one-pot synthesis of a pharmaceutically interesting diverse kind of functionalized 2-amino-3-cyano-4H-pyrans and pyran-annulated heterocycles has been developed based on a low-cost and environmentally benign commercially available urea as a novel organo-catalyst. The reaction occurs via tandem Knoevenagel–cyclocondensation of aldehydes, malononitrile, and C–H-activated acidic compounds in aqueous ethanol at room temperature. Following this protocol, it was possible to synthesize 2-amino-3-cyano-pyrano[3,2-c]chromen-5(4H)-ones (4aa–4al), 2-amino-3-cyano-pyrano[4,3-b]pyran-5(4H)-ones (4ba–4be), 2-amino-3-cyano-7,8-dihydro-4H-chromen-5(6H)-one (4ca–4cr), 1H-pyrano[2,3-d]pyrimidine-2,4(3H,5H)-diones (4da–4dd), 2-amino-3-cyano-5,10-dioxo-5,10-dihydro-4H-benzo[g]chromenes (4ea–4ec), 2-amino-3-cyano-4H-pyrans (4fa–4fh), and 1,4-dihydropyrano[2,3-c]pyrazoles (4ga–4gb). The salient features of the present protocol are mild reaction conditions, excellen...

Facile and One-Pot Access to Diverse and Densely Functionalized 2-Amino-3-cyano-4H-pyrans and Pyran-Annulated Heterocyclic Scaffolds via an Eco-Friendly Multicomponent Reaction at Room Temperature Using Urea as a Novel Organo-Catalyst

Potassium phthalimide-N-oxyl: a novel, efficient, and simple organocatalyst for the one-pot three-component synthesis of various 2-amino-4H-chromene derivatives in water

Comprehensive investigation of steel corrosion inhibition at macro/micro level by ecofriendly green corrosion inhibitor in 15% HCl medium.

Asymmetric organocatalytic reactions by bifunctional amine-thioureas

In our continuing effort to discover and develop apoptosis inducing 4-aryl-4H-chromenes as novel anticancer agents, we explored the structure-activity relationship (SAR) of alkyl substituted pyrrole fused at the 7,8-positions. A methyl group substituted at the nitrogen in the 7-position of the pyrrole ring led to a series of potent apoptosis inducers with potency in the low nanomolar range. These compounds were also found to be low nanomolar or subnanomolar inhibitors of cell growth, and they inhibited tubulin polymerization, indicating that methylation of the 7-position nitrogen does not change the mechanism of action of these chromenes. Compound 2d was identified as a highly potent apoptosis inducer with an EC50 value of 2 nM and a highly potent inhibitor of cell growth with a GI50 value of 0.3 nM in T47D cells.

Discovery of 4-Aryl-4H-chromenes as a New Series of Apoptosis Inducers Using a Cell- and Caspase-Based High Throughput Screening Assay. 4. Structure–Activity Relationships of N-Alkyl Substituted Pyrrole Fused at the 7,8-Positions

Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 2. Structure–activity relationships of the 7- and 5-, 6-, 8-positions

As a continuation of our efforts to discover and develop the apoptosis-inducing 4-aryl-4H-chromenes as novel anticancer agents, we explored the SAR of fused rings at the 7,8-positions. It was found that a five-member aromatic ring, such as pyrrolo with nitrogen at either the 7- or 9-position, is preferred. A six-member aromatic ring, such as benzo or pyrido, also led to potent compounds. The SAR of the 4-aryl group was found to be similar for chromenes with a fused ring at the 7,8-positions. These compounds were found to inhibit tubulin polymerization, indicating that cyclization of the 7,8-positions into a ring does not change the mechanism of action. Compound 2h was identified to be a highly potent apoptosis inducer with an EC 50 of 5 nM and a highly potent inhibitor of cell proliferation with a GI 50 of 8 nM in T47D cells.

Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 3. Structure-activity relationships of fused rings at the 7,8-positions.

Lifen Xu

Papers

Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 2. Structure–activity relationships of the 7- and 5-, 6-, 8-positions

Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 3. Structure-activity relationships of fused rings at the 7,8-positions.

Addition of polyethylene glycol for the synthesis of anatase-free TS-1 zeolites with excellent catalytic activity in 1-hexene epoxidation