With the aim of discovering novel IDO1 inhibitors, a combined similarity search and molecular docking approach was employed to the discovery of 32 hit compounds. Testing the screened hit compounds has led to several novel submicromolar inhibitors. Especially for compounds LVS-019 with cyanopyridine scaffold, showed good IDO1 inhibitory activity. To discover more compounds with similar structures to LVS-019, a shape-based model was then generated on the basis of it and the second-round virtual screening was carried out leading to 23 derivatives. Molecular docking studies suggested a possible binding mode of LVS-019, which provides a good starting point for the development of cyanopyridine scaffold compounds as potent IDO1 inhibitor. To improve potency of these hits, we further designed and synthesised another 14 derivatives of LVS-019. Among these compounds, LBJ-10 showed improved potency compared to the hits and displayed comparable potency to the control GDC-0919 analogue. LBJ-10 can serve as ideal leads for further modifications as IDO1 inhibitors for cancer treatment.

An organocatalytic domino aza/oxa-Michael/1,6-addition reaction of ortho-tosylaminophenyl or ortho-hydroxyphenyl-substituted para-quinone methides and ynals has been developed. In the presence of 20 mol % of morpholine, this unprecedented cascade reaction occurs readily in good yield (up to 99%), providing a highly efficient synthetic approach to synthetically valuable 1,4-dihydroquinolines and 4H-chromenes.

A palladium-catalyzed asymmetric [3+2] cycloaddition reaction of methyleneindolinones with vinylethylene carbonates has been successfully developed, which provides a highly efficient method for the synthesis of structurally diverse 3,3′-tetrahydrofuryl spirooxindoles in high yields (≤99%) with excellent stereoselectivities (>20:1 dr, ≤99% ee). Furthermore, this methodology shows a wide substrate scope and high utility in diversity-oriented synthesis.

A facile one-pot synthesis has been developed through alkylation/acylation of ortho-tosylaminophenyl-substituted para-quinone methides followed by an intramolecular 1,6-conjugate addition and oxidation sequence.

Inhibiting the polarization or survival of tumor-associated macrophages through blocking CSF-1/CSF-1R signal transduction has become a promising strategy for cancer immunotherapy. Herein, a series of (Z)-1-(3-((1H-pyrrol-2-yl)­methylene)-2-oxoindolin-6-yl)-3-(isoxazol-3-yl)­urea derivatives were designed, synthesized, and evaluated as novel and orally highly effective CSF-1R inhibitors for colorectal cancer immunotherapy. Among these derivatives, compound 21 was found to possess excellent CSF-1R inhibitory activity (IC50 = 2.1 nM) and potent antiproliferative activity against colorectal cancer cells. Compound 21 inhibited the progression of colorectal cancer by suppressing the migration of macrophages, reprograming M2-like macrophages to the M1 phenotype, and enhancing the antitumor immunity. More importantly, compound 21, as a single agent, showed significantly superior in vivo anticolorectal cancer efficacy over PLX3397, highlighting a promising candidate for the immunotherapy of colorectal cancer.