Efficacy and safety of immune checkpoint inhibitors combined with anti-VEGF therapy in the treatment of unresectable or advanced liver cancer: a systematic review.

OBJECTIVE: This study aimed to evaluate the clinical effects and safety of immune checkpoint inhibitors (ICIs) combined with anti-VEGF therapy for the treatment of unresectable or advanced liver cancer. METHOD: Related databases were searched from inception to December 2022 to identify randomized controlled studies and clinical trials that evaluated the combination of ICIs and anti-VEGF therapy for the treatment of unresectable liver cancer. The outcome index was extracted and analyzed by RevMan5.4.ResultsA total of 8 clinical trials were included. In terms of efficacy, the intervention group had longer OS and PFS for unresectable or advanced liver cancer than the control group. In terms of safety, (1) Adverse events of all grades showed that the combination treatment led to significantly higher risks of urinary system disorders, cardiovascular system disorder, blood system disorders and liver dysfunction than the control treatment. Compared with monotherapy, the combination treatment led to lower risks of gastrointestinal disorders. (2) Adverse events above grade 3 showed that, compared with the control treatment, the combination treatment led to significantly higher risks of urinary system disorders, blood systeam disorders, cardiovascular system disorders and liver dysfunction. Additionally, compared with monotherapy, the combination treatment led to significantly lower risks of gastrointestinal disorders. CONCLUSIONS: ICIs combined with anti-VEGF therapy exerts significant clinical effects in patients with unresectable or advanced liver cancer, can prolong the survival of these patients and can improve their quality of life. However, clinical attention should be given to the occurrence of adverse reactions.

Biomimetic Carbene Cascades Enabled Imine Derivative Migration from Carbene-Bearing Thiocarbamates.

Inspired by the body circulation of Omeprazole (irreversible proton pump inhibitor), we disclose the carbene-triggered cascades for the synthesis of 2-aminobenzofuran derivatives from N-sulfonyl-1,2,3-triazoles or benzothioazole-bearing thiocarbamates, which represents an unprecedented imine derivative migration process. Furthermore, the desulfurizing reagent-free Barton-Kellogg-type reactions starting from N-sulfonyl-1,2,3-triazoles have also been achieved for the first time, and elemental sulfur is confirmed as a byproduct during this transformation. Both experimental data and DFT calculations further thoroughly explained the unique reactivity.

Preparation of anthranils via chemoselective oxidative radical cyclization of 3-(2-azidoaryl) substituted propargyl alcohols.

In the presence of K2S2O8 and HOAc, 3-(2-azidoaryl) substituted propargyl alcohols can go through chemoselective oxidative radical cyclizations to give a pool of anthranils based on Meyer-Schuster rearrangement. It's proposed that the cyclizations were triggered exclusively by the direct attack of oxygen radicals on the azides. The weak N-O bonds in anthranils could be easily cleaved in the presence of transition metal catalysts and went through aminations with 2-oxo-2-phenylacetic acid and iodobenzene.

Gold-Catalyzed Radical-Involved Intramolecular Cyclization of Internal N-Propargylamides for the Construction of 5-Oxazole Ketones.

An expedient strategy for the synthesis of 5-oxazole ketones was developed via homogeneous gold catalysis with 4-MeO-TEMPO as an oxidant. The desired 5-oxazole ketones were achieved in decent yields with an excellent functional group compatibility under mild conditions. The current protocol also represents the first example for merging a gold catalyst and radical chemistry in one-pot synthesis with internal N-propargylamides.

Copper(I)-Catalyzed Chemoselective Reduction of Benzofuran-2-yl Ketones to Alcohols with B2pin2 via a Domino-Borylation-Protodeboronation Strategy.

A novel copper(I)-catalyzed chemoselective reduction of the carbonyls of benzofuran-2-yl ketones over furan rings with B2pin2 has been developed. This reaction proceeded under mild conditions. High valuable secondary alcohol derivatives of benzofurans were obtained in good to excellent yields with a broad substrate scope. The mechanistic studies suggested that a domino-borylation-protodeboronation pathway was involved in this reaction.

Umpolung of protons from H2O: a metal-free chemoselective reduction of carbonyl compounds via B2pin2/H2O systems.

H2O is routinely described as a proton donor, however, in the presence of diboron compounds, the umpolung reaction of H2O under metal-free conditions was successfully developed, which could afford hydride species, leading to a highly efficient and chemoselective reduction of C[double bond, length as m-dash]O bonds. This strategy exhibits excellent chemoselectivities toward carbonyl groups in the presence of ester, olefin, halogen, thioether, sulfonyl, cyano as well as heteroaromatic groups.

Diboron-Assisted Palladium-Catalyzed Transfer Hydrogenation of N-Heteroaromatics with Water as Hydrogen Donor and Solvent.

A Pd-catalyzed transfer hydrogenation of various N-heteroaromatic compounds with B2pin2 as a mediator and environmentally benign water as both solvent and hydrogen donor has been disclosed. This reaction proceeded under ambient temperature with a broad range of N-heteroaromatic compounds among which imidazo[1,2-a]pyridine derivatives were for the first time selectively reduced to 5,6,7,8-tetrahydroimidazo[1,2-a]pyridines, which are the core structural motifs of an inhibitor of human O-GlcNAcase. Mechanistic studies suggested that the new protons in products are from water and Pd-H might be the key intermediate with B2pin2 as the H2O activator.

Copper(II)-catalyzed highly regio- and stereo-selective hydrosilylation of unactivated internal alkynes with silylborate in water.

The highly regio- and stereoselective hydrosilylation of internal alkynes with silylborate catalyzed by Cu(OTf)2 with 1,10-phenanthroline as the ligand in the presence of Cs2CO3 in water is developed. This protocol was applied efficiently in the aqueous synthesis of multi-substituted vinylsilanes.

Highly enantioselective reaction of 2-oxindoles with (3-indolyl)methanols by cooperative catalysis of a Lewis acid and organocatalyst.

An efficient cooperative biscinchona alkaloid and Lewis acid catalytic system was developed in the enantioselective α-alkylation of 2-oxindoles with (3-indolyl)(phenyl)methanols to provide (2-oxindole)-linker-indole derivatives in good yields (70-83%) with high enantioselectivities (81%-92%).

Cu(II)-catalyzed allylic silylation of Morita-Baylis-Hillman alcohols via dual activation of Si-B bond and hydroxyl group.

The reaction of Morita-Baylis-Hillman (MBH) alcohols with Me2PhSiBpin under the catalysis of Cu(OTf)2/pyridine in methanol has been developed. The direct silylation of allylic alcohols via dual activation of the Si-B bond and the hydroxyl group of the MBH alcohol provides an efficient and convenient method for the synthesis of functionalized allylsilanes.

Highly diastereo- and enantioselective [3+2] annulation of isatin-derived Morita-Baylis-Hillman carbonates with trifluoropyruvate catalyzed by tertiary amines.

An enantioselective [3+2] annulation of Morita-Baylis-Hillman carbonates with trifluoropyruvate catalyzed by modified cinchona alkaloids was developed in good to excellent yields with excellent diastereo- and enantioselectivities.

A Pd(0)-catalyzed direct dehydrative coupling of terminal alkynes with allylic alcohols to access 1,4-enynes.

A direct dehydrative coupling of terminal alkynes with allylic alcohols catalyzed by Pd(PPh3)4 with an N,P-ligand assisted by Ti(OiPr)4 has been developed. The coupling reaction tolerates various functional groups, providing a valuable synthetic tool to access 1,4-enynes.