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Abstract: A three-component reaction based on trapping of ammonium ylides with formaldehyde was first reported. This reaction offers a new strategy for the synthesis of α-aryl serine derivatives and can be extended to the preparation of α-aryl threonine derivatives. Synthetic application of the three component reaction for the preparation of hydroquinoxaline derivative was also demonstrated. [Copyright &y& Elsevier]

Chemotherapy combining with surgical treatment has been the main strategy for osteosarcoma treatment in clinical. Due to unclear pathogenesis and unidentified drug targets, significant progress has not been made in the development of targeted drugs for osteosarcoma during the past 50 years. Our previous discovery reported compound R - 8i with a high potency for the treatment of osteosarcoma by phenotypic screening. However, both the metabolic stability and bioavailability of R - 8i are poor (T 1/2 = 5.36 min, mouse liver microsome; and bioavailability in vivo F = 52.1 %, intraperitoneal administration) which limits it use for further drug development. Here, we described an extensive structure−activity relationship study of thiazolidine-4-one sulfone inhibitors from R - 8i , which led to the discovery of compound 68. Compound 68 had a potent cellular activity with an IC 50 value of 0.217 μM, much higher half-life (T 1/2 = 73.8 min, mouse liver microsome) and an excellent pharmacokinetic profile (in vivo bioavailability F = 115 %, intraperitoneal administration). Compound 68 also showed good antitumor effects and low toxicity in a xenograft model (44.6 % inhibition osteosarcoma growth in BALB/c mice). These results suggest that compound 68 is a potential drug candidate for the treatment of osteosarcoma. [Display omitted] • Discovering lead compound 68 from the metabolites for anti-osteosarcoma. • 68 shows an obviously improved metabolic stability with 115 % bioavailability in vivo. • Compound 68 possesses 44.6 % inhibition osteosarcoma growth and low toxicity in mice. • Compound 68 significantly suppresses osteosarcoma cell migration in vitro. [ABSTRACT FROM AUTHOR]

A formal carbene insertion into C O double bonds of 2-hydroxycinnamaldehydes catalyzed by Rh 2 (esp) 2 with Na 2 CO 3 as additive has been disclosed by using aryldiazoacetates as carbene precursors. 2 H -chromenes with a quaternary carbon at C-2 position were readily obtained from simple starting materials in good yields with excellent diastereoselectivity under mild reaction conditions in one pot. The reaction mechanism was investigated and proposed as the formation of epoxide intermediate from Rh(II)-associated carbene and ( E )-2-hydroxycinnamaldehyde and followed by a cascade epoxide ring-opening procedure in which the ( E )-intermediate was converted into the ( Z )-intermediate to give ( Z )-products. [ABSTRACT FROM AUTHOR]

Protein tyrosine phosphatase 1B (PTP1B) has been proposed to be an ideal target for treatment of type II diabetes and obesity. However, no druggable PTP1B inhibitor has been established and there is still an urgent demand for the development of structurally novel PTPIB inhibitor. Herein, we reported core-structurally novel PTP1B inhibitors with low micromole-ranged inhibitory activity by one-pot reaction from simple starting materials. Further studies demonstrated some of these active compounds had a specific selectivity over other PTPs. The structure and activity relationship was also described. The best active and selective compound 5e inhibited PTP1B activity with an IC 50 of 4.53 μM. Molecular docking analysis further demonstrated that compound 5e bound to the active pocket of PTP1B. The results might provide some insights for further development of new drugs for type II diabetes and obesity. [ABSTRACT FROM AUTHOR]

A transformation of cyclopropyl carbene generated from 2-cyclopropyl-2-diazoacetate via oxonium ylide was found by trapping the resulting ylide with imine. The asymmetric three-component reaction of cycloproyl diazoacetates, benzenemethanols and imines afforded a rapid and efficient method to synthesize complex cyclopropane derivatives with excellent diastereoselectivity and enantioselectivity. [ABSTRACT FROM AUTHOR]

Abstract: Three-component reactions of aryl diazoacetates, arylamines and N-sulfonyl aldimines cooperatively catalyzed by squaramides and dirhodium acetate are reported to afford N-sulfonyl α,β-diamino acid derivatives in moderate to good yields and diastereoselectivity. [Copyright &y& Elsevier]

An efficient one-pot two-step synthetic strategy to access highly selective N 2-substituted-1,2,3-triazole from aryl ethynylenes, azides and furan has been developed via a radical transformation. 17 examples of aryl ethynylene with various substituents were converted into their corresponding functionalized N 2-substituted-1,2,3-triazole derivatives in good yields. [Display omitted] [ABSTRACT FROM AUTHOR]

Due to unknown pathogenesis and unidentified drug target, no drug for the treatment of osteosarcoma (OS) has been launched to the market. Herein, thiazolidinone 1a was discovered as a hit compound by phenotypic screening with an in-house patrimonial collection of structural diversity. The following SAR (Structure-Activity Relationship) study affords the final water-soluble lead compound (R)- 8i as a potential inhibitor for the proliferation of OS cells by the modulation of solubility of the compounds with remarkable cellular potency (IC 50 = 21.9 nM for MNNG/HOS cells) and in vivo efficacy (52.9% inhibition OS growth in mice), as well as pharmacokinetic properties. (R)- 8i also significantly suppresses OS cell migration in vitro and showed to be well-tolerated. Our preliminary investigation shows that the effects of (R)- 8i are not dependent on p53 and myoferlin (MYOF). These results suggest that (R)- 8i might be a potential drug candidate for OS treatment. [Display omitted] • Thiazolidinones were discovered for treating osteosarcoma by phenotypic screening. • The screening used an in-house patrimonial collection of structural diversity. • Lead compound (R)- 8i selectively inhibit osteosarcoma cell in vitro and in vivo. • (R)- 8i also significantly suppresses osteosarcoma cell migration in vitro. • (R)- 8i presents a considerable bioavailability and a low toxicity. [ABSTRACT FROM AUTHOR]