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The synthesis of polysubstituted spirocyclopropyl oxindoles using a series of rare-earth metal (REM) salts is reported. REMs, in particular Sc(OTf), allowed access to the target compounds by a multicomponent reaction with high diastereoselectivity (≤94:6:0:0). Density functional theory calculations on the model reaction are consistent with the observed selectivity and revealed that the special coordinating capabilities and the oxophilicity of the metal are key factors in inducing the formation of one main diastereoisomer.
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http://dx.doi.org/10.1021/acs.orglett.3c00772 | DOI Listing |
Bioorg Chem
August 2025
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India. Electronic address:
Dual-targeting agents represent a promising approach in cancer treatment, offering several significant advantages over traditional single-target therapies or drug combinations. In this connection, herein a series of spirocyclopropyl oxindole-piperazine/morpholine based carboxamides were rationally designed, synthesized, and evaluated for their dual inhibition (tubulin polymerization and VEGFR-2 kinase) activity. Among the synthesized derivatives, compound 8u exhibited potent cytotoxicity against the HepG-2 cell line with an IC of 1.
View Article and Find Full Text PDFChem Biodivers
May 2025
Department of Chemistry, Guru Nanak Dev University, Amritsar, India.
A series of 1H-1,2,3-triazole-tethered spirocyclopropyl oxindole-isatin hybrids were synthesized using a copper-promoted click reaction and evaluated for their anti-proliferative activities against triple-negative breast cancer cell lines. The most potent compound in the series outperformed tamoxifen and 5-fluorouracil, with selectivity indices of 1.60 and 1.
View Article and Find Full Text PDFChemistry
December 2024
School of Chemistry and Chemical Engineering, Guangzhou University, 230 Wai Huan Xi Road, Guangzhou, 510006, China.
ChemMedChem
November 2024
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037, India.
Tumor progression depends on angiogenesis, which is stimulated by growth factors like VEGF, targeting VEGFR kinase with small molecules is an effective anti-angiogenic therapeutic approach. The rational modification of sunitinib (VEGFR-2 inhibitor) to spirocyclopropyloxindoline carboxamides have been performed and their in vitro cytotoxic profiling was evaluated. The molecular modelling studies enabled the screening of designed analogues and identifying the possible interactions within the type III allosteric inhibitor binding site of VEGFR-2.
View Article and Find Full Text PDFOrg Lett
June 2024
Department of Chemistry, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India.
We have demonstrated a Pd(0)-catalyzed Heck/C(sp)-H activation cascade for the synthesis of spirocyclopropyl oxindoles in high yields from easily accessible -bromoacrylamides. The formation of spirocyclopropyl oxindole is guided by an unconventional four-membered palladacycle through C(sp)-H activation. The reaction exhibits a wide range of substrate scope and operates efficiently with a mere 0.
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