- Synthesis and biological evaluation of heterocyclic bis-aryl amides as novel Src homology 2 domain containing protein tyrosine phosphatase-2 (SHP2) inhibitors
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The Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) is a convergent node for oncogenic cell-signaling cascades including the PD-L1/PD-1 pathway. Consequently, SHP2 has emerged as a compelling target for novel anti-cancer agents. Replacing one of phenyl ring in PTP1B inhibitor 1 with heterocyclic ring led to a series of heterocyclic bis-aryl amide derivatives. The representative compound 7b displayed SHP2 inhibitory activity with IC50 of 2.63 ± 0.08 μM, exhibited about 4-fold selectivity for SHP2 over TCPTP and had no detectable activity against SHP1 and PTP1B. These preliminary results could provide a possible opportunity for the development of novel SHP2 inhibitors with optimal potency and improved pharmacological properties.
- Feng, Bo,Gao, Li-Xin,Gao, Ya,Hou, Ting-Jun,Huang, Chao,Li, Jia,Satheeshkumar, Rajendran,Shen, Chao,Wang, Wen-Long,Xu, Lei,Zhou, Yu-Bo,Zhu, Rui,Zhu, Yun-Long
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- Discovery and development of novel salicylate synthase (MbtI) furanic inhibitors as antitubercular agents
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We report on the virtual screening, synthesis, and biological evaluation of new furan derivatives targeting Mycobacterium tuberculosis salicylate synthase (MbtI). A receptor-based virtual screening procedure was applied to screen the Enamine database, identifying two compounds, I and III, endowed with a good enzyme inhibitory activity. Considering the most active compound I as starting point for the development of novel MbtI inhibitors, we obtained new derivatives based on the furan scaffold. Among the SAR performed on this class, compound 1a emerged as the most potent MbtI inhibitor reported to date (Ki = 5.3 μM). Moreover, compound 1a showed a promising antimycobacterial activity (MIC99 = 156 μM), which is conceivably related to mycobactin biosynthesis inhibition.
- Chiarelli, Laurent R.,Mori, Matteo,Barlocco, Daniela,Beretta, Giangiacomo,Gelain, Arianna,Pini, Elena,Porcino, Marianna,Mori, Giorgia,Stelitano, Giovanni,Costantino, Luca,Lapillo, Margherita,Bonanni, Davide,Poli, Giulio,Tuccinardi, Tiziano,Villa, Stefania,Meneghetti, Fiorella
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p. 754 - 763
(2018/06/26)
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- A kind of benzene ring - aromatic ring series compound, its preparation method and medical use
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The invention relates to a phenyl ring-aromatic ring cascaded micro-molecular organic compound which can be used as a protein-tyrosine-phosphatase subtype inhibitor and is shown in a general formula I as described in the specification. The compound can be used as a tool compound for research on the biological functions of a variety of subtypes of a protein-tyrosine-phosphatase family in cell signal transduction, so novel means is provided for prevention and treatment of cancers, metabolism and immunological diseases, cardiovascular diseases and nervous diseases. The invention also relates to a preparation method and medicinal application of the compound.
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Paragraph 0152-0155
(2017/12/05)
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- Synthesis of new cyano-substituted bis-benzothiazolyl arylfurans and arylthiophenes
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The new compounds 2-[4-(6-cyanobenzothiazol-2-yl)phenyl]-5-(6-cyano- benzothiazol-2-yl)furan (6a) and 2-[4-(6-Cyanobenzothiazol-2-yl)phenyl]-5-(6- cyano-benzothiazol-2-yl)thiophene (6b) were synthesized by multi-step reactions from the corresponding 2-fur
- Racanè, Livio,Trali?-Kulenovi?, Vesna,Boykin, David W.,Karminski-Zamola, Grace
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p. 342 - 349
(2007/10/03)
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- Suzuki cross-coupling reactions using reverse-phase glass beads in aqueous media
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Reverse-phase glass beads have been employed in Suzuki reactions to provide, in aqueous media, a route to diverse polar substrates in good yield and with low levels of palladium leaching.
- Lawson Daku, Kokovi M.,Newton, Roger F.,Pearce, Simon P.,Vile, Julia,Williams, Jonathan M. J.
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p. 5095 - 5098
(2007/10/03)
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