2296-23-3Relevant articles and documents
Synthesis and SAR of 5-amino- and 5-(aminomethyl)benzofuran histamine H3 receptor antagonists with improved potency
Sun, Minghua,Zhao, Chen,Gfesser, Gregory A.,Thiffault, Christine,Miller, Thomas R.,Marsh, Kennan,Wetter, Jill,Curtis, Michael,Faghih, Ramin,Esbenshade, Timothy A.,Hancock, Arthur A.,Cowart, Marlon
, p. 6482 - 6490 (2005)
A new series of H3 receptor antagonists was discovered with nanomolar and subnanomolar affinities at human and rat H3 receptors. Starting from an earlier, more structurally limited series of benzofurans, the present series of compounds demonstrated increased structural variety and flexibility with greater in vitro potency. One compound in particular, {2-[2-(2-(R)-methylpyrrolidin-1-yl)ethyl]benzofuran-5-yl}(5-nitropyridin-2-yl) amine (7h), gave the best binding potency (human Ki of 0.05 nM, rat Ki of 0.11 nM), which represented a 9-fold (in human) and an 11-fold (in rat) improvement over ABT-239 (compound 5), a compound previously reported to have excellent in vitro potency and in vivo efficacy. The synthesis, SAR of the H3 binding affinities, in vitro assay for phospholipidosis, and pharmacokinetic properties of the new compounds are described.
Discovery of 5-(N-hydroxycarbamimidoyl) benzofuran derivatives as novel indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors
Jung, Juyoung,Yoon, Hongchul,Sohn, Te-ik,Jang, Kyusic,Yoo, Yeongran,Jeong, Ilji,Shin, Jae Eui,Lee, Jin Hee,Ann, Jihyae,Lee, Jeewoo
, (2021)
Human indoleamine 2,3-dioxygenase 1 (hIDO1) and tryptophan dioxygenase (hTDO) are rate-limiting enzymes in the kynurenine pathway (KP) of L-tryptophan (L-Trp) metabolism and are becoming key drug targets in the combination therapy of checkpoint inhibitors in immunoncology. To discover a selective and potent IDO1 inhibitor, a structure–activity relationship (SAR) study of N-hydroxybenzofuran-5-carboximidamide as a novel scaffold was investigated in a systematic manner. Among the synthesized compounds, the N-3-bromophenyl derivative 19 showed the most potent inhibition, with an IC50 value of 0.44 μM for the enzyme and 1.1 μM in HeLa cells. The molecular modeling of 19 with the X-ray crystal structure of IDO1 indicated that dipole-ionic interactions with heme iron, halogen bonding with Cys129 and the two hydrophobic interactions were important for the high potency of 19.
Pd-Catalyzed ipso, meta-Dimethylation of ortho-Substituted Iodoarenes via a Base-Controlled C-H Activation Cascade with Dimethyl Carbonate as the Methyl Source
Wu, Zhuo,Wei, Feng,Wan, Bin,Zhang, Yanghui
supporting information, p. 4524 - 4530 (2021/05/04)
A methyl group can have a profound impact on the pharmacological properties of organic molecules. Hence, developing methylation methods and methylating reagents is essential in medicinal chemistry. We report a palladium-catalyzed dimethylation reaction of ortho-substituted iodoarenes using dimethyl carbonate as a methyl source. In the presence of K2CO3 as a base, iodoarenes are dimethylated at the ipso- and meta-positions of the iodo group, which represents a novel strategy for meta-C-H methylation. With KOAc as the base, subsequent oxidative C(sp3)-H/C(sp3)-H coupling occurs; in this case, the overall transformation achieves triple C-H activation to form three new C-C bonds. These reactions allow expedient access to 2,6-dimethylated phenols, 2,3-dihydrobenzofurans, and indanes, which are ubiquitous structural motifs and essential synthetic intermediates of biologically and pharmacologically active compounds.
PHENOXYMETHYL DERIVATIVES
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Page/Page column 186, (2017/03/21)
The invention provides novel compounds having the general formula (I), wherein RA, RB, RC, RC1 and W are as defined herein, compositions including the compounds and methods of using the compounds.
