80494-75-3

Usage

InChI:InChI=1/C11H13ClO3/c1-2-14-11(13)8-15-10-5-3-9(7-12)4-6-10/h3-6H,2,7-8H2,1H3

Upstream product

• 623-05-2 (4-hydroxyphenyl)methanol 
• 99-96-7 4-hydroxy-benzoic acid 
• 103258-64-6 ethyl 2-(4-hydroxymethylphenoxy)acetate 

Downstream Products

• 141286-08-0 ethyl 4-<2-(phenylsulfonylamino)ethylthiomethyl>phenoxyacetate 
• 141286-09-1 ethyl 4-<2-(4-chlorophenylsulfonylamino)ethylthiomethyl>phenoxyacetate 
• 198479-82-2 {4-[5-benzyloxy-2-(4-benzyloxy-phenyl)-3-methyl-indol-1-ylmethyl]-phenoxy}-acetic acid ethyl ester 
• 198480-55-6 pipendoxifene 
• 198481-32-2 bazedoxifene 
• 198479-95-7 2-(4-((5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-3-methyl-1H-indol-1-yl)methyl)phenoxy)ethanol 
• 198480-07-8 5-benzyloxy-2-(4-benzyloxy-phenyl)-1-[4-(2-bromo-ethoxy)-benzyl]-3-methyl-1H-indole 
• 198480-20-5 5-benzyloxy-2-(4-benzyloxy-phenyl)-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-1H-indole 
• 198480-21-6 5-benzyloxy-2-(4-benzyloxy-phenyl)-3-methyl-1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-1H-indole 
• 1310744-81-0 1-(4-(2-ethoxy-2-oxoethoxy)benzyl)-1H-indole-6-carboxylic acid 
• 1310744-82-1 (R)-dimethyl 2-(1-(4-(2-ethoxy-2-oxoethoxy)benzyl)-1H-indole-6-carboxamido) pentanedioate 
• 1310744-83-2 (R)-2-(1-(4-(carboxymethoxy)benzyl)-1H-indole-6-carboxamido)pentanedioic acid 
• 1310744-80-9 benzyl 1-(4-(2-ethoxy-2-oxoethoxy)benzyl)-1H-indole-6-carboxylate 
• 85938-30-3 1-ethoxycarbonyl-3-(4-ethoxycarbonylmethoxybenzyl)imidazolium iodide 

Relevant academic research and scientific papers

Investigation of the effect of different linker chemotypes on the inhibition of histone deacetylases (HDACs)

Histone Deacetylases (HDACs) are among the most attractive and interesting targets in anticancer drug discovery. The clinical relevance of HDAC inhibitors (HDACIs) is testified by four FDA-approved drugs for cancer treatment. However, one of the main drawbacks of these drugs resides in the lack of selectivity against the different HDAC isoforms, resulting in severe side effects. Thus, the identification of selective HDACIs represents an exciting challenge for medicinal chemists. HDACIs are composed of a cap group, a linker region, and a metal-binding group interacting with the catalytic zinc ion. While the cap group has been extensively investigated, less information is available about the effect of the linker on isoform selectivity. To this aim, in this work, we explored novel linker chemotypes to direct isoform selectivity. A small library of 25 hydroxamic acids with hitherto unexplored linker chemotypes was prepared. In vitro tests demonstrated that, depending on the linker type, some candidates selectively inhibit HDAC1 over HDAC6 isoform or vice versa. Docking calculations were performed to rationalize the effect of the novel linker chemotypes on biologic activity. Moreover, four compounds were able to increase the levels of acetylation of histone H3 or tubulin. These compounds were also assayed in breast cancer MCF7 cells to test their antiproliferative effect. Three compounds showed a significant reduction of cancer proliferation, representing valuable starting points for further optimization.

In vitro bioactivation of bazedoxifene and 2-(4-hydroxyphenyl)-3-methyl-1H- indol-5-ol in human liver microsomes

Bazedoxifene is a selective estrogen receptor modulator (SERM) that has been developed for use in post-menopausal osteoporosis. However, it contains a potentially toxic 5-hydroxy-3-methylindole moiety. Previous studies on the 5-hydroxyindole and the 3-alkylindole-containing drugs indometacine, zafirlukast and MK-0524 structural analogs have shown that they are bioactivated by cytochrome P450s through a dehydrogenation process to form quinoneimine or 3-methyleneindolenine electrophilic species. In the present study, bazedoxifene was synthesized and then evaluated, together with raloxifene and 2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol (13), a 3-methyl-5-hydroxyindole- based structural fragment of bazedoxifene, for its ability to form reactive electrophilic species when incubated with human liver microsomes (HLMs) or recombinant CYP isozymes. We showed that bazedoxifene was bioactivated only in trace amounts with recombinant CYP isozymes. In contrast, the N-dealkylated fragment of bazedoxifene (2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol) was bioactivated in considerable amounts to an electrophilic intermediate, which was trapped with glutathione and identified by LC-MS/MS. This suggests that bazedoxifene would require initial N-dealkylation, which could subsequently lead to the formation of the reactive intermediate. However, such an N-dealkylated metabolite of bazedoxifene was not detected after the incubation of bazedoxifene in HLM or recombinant CYP isozymes.

Structure-based design of a new series of d-glutamic acid based inhibitors of bacterial UDP-N-acetylmuramoyl-l-alanine: D-glutamate ligase (MurD)

MurD ligase is one of the key enzymes participating in the intracellular steps of peptidoglycan biosynthesis and constitutes a viable target in the search for novel antibacterial drugs to combat bacterial drug-resistance. We have designed, synthesized, and evaluated a new series of d-glutamic acid-based Escherichia coli MurD inhibitors incorporating the 5-benzylidenethiazolidin-4- one scaffold. The crystal structure of 16 in the MurD active site has provided a good starting point for the design of structurally optimized inhibitors 73-75 endowed with improved MurD inhibitory potency (IC50 between 3 and 7 μM). Inhibitors 74 and 75 showed weak activity against Gram-positive Staphylococcus aureus and Enterococcus faecalis. Compounds 73-75, with IC 50 values in the low micromolar range, represent the most potent d-Glu-based MurD inhibitors reported to date.

Structure-activity relationship study of TXA2 receptor antagonists. 4- [2-(4-Substituted phenylsulfonylamino)ethylthio]phenoxyacetic acids and related compounds

We have recently reported that 4-[2-(4-substituted phenylsulfonylamino)ethylthio]phenoxyacetic acids and related compounds showed potent thromboxane A2 (TXA2) receptor antagonist activity. To understand how substituents affect the bi

Synthesis and evaluation of novel sulfonamide derivatives as thromboxane A2 receptor antagonists I

A series of 4-phenoxyacetic acids and related compounds were synthesized.The compounds were tested for their thromboxane A2 (TXA2) receptor antagonizing effects on (15S)-15-hydroxy-11a,9a-(epoxymethano)prosta-5(Z),13(E)-dienoic acid (U-46619)-induced aggregation of rabbit platelet-rich plasma (PRP).Among the compounds synthesized, 3-phenyl>propionic acids 26a-e,g showed potent TXA2 receptor antagonist activity.The most potent compound, 3-phenyl>propionic acid 26c was more than 10-fold more potent in TXA2 receptor antagonizing activity (IC50 = 1.1*106 M) than sulotroban (BM-13177) on rabbit platelets.Compound 26c was also more than 10-fold more potent in TXA2-inhibitory activity than sulotroban on rat aorta smooth muscle (pA2 7.7) thromboxane A2 / TXA2 / receptor antagonist / sulfonamide derivative / sulotroban

Thiadizazole compounds as antagonists of SRS-A

This invention relates to novel heterocyclic compounds structurally characterized by containing a specific heterocyclic group and by the presence of --CH2 --S-- directly bound to the specific heterocyclic group. These heterocyclic compounds are useful as medicines, particularly as antagonists of SRS-A (slow reacting substance of anaphylaxis).