Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Design and Synthesis of 4-(4-Benzoylaminophenoxy)phenol Derivatives As Androgen Receptor Antagonists.

ABSTRACT: We report the design and synthesis of novel 4-(4-benzoylaminophenoxy)phenol derivatives that bind to the androgen receptor (AR) ligand-binding domain and exhibit potent androgen-antagonistic activity. Compound 22 is one of the most potent of these derivatives, inhibiting the dihydrotestosterone-promoted growth of SC-3 cell line bearing wild-type AR (IC50 0.75 ?M), LNCaP cell line bearing T877A-mutated AR (IC50 0.043 ?M), and 22Rv1 cell line bearing H874Y-mutated AR (IC50 0.22 ?M). Structure-activity relationship studies confirmed that the pharmacophore of these novel AR antagonists is distinct from the nitro- or cyano-substituted anilide substructure of other nonsteroidal AR antagonists. This novel pharmacophore is expected to provide a basis for designing new antiprostate cancer agents.

SUBMITTER: Yamada A

PROVIDER: S-EPMC4027134 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Design and Synthesis of 4-(4-Benzoylaminophenoxy)phenol Derivatives As Androgen Receptor Antagonists.

Yamada Ayumi A Fujii Shinya S Mori Shuichi S Kagechika Hiroyuki H

ACS medicinal chemistry letters 20130819 10

We report the design and synthesis of novel 4-(4-benzoylaminophenoxy)phenol derivatives that bind to the androgen receptor (AR) ligand-binding domain and exhibit potent androgen-antagonistic activity. Compound 22 is one of the most potent of these derivatives, inhibiting the dihydrotestosterone-promoted growth of SC-3 cell line bearing wild-type AR (IC50 0.75 μM), LNCaP cell line bearing T877A-mutated AR (IC50 0.043 μM), and 22Rv1 cell line bearing H874Y-mutated AR (IC50 0.22 μM). Structure-acti ...[more]

PMID: 24900588

Similar Datasets

Design, synthesis and biological evaluation of novel biphenylsulfonamide derivatives as selective AT2 receptor antagonists.

Project description:A novel series of benzenesulfonamide derivatives that selectively act on the AT2 receptor have been designed and synthesized. The binding affinity and functional activity were evaluated by radio-ligand binding analysis and cell neurite outgrowth assay, respectively. The compounds 8d, 8h, 8i, 8j, 8l, and 9h exhibited moderate selectivity and affinity for the AT2 receptor. Among them, 8j exhibited agonist activity and 8l displayed similar selectivity to the AT2 receptor with PD123,319. Molecular docking was carried out to analyze the binding mode and binding site between the compound and the AT2 receptor to provide a reference for further development.

| S-EPMC9458978 | biostudies-literature

Design, synthesis and biological evaluation of novel piperazine derivatives as CCR5 antagonists.

Project description:By using a fragment-assembly strategy and bioisosteric-replacement principle, a series of novel piperazine derivatives were designed, synthesized, and evaluated for their cellular target-effector fusion activities and in vitro antiviral activities against HIV-1. Preliminary structure-activity relationships (SARs) of target compounds were concluded in this study, and five compounds were found to exhibited medium to potent CCR5 fusion activities with IC(50) values in low micromolar level. Among evaluated compounds, 23 h was found to be a CCR5 antagonist with an IC(50) value of 6.29 µM and an anti-HIV-1 inhibitor with an IC(50) value of 0.44 µM.

| S-EPMC3538727 | biostudies-literature

Design, Synthesis, and Evaluation of B-(Trifluoromethyl)phenyl Phosphine-Borane Derivatives as Novel Progesterone Receptor Antagonists.

Project description:We previously revealed that phosphine-boranes can function as molecular frameworks for biofunctional molecules. In the present study, we exploited the diversity of available phosphines to design and synthesize a series of B-(trifluoromethyl)phenyl phosphine-borane derivatives as novel progesterone receptor (PR) antagonists. We revealed that the synthesized phosphine-borane derivatives exhibited LogP values in a predictable manner and that the P-H group in the phosphine-borane was almost nonpolar. Among the synthesized phosphine-boranes, which exhibited PR antagonistic activity, B-(4-trifluoromethyl)phenyl tricyclopropylphosphine-borane was the most potent with an IC50 value of 0.54 μM. A docking simulation indicated that the tricyclopropylphosphine moiety plays an important role in ligand-receptor interactions. These results support the idea that phosphine-boranes are versatile structural options in drug discovery, and the developed compounds are promising lead compounds for further structural development of next-generation PR antagonists.

| S-EPMC11013038 | biostudies-literature

Synthesis of Hydantoin Androgen Receptor Antagonists and Study on Their Antagonistic Activity.

Project description:Hydroxymethylthiohydantoin, hydroxymethylthiohydantoin, and hydantoin, containing a pyridine group, were synthesized to study their androgen receptor antagonistic activities. Among them, compounds 6a/6c/7g/19a/19b exhibited excellent androgen receptor antagonistic activity, which was consistent with or even superior to enzalutamide. In addition, compounds 19a and 19b exhibited better antiproliferative activity than enzalutamide in prostate cancer cells. The results show that compound 19a has great potential as a new AR antagonist.

| S-EPMC9505067 | biostudies-literature

Design, Synthesis and Bioactivities of Novel Dichloro-Allyloxy-Phenol-Containing Pyrazole Oxime Derivatives.

Project description:In this study, in order to find novel biologically active pyrazole oxime compounds, a number of dichloro-allyloxy-phenol-containing pyrazole oximes were designed and synthesized according to the method of active group combination. All of the target compounds were confirmed by ¹H-NMR, (13)C-NMR and elemental analysis. In addition, bioassays showed that all of the newly synthesized compounds had no acaricidal activity against Tetranychus cinnabarinus and low insecticidal activity against Aphis craccivora at tested concentrations. However, most of them displayed excellent insecticidal activity against Oriental armyworm at a concentration of 500 μg/mL, and some designed compounds still exhibited potent insecticidal activity against Oriental armyworm even at the dose of 20 μg/mL, especially compounds 7f, 7n and 7p had 100%, 90% and 90% inhibition rates, respectively, which were comparable to that of the control pyridalyl.

| S-EPMC6332197 | biostudies-literature

Design, Synthesis, and Biological Activity Studies of Istradefylline Derivatives Based on Adenine as A2A Receptor Antagonists.

Project description:Due to its double bond, istradefylline rapidly isomerizes to Z-istradefylline when exposed to normal daylight in dilute solution. To solve the poor photostability of the istradefylline solution, a series of istradefylline derivatives (in total 17 compounds, including II-1 and II-2 series) were designed and synthesized, and their biological activity in inhibiting cAMP was evaluated. The IC50 values of compounds II-1-3, II-2-1, II-2-2, II-2-3, II-2-4, and II-2-6 were 7.71, 6.52, 6.16, 7.23, 7.96, and 9.68 μg/mL, respectively, which had the same order of activity as that of istradefylline (IC50 value was 1.94 μg/mL). The preliminary structure-activity relationship suggested that the 6-amino in adenine played an important role in binding an A2A receptor. The results of photostability experiments showed that the photostability of the target compounds of II-1 and II-2 series was improved when compared with that of istradefylline.

| S-EPMC7906590 | biostudies-literature

14-O-Heterocyclic-substituted naltrexone derivatives as non-peptide mu opioid receptor selective antagonists: design, synthesis, and biological studies.

Project description:Mu opioid receptor antagonists have clinical utility and are important research tools. To develop non-peptide and highly selective mu opioid receptor antagonist, a series of 14-O-heterocyclic-substituted naltrexone derivatives were designed, synthesized, and evaluated. These compounds showed subnanomolar-to-nanomolar binding affinity for the mu opioid receptor. Among them, compound 1 exhibited the highest selectivity for the mu opioid receptor over the delta and kappa receptors. These results implicated an alternative 'address' domain in the extracellular loops of the mu opioid receptor.

| S-EPMC2802822 | biostudies-literature

Design, synthesis, and biological evaluation of 6alpha- and 6beta-N-heterocyclic substituted naltrexamine derivatives as mu opioid receptor selective antagonists.

Project description:Opioid receptor selective antagonists are important pharmacological probes in opioid receptor structural characterization and opioid agonist functional study. Thus far, a nonpeptidyl, highly selective and reversible mu opioid receptor (MOR) antagonist is unavailable. On the basis of our modeling studies, a series of novel naltrexamine derivatives have been designed and synthesized. Among them, two compounds were identified as leads based on the results of in vitro and in vivo assays. Both of them displayed high binding affinity for the MOR (K(i) = 0.37 and 0.55 nM). Compound 6 (NAP) showed over 700-fold selectivity for the MOR over the delta receptor (DOR) and more than 150-fold selectivity over the kappa receptor (KOR). Compound 9 (NAQ) showed over 200-fold selectivity for the MOR over the DOR and approximately 50-fold selectivity over the KOR. Thus these two novel ligands will serve as leads to further develop more potent and selective antagonists for the MOR.

| S-EPMC2880636 | biostudies-literature

Design, Synthesis, and Biological Evaluation of a Series of 5- and 7-Hydroxycoumarin Derivatives as 5-HT1A Serotonin Receptor Antagonists.

Project description:We have designed and synthesized a series of 60 new 5- and 7-hydroxycoumarin derivatives bearing the piperazine moiety with the expected binding to 5-HT1A and 5-HT2A receptors. Molecular docking of all investigated compounds revealed subnanomolar estimates of 5-HT1AR Ki for three ligands and 5-HT2AR Ki for one ligand as well as numerous low nanomolar estimates of Ki for both receptors. Intrigued by these results we synthesized all 60 new derivatives using microwave-assisted protocols. We show that three new compounds show a relatively high antagonistic activity against the 5HT1A receptor, although lower than the reference compound WAY-100635. These compounds also showed relatively low binding affinities to the 5-HT2A receptor. We also provide a detailed structure-activity analysis of this series of compounds and compare it with previously obtained results for an exhaustive series of coumarin derivatives.

| S-EPMC7996328 | biostudies-literature

Design, synthesis and SAR study of novel trisubstituted pyrimidine amide derivatives as CCR4 antagonists.

Project description:The design, synthesis and structure-activity relationship studies of some novel trisubstituted pyrimidine amide derivatives prepared as CCR4 antagonists are described. The activities of these compounds were evaluated by the CCR4-MDC chemotaxis inhibition assay. Compound 1, which we have previously reported as a potent antagonist of CCR4, was employed as the positive control. The results indicated that most of the synthesized compounds exhibited some chemotaxis inhibition activity against CCR4. Of these new compounds, compounds 6c, 12a and 12b, with IC₅₀ values of 0.064, 0.077 and 0.069 μM, respectively, showed higher or similar activity compared with compound 1 (IC₅₀ of 0.078 μM). These compounds provide a basis for further structural modifications. The systematic structure-activity relationship of these trisubstituted pyrimidine amide derivatives was discussed based on the obtained experimental data. The results from the SAR study may be useful for identifying more potent CCR4 antagonists.

| S-EPMC6271259 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data