Synthesis and biological evaluation of novel, selective, nonsteroidal glucocorticoid receptor antagonists

Akritopoulou‐Zanze, Irini; Patel, Jyoti; Hartandi, Kresna; Brenneman, Jehrod B.; Winn, Martin; Pratt, John K.; Grynfarb, Marlene; Goos-Nisson, Annika; Geldern, Thomas W von; Kym, Philip R.

doi:10.1016/j.bmcl.2004.02.048

Cited by 21 publications

(6 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Aquatide was purified by semi-preparative reversed-phase HPLC purification system (SPD-20A, Shimadzu corporation, Kyoto, Japan) with a column of BDS Hypersil C18 (4.6×250 mm, 130 Å, 5 μm) and Alliance HPLC 2695 separations module equipped with 2489 UV/Vis detector (Waters, Milford, MA, USA). In addition, LCMS (SQD2, Waters) analysis was performed to measure the molecular weight of Aquatide, as described previously ( Akritopoulou-Zanze et al ., 2004 ).…”

Section: Methodsmentioning

confidence: 99%

Aquatide Activation of SIRT1 Reduces Cellular Senescence through a SIRT1-FOXO1-Autophagy Axis

Lim

Lee

Kang

et al. 2017

Biomolecules & Therapeutics

View full text Add to dashboard Cite

Ultraviolet (UV) irradiation is a relevant environment factor to induce cellular senescence and photoaging. Both autophagy- and silent information regulator T1 (SIRT1)-dependent pathways are critical cellular processes of not only maintaining normal cellular functions, but also protecting cellular senescence in skin exposed to UV irradiation. In the present studies, we investigated whether modulation of autophagy induction using a novel synthetic SIRT1 activator, heptasodium hexacarboxymethyl dipeptide-12 (named as Aquatide), suppresses the UVB irradiation-induced skin aging. Treatment with Aquatide directly activates SIRT1 and stimulates autophagy induction in cultured human dermal fibroblasts. Next, we found that Aquatide-mediated activation of SIRT1 increases autophagy induction via deacetylation of forkhead box class O (FOXO) 1. Finally, UVB irradiation-induced cellular senescence measured by SA-β-gal staining was significantly decreased in cells treated with Aquatide in parallel to occurring SIRT1 activation-dependent autophagy. Together, Aquatide modulates autophagy through SIRT1 activation, contributing to suppression of skin aging caused by UV irradiation.

show abstract

Section: Methodsmentioning

confidence: 99%

Aquatide Activation of SIRT1 Reduces Cellular Senescence through a SIRT1-FOXO1-Autophagy Axis

Lim

Lee

Kang

et al. 2017

Biomolecules & Therapeutics

View full text Add to dashboard Cite

show abstract

“…Chlorodifluoroacetates (ClCF 2 COONa or ClCF 2 COOMe) are also useful reagents for the preparation of aryl difluoromethyl ethers from phenols . Other reported methods, such as using CF 2 Br 2 , CF 3 COONa, FSO 2 CF 2 COOH, CF 3 ZnBr, CHF 2 I, CHF 2 Br, and XeF 2 , are scarcely used due to the low product yields of aryl difluoromethyl ethers and/or the difficulty in preparing the reagents themselves. On the other hand, chlorodifluoromethane (Freon-22) itself is a ozone-depleting substance (ODS), and chlorodifluoroacetic acid derivatives are commonly prepared directly or indirectly from ozone-depleting precursors .…”

mentioning

confidence: 99%

2-Chloro-2,2-difluoroacetophenone: A Non-ODS-Based Difluorocarbene Precursor and Its Use in the Difluoromethylation of Phenol Derivatives

Zhang

Zheng

2006

J. Org. Chem.

View full text Add to dashboard Cite

A novel and non-ODS-based (ODS = ozone-depleting substance) preparation of 2-chloro-2,2-difluoroacetophenone (1) was achieved in high yield by using 2,2,2-trifluoroacetophenone as the starting material. Compound 1 was found to act as a good difluorocarbene reagent, which readily reacts with a variety of structurally diverse phenol derivatives 4 in the presence of potassium hydroxide or potassium carbonate to produce aryl difluoromethyl ethers 5 in good yields. This new and easy-to-handle synthetic methodology offers an environmentally friendly alternative to other Freon- or Halon-based difluoromethylating approaches.

show abstract

“…Multiple groups attempted to address these limitations through the synthesis of selective nonsteroidal GR antagonists, namely, chromene 6 or arylindazole derivatives. 7 We focused on developing a novel, potent, and selective nonsteroidal GR antagonist for the treatment of depression.…”

Section: ■ Introductionmentioning

confidence: 99%

“…However, an abortifacient effect due to the potent progesterone receptor (PR) antagonist activity, rapid clearance from the body, and cross-reactivity with other steroid hormone receptors hampered its use as an antidepressant agent. Multiple groups attempted to address these limitations through the synthesis of selective nonsteroidal GR antagonists, namely, chromene or arylindazole derivatives . We focused on developing a novel, potent, and selective nonsteroidal GR antagonist for the treatment of depression.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Cyclopentaquinoline Derivatives as Nonsteroidal Glucocorticoid Receptor Antagonists

Eda¹,

Kuroda²,

Kaneko³

et al. 2015

J. Med. Chem.

View full text Add to dashboard Cite

The steroidal glucocorticoid antagonist mifepristone has been reported to improve the symptoms of depression. We report the discovery of 6-(3,5-dimethylisoxazol-4-yl)-2,2,4,4-tetramethyl-2,3,4,7,8,9-hexahydro-1H-cyclopenta[h]quinolin-3-one 3d (QCA-1093) as a novel nonsteroidal glucocorticoid receptor antagonist. The compound displayed potent in vitro activity, high selectivity over other steroid hormone receptors, and significant antidepressant-like activity in vivo.

show abstract

Synthesis and biological evaluation of novel, selective, nonsteroidal glucocorticoid receptor antagonists

Cited by 21 publications

References 11 publications

Aquatide Activation of SIRT1 Reduces Cellular Senescence through a SIRT1-FOXO1-Autophagy Axis

Aquatide Activation of SIRT1 Reduces Cellular Senescence through a SIRT1-FOXO1-Autophagy Axis

2-Chloro-2,2-difluoroacetophenone: A Non-ODS-Based Difluorocarbene Precursor and Its Use in the Difluoromethylation of Phenol Derivatives

Synthesis and Biological Evaluation of Cyclopentaquinoline Derivatives as Nonsteroidal Glucocorticoid Receptor Antagonists

Contact Info

Product

Resources

About