17044-70-1Relevant articles and documents
A general strategy to optimize the performance of aza-BODIPY-based probes for enhanced photoacoustic properties
Yadav, Anuj K.,Tapia Hernandez, Rodrigo,Chan, Jefferson
, p. 415 - 441 (2021/07/26)
In this chapter, we describe a generalizable strategy to obtain a high PA output platform that is optimized for ratiometric imaging. Our approach entails conformationally restricting pendant aryl rings on the aza-BODIPY core to enhance orbital overlap which consequently increases the extinction coefficient. This strategy can potentially be applied to other dye platforms to enhance their signal intensity. We provide detailed protocols for the synthesis, in vitro characterization, and in vivo application.
Development of pH-activatable fluorescent probes for rapid visualization of metastatic tumours and fluorescence-guided surgeryviatopical spraying
Cao, Wenwen,Li, Xiaoxin,Wu, Peng,Xiong, Hu
, p. 10636 - 10639 (2021/10/19)
A series of pH-activatable aza-BODIPY-based fluorescent probes were developed for rapid cancer visualization and real-time fluorescence-guided surgery by harnessing topical spraying. These probes exhibited good water-solubility, a tunable pKafrom 5.0 to 7.9, and stable intense NIR emission at ～725 nm under acidic conditions.AzaB5with a pKavalue of 6.7 was able to rapidly and clearly visualize pulmonary and abdominal metastatic tumours including tiny metastases less than 2 mmviatopical spraying, further improving intraoperative fluorescence-guided resection. We believe thatAzaB5is promising as a powerful tool to rapidly delineate a broad range of malignancies and assist surgical tumour resection.
BETA-HYDROXYETHYLAMINES FOR USE IN THE TREATMENT OR PREVENTION OF NON-ALCOHOLIC FATTY LIVER DISEASES
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, (2019/04/11)
There is herein provided a compound of formula (I) or a pharmaceutically acceptable salt thereof, for use in the treatment of a non-alcoholic fatty liver disease (NAFLD), such as non-alcoholic steatohepatitis (NASH), wherein X, R1, R2, R3 and n have meanings as provided in the description.
A Conformationally Restricted Aza-BODIPY Platform for Stimulus-Responsive Probes with Enhanced Photoacoustic Properties
Zhou, Effie Y.,Knox, Hailey J.,Liu, Chang,Zhao, Weili,Chan, Jefferson
supporting information, p. 17601 - 17609 (2019/11/11)
Photoacoustic (PA) dyes, which absorb near-infrared (NIR) light to generate an ultrasonic signal, can be detected at centimeter depths in tissues with significantly higher resolution than dyes imaged with fluorescence-based methods. As such, PA agents show great promise as research tools for the study of live-animal disease models. However, the development of activatable PA probes has been hampered by the relative scarcity of appropriate PA-active molecular platforms with properties that can be manipulated in a rational manner. Herein we synthesized and evaluated six modifications to the aza-BODIPY dye platform with respect to their absorbance, fluorescence, and PA properties. We identified a promising conformationally restricted aza-BODIPY (CRaB) scaffold that prioritizes three criteria necessary for the design of stimulus-responsive dyes with optimal ratiometric PA response: absorbance at NIR wavelengths, strong PA intensity, and large Δλ upon interaction with the desired stimulus. Using this scaffold, we synthesized three chemically diverse stimulus-responsive PA probes and demonstrated between 2- and 8-fold improvements in theoretical ratiometric response in vitro. This suggests that improvements in PA parameters are generalizable. Finally, we validated the in vitro turnover of each CRaB PA probe and demonstrated the in vivo potential of the CRaB scaffold by direct comparison to an established hypoxia-responsive probe for the detection of tumor hypoxia.
COMPOUNDS FOR THE TREATMENT OF HYPERGLYCAEMIA
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, (2017/09/28)
There is herein provided a compound of formula (I) or a pharmaceutically acceptable salt thereof, for use in the treatment of hyperglycaemia or a disorder characterized by hyperglycaemia, such as type 2 diabetes, wherein X, R1, R2, R3 and n have meanings as provided in the description.
Photoacoustic Probes for Ratiometric Imaging of Copper(II)
Li, Hao,Zhang, Pamela,Smaga, Lukas P.,Hoffman, Ryan A.,Chan, Jefferson
, p. 15628 - 15631 (2016/01/09)
Photoacoustic tomography has emerged as a promising alternative to MRI and X-ray scans in the clinical setting due to its ability to afford high-resolution images at depths in the cm range. However, its utility has not been established in the basic research arena owing to a lack of analyte-specific photoacoustic probes. To this end, we have developed acoustogenic probes for copper(II)-1 and -2 (APC-1 and APC-2, a water-soluble congener) for the chemoselective visualization of Cu(II), a metal ion which plays a crucial role in chronic neurological disorders such as Alzheimer's disease. To detect Cu(II), we have equipped both APCs with a 2-picolinic ester sensing module that is readily hydrolyzed in the presence of Cu(II) but not by other divalent metal ions. Additionally, we designed APC-1 and APC-2 explicitly for ratiometric photoacoustic imaging by using an aza-BODIPY dye scaffold exhibiting two spectrally resolved NIR absorbance bands which correspond to the 2-picolinic ester capped and uncapped phenoxide forms. The normalized ratiometric turn-on responses for APC-1 and APC-2 were 89- and 101-fold, respectively.
Synthesis and SAR studies of marine natural products ma'edamines A, B and their analogues
Saha, Sanjay,Reddy, Ch. Venkata Ramana,Xu, Shili,Sankar, Saranya,Neamati, Nouri,Patro, Balaram
, p. 5135 - 5139 (2013/09/12)
The synthesis of several analogues of ma'edamines A and B are reported. The synthesized compounds were tested on hormone receptor positive and HER2 positive breast cancer cell lines, by MTT assay. MED-114, 115, 117, 119, 120, 124, 128 and 131 were found to be equally active as Lapatinib on HER2 +ve cell line SKBR3.
Cu-Mn spinel oxide catalyzed regioselective halogenation of phenols and N-heteroarenes
Singh, Parvinder Pal,Thatikonda, Thanusha,Kumar, K. A. Aravinda,Sawant, Sanghapal D.,Singh, Baldev,Sharma, Amit Kumar,Sharma,Singh, Deepika,Vishwakarma, Ram A.
scheme or table, p. 5823 - 5828 (2012/09/05)
A novel simple, mild chemo- and regioselective method has been developed for the halogenation of phenols using Cu-Mn spinel oxide as a catalyst and N-halosuccinimide as halogenating agent. In the presence of Cu-Mn spinel oxide B, both electron-withdrawing and electron-donating groups bearing phenols gave monohalogenated products in good to excellent yields with highest para-selectivity. The para-substituted phenol gave monohalogenated product with good yield and ortho-selectivity. N-Heteroarenes such as indoles and imidazoles also gave monohalogenated products with high selectivity. Unlike the copper-catalyzed halogenation, the present method works well with electron-withdrawing group bearing phenols and gives comparatively better yields and selectivity. The Cu-Mn spinel catalyst is robust and reused three times under optimized conditions without any loss in catalytic activity. Nonphenolics did not undergo this transformation.
Thienopyridones as AMPK activators for the treatment of diabetes and obesity
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Page/Page column 38, (2010/02/10)
The present invention relates to compounds that activate AMP-activated protein kinase (AMPK), including the preparation of the compounds, compositions containing the compounds and the use of the compounds in the prevention or treatment of disorders such as diabetes, metabolic syndrome, and obesity.
Diarylspiro[2.4]heptenes as orally active, highly selective cyclooxygenase-2 inhibitors: Synthesis and structure-activity relationships
Huang, Horng-Chih,Li, James J.,Garland, Danny J.,Chamberlain, Timothy S.,Reinhard, Emily J.,Manning, Robert E.,Seibert, Karen,Koboldt, Carol M.,Gregory, Susan A.,Anderson, Gary D.,Veenhuizen, Amy W.,Zhang, Yan,Perkins, William E.,Burton, Earl G.,Cogburn, J. Nita,Isakson, Peter C.,Reitz, David B.
, p. 253 - 266 (2007/10/03)
A novel series of 5,6-diarylspiro[2.4]hept-5-enes was shown to provide highly potent and selective cyclooxygenase-2 (COX-2) inhibitors. A study of structure-activity relationships in this series suggests that 3,4- disubstituted phenyl analogs are generally more selective than 4-substituted phenyl analogs and that replacement of the methyl sulfone group on the 6- phenyl ring with a sulfonamide moiety results in compounds with superior in vivo pharmacological properties, although with lower COX-2 selectivity. Several compounds have been shown to possess promising pharmacological properties in adjuvant-induced arthritis and edema analgesia models. The absence of gastrointestinal (GI) toxicity at 200 mpk of several selected compounds in rats and mice corresponds well with the weak potency for inhibition of COX-1 observed in the enzyme assay. Methyl sulfone 55 and sulfonamide 24 were shown to have superior in vivo pharmacological profiles, low GI toxicity, and good oral bioavailability and duration of action.
