- Synthesis and pharmacological evaluation of pomalidomide derivatives useful for sickle cell disease treatment
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Fetal hemoglobin (HbF) induction constitutes a valuable and validated approach to treat the symptoms of sickle cell disease (SCD). Here, we synthesized pomalidomide–nitric oxide (NO) donor derivatives (3a–f) and evaluated their suitability as novel HbF in
- de Melo, Thais Regina Ferreira,Dulmovits, Brian,Fernandes, Guilherme Felipe dos Santos,de Souza, Cristiane M.,Lanaro, Carolina,He, Minghzu,Al Abed, Yousef,Chung, Man Chin,Blanc, Lionel,Costa, Fernando Ferreira,dos Santos, Jean Leandro
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- Synthesis and chemiluminescent properties of amino-acylated luminol derivatives bearing phosphonium cations
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The monitoring of reactive oxygen species in living cells provides valuable information on cell function and performance. Lately, the development of chemiluminescence-based reactive oxygen species monitoring has gained increased attention due to the advantages posed by chemiluminescence, including its rapid measurement and high sensitivity. In this respect, specific organelle-targeting trackers with strong chemiluminescence performance are of high importance. We herein report the synthesis and chemiluminescence properties of eight novel phosphonium-functionalized amino-acylated luminol and isoluminol derivatives, designed as mitochondriotropic chemiluminescence reactive oxygen species trackers. Three different phosphonium cationic moieties were employed (phenyl, p-tolyl, and cyclohexyl), as well as two alkanoyl chains (hexanoyl and undecanoyl) as bridges/linkers. Synthesis is accomplished via the acylation of the corresponding phthalimides, as phthalhydrazide precursors, followed by hydrazinolysis. This method was chosen because the direct acylation of (iso)luminol was discouraging. The new derivatives’ chemiluminescence was evaluated and compared with that of the parent molecules. A relatively poor chemiluminescence performance was observed for all derivatives, with the isoluminol-based ones being the poorest. This result is mainly attributed to the low yield of the fluorescence species formation during the chemiluminescence oxidation reaction.
- Pantelia, Anna,Daskalaki, Ira,Consuelo Cuquerella,Rotas, Georgios,Miranda, Miguel A.,Vougioukalakis, Georgios C.
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- METHODS FOR THE TREATMENT OF OBESITY USING APREMILAST
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Methods of treating, managing or preventing obesity and overweight are disclosed. Specific methods encompass the administration of apremilast, alone or in combination with additional active agents or treatment regimens.
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Paragraph 0080
(2019/05/22)
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- APREMILAST FOR THE TREATMENT OF A LIVER DISEASE OR A LIVER FUNCTION ABNORMALITY
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Methods of treating, managing or preventing liver disease are disclosed. Specific methods encompass the administration of apremilast, alone or in combination with additional active agents or treatment regimens.
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Paragraph 0099
(2019/09/15)
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- HETEROCYCLIC DEGRONIMERS FOR TARGET PROTEIN DEGRADATION
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This invention provides heterocyclic compounds that bind to E3 Ubiquitin Ligase (typically through cereblon) ("Degrons"), which can be used as is or linked to a Targeting Ligand for a selected Target Protein for therapeutic purposes and methods of use and compositions thereof as well as methods for their preparation.
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Page/Page column 221; 222
(2017/12/02)
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- BROMODOMAIN TARGETING DEGRONIMERS FOR TARGET PROTEIN DEGRADATION
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This invention provides a Degronimer that has an E3 Ubiquitin Ligase targeting moiety (Degron) that can be linked to a Targeting Ligand for a bromodomain protein selected for in vivo degradation to achieve a therapeutic effect, and methods of use and compositions thereof as well as methods for their preparation.
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Page/Page column 248
(2017/12/05)
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- An improved economical process for preparation of apremilast and identified their impurities
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The object of the present study is to provide an improved and commercially viable process for the preparation of apremilast, which is simple, cost effective and non-hazardous. In this process avoided the usage of acetic anhydride and high temperature. In this method, an alternative process using protected 3-aminophthalic acid (2) with acetyl chloride in the presence of triethanolamine as catalyst in dichloromethane solvent at 0 to 5 °C for 1 h. then followed by condensed with compound 3 to get the final compound 4. Besides, there were two unknown impurities like 3-(amino-1,3-dioxoisoindolin-2-yl)phthalic acid (5) and 4-aminoisobenzofuran-1,3-dione (6) identified by HPLC. A thorough study has been under taken to synthesize and characterize these unknown impurities. This improved process has a number of industrial advantages, such as economical material cost and relatively high yield. The structure of the synthesized compounds was elucidated by IR, 1H NMR, 13C NMR, mass spectroscopy and elemental analyses.
- Jagannadham,Ramadevi,Prasanna
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p. 2749 - 2751
(2016/10/18)
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- Practical synthesis of a phthalimide-based Cereblon ligand to enable PROTAC development
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The use of small molecules to regulate cellular levels of specific proteins is poised to become a powerful technique in the coming years. Critical to the success of any project utilizing such an approach will be the ability to synthesize libraries of candidate small molecules for testing in cellular systems. Herein, we describe a practical synthesis of a phthalimide-based scaffold, which can be easily diversified to make Cereblon-targeting PROTACs. We demonstrate the effectiveness of this approach by synthesizing a ‘PROTAC toolbox’ of four amines which can be coupled to inhibitors in a straightforward manner.
- Lohbeck, Jasmin,Miller, Aubry K.
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supporting information
p. 5260 - 5262
(2016/10/30)
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- Reduction of 3-nitrophthalic anhydride by SnCl2 in different alcohols: A simple synthesis of alkyl 1,3-dihydro-3-oxo-2,1-benzisoxazole-4- carboxylates
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A new, mild and efficient process is developed for the synthesis of alkyl 1,3-dihydro-3-oxo-2,1-benzisoxazole-4-carboxylates through the reduction of 3-nitrophthalic anhydride by SnCl2 in different alcohols. The synthesis of benzisoxazoles bearing a sulfonamide functionality is also reported. The structure of sulfonamide 8d is confirmed by X-ray diffraction analysis.
- Chicha, Hakima,Abbassi, Najat,Rakib, El Mostapha,Khouili, Mostafa,El Ammari, Lahcen,Spinelli, Domenico
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supporting information
p. 1569 - 1571
(2013/03/28)
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