50651-75-7Relevant academic research and scientific papers
Pd(II)-Catalyzed Alkylation of Tertiary Carbon via Directing-Group-Mediated C(sp3)-H Activation: Synthesis of Chiral 1,1,2-Trialkyl Substituted Cyclopropanes
Hoshiya, Naoyuki,Takenaka, Kei,Shuto, Satoshi,Uenishi, Jun'ichi
, p. 48 - 51 (2016)
A Pd(OAc)2-catalyzed alkylation reaction of the tertiary carbon of chiral cyclopropane substrates with alkyl iodides and bromides via C(sp3)-H activation has been developed. This is an elusive example of a C-H activation-mediated alkylation of tertiary carbon to effectively construct a quaternary carbon center. The alkylation proceeded with various alkyl halides, including those of functional groups, to provide a variety of chiral cis- and trans-1,1,2,-trialkyl substituted cyclopropanes of medicinal chemical importance.
Tunable phosphatase-sensitive stable prodrugs of 5-aminolevulinic acid for tumor fluorescence photodetection
Babi?, Andrej,Herceg, Viktorija,Ateb, Imène,Allémann, Eric,Lange, Norbert
, p. 155 - 164 (2016)
5-Aminolevulinic acid (5-ALA) has been at the forefront of small molecule based fluorescence-guided tumor resection and photodynamic therapy. 5-ALA and two of its esters received marketing authorization but suffer from several major limitations, namely low stability and poor pharmacokinetic profile. Here, we present a new class of 5-ALA derivatives aiming at the stabilization of 5-ALA by incorporating a phosphatase sensitive group, with or without self-cleavable linker. Compared to 5-ALA hexyl ester (5-ALA-Hex), these compounds display an excellent stability under acidic, basic and physiological conditions. The activation and conversion into the 5-ALA is controlled and can be structure-tailored. The prodrugs display reduced acute toxicity compared to 5-ALA-Hex with superior dose response profiles of protoporphyrin IX synthesis and fluorescence intensity in human glioblastoma cells in vitro. Clinically relevant fluorescence kinetics in vivo shown in U87MG glioblastoma spheroid tumor model in chick embryos provide a solid basis for their further development and translation to clinical fluorescence guided tumor resection and photodynamic therapy.
Prodrug Strategies to Improve the Solubility of the HCV NS5A Inhibitor Pibrentasvir (ABT-530)
Randolph, John T.,Voight, Eric A.,Greszler, Stephen N.,Uno, Brice E.,Newton, James N.,Gleason, Kenneth M.,Stolarik, DeAnne,Van Handel, Cecilia,Bow, Daniel A. J.,Degoey, David A.
supporting information, p. 11034 - 11044 (2020/11/09)
A research program to discover solubilizing prodrugs of the HCV NS5A inhibitor pibrentasvir (PIB) identified phosphomethyl analog 2 and trimethyl-lock (TML) prodrug 9. The prodrug moiety is attached to a benzimidazole nitrogen atom via an oxymethyl linkage to allow for rapid and complete release of the drug for absorption following phosphate removal by intestinal alkaline phosphatase. These prodrugs have good hydrolytic stability properties and improved solubility compared to PIB, both in aqueous buffer (pH 7) and FESSIF (pH 5). TML prodrug 9 provided superior in vivo performance, delivering high plasma concentrations of PIB in PK studies conducted in mice, dogs, and monkeys. The improved dissolution properties of these phosphate prodrugs provide them the potential to simplify drug dosage forms for PIB-containing HCV therapy.
PRODRUG MODULATORS OF THE INTEGRATED STRESS PATHWAY
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Paragraph 00276; 00278, (2020/05/19)
Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases, disorders and conditions.
Posaconazole derivative, pharmaceutical composition and use thereof
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Page/Page column 277-278, (2020/01/22)
The present disclosure provides a posaconazole derivative, a pharmaceutical composition and use thereof, which specifically include a compound represented by the following formula (I), a racemate, stereoisomer, tautomer, oxynitride, or a pharmaceutically acceptable salt thereof: The compounds of the present disclosure have strong antifungal activity, high safety, and good water solubility, without the need for the addition of a cosolvent (such as hydroxypropyl-β-cyclodextrin, sulfobutyl ether-β-cyclodextrin, and the like) with potential safety risks. Furthermore, the formulation process of the compound could have less difficulty and less cost, and therefore can be used to prepare improved antifungal drugs.
Methylphenidate-Prodrugs, Processes of Making and Using the Same
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Paragraph 0284, (2015/11/10)
The present technology is directed to prodrugs and compositions for the treatment of various diseases and/or disorders comprising methylphenidate, or methylphenidate derivatives, conjugated to at least one alcohol, amine, oxoacid, thiol, or derivatives thereof. In some embodiments, the conjugates further include at least one linker. The present technology also relates to the synthesis of methylphenidate, or methylphenidate derivatives, conjugated to at least one alcohol, amine, oxoacid, thiol, or derivatives thereof or combinations thereof.
METHYLPHENIDATE-PRODRUGS, PROCESSES OF MAKING AND USING THE SAME
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Paragraph 00249; 00250, (2013/03/26)
The present technology is directed to prodrugs and compositions for the treatment of various diseases and/or disorders comprising methylphenidate, or methylphenidate derivatives, conjugated to at least one alcohol, amine, oxoacid, thiol, or derivatives thereof. In some embodiments, the conjugates further include at least one linker. The present technology also relates to the synthesis of methylphenidate, or methylphenidate derivatives, conjugated to at least one alcohol, amine, oxoacid, thiol, or derivatives thereof or combinations thereof.
