61413-67-0Relevant academic research and scientific papers
Prodrugs of pioglitazone for extended-release (XR) injectable formulations
Sanrame, Carlos N.,Remenar, Julius F.,Blumberg, Laura C.,Waters, Julie,Dean, Reginald L.,Dong, Nan,Kriksciukaite, Kristi,Cao, Peixin,Almarsson, ?rn
, p. 3617 - 3623 (2014)
N-Acyloxymethyl derivatives of pioglitazone (PIO) have been prepared and characterized as model candidates for extended-release injectable formulations. All PIO derivatives prepared are crystalline solids as determined by powder X-ray diffraction, and the solubility in aqueous media is below 1 μM at 37 °C. The melting points steadily increase from 55 °C, for the hexanoyloxymethyl derivative, to 85 °C, for the palmitoyloxymethyl derivative; inversely, the solubilities in ethyl oleate decrease as a function of increasing acyl chain length. The butyroyloxymethyl ester has a higher melting point and a lower solubility in ethyl oleate than expected from the trend. The 13C solid-state NMR spectra of the PIO homologues between the hexanoyloxymethyl derivative and stearoyloxymethyl derivative suggest a common structural motif with the acyl chains exchanging between two distinct conformations, and the rate of exchange is slower for longer chain derivatives. The butyroyloxymethyl derivative is efficiently converted to PIO in in vitro rat plasma with a half-life of o C, while the rate of enzymatic cleavage in rat plasma decreases as the ester chain length increases for the longer acyloxymethyl derivatives. The concentration of PIO in plasma increases rapidly, or "spikes," in the hours following intramuscular (IM) injection of either the HCl salt or the butyroyloxymethyl derivative. In contrast, the more lipophilic palmitoyloxymethyl derivative provides slow growth in the PIO concentration over the first day to reach levels that remain steady for 2 weeks. On the basis of its in vivo pharmacokinetic profile, as well as material and solubility properties, the PIO palmitoyloxymethyl derivative has potential as a once-monthly injectable medication to treat diabetes.
Erufosine (ErPC3) Cationic Prodrugs as Dual Gene Delivery Reagents for Combined Antitumor Therapy
Gaillard, Boris,Seguin, Cendrine,Remy, Jean-Serge,Pons, Fran?oise,Lebeau, Luc
, p. 15662 - 15679 (2019)
Sixteen cationic prodrugs of the antitumor alkylphospholipid (APL) erufosine were rationally synthesized to provide original gene delivery reagents with improved cytotoxicity profile. The DNA complexation properties of these cationic lipids were determined and associated transfection rates were measured. Furthermore, the self-assembly properties of the pro-erufosine compounds were investigated and their critical aggregation concentration was determined. Their hydrolytic stability under pH conditions mimicking the extracellular environment and the late endosome milieu was measured. Hemolytic activity and cytotoxicity of the compounds were investigated. The results obtained in various cell lines demonstrate that the prodrugs of erufosine display antineoplastic activity similar to that of the parent antitumor drug but are not associated with hemolytic toxicity, which is a dose-limiting side effect of APLs and a major obstacle to their use in anticancer therapeutic regimen. Furthermore, by using lipoplexes prepared from a prodrug of erufosine and a plasmid DNA encoding a pro-apoptotic protein (TRAIL), evidence was provided for selective cytotoxicity towards tumor cells while nontumor cells were resistant. This study demonstrates that the combination approach involving well tolerated erufosine cationic prodrugs and cancer gene therapy holds significant promise in tumor therapy.
PRODRUGS OF CGRP ANTAGONISTS
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Page/Page column 58; 59, (2020/05/19)
Disclosed are prodrugs of CGRP antagonists, methods of treating CGRP related disorders, e.g., migraine, by administering to a patient in need thereof the prodrugs, pharmaceutical compositions comprising prodrugs and kits including the pharmaceutical compositions and instructions for use.
ORGANIC COMPOUNDS
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Paragraph 00203, (2020/07/14)
The invention relates to particular substituted heterocycle fused gamma-carbolines, in free, solid, pharmaceutically acceptable salt and/or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use in the treatme
PRODRUGS OF A CDK INHIBITOR FOR TREATING CANCERS
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Paragraph 00120, (2020/11/03)
There are provided compounds of Formula I, and pharmaceutically acceptable salts and esters thereof, and pharmaceutical compositions thereof, used for inhibition or modulation of the activity of cyclin dependent kinases (CDK) and/or glycogen synthase kinase-3 (GSK-3), for the treatment of disease states or conditions mediated by cyclin dependent kinases and/or glycogen synthase kinase-3, including cancers. (I)
Opioid receptor antagonist prodrugs
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Page/Page column 115-116, (2020/02/03)
Provided herein are prodrugs of opioid receptor antagonists such as nalmefene and naltrexone, pharmaceutical compositions comprising said compounds, and methods for using said compounds for the treatment of behavioral disorders.
PRODRUGS OF 4-((1R,3S)-6-CHLORO-3-PHENYL-2,3-DIHYDRO-1H-INDEN-1-YL)-1,2,2-TRIMETHYLPIPERAZINE AND 4-((1/R,3S)-6-CHLORO-3-(PHENYL-D5)-2,3-DIHYDRO-1H-INDEN-1-YL)-2,2-DIMETHY-1-(METHYL-D3)PIPERAZINE
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Page/Page column 14, (2020/07/06)
The present invention relates to prodrugs of 4-((1R,3S)-6-chloro-3-phenyl-2,3-dihydro-1H-inden-1-yl)- 1,2,2-trimethylpiperazine in the form of 1a and 1b; and 4-((1R,3S)-6-chloro-3-(phenyl-d5)-2,3-dihydro- 1H-inden-1-yl)-2,2-dimethyl-1-(methyl-d
2, 4-dinitrophenol derivative and application thereof
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Paragraph 0115-0116; 0118, (2020/08/18)
The present invention relates to a 2, 4-dinitrophenol derivative represented by a general formula (I) or a pharmaceutically acceptable salt thereof, in which L and R are as described in the text, anda composition comprising an effective dose of a compound of general formula (I) or a pharmaceutically acceptable salt thereof. The compound with the general formula (I) or the pharmaceutical salt thereof is used for treating the non-alcoholic fatty liver disease. The invention also discloses application of the traditional Chinese medicine composition in medicines for treating non-alcoholic steatohepatitis, hepatic steatosis, type 2 diabetes mellitus, acquired dyslipidemia, dyslipidemia, local dyslipidemia, hypertriglyceridemia, obesity, metabolic syndrome, Rette's syndrome, aging-related metabolic syndrome or insulin resistance and the like.
COMPOUNDS WITH HIV MATURATION INHIBITORY ACTIVITY
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Page/Page column 11-12, (2019/11/12)
The present invention relates to compound of Formula I or a pharmaceutically acceptable salt thereof (Formula I) wherein R1 is Formula (AA) or Formula (BB) where the squiggly line indicates the point of attachment to the rest of the molecule; R2 is F or Formula (CC) where the squiggly line indicates the point of attachment to the rest of the molecule; R3 is H or CH3; Z is O or is absent; and R4 is -OC1-3alkyl, C1-30alkyl, or -N(CH3)2.
ORGANIC COMPOUNDS
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Paragraph 0178-0180, (2019/02/13)
The invention relates to particular prodrugs of substituted heterocycle fused gamma-carbolines, in free, solid, pharmaceutically acceptable salt and/or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use in the treatment of diseases involving the 5-HT2A receptor, the serotonin transporter (SERT), pathways involving the dopamine D1 and D2 receptor signaling system, and/or the μ-opioid receptor.
