61413-67-0Relevant articles and documents
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.
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)
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.
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.
