229625-50-7Relevant academic research and scientific papers
Synthesis and evaluation of prodrugs of corticotropin-releasing factor-1 (CRF1) receptor antagonist BMS-665053 leading to improved oral bioavailability
Hartz, Richard A.,Vrudhula, Vivekananda M.,Ahuja, Vijay T.,Grace, James E.,Lodge, Nicholas J.,Bronson, Joanne J.,Macor, John E.
, p. 1360 - 1363 (2017)
A series of phosphate and ester-based prodrugs of anilinopyrazinone 1 (BMS-665053) containing either a methylene or an (acyloxy)alkoxy linker was prepared and evaluated in rat pharmacokinetic studies with the goal of improving the oral bioavailability of the parent (1). The prodrugs, in general, had improved aqueous solubility and oral bioavailability compared to 1. Prodrug 12, which contains an (acyloxy)alkoxy linker, showed the greatest improvement in the oral bioavailability relative to the parent (1), with a seven-fold increase (from 5% to 36%) in rat pharmacokinetic studies.
Novel triclabendazole prodrug: A highly water soluble alternative for the treatment of fasciolosis
Flores-Ramos, Miguel,Ibarra-Velarde, Froylán,Jung-Cook, Helgi,Hernández-Campos, Alicia,Vera-Montenegro, Yolanda,Castillo, Rafael
, p. 616 - 619 (2017)
In this work we present the synthesis, aqueous solubility and stability, hydrolysis by alkaline phosphatase, and in vivo fasciolicidal activity in sheep of a highly water soluble phosphate salt prodrug of triclabendazole (MFR-5). The aqueous solubility of MFR-5 at pH 7 was 88,000-fold that of triclabendazole. MFR-5 showed excellent aqueous stability (>95% after 26?h) at pH 7, making it ideal for developing pharmaceutical compositions in the form of solutions that can easily be hydrolyzed by the enzyme alkaline phosphatase (t?=?13.6?s) to liberate the precursor compound. An aqueous solution of MFR-5 administered intramuscularly to sheep at concentrations of 4, 6 and 8?mg/kg presented a fasciolicidal efficiency of 96.5%, 98.4% and 99.2%, respectively. In the in vivo experiments, MFR-5 reduced 100% the excretion of eggs in all of the above concentrations.
A novel synthetic route for the preparation of alkyl and benzyl chloromethyl phosphates
M?ntyl?, Antti,Veps?l?inen, Jouko,J?rvinen, Tomi,Nevalainen, Tapio
, p. 3793 - 3794 (2002)
An efficient and simple synthesis is described for the production of various chloromethyl phosphates as useful reagents for the preparation of phosphonooxymethyl prodrugs.
A highly water soluble benzimidazole derivative useful for the treatment of fasciolosis
Flores-Ramos, Miguel,Ibarra-Velarde, Froyln,Hernndez-Campos, Alicia,Vera-Montenegro, Yolanda,Jung-Cook, Helgi,Cant-Alarcn, Germinal J.,Del Rivero, Lauro Misael,Castillo, Rafael
, p. 5814 - 5817 (2014)
This study describes the synthesis of compound (7), a highly hydrosoluble phosphonooxymethyl prodrug of compound alpha (4). Compound (7) improved the aqueous solubility of its precursor compound (4) by 50,000 times and it is stable at neutral pH. The prodrug showed faciolicidal activity when evaluated in vitro against excysted Fasciola hepatica metacercariae. The in vivo evaluation of (7) was carried out via oral, intramuscular and subcutaneous administration in sheep artificially infected with F. hepatica metacercariae. At an intramuscular dose of 4 mg/kg, the activity of (7) was similar to that of compound alpha (4) at an oral dose of 15 mg/kg.
PRODRUGS IN THE MODULATION OF INTERLEUKIN
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Page/Page column 33-34, (2021/02/12)
There are disclosed prodrugs of the compounds of the formula. The prodrugs are useful in the modulation of IL-12, IL-23 and/or IFNα, by acting on Tyk-2 to cause signal transduction inhibition.
POMALIDOMIDE DERIVATIVE AND PREPARATION METHOD THEREFOR
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Paragraph 0120-0121, (2020/07/14)
Disclosed in the present invention are a Pomalidomide derivative and a preparation method therefor. Specifically, the present invention relates to the Pomalidomide derivative and a stereoisomer thereof, or a pharmaceutically acceptable salt, and applications thereof in the preparation of drugs for treating cancers.
TRIAZOLE ANTIMICROBIAL DERIVATIVE, PHARMACEUTICAL COMPOSITION AND USE THEREOF
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Paragraph 0259-0261, (2020/01/04)
The present disclosure provides a triazole antibacterial derivative and a pharmaceutical composition thereof and a use thereof and in particular relates to a compound represented by the following formula (I), and a racemate, a stereoisomer, a tautomer, an oxynitride or a pharmaceutically acceptable salt thereof: The compound of the present disclosure has a desirable water solubility and can be formulated into an injection for use without adding a cosolvent having a potential safety risk (such as hydroxypropyl-β-cyclodextrin, sulfobutylether-β-cyclodextrin, and the like), facilitating drug administration for patients, and greatly improving clinical safety. The drug can be used even by patients with moderate or severe renal impairment, thereby expanding the application scope of the drug.
Posaconazole derivative, pharmaceutical composition and use thereof
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Page/Page column 256-258, (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.
POMALIDOMIDE DERIVATIVES AND THE PREPARING METHOD THEREOF
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Paragraph 0111-0113, (2019/08/01)
The invention relates to pomalidomide derivatives and their stereoisomers or pharmaceutically acceptable salts, and their use in preparing medicaments for treating cancers.
PHENYL-HETEROCYCLE-PHENYL DERIVATIVES FOR USE IN THE TREATMENT OR PREVENTION OF MELANOMA
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Page/Page column 34; 35; 36, (2018/12/02)
The present invention relates to a compound represented by the formula (E) which is useful for treating or preventing melanoma.
