- Synthesis and characterization of polymethacrylate-based nitric oxide donors
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A synthetic path for the preparation of methacrylic homo- and copolymers containing secondary amine groups that can be converted into nitric oxide (NO) releasing N-diazeniumdiolates is described. The polymers are obtained by a multistep procedure involving synthesis of methacrylate monomers containing boc-protected secondary amine sites, free radical benzoyl peroxide initiated polymerization, deprotection of the amine sites, and subsequent reaction of the polymers with NO in the presence of sodium methoxide. Monomers with both linear and cyclic pendant secondary amines are examined as polymer building blocks. In most cases, polymers are obtained for both types with compositions that agree well with initial monomer ratios and with number average molecular weights (Mn) ranging from 1.69 to 2.58 × 106 Da. The final N-diazeniumdiolated methacrylic amine polymers are shown to release NO for extended periods of time with "apparent" t1/2 values ranging from 30 to 60 min when suspended in phosphate buffer, pH 7.4. Total NO loading and release for these materials can reach 1.99 μmol per mg of polymer and is proportional to the amine content of the polymer. It is further shown that by using a dimethacrylate cross-linking agent in conjunction with the various methacrylate amines, suspension polymerization methods can be employed to create small (100-200 μm) polymeric methacrylate microbeads. Such microbeads that can be sequentially deprotected and converted to NO release particles via in-situ diazeniumdiolate formation as carried out for the non-crosslinked polymers.
- Parzuchowski, Pawel G.,Frost, Megan C.,Meyerhoff, Mark E.
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Read Online
- ADENOSINE RECEPTOR BINDING COMPOUNDS
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The present invention relates to pharmaceutical compounds and compositions of Formula (I) and methods of treatment using the compounds and compositions, especially for the treatment and/or prevention of a proliferation disorder, such as cancer. Compounds of Formula (I) as further described herein are shown modulators of the adenosine A2A receptor and exhibit antiproliferative activity. Accordingly, these compounds are useful to treat proliferative disorders such as cancer, and other adenosine receptor-related conditions including an inflammatory disease, renal disease, diabetes, vascular disease, lung disease, or an autoimmune disease.
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Paragraph 00366
(2020/02/06)
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- Hierarchically assembled helicates as reaction platform – from stoichiometric Diels–Alder reactions to enamine catalysis
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The stereoselectivity of a Diels–Alder reaction within the periphery of hierarchically assembled titanium(IV) helicates formed from mixtures of achiral, reactive and chiral, unreactive ligands was investigated in detail. Following the pathway of the chiral induction, the chiral ligands, solvents as well as substituents at the dienophile were carefully varied. Based on the results of the stoichiometric reaction, a secondary amine-catalyzed nitro-Michael reaction is performed as well which afforded reasonable diastereoselectivities.
- Albrecht, Markus,Begall, Jenny,Craen, David Van,Gro?kurth, Johannes,Himmel, Leonard,Isaak, Elisabeth,Linnenberg, Oliver
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supporting information
p. 2338 - 2345
(2020/11/02)
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- Rigorous control of vesicle-forming lipid pKa by fluorine-conjugated bioisosteres for gene-silencing with siRNA
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While the influence of pKa provided by amine-containing materials in siRNA delivery vectors for use in gene-silencing has been widely studied, there are little reports in which amine pKa is controlled rigorously by using bioisosteres and its effect on gene-silencing. Here, we report that amine pKa could be rigorously controlled by replacement of hydrogen atom(s) with fluorine atom(s). A series of mono- and di-amine lipids with a different number of fluorine atoms were synthesized. The pKa of the polyamine lipids was shifted to a lower value with an increase in the number of fluorine atoms. The optimal pKa for high gene-silencing efficiency varied according to the number of amine residues in the polyamine lipid. Whereas the endosomal escape ability of mono-amine lipid-containing lipid vesicles (LVs) depended on the pKa, that of all tested di-amine lipid-containing LVs showed equal membrane-destabilizing activity. LVs showing moderately weak interactions with siRNA facilitated cytoplasmic release of siRNA, resulting in strong gene-silencing. These findings indicate that appropriate amine pKa engineering depending on the number of amines is important for the induction of effective RNA interference.
- Okamoto, Ayaka,Koide, Hiroyuki,Morita, Naoki,Hirai, Yusuke,Kawato, Yuji,Egami, Hiromichi,Hamashima, Yoshitaka,Asai, Tomohiro,Dewa, Takehisa,Oku, Naoto
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- XANTHENE COMPOUND
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PROBLEM TO BE SOLVED: To provide a novel xanthene compound having high oil solubility, and a dye composition prepared with the compound. SOLUTION: The present invention provides a compound represented by the formula (1) and an oily or aqueous dye composit
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Paragraph 0076
(2017/08/26)
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- Compounds
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Pyrimidone compounds of formula (I): are inhibitors of the enzyme Lp-PLA2 and are of use in treating atherosclerosis.
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Page/Page column 18
(2016/05/11)
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- CONTROLLED RELEASE PREPARATION
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A controlled release preparation wherein the release of active ingredient is controlled, which releases an active ingredient for an extended period of time by staying or slowly migrating in the gastrointestinal tract, is provided by means such as capsulating a tablet, granule or fine granule wherein the release of active ingredient is controlled and a gel-forming polymer. Said tablet, granule or fine granule has a release-controlled coating-layer formed on a core particle containing an active ingredient.
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Paragraph 0438; 0439; 0440
(2016/06/06)
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- Reversible pH-controlled switching of an artificial antioxidant selenoenzyme based on pseudorotaxane formation and dissociation
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A pH-responsive artificial selenoenzyme was constructed by reversible binding between organoselenium compound 1 and CB[6] to form a pseudorotaxane-based molecular switch in response to pH stimuli. The glutathione peroxidase (GPx) activity of the artificia
- Li, Jiaxi,Si, Chengye,Sun, Hongcheng,Zhu, Junyan,Pan, Tiezheng,Liu, Shengda,Dong, Zeyuan,Xu, Jiayun,Luo, Quan,Liu, Junqiu
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supporting information
p. 9987 - 9990
(2015/06/22)
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- Structure-property relationships of antibacterial amphiphilic polymers derived from 2-aminoethyl acrylate
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The findings from the investigation of an ensemble of amphiphilic polymers derived from 2-aminoethyl acrylate establish significant effects of variation in the topographical position of the cationic center and hydrophobic segments on their biological activities. For example, the isomeric polymer pair of poly(6-aminohexylacrylate) and poly(2-(butylamino)ethyl acrylate) show striking differences in their biological activities, with the former having biological activities orders of magnitude higher. The trend of the activities of alkyl tails attached to the charge center shows an abrupt increase in biological activity at butyl length in the series of methyl to butyl tail. The distribution and interaction of the charge center in the chain domain is one of the main parameters in influencing polymer activities. Within the 2-aminoethyl acrylate system of homo- and copolymer, the homopolymer has its cationic centers closely distributed along the amphiphilic macromolecular chain with proximity to the backbone leading to rigid conformations not conducive to the attachment of the polymer to the cell surface. In copolymers, the incorporation of uncharged counits increases the distance between the cationic centers, resulting in significant reduction of charge repulsion and thus enhancing the flexibility of the chain conformation. This is conducive for polymer-cell association, leading to a remarkable surge in orders of magnitude of biological activity but with low selectivity against bacteria over red blood cells.
- Punia, Ashish,Debata, Priya R.,Banerjee, Probal,Yang, Nan-Loh
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p. 95300 - 95306
(2015/11/24)
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- Novel 2,4-Dianilinopyrimidine Derivatives, the Preparation Thereof, Their Use as Medicaments, Pharmaceutical Compositions and, in Particular, as IKK Inhibitors
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The disclosure relates to compounds of formula (I): wherein R1-R5, A and Y are as defined in the disclosure, to compositions comprising said compounds, and to processes for making and methods of using the same.
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Page/Page column 49
(2008/12/04)
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- PYRAZOLE DERIVATIVES AS THERAPEUTIC AGENTS
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Salts of 1,5-diarylpyrazole-3-carboxamides and processes for preparing such compounds, their use in the treatment of obesity, psychiatric and neurological disorders, to methods for their therapeutic use and to pharmaceutical compositions containing them.
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Page/Page column 49
(2010/11/26)
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- Design, synthesis, and biological activity of novel PPARγ ligands based on rosiglitazone and 15d-PGJ2
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To develop novel PPARγ ligands, we synthesized thirteen 3-{4-(2-aminoethoxy)phenyl}propanoic acid derivatives, which are designed based on the structures of rosiglitazone and 15d-PGJ2. Among these compounds, compound 9 was found to be as potent as rosiglitazone in a binding assay and a preadipocyte differentiation test. Molecular modeling suggested that the nonyl group of 9 interacted with hydrophobic amino acid residues constructing the hydrophobic region of PPARγ protein where the alkyl chain of 15d-PGJ2 is expected to be located.
- Usui, Shinya,Suzuki, Takayoshi,Hattori, Yoshifumi,Etoh, Kazuma,Fujieda, Hiroki,Nishizuka, Makoto,Imagawa, Masayoshi,Nakagawa, Hidehiko,Kohda, Kohfuku,Miyata, Naoki
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p. 1547 - 1551
(2007/10/03)
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- THERAPEUTIC AGENTS
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The present invention relates to compounds of formula (I) and processes for preparing such compounds, their use in the treatment of obesity, psychiatric and neurological disorders, to methods for their therapeutic use and to pharmaceutical compositions containing them.
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Page/Page column 51-52
(2008/06/13)
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- DRUG COMPOSITION HAVING ACTIVE INGREDIENT ADHERED AT HIGH CONCENTRATION TO SPHERICAL CORE
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Granule, fine particle or tablet of excellent leaching property, comprising a drug active ingredient in high content realized by forming a layer containing drug active ingredient on core particles through a combination of a method of dispersing and adhering an active ingredient while spraying or adding a binder with a method of spraying or adding a solution or suspension wherein an active ingredient and a binder are contained so as to effect adhesion. Further, there are provided a drug composition containing such a granule, fine particle or tablet and a process for producing the same.
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Page/Page column 42
(2010/02/14)
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- CONTROLLED RELEASE COMPOSITION
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The present invention provides a controlled release composition showing release of an active ingredient (proton pump inhibitor) controlled in two or more steps at different release rates, which contains1) a release-controlled part A capable of controlling release of the active ingredient to occur at a predetermined rate,2) a release-controlled part B capable of controlling release of the active ingredient to occur at a predetermined rate lower than the release rate of the release-controlled part A, and where necessary, 3) a release-controlled part C capable of controlling release of the active ingredient to occur at a predetermined rate faster than the release rate of the release-controlled part B, wherein the release of the active ingredient from the release-controlled part B precedes the release of the active ingredient from the release-controlled part A (when release-controlled part C is contained, the release of the active ingredient from the release-controlled part C precedes the release of the active ingredient from the release-controlled part B).
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Page/Page column 49
(2010/02/15)
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- PRODRUGS OF IMIDAZOLE DERIVATIVES, FOR USE AS PROTON PUMP INHIBITORS IN THE TREATMENT OF E.G. PEPTIC ULCERS
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An imidazole compound represented by the formula (I), a salt thereof and a compound of the formula (V), which is one of the intermediates thereof. wherein each symbol is as defined in the present specification. The compound of the present invention shows a superior anti-ulcer activity, a gastric acid secretion inhibitory action, a mucosa-protecting action, an anti-Helicobacter pylori action and the like. Since it shows low toxicity, the compound is useful as a pharmaceutical product.
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- SRC kinase inhibitor compounds
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Pyrimidine compounds (Formula I), or their pharmaceutically acceptable salts, hydrates, solvates, crystal forms and individual diastereomers, and pharmaceutical compositions including the same, which are inhibitors of tyrosine kinase enzymes, and as such are useful in the prophylaxis and treatment of protein tyrosine kinase-associated disorders, such as immune diseases, hyperproliferative disorders and other diseases in which inappropriate protein kinase action is believed to play a role, such as cancer, angiogensis, atheroscelerosis, graft rejection, rheumatoid arthritis and psoriasis.
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