- LIPOCATIONIC POLYMERS AND USES THEREOF
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Polymers produced by ring opening polymerization which comprises an amino group that can be used in compositions to deliver a nucleic acid such as a miRNA or a siRNA. In some embodiments, compositions which comprise the polymers described herein and a nucleic acid are also provided herein. In some embodiments, these compositions are used to silence one or more genes in vivo or treat a disease or disorder.
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Page/Page column 46;47
(2016/07/05)
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- Rapid Synthesis of a Lipocationic Polyester Library via Ring-Opening Polymerization of Functional Valerolactones for Efficacious siRNA Delivery
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The ability to control chemical functionality is an exciting feature of modern polymer science that enables precise design of drug delivery systems. Ring-opening polymerization of functional monomers has emerged as a versatile method to prepare clinically translatable degradable polyesters.1 A variety of functional groups have been introduced into lactones; however, the direct polymerization of tertiary amine functionalized cyclic esters has remained elusive. We report a strategy that enabled the rapid synthesis of >130 lipocationic polyesters directly from functional monomers without protecting groups. These polymers are highly effective for siRNA delivery at low doses in vitro and in vivo.
- Hao, Jing,Kos, Petra,Zhou, Kejin,Miller, Jason B.,Xue, Lian,Yan, Yunfeng,Xiong, Hu,Elkassih, Sussana,Siegwart, Daniel J.
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supporting information
p. 9206 - 9209
(2015/08/06)
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- NOVEL CYCLOSPORIN DERIVATIVES AND USES THEREOF
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The present invention relates to a compound of the Formula (I)): or pharmaceutically acceptable salt thereof, wherein the symbols are as defined in the specification; a pharmaceutical composition comprising the same, a method for treating or preventing viral infections, inflammation, dry eye, central nervous disorders, cardiovascular diseases, cancer, obesity, diabetes, muscular dystrophy, and hair loss.
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- Discovery and SAR of novel pyrazole-based thioethers as cathepsin S inhibitors. Part 2: Modification of P3, P4, and P5 regions
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A novel class of tetrahydropyrido-pyrazole thioether amines that display potency against human Cathepsin S have been previously reported. Here, further SAR investigations of the P3, P4, and P5 regions are described. In particular, 4-fluoropiperidine is identified as a competent P3 binding element when utilized in conjunction with a (S)-2-hydroxypropyl linker-containing P5 moiety and oxamide or sulfonamide P4 substitution.
- Wiener, John J.M.,Wickboldt Jr., Alvah T.,Wiener, Danielle K.,Lee-Dutra, Alice,Edwards, James P.,Karlsson, Lars,Nguyen, Steven,Sun, Siquan,Jones, Todd K.,Grice, Cheryl A.
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scheme or table
p. 2375 - 2378
(2010/07/14)
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- Substituted benzo(b)thiophene compounds having activity as selective estrogen receptor modulators
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The present invention provides compounds with nitrogen, sulfur or carbon linked basic side chains of formula where R1and R2are independently hydrogen, halo, hydroxy, alkoxy, alkylcarbonyloxy, alkoxycarbonyl, alkoxycarbonyloxy, arylca
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- Omega-quaternary ammonium alkyl esters and thioesters of acidic nonsteroidal antiinflammatory drugs
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Quaternary ammonium alkyl esters and thioesters of acidic nonsteroidal anti-inflammatory drugs (NSAIDs) are disclosed. These esters and thioesters display the anti--inflammatory profile of the parent NSAIDs with greatly reduced gastrointestinal irritancy, providing a more favorable separation of therapeutic activity and toxicological side effects than the parent NSAIDs.
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- Structure-Activity Relationships among Di- and Tetramine Disulfides Related to Benextramine
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The synthesis and irreversible α-blocking activity in the rat vas deferens of a series of tetra- and diamine disulfides 2-38, structural analogues of benextramine (BHC), are described. All compounds containing a central cystamine moiety displayed an irreversible α-adrenergic blockade at concentrations ranging from 10-4 to 6*10-6 M. Potency was increased in cystamines N,N'-disubstituted with 6-aminohexyl groups, especially when the outer nitrogen atoms bear arylalkyl substituents or are enclosed in a ring. However, N,N,N',N'-tetrasubstituted cystamines were poor blockers. Structural specificity in the outer portion of the tetramine disulfide is low, since many types of substituents gave rise to potent α-blockers. Even replacement of the outer amines with nonbasic ethers or amides was observed to maintain irreversible α-blockade.
- Alvarez, M.,Granados, R.,Mauleon, D.,Rosell, G.,Salas, M.,et al.
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p. 1186 - 1193
(2007/10/02)
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