165196-44-1

Upstream product

• 57260-73-8 N-BOC-1,2-diaminoethane 
• 814-68-6 acryloyl chloride 
• 24424-99-5 di-tert-butyl dicarbonate 
• 79513-35-2 N-(tert-butyloxycarbonyl)-1,2-ethanediamine hydrochloride 
• 79-10-7 acrylic acid 
• 107-15-3 ethylenediamine 

Downstream Products

• 23918-29-8 N-[beta-aminoethyl]acrylamide 
• 54641-27-9 N-(2-aminoethyl)prop-2-enamide hydrochloride 

Relevant academic research and scientific papers

Rational Design of Single-Chain Polymeric Nanoparticles That Kill Planktonic and Biofilm Bacteria

Infections caused by multidrug-resistant bacteria are on the rise and, therefore, new antimicrobial agents are required to prevent the onset of a postantibiotic era. In this study, we develop new antimicrobial compounds in the form of single-chain polymeric nanoparticles (SCPNs) that exhibit excellent antimicrobial activity against Gram-negative bacteria (e.g., Pseudomonas aeruginosa) at micromolar concentrations (e.g., 1.4 μM) and remarkably kill ≥99.99% of both planktonic cells and biofilm within an hour. Linear random copolymers, which comprise oligoethylene glycol (OEG), hydrophobic, and amine groups, undergo self-folding in aqueous systems due to intramolecular hydrophobic interactions to yield these SCPNs. By systematically varying the hydrophobicity of the polymer, we can tune the extent of cell membrane wall disruption, which in turn governs the antimicrobial activity and rate of resistance acquisition in bacteria. We also show that the incorporation of OEG groups into the polymer design is essential in preventing complexation with proteins in biological medium, thereby maintaining the antimicrobial efficacy of the compound even in in vivo mimicking conditions. In comparison to the last-resort antibiotic colistin, our lead agents have a higher therapeutic index (by ca. 2-3 times) and hence better biocompatibility. We believe that the SCPNs developed here have potential for clinical applications and the information pertaining to their structure-activity relationship will be valuable toward the general design of synthetic antimicrobial (macro)molecules.

Discovery of a novel covalent CDK4/6 inhibitor based on palbociclib scaffold

Cyclin-dependent kinases 4 and 6 (CDK4/6), which are involved in dynamic regulation of cell cycle, play an indispensable role in controlling the tumor growth. Here, based on the scaffold of palbociclib, we designed and synthesized a series of covalent CDK4/6 inhibitors that targeted amino acid Thr107. The optimized compound C-13 exhibited potent in vitro anticancer activity against CDK4/6 with high selectivity over CDK4/6. Moreover, C-13 showed significant tumor growth inhibition in MDA-MB-231 tumor xenograft model (TGI of 93.49% at dose of 40 mg/kg) without causing significant weight loss and toxicity during the treatment period.

Multi-modal detection of colon malignancy by NIR-tagged recognition polymers and ultrasound contrast agents

To increase colonoscopy capability to discriminate benign from malignant polyps, we suggest combining two imaging approaches based on targeted polymeric platforms. Water-soluble cationized polyacrylamide (CPAA) was tagged with the near infrared (NIR) dye IR-783-S-Ph-COOH to form Flu-CPAA. The recognition peptide VRPMPLQ (reported to bind specifically to CRC tissues) was then conjugated with the Flu-CPAA to form Flu-CPAA-Pep which was then incorporated into echogenic microbubbles (MBs) made of polylactic acid (PLA) that are highly responsive to ultrasound. The ultimate design includes intravenous administration combined with local ultrasound and intra-colon inspection at the NIR range. In this proof of principle study PLA MBs were prepared by the double emulsion technique and loaded with several types of Flu-CPAA-Pep polymers. After insonation the submicron PLA fragments (SPF)-containing Flu-CPAA-Pep were examined in vitro for their ability to attach to colon cancer cells and in vivo (DMH induced rat model) for their ability to attach to colon malignant tissues and compared to the specific attachment of the free Flu-CPAA-Pep. The generation of SPF-containing Flu-CPAA-Pep resulted in a tissue attachment similar to that of the free, unloaded Flu-CPAA-Pep. The addition of VRPMPLQ to the polymeric backbone of the Flu-CPAA reduced cytotoxicity and improved the specific binding.

Synergy between Synthetic Antimicrobial Polymer and Antibiotics: A Promising Platform to Combat Multidrug-Resistant Bacteria

The failure of many antibiotics in the treatment of chronic infections caused by multidrug-resistant (MDR) bacteria necessitates the development of effective strategies to combat this global healthcare issue. Here, we report an antimicrobial platform based on the synergistic action between commercially available antibiotics and a potent synthetic antimicrobial polymer that consists of three key functionalities: low-fouling oligoethylene glycol, hydrophobic ethylhexyl, and cationic primary amine groups. Checkerboard assays with Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli demonstrated synergy between our synthetic antimicrobial polymer and two antibiotics, doxycycline and colistin. Coadministration of these compounds significantly improved the bacteriostatic efficacy especially against MDR P. aeruginosa strains PA32 and PA37, where the minimal inhibitory concentrations (MICs) of polymer and antibiotics were reduced by at least 4-fold. A synergistic killing activity was observed when the antimicrobial polymer was used in combination with doxycycline, killing >99.999% of planktonic and biofilm P. aeruginosa PAO1 upon a 20 min treatment at a polymer concentration of 128 μg mL-1 (4.6 μM) and doxycycline concentration of 64 μg mL-1 (133.1 μM). In addition, this synergistic combination reduced the rate of resistance development in P. aeruginosa compared to individual compounds and was also capable of reviving susceptibility to treatment in the resistant strains.

Towards Sequence-Controlled Antimicrobial Polymers: Effect of Polymer Block Order on Antimicrobial Activity

Synthetic polymers have shown promise in combating multidrug-resistant bacteria. However, the biological effects of sequence control in synthetic antimicrobial polymers are currently not well understood. As such, we investigate the antimicrobial effects o

Photo-Enhanced Antimicrobial Activity of Polymers Containing an Embedded Photosensitiser

This work presents the synthesis of a novel photosensitive acrylate monomer for use as both a self-catalyst in the photoinduced electron/energy transfer–reversible addition fragmentation chain transfer (PET-RAFT) polymerisation process and a photosensitis

Effect of Hydrophobic Groups on Antimicrobial and Hemolytic Activity: Developing a Predictive Tool for Ternary Antimicrobial Polymers

Antimicrobial polymers have emerged as a potential solution to the growing problem of antimicrobial resistance. Although several studies have examined the effects of various parameters on the antimicrobial and hemolytic activity of statistical copolymers,

CHARGE-SWITCHABLE POLYMERIC DEPOT FOR GLUCOSE-TRIGGERED INSULIN DELIVERY WITH ULTRAFAST RESPONSE

A composition comprising a glucose-responsive charge-switchable polymer is described. In the absence of glucose or under normoglycemic conditions, the positively charged polymer can be complexed with negatively charged therapeutic agents, such as insulin.

COMPOUNDS USEFUL AS IMMUNOMODULATORS

The present disclosure generally relates to compounds useful as immunomodulators. Provided herein are compounds, compositions comprising such compounds, and methods of their use. The disclosure further pertains to pharmaceutical compositions comprising at least one compound according to the disclosure that are useful for the treatment of various diseases, including cancer and infectious diseases.

CROSSLINKED POLYVINYLAMINE, POLYALLYLAMINE, AND POLYETHYLENEIMINE FOR USE AS BILE ACID SEQUESTRANTS

The present invention provides a crosslinked amine and amide polymers effective for binding and removing bile salts from the gastrointestinal tract. These bile acid binding polymers or pharmaceutical compositions thereof can be administered to subjects to treat various conditions, including hypercholesteremia, diabetes, pruritis, irritable bowel syndromediarrhea (IBS-D), bile acid malabsorption, and the like.