59178-92-6

Usage

InChI:InChI=1/C10H17NO3/c1-8(2)10(14)11-7-5-3-4-6-9(12)13/h1,3-7H2,2H3,(H,11,14)(H,12,13)

Upstream product

• 760-93-0 methacryloyl anhydride 
• 60-32-2 6-aminohexanoic acid 
• 920-46-7 Methacryloyl chloride 

Downstream Products

• 1372411-07-8 9-(N-methacryloyl-ε-aminohexanoyloxy)-3,3-diphenyl-3H-naphtho[2,1-b]pyran 
• 1372411-09-0 5-(N-methacryloyl-ε-aminohexanoyloxy)-3,3-di(4-methoxyphenyl)-3H-naphtho[2,1-b]pyran 
• 64407-57-4 N,N-dicyclohexylurea 
• 554-68-7 triethylamine hydrochloride 
• 2387-23-7 1,3-Dicyclohexylurea 

Relevant academic research and scientific papers

COMPOSITIONS AND METHODS OF MANUFACTURING STAR POLYMERS FOR LIGAND DISPLAY AND/OR DRUG DELIVERY

A star polymer of formula O[P1]-([X]-A[P2]-[Z]-[P3])n where O is a core; A is a polymer arm attached to the core; X is a linker molecule between the core and the polymer arm; Z is a linker molecule between the end of the polymer arm and P3; P1, P2 and P3 are each independently one or more pharmaceutically active compounds that act extracellularly or intracellularly, n is an integer number; [ ] denotes that the group is optional; and at least one of P1, P2 or P3 is present.

Abiotic Mimic of Endogenous Tissue Inhibitors of Metalloproteinases: Engineering Synthetic Polymer Nanoparticles for Use as a Broad-Spectrum Metalloproteinase Inhibitor

We describe a process for engineering a synthetic polymer nanoparticle (NP) that functions as an effective, broad-spectrum metalloproteinase inhibitor. Inhibition is achieved by incorporating three functional elements in the NP: a group that interacts with the catalytic zinc ion, functionality that enhances affinity to the substrate-binding pocket, and fine-tuning of the chemical composition of the polymer to strengthen NP affinity for the enzyme surface. The approach is validated by synthesis of a NP that sequesters and inhibits the proteolytic activity of snake venom metalloproteinases from five clinically relevant species of snakes. The mechanism of action of the NP mimics that of endogenous tissue inhibitors of metalloproteinases. The strategy provides a general design principle for synthesizing abiotic polymer inhibitors of enzymes.

Overcoming resistance to rituximab in relapsed non-Hodgkin lymphomas by antibody-polymer drug conjugates actively targeted by anti-CD38 daratumumab

B-cell non-Hodgkin lymphomas (B-NHL) represent the most common type of hematologic malignancies in the Western hemisphere. The therapy of all B-NHL is based on the combination of different genotoxic cytostatics and anti-CD20 monoclonal antibody (mAb) rituximab. Unfortunately, many patients relapse after the mentioned front-line treatment approaches. The therapy of patients with relapsed/refractory (R/R) B-NHL represents an unmet medical need. We designed, developed and tested novel actively targeted hybrid mAb-polymer-drug conjugate (APDC) containing anti-CD20, anti-CD38 or anti-CD19 mAbs. Biocompatible copolymers based on N-(2-hydroxypropyl)methacrylamide (HPMA) with cytostatic agent doxorubicin attached via stimuli-sensitive hydrazone bond were employed for the mAb grafting. Anti-lymphoma efficacy of the APDC nanotherapeutics was evaluated in vivo on a panel of three patient-derived lymphoma xenografts derived from two patients with R/R B-NHL and one patient with so far untreated B-NHL. In both PDX models derived from patients with R/R B-NHL, the targeting with anti-CD38 antibody daratumumab demonstrated highly improved anti-lymphoma efficacy compared to the targeting with anti-CD20 rituximab, two experimental anti-CD19 antibodies and non-targeted controls. The results represent a proof-of-concept of a new algorithm of personalized anti-tumor therapy based on highly innovative APDC biomaterials.

Impact of Polymer-TLR-7/8 Agonist (Adjuvant) Morphology on the Potency and Mechanism of CD8 T Cell Induction

Small molecule Toll-like receptor-7 and -8 agonists (TLR-7/8a) can be used as vaccine adjuvants to induce CD8 T cell immunity but require formulations that prevent systemic toxicity and focus adjuvant activity in lymphoid tissues. Here, we covalently attached TLR-7/8a to polymers of varying composition, chain architecture and hydrodynamic behavior (～300 nm submicrometer particles, ～10 nm micelles and ～4 nm flexible random coils) and evaluated how these parameters of polymer-TLR-7/8a conjugates impact adjuvant activity in vivo. Attachment of TLR-7/8a to any of the polymer compositions resulted in a nearly 10-fold reduction in systemic cytokines (toxicity). Moreover, both lymph node cytokine production and the magnitude of CD8 T cells induced against protein antigen increased with increasing polymer-TLR-7/8a hydrodynamic radius, with the submicrometer particle inducing the highest magnitude responses. Notably, CD8 T cell responses induced by polymer-TLR-7/8a were dependent on CCR2+ monocytes and IL-12, whereas responses by a small molecule TLR-7/8a that unexpectedly persisted in vaccine-site draining lymph nodes (T1/2 = 15 h) had less dependence on monocytes and IL-12 but required Type I IFNs. This study shows how modular properties of synthetic adjuvants can be chemically programmed to alter immunity in vivo through distinct immunological mechanisms.

Synthesis and structures of zwitterionic polymers to induce electrostatic interaction with PDMS surface treated by air-plasma

Various zwitterionic polymers, sulfobetaine and phosphoryl choline derivatives were synthesized in order to investigate zwitterionic polymer structures toward surface modification of PDMS, where the adsorption of zwitterionic polymers on polydimethylsiloxane surface treated with air-plasma was induced by the electrostatic interaction,. The electrostatic interaction was evaluated with hydrophilicity. The results suggested that a sulfobetaine polymer with higher molecular weight, lower molecular weight distribution, and shorter alkyl chain afforded high electrostatic interaction. A sulfobetaine polymer bearing phenylazide group showed similar electrostatic interaction with the PDMS surface, and it is a promising material for surface modification ofpolydimethylsiloxane.

POLYMER PARTICLES

Described are polymers and methods of forming and using same.

Synthesis and study of photochromic properties of copolymers based on functionalized chromenes

Chromenes functionalized with methacryl groups were synthesized and involved into the radical polymerization to obtain copolymers with ethyl acrylate. Comparison of spectral kinetic characteristics of poly(methyl methacrylate) glasses containing chromenes and photochromic copolymers as additives led to a conclusion that incorporation of a photochromic compound as a part of a copolymer into the polymeric glass increases efficiency of photocoloration of photochromic compounds in the polymeric layer.

MICELLAR CARRIERS FOR DRUGS WITH ANTI-CANCER ACTIVITY

A micellar system destined for controlled release of medical drug is formed by a micellar structure, constituted by a hydrophilic or amphiphilic polymer, to which the drug is bound by a covalent linkage, the molecules of which are arranged on the hydrophilic surface of the micelle, while the nucleus of the micelle is constituted by hydrophobic components of the system, which are linked with the polymer on the surface by a chemical bond.

Synthesis of 3'-, or 5'-, or internal methacrylamido-modified oligonucleotides

New modifiers were synthesized for incorporation of a methacrylic function in 3′-, 5′- and internal positions of oligonucleotides during solid phase synthesis. A modifier was used for synthesis of 5′-methacrylated oligonucleotides for preparation of microarrays by a co-polymerization method.

POLYMERIZABLE MONOMERS AND PROCESS OF PREPARATION THEREOF

The present invention relates to polymerizable monomers for applications in medicine and biotechnology and synthesis thereof. The polymerizable ligands containing NAcetyl Glucosamine bind more strongly to lysozyme than NAG itself. The binding is further enhanced when a spacer arm, for example 6- Amino Caproic Acid (6-ACA) is introduced in the structure. The conjugated ligands could be used for prevention and treatment of bacterial and viral infections. Moreover these ligands can be coupled to stimuli sensitive polymers and used for the recovery of biomolecules. The methodology can be extended to other ligands such as sialic acid and the corresponding polymers used for preventilIg influenza and for rotavirus infections.