40662-14-4

Upstream product

• 40662-08-6 3-(2-Hydroxy-4,6-dimethyl-phenyl)-3-methyl-butyric acid 
• 129967-47-1 4-Methoxyaniline 3-(2'-Hydroxy-4',6'-dimethylphenyl)-3,3-dimethylpropionic Acid Amide 
• 924-50-5 Methyl 3,3-dimethylacrylate 
• 108-68-9 3,5-Dimethylphenol 
• 183867-91-6 Phosphoric acid mono-{2-[2-(4-methoxy-phenylcarbamoyl)-1,1-dimethyl-ethyl]-3,5-dimethyl-phenyl} ester 
• 129967-42-6 2‐(3‐hydroxy‐1,1‐dimethylpropyl)‐3,5‐dimethylphenol 
• 129967-44-8 3-(2'-(Benzyloxy)-4',6'-dimethylphenyl)-3,3-dimethylpropionaldehyde 
• 129967-43-7 3-(2'-(Benzyloxy)-4',6'-dimethylphenyl)-3,3-dimethylpropanol 
• 129967-45-9 3-(2'-(Benzyloxy)-4',6'-dimethylphenyl)-3,3-dimethylpropionic Acid 
• 129967-46-0 4-Methoxyaniline 3-(2'-(Benzyloxy)-4',6'-dimethylphenyl)-3,3-dimethylpropionic Acid Amide 
• 638-10-8 ethyl 3-methylbut-2-enoate 
• 1096058-76-2 C₄₀H₄₁N₃O₇ 
• 541-47-9 3-Methylbutenoic acid 

Downstream Products

• 40662-08-6 3-(2-Hydroxy-4,6-dimethyl-phenyl)-3-methyl-butyric acid 
• 129967-42-6 2‐(3‐hydroxy‐1,1‐dimethylpropyl)‐3,5‐dimethylphenol 
• 129967-45-9 3-(2'-(Benzyloxy)-4',6'-dimethylphenyl)-3,3-dimethylpropionic Acid 

Relevant academic research and scientific papers

Phenylpropionic acid-based cyclic prodrugs of opioid peptides that exhibit metabolic stability to peptidases and excellent cellular permeation

Purpose. To evaluate the cellular permeation characteristics and the chemical and enzymatic stability of phenylpropionic acid-based cyclic prodrugs 1 and 2 of opioid peptides [Leu5]-enkephalin (H-Tyr-Gly-Gly-Phe- Leu-OH) and DADLE (H-Tyr-D-Ala-Gly-Phe-D-Leu-OH), respectively. Methods. The rates of conversion of cyclic prodrugs 1 and 2 to [Leu5]-enkephalin and DADLE, respectively, in HBSS, pH 7.4 (Caco-2 cell transport buffer) and in various biological media having measurable esterase activity were determined by HPLC. The cell permeation characteristics of [Leu5]-enkephalin, DADLE, and cyclic prodrugs 1 and 2 were measured using Caco-2 cell monolayers grown onto microporus membranes and monitored by HPLC. Results. In HBSS, pH 7.4, cyclic prodrugs 1 and 2 degraded to [Leu5]-enkephalin and DADLE, respectively, in stoichiometric amounts. In 90% human plasma, the rates of disappearance of cyclic prodrugs 1 and 2 were slightly faster than in HBSS, pH 7.4. These accelerated rates of disappearance in 90% human plasma could be reduced to the rates observed in HBSS, pH 7.4, by pretreatment of the plasma with paraoxon, a known inhibitor of serine-dependent esterases. In homogenates of Caco-2 cells and rat liver, accelerated rates of disappearance of cyclic prodrugs 1 and 2 were not observed. When applied to the AP side of a Caco-2 cell monolayer, cyclic prodrug 1 exhibited significantly greater stability against peptidase metabolism than did [Leu5]-enkephalin. Cyclic prodrug 2 find DADLE exhibited stability similar to prodrug 1 when applied to the AP side of the Caco-2 cell monolayers. Prodrug 1 was 1680 fold more able to permeate the Caco-2 cell monolayers than was [Leu5]-enkephalin, in part because of its increased enzymatic stability. Prodrug 2 was shown to be approximately 77 fold more able to permeate a Caco-2 cell monolayer than was DADLE. Conclusions. Cyclic prodrugs 1 and 2, prepared with the phenylpropionic acid promoiety, were substantially more able to permeate Caco-2 cell monolayers than were the corresponding opioid peptides. Prodrug 1 exhibited increased stability to peptidase metabolism compared to [Leu5]- enkephalin. In 90% human plasma but not in Caco-2 cell and rat liver homogenates, the opioid peptides were released from the cyclic prodrugs by an esterase-catalyzed reaction that is sensitive to paraoxon inhibition. However, the rate of this bioconversion appears to be extremely slow.

Toward Direct Protein S-Persulfidation: A Prodrug Approach That Directly Delivers Hydrogen Persulfide

A general strategy of delivering hydrogen persulfide (H2S2) is described herein. Esterase- and phosphatase-sensitive H2S2 prodrugs with tunable release rates have been synthesized. Their utility is validated in examining protein S-persulfidation. With this unique approach of directly delivering H2S2, our findings reaffirmed that S-persulfidation leads to decreased activity of glyceraldehyde 3-phosphate dehydrogenase. This new approach complements available prodrugs/donors that directly deliver a single species, including hydrogen sulfide, perthiol, and COS, and will be very useful as part of the toolbox for delineating the mechanisms of sulfur signaling.

Esterase-Sensitive Glutathione Persulfide Donor

An esterase-sensitive glutathione persulfide (GSSH) donor (BW-GP-401) is described. The release profile was studied by monitoring the formation of lactone and direct trapping of GSSH with 1-fluoro-2,4-dinitrobenzene (DNFB). The donor was examined for its

Molecular umbrella as a nanocarrier for antifungals

A molecular umbrella composed of two O‐sulfated cholic acid residues was applied for the construction of conjugates with cispentacin, containing a “trimethyl lock” (TML) or o‐dithiobenzylcarbamoyl moiety as a cleavable linker. Three out of five conjugates

COMPOUNDS USEFUL IN HIV THERAPY

The invention relates to compounds of Formula (I), salts thereof, pharmaceutical compositions thereof, as well as methods of treating or preventing HIV in subjects.

A General Approach to Enzyme-Responsive Liposomes

Liposomes are effective nanocarriers due to their ability to deliver encapsulated drugs to diseased cells. Nevertheless, liposome delivery would be improved by enhancing the ability to control the release of contents at the target site. While various stimuli have been explored for triggering liposome release, enzymes provide excellent targets due to their common overexpression in diseased cells. We present a general approach to enzyme-responsive liposomes exploiting targets that are commonly aberrant in disease, including esterases, phosphatases, and β-galactosidases. Responsive lipids correlating with each enzyme family were designed and synthesized bearing an enzyme substrate moiety attached via a self-immolating linker to a non-bilayer lipid scaffold, such that enzymatic hydrolysis triggers lipid decomposition to disrupt membrane integrity and release contents. Liposome dye leakage assays demonstrated that each enzyme-responsive liposome yielded significant content release upon enzymatic treatment compared to minimal release in controls. Results also showed that fine-tuning liposome composition was critical for controlling release. DLS analysis showed particle size increases in the cases of esterase- and β-galactosidase-responsive lipids, supporting alterations to membrane properties. These results showcase an effective modular strategy that can be tailored to target different enzymes, providing a promising new avenue for advancing liposomal drug delivery.

NRTI THERAPIES

Polymer-of-prodrug (POP) materials enable new nucleoside reverse transcriptase inhibitor (NRTI) therapy strategies. The materials are prodrugs of NRTIs in the form of polymers. Suitable materials include products which are polymeric NRTI delivery systems comprising polymeric materials which are capable of degradation after administration to release NRTIs or NRTI prodrugs which themselves are capable of metabolism to the parent NRTIs. The NRTIs may optionally be selected from tenofovir (TFV), emtricitabine (FTC), lamivudine (3TC) and MK-8591 (EFdA). The invention facilitates long-acting (LA) regimens. Constructs of the materials may be in the form of injectable compositions or implants.

INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE AND METHODS OF THEIR USE

The present invention provides a compound of formula (II): an inhibitor of indoleamine 2,3-dioxygenase (IDO), which may be used as medicaments for the treatment of proliferative disorders, such as cancer, viral infections and/or autoimmune diseases. Its prodrugs are disclosed.

Design, Synthesis, and Cellular Uptake of Oligonucleotides Bearing Glutathione-Labile Protecting Groups

Glutathione-labile protecting groups for phosphodiester moieties in oligonucleotides were designed, synthesized, and incorporated into oligonucleotides. The protecting groups on the phosphodiester moieties were cleaved in a buffer containing 10 mM glutath

Combretastatin analogue water-soluble pre-- prodrug and its preparation method

The invention relates to a combretastatin A-4 analogue pro-prodrug, and a preparation method thereof. The structure formula of the combretastatin A-4 analogue pro-prodrug is represented by a formula in the invention; and the combretastatin A-4 analogue pr