67852-87-3Relevant academic research and scientific papers
Synthesis and preliminary in vitro investigation of bivalent ligands containing homo- and heterodimeric pharmacophores at μ, δ, and κ opioid receptors
Peng, Xuemei,Knapp, Brian I.,Bidlack, Jean M.,Neumeyer, John L.
, p. 256 - 262 (2006)
A series of homo- and heterodimeric ligands containing κ agonist and μ agonist/antagonist pharmacophores joined by a linker chain of varying lengths was synthesized and evaluated in vitro by their binding affinity at μ, δ, and κ opioid receptors. The func
Synthesis and structure-property evaluation of cellulose ω-carboxyesters for amorphous solid dispersions
Liu, Haoyu,Ilevbare, Grace A.,Cherniawski, Benjamin P.,Ritchie, Earl T.,Taylor, Lynne S.,Edgar, Kevin J.
, p. 116 - 125 (2013/12/04)
The use of amorphous solid dispersions (ASDs) is an effective and increasingly widely used approach for solubility enhancement of drugs and drug candidates with poor aqueous solubility. Successful molecular dispersion of drugs in polymer matrices requires new polymers that are designed to meet all ASD requirements, including drug release and prevention of drug recrystallization in storage or from solution. We describe herein design and synthesis of a new series of cellulose ω-carboxyalkanoates for ASDs, by reaction of cellulose with long-chain diacids that have been monoprotected as benzyl esters at one end, and monoactivated as acid chlorides at the other. Glass transition temperatures (Tg) of these cellulose ω-carboxyesters exceed ambient temperature by at least 50 C, providing a sufficient ΔT to prevent drug mobility and crystallization. Cellulose acetate suberates and sebacates prepared in this way are extraordinary solution crystal growth inhibitors for the poorly soluble anti-HIV drug ritonavir. These new cellulose ω-carboxyesters have strong potential as ASD polymers for enhancement of drug solubility and bioavailability.
Synthesis and structure-property evaluation of cellulose ω-carboxyesters for amorphous solid dispersions
Liu, Haoyu,Ilevbare, Grace A.,Cherniawski, Benjamin P.,Ritchie, Earl T.,Taylor, Lynne S.,Edgar, Kevin J.
, p. 116 - 125 (2015/03/30)
The use of amorphous solid dispersions (ASDs) is an effective and increasingly widely used approach for solubility enhancement of drugs and drug candidates with poor aqueous solubility. Successful molecular dispersion of drugs in polymer matrices requires new polymers that are designed to meet all ASD requirements, including drug release and prevention of drug recrystallization in storage or from solution. We describe herein design and synthesis of a new series of cellulose ω-carboxyalkanoates for ASDs, by reaction of cellulose with long-chain diacids that have been monoprotected as benzyl esters at one end, and monoactivated as acid chlorides at the other. Glass transition temperatures (Tg) of these cellulose ω-carboxyesters exceed ambient temperature by at least 50 °C, providing a sufficient ΔT to prevent drug mobility and crystallization. Cellulose acetate suberates and sebacates prepared in this way are extraordinary solution crystal growth inhibitors for the poorly soluble anti-HIV drug ritonavir. These new cellulose ω-carboxyesters have strong potential as ASD polymers for enhancement of drug solubility and bioavailability.
Synthesis and binding affinity of novel mono- and bivalent morphinan ligands for κ, μ, and δ opioid receptors
Zhang, Bin,Zhang, Tangzhi,Sromek, Anna W.,Scrimale, Thomas,Bidlack, Jean M.,Neumeyer, John L.
experimental part, p. 2808 - 2816 (2011/06/17)
A novel series of homo- and heterodimeric ligands containing κ/μ agonist and μ agonist/antagonist pharmacophores joined by a 10-carbon ester linker chain were synthesized and evaluated for their in vitro binding affinity at κ, μ, and δ opioid receptors, and their functional activities were determined at κ and μ receptors in [35S]GTPγS functional assays. Most of these compounds had high binding affinity at μ and κ receptors (Ki values less than 1 nM). Compound 15b, which contains butorphan (1) at one end of linking chain and butorphanol (5) at the other end, was the most potent ligand in this series with binding affinity Ki values of 0.089 nM at the μ receptor and 0.073 nM at the κ receptor. All of the morphinan-derived ligands were found to be partial κ and μ agonists; ATPM-derived ligands 12 and 11 were found to be full κ agonists and partial μ agonists.
Synthesis and biological evaluation of oleanolic acid derivatives as inhibitors of protein tyrosine phosphatase 1B
Qian, Shan,Li, Haijiao,Chen, Yin,Zhang, Weiyu,Yang, Shengyong,Wu, Yong
experimental part, p. 1743 - 1750 (2011/03/18)
Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator in the process of insulin signaling and a promising drug target for diabetes and obesity. Derivatives of oleanolic acid were synthesized and evaluated as PTP1B inhibitors. Several derivatives exhibited moderate to good inhibitory activities against PTP1B, with 25f displaying the most promising inhibition (IC 50 = 3.12 μM). Structure-activity relationship analyses of these derivatives demonstrated that the integrity of the A ring and 12-ene moieties was important in the retention of PTP1B enzyme inhibitory activities. In addition, hydrophilic and acidic groups as well as the distance between the oleanene and acid moieties were associated with PTP1B inhibitory activities. Possible binding modes of 25f were explored by molecular docking simulations.
