21754-55-2Relevant academic research and scientific papers
Preparation and biological evaluation of soluble tetrapeptide epoxyketone proteasome inhibitors
Lei, Meng,Zhang, Haoyang,Miao, Hang,Du, Xiao,Zhou, Hui,Wang, Jia,Wang, Xueyuan,Feng, Huayun,Shi, Jingmiao,Liu, Zhaogang,Shen, Jian,Zhu, Yongqiang
, p. 4151 - 4162 (2019/08/07)
A series of novel tetrapeptidyl epoxyketone inhibitors of 20S proteasome was designed and synthesized. To fully understand the SAR, various groups at R1, R2, R3, R4 and R5 positions, including aromatic and aliphatic substituents were designed, synthesized and biologically assayed. Based on the enzymatic results, seven compounds were selected to evaluate their cellular activities and soluble compound 36 showed strong potency against human multiple myeloma (MM) cell lines. Microsomal stability results indicated that compound 36 was more stable in mice, rat and human microsomes than marketed carfilzomib. The in vivo activities of this compound were evaluated with the xenograft mice models of MM cell lines ARH77 and RPMI-8226 with luciferase expression and the T/C value of the two models were 49.5% and 37.6%, respectively. To evaluate the potential cardiovascular toxicity, inhibition of hERG ion channel in HEK293 cells by compound 36 and carfilzomib was carried out. The results indicated that 36 had no binding affinity for the hERG ion channel while carfilzomib could bind it with IC50 of 92.1 μM.
Exciton-Coupled Circular Dichroism Characterization of Monotopically Binding Guests in Host?Guest Complexes with a Bis(zinc porphyrin) Tweezer
Olsson, Sandra,Sch?fer, Clara,Blom, Magnus,Gogoll, Adolf
, p. 1169 - 1178 (2019/01/04)
A stiff-stilbene-linked bisporphyrin tweezer with inherent helicity was used for exciton-coupled circular dichroism (ECCD) characterization of a series of monotopically binding amine guest molecules. CD signals were observed for a variety of monoamines at relatively low tweezer/amine (host/guest) ratios between 1 : 10 to 1 : 70. For the amines producing the most intense CD signals, a binding stoichiometry of 1 : 2 was found. A likely explanation is the presence of guest-guest interactions in the complexes. This is supported by the correlation observed between CD signal intensity and magnitude of possible noncovalent binding between the guests, which can be divided into three groups showing no, moderate and strong response, respectively. Further support for this rationalization comes from molecular modelling.
Simplifying pyridoxal: Practical methods for amino acid dynamic kinetic resolution
Felten, Albert E.,Zhu, Gangguo,Aron, Zachary D.
supporting information; experimental part, p. 1916 - 1919 (2010/07/06)
Figure presented Metal complexes of picolinaldehyde are identified as low-cost and environmentally benign catalysts, providing high reaction rates and turnovers for the racemization of amino acids. These pyridoxal surrogates demonstrate activity toward a variety of amino acid esters. Applications to chemoenzymatic dynamic kinetic resolutions provide access to amino acids in high yields and with excellent enantioselectivities, demonstrating their compatibility with protease-mediated transformations.
Anthranilimide-based glycogen phosphorylase inhibitors for the treatment of Type 2 diabetes: 2. Optimization of serine and threonine ether amino acid residues
Sparks, Steven M.,Banker, Pierette,Bickett, David M.,Clancy, Daphne C.,Dickerson, Scott H.,Garrido, Dulce M.,Golden, Pamela L.,Peat, Andrew J.,Sheckler, Lauren R.,Tavares, Francis X.,Thomson, Stephen A.,Weiel, James E.
scheme or table, p. 981 - 985 (2009/08/15)
Optimization of the amino acid residue of a series of anthranilimide-based glycogen phosphorylase inhibitors is described leading to the identification of serine and threonine ether analogs. t-Butylthreonine analog 20 displayed potent in vitro inhibition of GPa, low potential for P450 inhibition, and excellent pharmacokinetic properties.
Chemo-enzymatic synthesis of optically active amino acids and peptides
Chen, Shui-Tein,Wang, Kung-Tsung
, p. 301 - 311 (2007/10/03)
The industrial alkaline protease, alcalase, is stable and active in a high concentration of organic solvents and useful as a biocatalyst for (i) diastereoselective hydrolysis of peptide esters and preparation of racemization-free peptides; (ii) selective incorporation of esters of D-amino acid into peptides in t-butanol via a selective hydrolysis of esters of D,L-amino acid, followed by using the unhydrolyzed D-esters as a nucleophile in a kinetically controlled peptide bond formation; (iii) resolution of esters of amino acid in 95% t-butanol/5% water, followed by saponification of the unreacted esters to offer both enantiomers with high yield and optical purity; (iv) completely resolve amino-acid esters with high yield and optical purity via in situ racemization of the unreacted antipode catalyzed by pyridoxal 5-phosphate; (v) cryobioorganic synthesis of peptides with increased yields 15%-40% of peptide bond formation by reaction at 5 °C instead of 25-30 °C of a kinetically controlled enzymatic reaction in alcohols.
SYNTHESIS OF THE RACEMIC FORM OF (Z)-1,17-DIAMINOOCTADEC-9-ENE, AN ALIPHATIC DIAMINE FROM COCCINELLIDAE. DETERMINATION OF THE ABSOLUTE CONFIGURATION OF THE (+)-NATURALLY-OCCURRING ANTIPODE
Braconnier, M.F.,Braekman, J.C.,Daloze, D.
, p. 605 - 614 (2007/10/02)
The total synthesis of the title compound (1) has been achieved.Also reported is the use of lanthanide induced shifts in 1H NMR spectroscopy to assign the absolute configuration of the α-carbon atom in chiral primary α-methylalkylamines.Application of this empirical method to natural (+)-1 shows that it has the R-configuration at C-17.
