3235-67-4Relevant academic research and scientific papers
Piperidine scaffold as the novel P2-ligands in cyclopropyl-containing HIV-1 protease inhibitors: Structure-based design, synthesis, biological evaluation and docking study
Cen, Shan,Dong, Biao,Ma, Ling,Wang, Juxian,Wang, Yucheng,Zhang, Guoning,Zhou, Huiyu,Zhou, Jinming,Zhu, Mei
, (2020/11/03)
A series of potent HIV-1 protease inhibitors, containing diverse piperidine analogues as the P2-ligands, 4-substituted phenylsulfonamides as the P2'-ligands and a hydrophobic cyclopropyl group as the P1'-ligand, were designed, synthesized and evaluated in this work. Among these twenty-four target compounds, many of them exhibited excellent activity against HIV-1 protease with half maximal inhibitory concentration (IC50) values below 20 nM. Particularly, compound 22a containing a (R)-piperidine-3-carboxamide as the P2-ligand and a 4-methoxylphenylsulfonamide as the P2'-ligand exhibited the most effective inhibitory activity with an IC50 value of 3.61 nM. More importantly, 22a exhibited activity with inhibition of 42% and 26% against wild-type and Darunavir (DRV)-resistant HIV-1 variants, respectively. Additionally, the molecular docking of 22a with HIV-1 protease provided insight into the ligand-binding properties, which was of great value for further study.
Nitrogen-containing cyclic compounds as iminium ion sources for selected reaction monitoring detection of derivatized analytes
?ilionis, Andrius
supporting information, p. 25 - 35 (2019/09/03)
Liquid chromatography–tandem mass spectrometry is one of the most sensitive tools for determination of trace amounts of analytes in metabolomics and proteomics. The highest sensitivity is achieved in selected reaction monitoring detection, which involves fragmentation of the molecular ion between two levels of mass selection. However, fragmentation of some compounds is complicated. Detection sensitivity of such analytes may be increased by derivatizing them with a specific moiety fragmentation of which results in product ion of high abundance. In this work, we reveal the influence of iminium ions' structures on their stability by comparing six nitrogen-containing cyclic compounds as derivatization reagents for tandem mass spectrometric analysis of amino group-containing analyte. Commercially available starting materials (piperidine, 2,6-dimethylpiperidine, 1-methylpiperazine, morpholine, pyrrolidine and 1-cyanomethyl-3-methylimidazolium ionic liquid) were used for the synthesis of corresponding carboxylic acids which were further used for derivatization of the model analyte tryptamine. Liquid chromatographic–mass spectrometric analysis of differently derivatized tryptamine was performed for the evaluation of release and stability of corresponding iminium ions under collision-induced dissociation conditions. As a result, morpholine moiety was shown being the most promising iminium ion source among tested compounds. Possible sub-fragmentation pathways of investigated iminium ions were discussed, and the structures of secondary product ions were proposed.
Photolysis of Tertiary Amines in the Presence of CO2: The Paths to Formic Acid, α-Amino Acids, and 1,2-Diamines
Berton, Mateo,Mello, Rossella,Acerete, Rafael,González Núnez, María Elena
, p. 96 - 103 (2018/02/19)
The photolysis of triethylamine (1a) in the presence of carbon dioxide leads to the hydrogenation of CO2, the α-C-C coupling of 1a, and the CO2 insertion into the α-C-H σ-bond of amine 1a. This reaction is proposed to proceed through the radical ion pair [R3N?+·CO2?-] generated by the photoionization of amine 1a and the electron capture by CO2. The presence of lithium tetrafluoroborate in the reaction medium promotes the efficient and stereoselective α-C-C coupling of 1a by enhancing the production of α-dialkylamino radicals and the isomerization of N,N,N′,N′-tetraethylbutane-2,3-diamine (4a).
Silver(I)-Catalyzed Widely Applicable Aerobic 1,2-Diol Oxidative Cleavage
Zhou, Zhong-Zhen,Liu, Mingxin,Lv, Leiyang,Li, Chao-Jun
supporting information, p. 2616 - 2620 (2018/02/13)
The oxidative cleavage of 1,2-diols is a fundamental organic transformation. The stoichiometric oxidants that are still predominantly used for such oxidative cleavage, such as H5IO6, Pb(OAc)4, and KMnO4, generate stoichiometric hazardous waste. Herein, we describe a widely applicable and highly selective silver(I)-catalyzed oxidative cleavage of 1,2-diols that consumes atmospheric oxygen as the sole oxidant, thus serving as a potentially greener alternative to the classical transformations.
Development of a series of bis-triazoles as G-quadruplex ligands
Saleh, Maysaa M.,Laughton, Charles A.,Bradshaw, Tracey D.,Moody, Christopher J.
, p. 47297 - 47308 (2017/10/19)
Maintenance of telomeres-specialized complexes that protect the ends of chromosomes-is provided by the enzyme complex telomerase, which is a key factor that is activated in more than 80% of cancer cells, but absent in most normal cells. Targeting telomere maintenance mechanisms could potentially halt tumour growth across a broad spectrum of cancer types. Telomeric ends of chromosomes consist of noncoding repeat sequences of guanine-rich DNA. These G-rich ends can fold into structures called G-quadruplexes. Stabilization of G-quadruplexes by small binding molecules called G4 ligands can prevent telomerase enzyme from maintaining telomere integrity in cancer cells. G-quadruplexes can exist in other parts of the genome too, especially within promoter sequences of oncogenes, and also be interesting drug targets. Here, we describe the development of a new series of novel bis-triazoles, designed to stabilize G-quadruplex structures selectively as G4 ligands. FRET assays showed two compounds to be moderately effective G4 binders, with particular affinity for the quadruplex formed by the Hsp90a promoter sequence, and good selectivity for G-quadruplex DNA vs. duplex DNA. However, CD spectroscopy failed to provide any information about the folding topology of the human telomeric G-quadruplex resulting from its interaction with one of the ligands. All the new ligands showed potent cell growth inhibitory properties against human colon and pancreatic cancer cell lines, as evidenced by the MTT assay; notably, they were more potent against cancer cells than in fetal lung fibroblasts. Docking studies were performed to rationalize the affinity of these ligands for binding to the telomeric parallel G-quadruplex DNA.
Reagent-free continuous thermal tert-butyl ester deprotection
Cole, Kevin P.,Ryan, Sarah J.,Groh, Jennifer McClary,Miller, Richard D.
, p. 6209 - 6217 (2017/09/30)
Continuous processing enables the use of non-standard reaction conditions such as high temperatures and pressures while in the liquid phase. This expands the chemist's toolbox and can enable previously unthinkable chemistry to proceed with ease. For a series of amphoteric amino acid derivatives, we have demonstrated the ability to hydrolyze the tert-butyl ester functionality in protic solvent systems. Using a continuous plug flow reactor at 120–240 °C and 15–40 min reaction times, no pH modification or additional reagents are needed to achieve the desired transformation. The method was then expanded to encompass a variety of more challenging substrates to test selectivity and racemization potential. The acid products were generally isolated as crystalline solids by simple solvent exchange after the deprotection reaction in good to high yield and purity.
PROTEIN KINASE INHIBITORS
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Paragraph 0164; 0175, (2015/02/18)
A compound of formula (I), wherein R3, R4, G, B, M, and Z are as defined in the claims, and pharmaceutically acceptable salts thereof are disclosed. The compounds of formula (I) possess utility as FGFR inhibitors and are useful in the treatment of a condition, where FGFR kinase inhibition is desired, such as cancer.
PROTEIN KINASE INHIBITORS
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Page/Page column 41, (2013/04/25)
A compound of formula (I), wherein R3, R4, G, B, M, and Z are as defined in the claims, and pharmaceutically acceptable salts thereof are disclosed. The compounds of formula (I) possess utility as FGFR inhibitors and are useful in the treatment of a condition, where FGFR kinase inhibition is desired, such as cancer.
NK1 and NK3 antagonists
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Page/Page column 27, (2010/02/14)
The invention is to a compound exhibiting neurokinin inhibitory properties, a pharmaceutical composition comprising same and a method of treatment for neurokinin-mediated conditions.
Synthesis and pharmacological evaluation of glycine-modified analogues of the neuroprotective agent glycyl-L-prolyl-L-glutamic acid (GPE)
Lai, Michelle Y.H.,Brimble, Margaret A.,Callis, David J.,Harris, Paul W.R.,Levi, Mark S.,Sieg, Frank
, p. 533 - 548 (2007/10/03)
The synthesis of 10 G*PE analogues, wherein the glycine residue has been modified, is described by coupling readily accessible dibenzyl-l-prolyl-l- glutamate 2 with various analogues of glycine. Pharmacological evaluation of the novel compounds was undertaken to further understand the role of the glycine residue on the observed neuroprotective properties of the endogenous tripeptide GPE.
