956-09-2Relevant academic research and scientific papers
Catalytic synthesis of N-benzoyl (N-nitrobenzoyl) derivatives of ε-aminocaproic acid oligomers
Rakhimov,Storozhakova,Akhmed, Khaled Khedar Nasser,Fedunov
, p. 421 - 424 (2006)
The synthesis of N-benzoyl [N-(m-nitrobenzoyl)] derivatives of ε-aminocaproic acid oligomers by the reaction of ε-caprolactam with benzoic (nitrobenzoic) acid in the presence of p-toluenesulfonic acid as catalyst was studied. Pleiades Publishing, Inc., 2006.
Site-Specific Immuno-PET Tracer to Image PD-L1
Wissler, Haley L.,Ehlerding, Emily B.,Lyu, Zhigang,Zhao, Yue,Zhang, Si,Eshraghi, Anisa,Buuh, Zakey Yusuf,McGuth, Jeffrey C.,Guan, Yifu,Engle, Jonathan W.,Bartlett, Sarah J.,Voelz, Vincent A.,Cai, Weibo,Wang, Rongsheng E.
, p. 2028 - 2036 (2019/05/15)
The rapid ascension of immune checkpoint blockade treatments has placed an emphasis on the need for viable, robust, and noninvasive imaging methods for immune checkpoint proteins, which could be of diagnostic value. Immunoconjugate-based positron emission tomography (immuno-PET) allows for sensitive and quantitative imaging of target levels and has promising potential for the noninvasive evaluation of immune checkpoint proteins. However, the advancement of immuno-PET is currently limited by available imaging tools, which heavily rely on full-length IgGs with Fc-mediated effects and are heterogeneous mixtures upon random conjugation with chelators for imaging. Herein, we have developed a site-specific αPD-L1 Fab conjugate with the chelator 1,4,7-triazacyclononane-N,N′,N″-triacetic acid (NOTA), enabling radiolabeling for PET imaging, using the amber suppression-mediated genetic incorporation of unnatural amino acid (UAA), p-azidophenylalanine. This Fab conjugate is homogeneous and demonstrated tight binding toward the PD-L1 antigen in vitro. The radiolabeled version, 64Cu-NOTA-αPD-L1, has been employed in PET imaging to allow for effective visualization and mapping of the biodistribution of PD-L1 in two normal mouse models, including the capturing of different PD-L1 expression levels in the spleens of the different mouse types. Follow-up in vivo blocking studies and ex vivo fluorescent staining further validated specific tissue uptakes of the imaging agent. This approach illustrates the utility of UAA-based site-specific Fab conjugation as a general strategy for making sensitive PET imaging probes, which could facilitate the elucidation of the roles of a wide variety of immune checkpoint proteins in immunotherapy.
Preparation method and application of benzamide derivative
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Paragraph 0015, (2018/05/07)
The invention discloses a preparation method and application of a benzamide derivative as shown in a formula (I) which is described in the specification. The objective of the invention is to improve the chelation stability of zinc ions of histone deacetylase in the prior art so as to obtain HDACi with better histone deacetylase inhibition effect and stronger selectivity. The derivative provided bythe invention can be applied to preparation of antitumor drugs and is capable of improving the capability of HDACi in selection of a part of tumor cells and substantially reducing cytotoxicity.
Cross aldol condensation of acetaldehyde and formaldehyde in the presence of bifunctional systems
Dashko, L. V.,Dmitriev, D. V.,Pestov, S. M.,Flid, V. R.
, p. 1732 - 1737 (2015/02/05)
Liquid-phase cross-aldol condensation of acetaldehyde and formaldehyde in the presence of salts of various saturated and unsaturated linear amines, aromatic amines, diamines, and nitrogen bases, as well as in the presence of substituted piperazines, linear and cyclic amino acids and their derivatives, and nitrogen-containing ionic liquids, was studied. The cross-condensation products were formed in considerable amounts when amine hydrochlorides, N-benzoyl amino acids, and amino acid esters were used as catalyst. The formation of cross-condensation products is favored by increased basicity of the amino nitrogen atom in the salt and of the solvent.
Novel amide derivatives as inhibitors of histone deacetylase: Design, synthesis and SAR
Andrianov, Victor,Gailite, Vija,Lola, Daina,Loza, Einars,Semenikhina, Valentina,Kalvinsh, Ivars,Finn, Paul,Petersen, Kamille Dumong,Ritchie, James W.A.,Khan, Nagma,Tumber, Anthony,Collins, Laura S.,Vadlamudi, Sree M.,Bjoerkling, Fredrik,Sehested, Maxwell
experimental part, p. 1067 - 1085 (2009/08/14)
Enzymatic inhibition of histone deacetylase (HDAC) activity is emerging as an innovative and effective approach for the treatment of cancer. A series of novel amide derivatives have been synthesized and evaluated for their ability to inhibit human HDACs. Multiple compounds were identified as potent HDAC inhibitors (HDACi), with IC50 values in the low nanomolar (nM) range against enzyme activity in HeLa cell extracts and sub-μM for their in vitro anti-proliferative effect on cell lines. The introduction of an unsaturated linking group between the terminal aryl ring and the amide moiety was the key to obtain good potency. This approach yielded compounds such as (E)-N-[6-(hydroxyamino)-6-oxohexyl]-3-(7-quinolinyl)-2-propenamide (27) (HDAC IC50 8 nM) which showed potent in vivo activity in the P388 mouse leukemia syngeneic model (an increased lifespan (ILS) of 111% was obtained).
SOLUBLE FORMS OF INCLUSION COMPLEXES OF HISTONE DEACETYLASE INHIBITORS AND CYCLODEXTRINS, THEIR PREPARATION PROCESSES AND USES IN THE PHARMACEUTICAL FIELD
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Page/Page column 19; 20, (2008/12/07)
The invention relates to the preparation of soluble forms of complexes of histone deacetylase inhibitors and cyclodextrins. The preparation process involves the formation of inclusion complexes with cyclodextrins with the aid of microwaves. Their use is in the pharmaceutical field.
pKa-dependent formation of amides in water from an acyl phosphate monoester and amines
Wodzinska, Jolanta,Kluger, Ronald
, p. 4753 - 4754 (2008/09/21)
(Chemical Equation Presented) Acyl phosphate monoesters are readily prepared biomimetically activated anionic derivatives of carboxylic acids that react rapidly with amines in water to form amides. A plot of the logarithms of the rate constants for the reactions of a series of primary amines with benzoyl methyl phosphate depends on the pKa of the conjugate acids of the amines (βnuc ≈ 0.9). This provides a simple and quantitative basis for regioselective acylation with these reagents.
Unique oxidation reaction of amides with pyridine-N-oxide catalyzed by ruthenium porphyrin: Direct oxidative conversion of N-acyl-L-proline to N-acyl-L-glutamate
Ito, Rina,Umezawa, Naoki,Higuchi, Tsunehiko
, p. 834 - 835 (2007/10/03)
Oxidations of alkanes, alkenes, and aromatic rings with pyridine N-oxides are efficiently catalyzed by ruthenium porphyrins under mild conditions. We show here that the oxidation of N-acyl cyclic amines with RuIVtetraarylporphyrin dichloride-2,6-substituted pyridine N-oxides directly gives N-acyl amino acids in modest to good yield via oxidative C-N bond cleavage. N-Acylpyrrolidines and N-acylpiperidines were converted to N-acyl-γ-aminobutyric acids and N-acyl-δ-aminovaleric acids, respectively. This type of reaction is a novel one in which the C-N bond is cleaved selectively at the less substituted carbon. Notably, the proline residue in proline-containing peptides was selectively converted to glutamate. A large intramolecular kinetic isotope effect (kH/kD = 9.8) was observed in the oxidation of N-benzoyl[2,2,-d2]pyrrolidine, indicating that the reaction should involve an α-hydrogen atom abstraction process as the rate-determining step. N-Acylcarbaldehyde, the putative intermediate ring-opened form of α-hydroxylated N-acyl cyclic amine, was readily oxidized with the oxidizing system to afford the corresponding N-acylamino acid in good yield. Further, lactams (1-methyl-2-pyrrolidone and 1-methyl- 2-piperidone) were also oxidized to give the corresponding imides (1-methylsuccinimide and 1-methylpiperidine-2,6-dione). Copyright
Carbamic acid compounds comprising an amide linkage as hdac inhibitors
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, (2008/06/13)
This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the formula (1) wherein: A is an aryl group; Q1 is an aryl leader group having a backbone of at least 2 carbon atoms; J is an amide linkage selected from: —NR1C(═O)—and —C(═O)NR1—; R1 is an amido substituent; and, Q2 is an acid leader group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and, e.g., to inhibit proliferative conditions, such as cancer and psoriasis.
Preparation of N-acyl derivatives of amino acids from acyl chlorides and amino acids in the presence of cationic surfactants. A variation of the Schotten-Baumann method of benzoylation of amino acids
Jursic,Neumann
, p. 555 - 564 (2007/10/03)
A very efficient method for the preparation of N-acylamino acids from the corresponding acyl chloride and amino acid is described. Amino acids, potassium carbonate, acyl chloride, and a catalytic amount of cationic surfactants were mixed in tetrahydrofuran and refluxed without ever obtaining a clear reaction mixture. After hot filtration, the product was isolated from the hot tetrahydrofuran solution in very high or almost quantitative yields.
