51219-55-7Relevant academic research and scientific papers
Trimethyl-substituted carbamate as a versatile self-immolative linker for fluorescence detection of enzyme reactions
Inoue, Kazuya,Nakamura, Noriaki,Ojida, Akio,Uchinomiya, Shohei
supporting information, (2020/05/25)
Self-immolative linker is a useful building block of molecular probes, with broad applications in the fields of enzyme activity analysis, stimuli-responsive material science, and drug delivery. This manuscript presents N-methyl dimethyl methyl (i.e., trimethyl) carbamate as a new class of self-immolative linker for the fluorescence detection of enzyme reactions. The trimethyl carbamate was shown to spontaneously undergo intramolecular cyclization upon formation of a carboxylate group, to liberate a fluorophore with the second time rapid reaction kinetics. Interestingly, the auto-cleavage reaction of trimethyl carbamate was also induced by the formation of hydroxyl and amino groups. Fluorescent probes with a trimethyl carbamate could be applicable for fluorescence monitoring of the enzyme reactions catalyzed by esterase, ketoreductase, and aminotransferase, and for fluorescence imaging of intracellular esterase activity in living cells, hence demonstrating the utility of this new class of self-immolative linker.
GLUCOPYRANOSYL DERIVATIVE AND USE THEREOF
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Paragraph 0321-0323, (2020/12/16)
The present invention relates to a glucopyranosyl derivative and a use thereof. In particular, the present invention relates to a glucopyranosyl derivative that is used as an inhibitor of sodium-dependent glucose transporters (SGLTs), particularly being used as an inhibitor of sodium-dependent glucose transporter-1 (SGLT1), and a pharmaceutically acceptable salt or stereoisomer thereof, further relating to a pharmaceutical composition containing the derivative. The present invention further relates to a use of the compound and a pharmaceutical composition thereof in the preparation of a drug for treating diabetes and diabetes-related diseases.
N,N-Dichloroaminosulfonic acids as novel topical antimicrobial agents
Low, Eddy,Nair, Satheesh,Shiau, Timothy,Belisle, Barbara,Debabov, Dmitri,Celeri, Chris,Zuck, Meghan,Najafi, Ron,Georgopapadakou, Nafsika,Jain, Rakesh
scheme or table, p. 196 - 198 (2009/05/07)
2-Dichloroamino-2-methyl-propane-1-sulfonic acid sodium salt (2a), a stable derivative of endogenous N,N-dichlorotaurine (1), has been identified and is under development as a topical antimicrobial agent. Structure-activity relationships of analogs were explored to achieve optimal antimicrobial activity with minimal mammalian toxicity while maintaining the desired stability. All the analogs synthesized showed antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans in the range of 1-128 μg/mL and cytotoxicity against mammalian L929 cells in the range 80-1900 μg/mL.
Quaternary ammonium N,N-dichloroamines as topical, antimicrobial agents
Francavilla, Charles,Low, Eddy,Nair, Satheesh,Kim, Bum,Shiau, Timothy P.,Debabov, Dmitri,Celeri, Chris,Alvarez, Nichole,Houchin, Ashley,Xu, Ping,Najafi, Ron,Jain, Rakesh
scheme or table, p. 2731 - 2734 (2010/03/03)
A series of backbone modified and sulfonic acid replacement analogs of our topical, clinical candidate (iii) were synthesized. Their antimicrobial activities and aqueous stabilities at pH 4 and pH 7 were determined, and has led us to identify quaternary ammonium N,N-dichloroamines as a new class of topical antimicrobial agents.
N-HALOGENATED AMINO COMPOUNDS AND DERIVATIVES
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Page/Page column 84-85, (2008/12/07)
The present invention relates to active bactericidal, antibacterial, anti-infective, antimicrobial, sporicidal, disinfectant, antifungal and antiviral compounds and compositions and to new uses of these compositions in therapy. This specification also describes methods of use for the new compounds and compositions. The specification further describes methods for preparing these compounds.
Dihydroquinone and dihydronaphthridine inhibitors of JNK
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Page/Page column 40, (2008/12/09)
Compounds of formula I are effective modulators of JNK: wherein X is CR11 or N;Y is —C(O)R3, 5-membered heteroaryl, or 5-membered heterocyclyl;Z is phenyl, cycloalkyl, heterocyclyl or heteroaryl, and is substituted with R1 and R2;R1 and R2 are each independently H, halo, CN, lower alkyl, or —Y1—Y2—Y3—R8, or R1 and R2 together form —O(CH2)nO—, where n is 1 or 2; Y1 is —O—, —C(O)—, —C(O)O—, —C(O)NR9—, —NR9C(O)—, —S—, —SO2—, or a bond;Y2 is cycloalkylene, heterocycloalkylene, lower alkylene or a bond;Y3 is —O—, —C(O)—, —C(O)O—, —C(O)NR9—, —NR9C(O)—, —SO2—, or a bond;R8 is H, lower alkyl, lower alkoxy, cycloalkyl, heterocycloalkyl, or —NR9R10, wherein R8 other than H is optionally substituted with lower alkyl, halo, —CF3, or —OH; R9 and R10 are each independently H or lower alkyl;R3 is OH, lower alkyl, lower alkoxy, (lower alkoxy)-lower alkoxy, or —NR9R10;R4 is lower alkyl, phenyl, heterocyclyl, cycloalkyl, heterocycloalkyl, or heteroaryl, and is optionally substituted with lower alkyl, hydroxy, lower alkoxy, halo, nitro, amino, cyano, or halo-lower alkyl;R5 and R6 are each independently H, halo, cyano, lower alkyl, —CF3, lower alkoxy, —OCHF2, —NO2, or —NR9R10;R7 is H, F, Cl, methyl, or OH;R11 is H, lower alkyl, lower cycloalkyl, or phenyl;or a pharmaceutically acceptable salt thereof.
Design and synthesis of C5 methylated L-arginine analogues as active site probes for nitric oxide synthase
Martin, Nathaniel I.,Woodward, Joshua J.,Winter, Michael B.,Beeson, William T.,Marletta, Michael A.
, p. 12563 - 12570 (2008/09/18)
The role of nitric oxide (NO) as a biological signaling molecule is well established. NO is produced by the nitric oxide synthases (NOSs, EC 1.14.13.39), a class of heme proteins capable of converting L-arginine to NO and L-citrulline. Despite the large body of knowledge associated with the NOSs, mechanistic details relating to the unique oxidative chemistry performed by these enzymes remain to be fully elucidated. Furthermore, a number of disease states are associated with either the over- or underproduction of NO, making the NOS pathway an attractive target for the development of therapeutics. For these reasons, molecular tools capable of providing mechanistic insights into the production of NO and/or the inhibition of the NOSs remain of interest. We report here the stereospecific synthesis and testing of a number of new L-arginine analogues bearing a minimal substitution, methylation at position 5 of the amino acid side chain (such analogues have not been previously reported). The synthetic approach employed a modified photolysis procedure whereby irradiation of the appropriate diacylperoxide precursors at 254 nm gave access to the required unnatural amino acids in good yields. A heme domain construct of the inducible NOS isoform (iNOSheme) was used to assess the binding of each compound to the enzyme active site. The compounds were also investigated as either inhibitors of, or alternate substrates for, the inducible NOS isoform. The results obtained provide new insight into the steric and stereochemical tolerance of the enzyme active site. These findings also further support the role of a conserved active site water molecule previously proposed to be necessary for NOS catalysis.
Effective methods for the synthesis of N-methyl β-amino acids from all twenty common α-amino acids using 1,3-oxazolidin-5-ones and 1,3-oxazinan-6-ones
Hughes, Andrew B.,Sleebs, Brad E.
, p. 2611 - 2637 (2007/10/03)
N-Methyl β-amino acids are generally required for application in the synthesis of potentially bioactive modified peptides and other oligomers. Previous work highlighted the reductive cleavage of 1,3-oxazolidin-5-ones to synthesise N-methyl α-amino acids. Starting from α-amino acids, two approaches were used to prepare the corresponding N-methyl β-amino acids. First, α-amino acids were converted to N-methyl α-amino acids by the so-called '1,3-oxazolidin-5-one strategy', and these were then homologated by the Arndt-Eistert procedure to afford N-protected N-methyl β-amino acids derived from the 20 common α-amino acids. These compounds were prepared in yields of 23-57% (relative to N-methyl α-amino acid). In a second approach, twelve N-protected α-amino acids could be directly homologated by the Arndt-Eistert procedure, and the resulting β-amino acids were converted to the 1,3-oxazinan-6-ones in 30-45% yield. Finally, reductive cleavage afforded the desired N-methyl β-amino acids in 41-63% yield. One sterically congested β-amino acid, 3-methyl-3-aminobutanoic acid, did give a high yield (95%) of the 1,3-oxazinan-6-one (65), and subsequent reductive cleavage gave the corresponding AIBN-derived N-methyl β-amino acid 61 in 71% yield (Scheme 2). Thus, our protocols allow the ready preparation of all N-methyl β-amino acids derived from the 20 proteinogenic α-amino acids.
Synthesis of new β-amino acids via 5-oxazolidinones and the arndt-eistert procedure
Hughes, Andrew B.,Sleebs, Brad E.
, p. 778 - 784 (2007/10/03)
N-Methyl β-amino acids are potentially useful amino acid derivatives for incorporation in lead peptide therapeutics. The syntheses of five such compounds are presented. Their synthesis via 6-oxazinanones was low yielding. Alternatively, reductive cleavage of a 5-oxazolidinone gave the N-methyl β-amino acid, which was then homologated via an Arndt-Eistert procedure in high yield to give the N-methyl α-amino acid. CSIRO 2005.
A potent, orally bioavailable benzazepinone growth hormone secretagogue
DeVita, Robert J.,Bochis, Richard,Frontier, Alison J.,Kotliar, Andrew,Fisher, Michael H.,Schoen, William R.,Wyvratt, Matthew J.,Cheng, Kang,Chan, Wanda W.-S.,Butler, Bridget,Jacks, Thomas M.,Hickey, Gerard J.,Schleim, Klaus D.,Leung, Kwan,Chen, Zhesheng,Lee Chiu,Feeney, William P.,Cunningham, Paul K.,Smith, Roy G.
, p. 1716 - 1728 (2007/10/03)
The identification of L-739,9.43 (8b), a potent, orally bioavailable benzolactam growth hormone secretagogue, is obtained from zwitterionic L- 692,429 through modification of its amino acid side chain and replacement of the acidic 2'-tetrazole with the ne
