- Isonitrile induced bioorthogonal activation of fluorophores and mutually orthogonal cleavage in live cells
-
Fluorophores with different emission wavelengths were efficiently quenched by a tert-butyl terminated tetrazylmethyl group and activated by an isonitrile–tetrazine click-to-release reaction. Nucleic acid templated chemistry significantly accelerated this
- Li, Jie,Li, Lin,Mao, Wuyu,Shen, Guohua,Su, Dunyan,Wu, Haoxing,Xu, Hui,Zhang, Xiaoyang
-
supporting information
p. 573 - 576
(2022/02/01)
-
- Synthesis of AD-Dihydrodipyrrins Equipped with Latent Substituents of Native Chlorophylls and Bacteriochlorophylls
-
Native chlorophylls and bacteriochlorophylls share a common trans-substituted pyrroline ring D (17-propionic acid, 18-methyl), whereas diversity occurs in ring A particularly at the 3-position. Two dihydrodipyrrins equipped with native-like D-ring substit
- Wang, Pengzhi,Lindsey, Jonathan S.
-
p. 11794 - 11811
(2021/08/24)
-
- Photo Cross-Linking Probes Containing ?-N-Thioacyllysine and ?-N-Acyl-(δ-aza)lysine Residues
-
Posttranslational modifications (PTMs) are important in the regulation of protein function, trafficking, localization, and marking for degradation. This work describes the development of peptide activity/affinity-based probes for the discovery of proteins that recognize novel acyl-based PTMs on lysine residues in the proteome. The probes contain surrogates of ?-N-acyllysine by introduction of either hydrazide or thioamide functionalities to circumvent hydrolysis of the modification during the experiments. In addition to the modified PTMs, the developed chemotypes were analyzed with respect to the effect of peptide sequence. The photo cross-linking conditions and subsequent functionalization of the covalent adducts were systematically optimized by applying fluorophore labeling and gel electrophoresis (in-gel fluorescence measurements). Finally, selected probes, containing the ?-N-glutaryllysine and ?-N-myristoyllysine analogues, were successfully applied for the enrichment of native, endogenous proteins from cell lysate, recapitulating the expected interactions of SIRT5 and SIRT2, respectively. Interestingly, the latter mentioned was able to pull down two different splice variants of SIRT2, which has not been achieved with a covalent probe before. Based on this elaborate proof-of-concept study, we expect that the technology will have broad future applications for pairing of novel PTMs with the proteins that target them in the cell.
- B?k, Michael,Chakladar, Saswati,Laursen, Jonas S.,Madsen, Julie L. H.,Martín-Gago, Pablo,Olsen, Christian A.
-
supporting information
(2020/03/11)
-
- PYRIDINE COMPOUND SUBSTITUTED WITH AZOLE
-
The present invention provides a compound represented by formula [I] shown below or a pharmaceutically acceptable salt thereof that has an inhibitory effect on 20-HETE producing enzyme. (in formula [I] above, the structure represented by formula [II] below: represents any of the structures represented by formula group [III] below: R1, R2, R3, and R4 independently represent a hydrogen atom, a fluorine atom, methyl, or the like, R5 represents any of the structures represented by formula group [IV]:
- -
-
Paragraph 0936
(2020/07/07)
-
- Bisubstrate inhibitors of nicotinamide N-methyltransferase (NNMT) with enhanced activity
-
Nicotinamide N-methyltransferase (NNMT) catalyzes the methylation of nicotinamide to form N-methylnicotinamide. Overexpression of NNMT is associated with a variety of diseases, including a number of cancers and metabolic disorders, suggesting a role for NNMT as a potential therapeutic target. By structural modification of a lead NNMT inhibitor previously developed in our group, we prepared a diverse library of inhibitors to probe the different regions of the enzyme's active site. This investigation revealed that incorporation of a naphthalene moiety, intended to bind the hydrophobic nicotinamide binding pocket via π-πstacking interactions, significantly increases the activity of bisubstrate-like NNMT inhibitors (half-maximal inhibitory concentration 1.41 μM). These findings are further supported by isothermal titration calorimetry binding assays as well as modeling studies. The most active NNMT inhibitor identified in the present study demonstrated a dose-dependent inhibitory effect on the cell proliferation of the HSC-2 human oral cancer cell line.
- Gao, Yongzhi,Van Haren, Matthijs J.,Moret, Ed E.,Rood, Johannes J. M.,Sartini, Davide,Salvucci, Alessia,Emanuelli, Monica,Craveur, Pierrick,Babault, Nicolas,Jin, Jian,Martin, Nathaniel I.
-
p. 6597 - 6614
(2019/08/20)
-
- AMIDE COMPOUNDS, METHODS FOR PREPARATION, AND USE THEREOF AS AGENTS FOR THE TREATMENT AND PREVENTION OF DISEASES CAUSED BY RNA- AND/OR DNA-CONTAINING VIRUSES, AND CONCOMITANT DISEASES
-
The present invention relates to medicine and includes a method for preventing and treating diseases caused by RNA- and DNA-containing viruses, and concomitant diseases, wherein the method comprises the use of an effective amount of compounds of general formula I or pharmaceutically acceptable salts thereof. The invention also relates to methods for preparing said compounds, pharmaceutical compositions for the prevention or treatment of diseases caused by RNA- and DNA-containing viruses, said compositions comprising an effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof. The invention addresses the object of providing a novel agent effective in the treatment of diseases caused by an RNA-containing virus belonging to the Enterovirus, Metapneumovirus, Pneumovirus, Respirovirus, or Alfa-coronavirus genus, and/or by a DNA-containing virus belonging to the Adenoviridae and/or Herpesviridae family, and in the prevention and treatment of asthma exacerbation, chronic obstructive pulmonary disease, mucoviscidosis, conjunctivitis, gastroenteritis, hepatitis, myocarditis; in the prevention and treatment of rhinorrhea, acute and infectious rhinitis, pharyngitis, nasopharyngitis, tonsillitis, laryngitis, laryngotracheitis, laryngotracheobronchitis, bronchitis, bronchiolitis, pneumonia, or airway obstructive syndrome.
- -
-
Paragraph 0207; 0208
(2017/07/14)
-
- Straightforward synthesis of functionalized (E)-3-acylacrylic acids
-
An experimentally simple, mild and straightforward synthetic route towards diversely functionalized (E)-3-acylacrylic acids is described, with Horner-Wadsworth-Emmons (HWE) reaction as the key step. The substrate scope and limitations of the HWE reaction were investigated with a range of β-ketophosphonates. Glyoxylic acid monohydrate was demonstrated to be fully compatible with the HWE reaction conditions, thus avoiding a troublesome hydrolysis of the corresponding 3-acylacrylates in the last step and providing a valuable synthetic shortcut.
- Sivák, Ivan,Václav, Jakub,Berke?, Du?an,Kolarovi?, Andrej
-
supporting information
p. 8871 - 8875
(2015/11/02)
-
- Oxidation of β-dicarbonyl compounds with tert-butyl hydroperoxide in the presence of vanadyl acetylacetonate
-
Oxidation of β-dicarbonyl compounds with tert-butyl hydroperoxide in the presence of vanadyl acetylacetonate (benzene, 20°C) involves the activated methylene group with intermediate formation of trioxo derivatives and is accompanied by decomposition of carbon skeleton. The oxidation products are carbon dioxide, carboxylic acids, and tert-butyl and peroxy esters derived from the latter.
- Stepovik,Gulenova,Kalacheva,Potkina, A. Yu.
-
scheme or table
p. 550 - 558
(2011/06/23)
-
- CONCISE BETA2-AMINO ACID SYNTHESIS VIA ORGANOCATALYTIC AMINOMETHYLATION
-
The present invention provides a method for the synthesis of ?2-amino acids. The method also provides methods yielding a-substituted ?-amino aldehydes and ?-substituted γ-amino alcohols. The present method according to this invention allows for increased yield and easier purification using minimal chromatography or crystallization. The methods described herein are based on an aldehyde aminomethylation which involves a Mannich reaction between an aldehyde and a formaldehyde-derived N,O-acetal (iminium precursor) and a catalyst, such as, for example, L-proline or a pyrrolidine. The invention allows for large scale, commercial preparation of ?2-amino acids.
- -
-
Page/Page column 51
(2010/11/28)
-
- Practical synthesis of enantiomerically pure β2-amino acids via proline-catalyzed diastereoselective aminomethylation of aldehydes
-
Proline-catalyzed diastereoselective aminomethylation of aldehydes using a chiral iminium ion, generated from a readily prepared precursor, provides α-substituted-β-amino aldehydes with 85:15 to 90: 10 dr. The α-substituted-β-amino aldehydes can be reduce
- Chi, Yonggui,English, Emily P.,Pomerantz, William C.,Horne, W. Seth,Joyce, Leo A.,Alexander, Lane R.,Fleming, William S.,Hopkins, Elizabeth A.,Gellman, Samuel H.
-
p. 6050 - 6055
(2008/02/08)
-
- Statine derivatives for the treatment of Alzheimer's disease III
-
The invention relates to a compound of the formula (I) wherein R1, R2, R3, R4, R5, R6, R7 and R8 are defined as in the specification and claims and to its use for treating or preventing Alzheimer's disease and other similar diseases.
- -
-
Page/Page column 31
(2010/11/08)
-
- Carbamic acid compounds comprising an amide linkage as hdac inhibitors
-
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.
- -
-
-
- Enantioselective preparation of β2-amino acids with aspartate, glutamate, asparagine, and glutamine side chains
-
(S)-β2-Homoamino acids with the side chains of Asp, Glu, Asn, and Gln have been prepared and suitably protected (N-Fmoc, CO 2′Bu CONHTrt) for solid-phase peptide syntheses. The key steps of the syntheses are: N-acylation of 5,5-diphe
- Lelais, Gerald,Campo, Marino A.,Kopp, Sascha,Seebach, Dieter
-
p. 1545 - 1560
(2007/10/03)
-
- Cyclodextrin-based rotaxane dyes, labeling agent using the dye, and a method for labeling
-
This invention provides rotaxane type dyes. Specifically, the rotaxane type dye according to the invention has a rotaxane structure which binds dye molecules to both of the termini of a chain group penetrating a cyclodextrin ring, which possesses excellent water-solubility, and which is capable of having a plurality of different dyes.
- -
-
-
- Building units for N-backbone cyclic peptides. Part 4. Synthesis of protected Nα-functionalized alkyl amino acids by reductive alkylation of natural amino acids
-
A new method for the synthesis of protected Nα-(ω-Y-alkyl) amino acids (Y is a thio, amino or carboxy group) and related compounds by reductive alkylation of natural amino acids is reported. These new amino acids serve as building units for the synthesis of backbone-cyclic peptides. They are orthogonally protected at the α-amino position by butoxycarbonyl (Boc) or 9-fluorenylmethoxycarbonyl (Fmoc), using trimethylsilyl temporary protection, to allow for their incorporation into peptides by solid phase peptide synthesis.
- Bitan, Gal,Muller, Dan,Kasher, Ron,Gluhov, Evgenia V.,Gilon, Chaim
-
p. 1501 - 1510
(2007/10/03)
-
- Enolic Radical Derived from Acetic Acid: A Useful Radical Alternative to Acetate Enolate in Michael-Type Reactions
-
The reaction of iodoacetic acid 1 with tributyltin chloride and sodium borohydride in the presence of different electrophilic olefins 2 (methyl, allyl or tert-butyl acrylates, N,N-dimethyl or N,N-di-iso-propyl acrylamides, acrylonitrile, methyl methacrylate, methacrylonitrile and 1,1-dichloroethylene) and AIBN as an initiator yields, after treatment with aqueous sodium fluoride, the corresponding products 3 through a radical Michael-type process.
- Foubelo, Francisco,Lloret, Francisco,Yus, Miguel
-
p. 8465 - 8470
(2007/10/02)
-
- 5-Fluorouracil derivatives, and their pharmaceutical compositions
-
A compound of the formula: STR1 wherein R is a bridged alicyclic group selected from the group consisting of norbornyl, norbornenyl, bicyclo[2,2,2]-heptyl and adamantyl optionally substituted by at least one substituent selected from the group consisting
- -
-
-