6066-82-6Relevant articles and documents
TRPA1 is activated by direct addition of cysteine residues to the N-hydroxysuccinyl esters of acrylic and cinnamic acids
Sadofsky, Laura R.,Boa, Andrew N.,Maher, Sarah A.,Birrell, Mark A.,Belvisi, Maria G.,Morice, Alyn H.
, p. 30 - 36 (2011)
The nociceptor TRPA1 is thought to be activated through covalent modification of specific cysteine residues on the N terminal of the channel. The precise mechanism of covalent modification with unsaturated carbonyl-containing compounds is unclear, therefore by examining a range of compounds which can undergo both conjugate and/or direct addition reactions we sought to further elucidate the mechanism(s) whereby TRPA1 can be activated by covalent modification. Calcium signalling was used to determine the mechanism of activation of TRPA1 expressed in HEK293 cells with a series of related compounds which were capable of either direct and/or conjugate addition processes. These results were confirmed using physiological recordings with isolated vagus nerve preparations. We found negligible channel activation with chemicals which could only react with cysteine residues via conjugate addition such as acrylamide, acrylic acid, and cinnamic acid. Compounds able to react via either conjugate or direct addition, such as acrolein, methyl vinyl ketone, mesityl oxide, acrylic acid NHS ester, cinnamaldehyde and cinnamic acid NHS ester, activated TRPA1 in a concentration dependent manner as did compounds only capable of direct addition, namely propionic acid NHS ester and hydrocinnamic acid NHS ester. These compounds failed to activate TRPV1 expressed in HEK293 cells or mock transfected HEK293 cells. For molecules capable of direct or conjugate additions, the results suggest for the first time that TRPA1 may be activated preferentially by direct addition of the thiol group of TRPA1 cysteines to the agonist carbonyl carbon of α,β-unsaturated carbonyl-containing compounds.
A Catalyst-Free Synthesis of Fused Perfluoroalkylated 2,3-Dihydroisoxazoles via Oxa-Michael-Aldol Annulation
Zhou, Wei,Yao, Lan,Liu, Yongxiurong,Shen, Lichun,Chen, Jie,Deng, Hongmei,Shao, Min,Zhang, Hui,Tang, Xiaojun,Cao, Weiguo
supporting information, p. 429 - 438 (2021/10/01)
A novel synthesis of fused perfluoroalkylated 2,3-dihydroisoxazoles is achieved via oxa-Michael-aldol annulation between perfluoroalk- 2-ynoates and N-hydroxyimides. This method provides a convenient route for the synthesis of pyrrolidin-2-one-fused perfluoroalkylated 2,3-dihydroisoxazoles in yields of up to 97%. Diverse and pharmaceutically attractive polycyclic scaffolds can be obtained rapidly and efficiently under these mild, catalyst-free conditions.
DLL3-TARGETING MULTISPECIFIC ANTIGEN-BINDING MOLECULES AND USES THEREOF
-
, (2021/10/02)
The disclosure provides multispecific antigen-binding molecules that comprise a first antigen-binding moiety and a second antigen-binding moiety, each of which is capable of binding to CD3 and CD137, but does not bind to CD3 and CD137 at the same time; and a third antigen-binding moiety that is capable of binding to DLL3, preferably human DLL3, which induce T-cell dependent cytotoxity more efficiently whilst circumventing adverse toxicity concerns or side effects that other multispecific antigen-binding molecules may have. The present invention provides multispecific antigen-binding molecules and pharmaceutical compositions that can treat various cancers, especially those associated with DLL3, by comprising the antigen-binding molecule as an active ingredient.
A METHOD FOR PREPARING N-SUBSTITUTED SUCCINIMIDE
-
Paragraph 0089; 0091-0093; 0095-0108; 0113, (2021/10/27)
N -substituted succinimides are disclosed. , The 1-substituted succinimide prepared by reacting a succinic acid with 1-order amine is reacted with an acid catalyst, a metal catalyst, and a reducing agent to produce N - N -substituted succinimide, which is industrially useful and can be widely applied to various industrial fields.
Synthesis method of N-(benzyloxycarbonyloxy)succinimide
-
Paragraph 0005; 0008; 0012; 0015, (2020/05/05)
The invention relates to a synthesis method of N-(benzyloxycarbonyloxy)succinimide; the invention mainly solves the technical problems of high raw material cost, overhigh reaction rate, severe heat release, high possibility of generating impurities, high product loss during refining and the like in an existing synthesis method. The synthesis method comprises the following steps: dissociating hydroxylamine hydrochloride in an aqueous solution by using NaOH, and carrying out a reaction with succinic anhydride to generate HOSu; carrying out a reaction of HOSu with Cbz-Cl in a mixed solution of water and ethyl acetate to generate a target compound Cbz-OSu. Cbz-OSu is commonly used as a polypeptide commonly used reagent, and a Z-amino protection reagent is selectively introduced in synthesis ofamino acids and aminoglycoside antibiotics.
Method for synthesizing 9-fluorenylmethylsuccinimido carbonate by one-pot two-phase method
-
Paragraph 0011; 0024-0029, (2020/03/03)
The invention relates to the technical field of organic synthesis, specifically to a method for synthesizing 9-fluorenylmethylsuccinimido carbonate by a one-pot two-phase method. The method comprisesthe following steps: adding purified water and hydroxylamine sulfate into a reaction container, dropwise adding liquid caustic soda under stirring, after the liquid caustic soda is dropwise added, adding butanedioic anhydride in batches, and carrying out high-temperature vacuum dehydration under acid catalysis until no water is extracted out so as to prepare an N-hydroxysuccinimide solution; adding a chloroformic acid-9-fluorenyl methyl ester solution into the N-hydroxysuccinimide solution, and controlling a temperature at 0 to 60 DEG C; after the chloroformic acid-9-fluorenyl methyl ester solution is added, starting to dropwise add an aqueous alkali solution; after the aqueous alkali solution is dropwise added, separating out an organic layer, carrying out concentrating to dryness, and carrying out recrystallizing so as to obtain a 9-fluorenylmethylsuccinimido carbonate finished product. The above-mentioned method provided by the invention innovatively adopts the one-pot two-phase method; a reaction liquid containing N-hydroxysuccinimide is directly used for synthesizing the 9-fluorenylmethylsuccinimido carbonate in a two-phase reaction manner; process steps are effectively reduced; and the method is applicable to large-scale industrial production.
Solvent-Controlled Synthesis of Thiocyanated Enaminones and 2-Aminothiazoles from Enaminones, KSCN, and NBS
Chen, Xue,Cuan, Xiaodan,Duan, Xiyan,Li, Huimin,Liu, Kun,Liu, Xiaojing,Wang, Junqin,Wang, Lin,Zhou, Huiyun
, (2019/10/11)
An effective and simple solvent-controlled synthesis of thiocyanated enaminones and 2-aminothiazoles has been demonstrated from enaminones, potassium thiocyanate, and N-bromosuccinimide. This process features mild reaction conditions, simple and easy oper
COMPOUNDS AND METHODS FOR DETECTING EARLY ATHEROSCLEROTIC LESIONS IN BLOOD VESSELS
-
Page/Page column 23; 24, (2019/10/04)
A biotin derivative of formula (I) (I) in which R is a peptide with the sequence VHPKQHRGGSKGC, linked to the succinimidyl ring through the -SH group of the C-terminal cysteine, which can be used in a method for detecting early atherosclerotic lesions in the blood vessels of a human subject, which method includes steps of a) forming a complex of this biotin derivative with avidin, neutravidin or streptavidin; b) parenterally administering the complex thus formed; c) subsequently, parenterally administering a chelating agent including a chelating moiety, a biotin moiety and a metal radionuclide, and d) subjecting the human subject to a diagnostic nuclear imaging technique; this biotin derivative can also be used in a method for treating a disease of a human patient characterized by an overexpression of VCAM-1, including inflammatory diseases, atherosclerosis, multiple sclerosis, neurodegenerative diseases and neuroinflammatory diseases.
Preparation method of N-hydroxysuccinimide
-
Paragraph 0034; 0035; 0036; 0038; 0039; 0041; 0042; 0043, (2018/10/19)
The invention provides a preparation method of N-hydroxysuccinimide, which uses succinic acid as raw materials and reacts with hydroxylamine in the presence of weak acidic substances to prepare the N-hydroxysuccinimide. The reaction yield is over 85 percent, thereby further reducing production cost and eliminating hidden dangers existing in the production process.
Metal-Free C(sp3)-H Allylation via Aryl Carboxyl Radicals Enabled by Donor-Acceptor Complex
Li, Yang,Zhang, Jing,Li, Defang,Chen, Yiyun
supporting information, p. 3296 - 3299 (2018/06/11)
The first aryl carboxyl radical generation by the donor-acceptor complex with N-acyloxyphthalimides and Hantzsch esters is reported. Regio- and chemoselective C(sp3)-H bond allylation is enabled by aryl carboxyl radicals with visible light irradiation under mild and metal-free conditions.
