144-80-9Relevant articles and documents
Exploring Ligand-Directed N-Acyl- N-alkylsulfonamide-Based Acylation Chemistry for Potential Targeted Degrader Development
Bae, Jae Hyun,Dhe-Paganon, Sirano,Donovan, Katherine A.,Ficarro, Scott B.,Fischer, Eric S.,Gray, Nathanael S.,Jiang, Jie,Marto, Jarrod A.,Seo, Hyuk-Soo,Teng, Mingxing,Zhang, Tinghu
, p. 1302 - 1307 (2021)
Ligand-directed bioconjugation strategies have been used for selective protein labeling in live cells or tissue samples in applications such as live-cell imaging. Here we hypothesized that a similar strategy could be used for targeted protein degradation. To test this possibility, we developed a series of CDK2-targeting N-acyl-N-alkylsulfonamide (NASA)-containing acylation probes. The probes featured three components: a CDK2 homing ligand, a CRL4CRBN E3 ligase recruiting ligand, and a NASA functionality. We determined that upon target binding, NASA-mediated reaction resulted in selective functionalization of Lys89 on purified or native CDK2. However, we were unable to observe CDK2 degradation, which is in contrast to the efficient degradation achieved by the use of a structurally similar reversible bivalent degrader. Our analysis suggests that the lack of degradation is due to the failure to form a productive CDK2:CRBN complex. Therefore, although this work demonstrates that NASA chemistry can be used for protein labeling, whether this strategy could enable efficient protein degradation remains an open question.
Synthesis method of sulfalacetamide sodium
-
Paragraph 0027-0051, (2020/07/02)
The invention relates to a synthesis method of sulfalacetamide sodium. The synthesis method is characterized by comprising the following steps: S1, sequentially adding sulfanilamide and alkaline ionicliquid into a reaction kettle, carrying out stirring for 20 to 30 minutes at a temperature of 100 to 150 DEG C, dropwise adding acetic anhydride within 2-4 hours, continuing stirring and reacting for3-6 hours at a temperature of 80-90 DEG C, adding water for diluting, adjusting a pH value to 4-5 by using hydrochloric acid, conducting standing for 1-3 hours, performing suction filtration, addingactivated carbon into a filtrate, carrying out decolorizing for 10-20 minutes at room temperature, and performing suction filtration to obtain sulfacetamide; and step S2, adding the sulfacetamide prepared in the step S1 and sodium hydroxide into a mixed solvent, carrying out stirring at room temperature until solids are completely dissolved, evaporating the mixed solvent in a water bath, and carrying out crystallizing and drying to obtain the sulfacetamide sodium. The synthesis method of sulfalacetamide sodium disclosed by the invention is high in production efficiency, high in yield and product purity and low in production cost; and the basic ionic liquid is used as a catalyst and a solvent, so a conversion rate, the yield and the product purity are improved to a great extent.
Ofloxacin-sulfacetamide hybrid drug as well as preparation method and application thereof
-
Paragraph 0030-0034; 042-0043, (2019/03/31)
The invention provides an ofloxacin-sulfacetamide hybrid drug as well as a preparation method and application thereof. The ofloxacin-sulfacetamide hybrid drug is prepared from acidized sulfacetamide sodium and ofloxacin under catalysis of dicyclohexylcarbodiimide. According to the ofloxacin-sulfacetamide hybrid drug disclosed by the invention, the ofloxacin is spliced onto sulfacetamide by formingcovalent bonds, so that the hybrid drug has properties of the ofloxacin and the sulfacetamide. Since mycobacterium tuberculosis difficultly produces drug resistance to sulfonamide drugs, the ofloxacin-sulfacetamide hybrid drug disclosed by the invention has excellent drug tolerance on the mycobacterium tuberculosis. Meanwhile, the ofloxacin and the sulfacetamide in the ofloxacin-sulfacetamide hybrid drug can be respectively combined with different targets, the pharmacological activity can be enhanced, and respective corresponding toxic and side effects are reduced.
3-PHOSPHOGLYCERATE DEHYDROGENASE INHIBITORS AND USES THEREOF
-
Paragraph 00278, (2017/10/06)
The present invention provides compounds, compositions thereof, and methods of using the same.
Compound capable of inhibiting activity of NEDD8 kinase as well as preparation method and pharmaceutical application of compound
-
, (2016/10/10)
The invention belongs to the field of medicines and in particular relates to a compound with the structure of a formula I, a stereomer of the compound or pharmaceutically acceptable salts of the compound as well as a preparation method of the compound and application of the compound to preparation of anti-tumor medicines. A pharmacological experiment result shows that the compound can be used for inhibiting the activity of NEDD8 kinase and has the inhibition effect on proliferation of a plurality of types of tumor cells, so that the compound can be used as an NEDD8 kinase activity inhibitor for preparing the anti-tumor medicines. The formula I is shown in the description.
ION CHANNEL MODULATORS AND METHODS OF USE
-
Page/Page column 49; 50, (2009/01/20)
In general, the invention relates to compounds useful as ion channel modulators. It has now been found that compounds of this invention, and pharmaceutically acceptable compositions thereof, are useful as inhibitors of voltage-gated sodium channels.
Inhibition of serine proteases by functionalized sulfonamides coupled to the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold
Groutas, William C,He, Shu,Kuang, Rongze,Ruan, Sumei,Tu, Juan,Chan, Ho-Kit
, p. 1543 - 1548 (2007/10/03)
A challenge associated with drug design is the development of selective inhibitors of proteases (serine or cysteine) that exhibit the same primary substrate specificty, that is, show a preference for the same P1 residue. While these proteases have similar active sites, nevertheless there are subtle differences in their S and S' subsites which can be exploited. We describe herein for the first time the use of functionalized sulfonamides as a design and diversity element which, when coupled to the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold yields potent, time-dependent inhibitors of the serine proteases human leukocyte elastase (HLE), proteinase 3 (PR 3) and cathepsin G(Cat G). Our preliminary findings suggest that (a) appending to the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold recognition and diversity elements that interact with both S and S' subsites of a target protease may result in optimal enzyme selectivity and potency and, (b) functionalized sulfonamides constitute a powerful design and diversity element with low intrinsic chemical reactivity and potentially wide applicability. Copyright
Acylation of benzenesulfamides in alkaline solutions
Kotlyar,Gorodnyuk,Grigorash,Zlotskii
, p. 1653 - 1654 (2007/10/03)
Acylation of 4-aminobenzenesulfamide with acetic anhydride in aqueous sodium hydroxide was studied, and the main acylation products were determined.
