Category: 42413-03-6

Nycholat, Corwin M.; Duan, Shiteng; Knuplez, Eva; Worth, Charli; Elich, Mila; Yao, Anzhi; O’Sullivan, Jeremy; McBride, Ryan; Wei, Yadong; Fernandes, Steve M.; Zhu, Zhou; Schnaar, Ronald L.; Bochner, Bruce S.; Paulson, James C. published the artcile< A sulfonamide sialoside analogue for targeting Siglec-8 and -F on immune cells>, Reference of 42413-03-6, the main research area is sulfonamide sialoside analog Siglec8 ligand immune cell targeting.

The Siglec family of cell surface receptors have emerged as attractive targets for cell-directed therapies due to their restricted expression on immune cells, endocytic properties, and ability to modulate receptor signaling. Human Siglec-8, for instance, has been identified as a therapeutic target for the treatment of eosinophil and mast cell disorders. A promising strategy to target Siglecs involves the use of liposomal nanoparticles with a multivalent display of Siglec ligands. A key challenge for this approach is the identification of a high affinity ligand for the target Siglec. Here, we report the development of a ligand of Siglec-8 and its closest murine functional orthologue Siglec-F that is capable of targeting liposomes to cells expressing Siglec-8 or -F. A glycan microarray library of synthetic 9-N-sulfonyl sialoside analogs was screened to identify potential lead compounds The best ligand, 9-N-(2-naphthyl-sulfonyl)-Neu5Acα2-3-[6-O-sulfo]-Galβ1-4GlcNAc (6′-O-sulfo NSANeu5Ac) combined the lead 2-naphthyl sulfonyl C-9 substituent with the preferred sulfated scaffold. The ligand 6′-O-sulfo NSANeu5Ac was conjugated to lipids for display on liposomes to evaluate targeted delivery to cells. Targeted liposomes showed strong in vitro binding/uptake and selectivity to cells expressing Siglec-8 or -F and, when administered to mice, exhibit in vivo targeting to Siglec-F+ eosinophils.

Journal of the American Chemical Society published new progress about B cell. 42413-03-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H6Cl2O2S, Reference of 42413-03-6.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Lorenz, Daniel A.; Kaur, Tanpreet; Kerk, Samuel A.; Gallagher, Erin E.; Sandoval, Jorge; Garner, Amanda L. published the artcile< Expansion of cat-ELCCA for the Discovery of Small Molecule Inhibitors of the Pre-let-7-Lin28 RNA-Protein Interaction>, Electric Literature of 42413-03-6, the main research area is catalytic enzyme linked click chem assay catELCCA.

Dysregulation of microRNA (miRNA) expression has been linked to many human diseases; however, because of the challenges associated with RNA-targeted drug discovery, addnl. approaches are needed for probing miRNA biol. The emerging regulatory role of miRNA-binding proteins in miRNA maturation presents such an alternative strategy. Exploiting our laboratory’s click chem.-based high-throughput screening (HTS) technol., catalytic enzyme-linked click chem. assay or cat-ELCCA, we have designed a modular method by which to discover new chem. tools for manipulating pre-miRNA-miRNA-binding protein interactions. Using the pre-let-7d-Lin28 interaction as proof-of-concept, the results presented demonstrate how HTS using cat-ELCCA can enable the discovery of small mols. targeting RNA-protein interactions.

ACS Medicinal Chemistry Letters published new progress about Bioassay. 42413-03-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H6Cl2O2S, Electric Literature of 42413-03-6.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Morrill, Charlotte; Gillespie, James E.; Phipps, Robert J. published the artcile< An Aminative Rearrangement of O-(Arenesulfonyl)hydroxylamines: Facile Access to ortho-Sulfonyl Anilines>, Name: 3-Chloro-4-methylbenzene-1-sulfonyl chloride, the main research area is ortho sulfonyl aniline regioselective preparation; arenesulfonyl hydroxylamine ortho aminative rearrangement ferrous sulfate catalyst; Arene Amination; Ion-Pairing; Non-Covalent Interactions; Radical Reactions; Regioselectivity.

The discovery of an aromatic rearrangement reaction of O-(arenesulfonyl)hydroxylamines which lead directly to ortho-aminoarylsulfonic acids and ortho-aminobenzenemethanesulfonic acids through formation of a new C-N bond with excellent levels of regiocontrol for the ortho position(s) over all others was reported. The rearrangement was proceeding through an intermol. mechanism and proposed that the regiocontrol observed was the result of attractive non-covalent interactions occurring during the C-N bond-forming step. Importantly, this method was complementary to classical aniline sulfonation in terms of the variously substituted regioisomers that could be obtained and it was also applicable to O-(benzylsulfonyl) hydroxylamines.

Angewandte Chemie, International Edition published new progress about Amination catalysts. 42413-03-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H6Cl2O2S, Name: 3-Chloro-4-methylbenzene-1-sulfonyl chloride.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Cheung, Yiu-Yin; Zamorano, Rocio; Blobaum, Anna L.; Weaver, C. David; Conn, P. Jeffrey; Lindsley, Craig W.; Niswender, Colleen M.; Hopkins, Corey R. published the artcile< Solution-Phase Parallel Synthesis and SAR of Homopiperazinyl Analogs as Positive Allosteric Modulators of mGlu4>, Related Products of 42413-03-6, the main research area is homopiperazinylsulfonamide preparation structure activity relationship pharmacokinetics mGlu4 modulator; pos allosteric modulator mGlu4 homopiperazinylsulfonamide preparation amidation sulfonamidation; sulfonyl chloride amine reactant homopiperazinylsulfonamide preparation.

Using a functional high-throughput screening (HTS) and subsequent solution-phase parallel synthesis approach, we have discovered a novel series of pos. allosteric modulators for mGlu4, a G-protein coupled receptor. This series is comprised of a homopiperazine central core, e.g. I and II. The solution-phase parallel synthesis and SAR of analogs derived from this series will be presented. This series of pos. allosteric modulators of mGlu4 provide critical research tools to further probe the mGlu4-mediated effects in Parkinson’s disease.

ACS Combinatorial Science published new progress about Amidation. 42413-03-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H6Cl2O2S, Related Products of 42413-03-6.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Taylor, Steven J.; Soleymanzadeh, Fariba; Eldrup, Anne B.; Farrow, Neil A.; Muegge, Ingo; Kukulka, Alison; Kabcenell, Alisa K.; DeLombaert, Stephane published the artcile< Design and synthesis of substituted nicotinamides as inhibitors of soluble epoxide hydrolase>, COA of Formula: C7H6Cl2O2S, the main research area is nicotinamide derivative preparation soluble epoxide hydrolase inhibitory activity.

A series of potent nicotinamide inhibitors, e.g., I, of soluble epoxides hydrolase (sEH) is disclosed. This series was designed using structure-based deconstruction and a combination of two HTS hit series, resulting in hybrid analogs that retained the optimal potency from one series, and acceptable in vitro metabolic stability from the other. Structure-guided optimization of these analogs gave rise to nanomolar inhibitors of human sEH that had acceptable plasma exposure to qualify them as probes to determine the in vivo phenotypic consequences of sEH inhibition.

Bioorganic & Medicinal Chemistry Letters published new progress about Aralkyl amines Role: RCT (Reactant), RACT (Reactant or Reagent). 42413-03-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H6Cl2O2S, COA of Formula: C7H6Cl2O2S.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Steinmetzer, Torsten; Baum, Bernhard; Biela, Adam; Klebe, Gerhard; Nowak, Goetz; Bucha, Elke published the artcile< Beyond Heparinization: Design of Highly Potent Thrombin Inhibitors Suitable for Surface Coupling>, Recommanded Product: 3-Chloro-4-methylbenzene-1-sulfonyl chloride, the main research area is dialysis equipment thrombin inhibitor SAR anticoagulant; X-ray crystallography; anticoagulants; inhibitors; serine proteases; thrombin.

During extracorporeal circulation, when blood comes in contact with artificial surfaces, patients receive a standard treatment with anticoagulants to avoid blood coagulation. Dialysis patients in particular are systemically treated with heparin up to four times a week, causing a high burden for the body. For potential anticoagulant modification of external materials, such as dialysis equipment, a series of highly potent thrombin inhibitors was developed. All inhibitors share the general formula arylsulfonyl-P3-Pro-4-amidinobenzylamide, where P3 is glycyl or a trifunctional amino acid residue in L-configuration. Among this series, several derivatives inhibit thrombin with Ki values of less than 1 nM. Specificity measurements revealed that this inhibitor type is highly specific for thrombin with negligible activity against related trypsin-like serine proteases. X-ray anal. of the most potent analog in complex with thrombin demonstrated that the N-terminal arylsulfonyl group occupies the aryl binding site, whereas the P3 side chain is directed into the solvent and therefore is well suited for further coupling. Based on their in vitro profile, these inhibitors are suitable candidates for the development of hemocompatible materials with anticoagulant properties.

ChemMedChem published new progress about Anticoagulants. 42413-03-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H6Cl2O2S, Recommanded Product: 3-Chloro-4-methylbenzene-1-sulfonyl chloride.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Amberg, Alexander; Harvey, James S.; Czich, Andreas; Spirkl, Hans-Peter; Robinson, Sharon; White, Angela; Elder, David P. published the artcile< Do Carboxylic/Sulfonic Acid Halides Really Present a Mutagenic and Carcinogenic Risk as Impurities in Final Drug Products?>, Safety of 3-Chloro-4-methylbenzene-1-sulfonyl chloride, the main research area is mutagenesis carboxylic sulfonic acid halide.

A substantial amount of mutagenicity data on acyl/sulfonyl halides is available in the public domain, and these data are the basis for many in silico models of mutagenicity (e.g., Derek Nexus and Leadscope). A review of these data indicates that the perceived mutagenic potential of this class of compounds is based on a number of nonreproducible pos. findings in the bacterial mutagenicity assay and pos. bacterial mutagenicity data on a series of compounds where formation of reactive halodimethyl sulfides (HDMSs) in DMSO may have compromised the interpretation of the Ames data (HDMSs are typically mutagenic). The only genuine mutagenic, genotoxic, and carcinogenic compound within the 50+ acyl/sulfonyl halides described herein is dimethylcarbamic chloride, which is appropriately considered to be a potential human carcinogen. Some in silico systems, such as Derek Nexus, contain rules detailing that the activity of this class should be considered a false pos. flag for mutagenicity, and ideally, any in silico structure-activity rules for mutagenicity in other systems should likewise be addressed. The data presented here support the view that these alerts should currently be interpreted as a false pos. flag for mutagenicity and that the entire class should be viewed as a low concern from a mutagenicity perspective. The formation of these reactive HDMSs is an example of the classical Pummerer rearrangement. The chem. reactivity of this class of compounds also supports the contention that they are of limited concern from a mutagenic and carcinogenic impurity risk perspective when used in the synthesis of drug products. They can be expected to rapidly purge from any reaction sequence with generic predicted purge factors in the range from 1 × 103 to 3 × 105 per stage and hence should be effectively eliminated at the stage of introduction. We would therefore recommend avoiding the use of DMSO as the solvent for mutagenicity tests with acyl/sulfonyl halides because of the potential for false pos. results arising from DMSO reaction products, which are not relevant under aqueous, physiol. conditions. Furthermore, as indicated by the Ames test data for mesyl chloride/2-fluorobenzoyl chloride, even non-DMSO organic solvents may not be appropriate for certain members of this class (acyl/sulfonyl halides), suggesting that they may not be amenable to adequate testing in the Ames assay.

Organic Process Research & Development published new progress about Acid halides Role: ADV (Adverse Effect, Including Toxicity), BSU (Biological Study, Unclassified), BIOL (Biological Study). 42413-03-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H6Cl2O2S, Safety of 3-Chloro-4-methylbenzene-1-sulfonyl chloride.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Barn, D. R.; Caulfield, W. L.; Cottney, J.; McGurk, K.; Morphy, J. R.; Rankovic, Z.; Roberts, B. published the artcile< Parallel synthesis and biological activity of a new class of high affinity and selective δ-opioid ligand>, Computed Properties of 42413-03-6, the main research area is tetrahydroisoquinoline sulfonamide based delta opioid ligand preparation.

A considerable number of research papers describing the synthesis and testing of the delta opioid receptor (DOR) ligands, SNC-80 and TAN-67, and analogs of these two compounds, have been published in recent years. However, there have been few reports of the discovery of completely new structural classes of selective DOR ligand. By optimizing a hit compound identified by high throughput screening, a new series of tetrahydroisoquinoline sulfonamide-based delta opioid ligands was discovered. The main challenge in this series was to simultaneously improve both affinity and physicochem. properties, notably aqueous solubility The most active ligand had an affinity (IC50) of 6 nM for the cloned human DOR, representing a 15-fold improvement relative to the original hit I (IC50 98 nM). Compounds from this new series show good selectivity for the DOR over μ and κ opioid receptors. However the most active and selective compounds had poor aqueous solubility Improved aqueous solubility was obtained by replacing the phthalimide group in I by basic groups, allowing the synthesis of salt forms. A series of compounds with improved affinity and solubility relative to I was identified and these compounds showed activity in an in vivo model of antinociception, the formalin paw test. In the case of compound II, this analgesic activity was shown to be mediated primarily via a DOR mechanism. The most active compound in vivo, III, showed superior potency in this test compared to the reference DOR ligand, TAN-67 and similar potency to morphine (68% and 58% inhibition in Phases 1 and 2, resp., at a dose of 10 mmol/kg i.v.).

Bioorganic & Medicinal Chemistry published new progress about Analgesics. 42413-03-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H6Cl2O2S, Computed Properties of 42413-03-6.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Shingare, M. S.; Ingle, D. B. published the artcile< Synthesis of 2-(substituted phenyl sulfonamido)-4-(3'-sulfamyl-4'-substituted phenyl)thiazoles - Part II>, Quality Control of 42413-03-6, the main research area is phenylsulfonamidosulfamylphenylthiazole bactericide; sulfamylphenylthiazole phenylsulfonamido bactericide.

Phenylsulfonamidothiazoles I (R = H, Me, Cl, Br; R1 = H, Cl; R2 = H, Me, Cl, NH2) were prepared in 35-52% yields by condensing aminothiazoles II with 3,4-R1R2C6H3SO2Cl. I were devoid of bactericidal activity.

Acta Ciencia Indica, Chemistry published new progress about 42413-03-6. 42413-03-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H6Cl2O2S, Quality Control of 42413-03-6.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Hanessian, Stephen; Therrien, Eric; van Otterlo, Willem A. L.; Bayrakdarian, Malken; Nilsson, Ingemar; Fjellstroem, Ola; Xue, Yafeng published the artcile< Phenolic P2/P3 core motif as thrombin inhibitors - design, synthesis, and X-ray co-crystal structure>, Formula: C7H6Cl2O2S, the main research area is trisubstituted phenol preparation thrombin inhibitor.

Prototypical thrombin inhibitors were synthesized based on a trisubstituted phenol as a core motif. A naphthylsulfonamide analog (I) showed excellent antithrombin activity. An X-ray co-crystal structure of I bound to thrombin showed the expected interactions.

Bioorganic & Medicinal Chemistry Letters published new progress about Phenols Role: PAC (Pharmacological Activity), SPN (Synthetic Preparation), BIOL (Biological Study), PREP (Preparation). 42413-03-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H6Cl2O2S, Formula: C7H6Cl2O2S.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics