Tag: M.W=200-250

Rajapaksa, Naomi S. published the artcileDiscovery of Potent Benzolactam IRAK4 Inhibitors with Robust in Vivo Activity, Application In Synthesis of 35112-05-1, the main research area is preparation benzolactam IRAK4 inhibitor structure.

IRAK4 kinase activity transduces signaling from multiple IL-1Rs and TLRs to regulate cytokines and chemokines implicated in inflammatory diseases. As such, there is high interest in identifying selective IRAK4 inhibitors for the treatment of these disorders. We previously reported the discovery of potent and selective dihydrobenzofuran inhibitors of IRAK4. Subsequent studies, however, showed inconsistent inhibition in disease-relevant pharmacodynamic models. Herein, we describe application of a human whole blood assay to the discovery of a series of benzolactam IRAK4 inhibitors. We identified potent mol. 19 which achieves robust in vivo inhibition of cytokines relevant to human disease.

ACS Medicinal Chemistry Letters published new progress about Enzyme inhibitors (IRAK4). 35112-05-1 belongs to class chlorides-buliding-blocks, name is 4-Chloro-2-fluoro-5-nitrobenzoic acid, and the molecular formula is C7H3ClFNO4, Application In Synthesis of 35112-05-1.

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

ter Wiel, Matthijs K. J. published the artcileSynthesis of functionalized molecular motors, Name: Pyrene-2-carboxylic acid, the main research area is mol motor biphenanthrenylidene bicyclopentanaphthalenylidene preparation.

Synthetic routes to two mol. motors are reported. The sterically hindered central olefinic bond connecting the two halves of these C2-sym. mols. was prepared by a McMurry reaction. In this way, a motor with two five-membered rings and a motor with two six-membered rings were prepared, both with two versatile methoxy substituents at positions not interfering with the rotary behavior.

Synthesis published new progress about McMurry coupling reaction. 36428-96-3 belongs to class chlorides-buliding-blocks, name is Pyrene-2-carboxylic acid, and the molecular formula is C17H10O2, Name: Pyrene-2-carboxylic acid.

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

Song, Hyeseung published the artcileDiscovery of potent and selective rhodanine type IKKβ inhibitors by hit-to-lead strategy, Recommanded Product: 4-(4-Chlorophenoxy)benzaldehyde, the main research area is preparation rhodanine IKK NFkappaB inhibitor antiinflammatory cancer; rheumatoid arthritis rhodanine derivative.

Regulation of NF-κB activation through the inhibition of IKKβ has been identified as a promising target for the treatment of inflammatory and autoimmune disease such as rheumatoid arthritis. In order to develop novel IKKβ inhibitors, we performed high throughput screening toward around 8000 library compounds, and identified a hit compound containing rhodanine moiety. We modified the structure of hit compound to obtain potent and selective IKKβ inhibitors. Throughout hit-to-lead studies, we have discovered optimized compounds which possess blocking effect toward NF-κB activation and TNFα production in cell as well as inhibition activity against IKKβ. Among them, compound 3q showed the potent inhibitory activity against IKKβ, and excellent selectivity over other kinases such as p38α, p38β, JNK1, JNK2, and JNK3 as well as IKKα.

Bioorganic & Medicinal Chemistry Letters published new progress about Anti-inflammatory agents. 61343-99-5 belongs to class chlorides-buliding-blocks, name is 4-(4-Chlorophenoxy)benzaldehyde, and the molecular formula is C13H9ClO2, Recommanded Product: 4-(4-Chlorophenoxy)benzaldehyde.

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

Calzaferri, Francesco published the artcileSynthesis and Pharmacological Evaluation of Novel Non-nucleotide Purine Derivatives as P2X7 Antagonists for the Treatment of Neuroinflammation, Application of 4-Fluoro-2-methylbenzene-1-sulfonyl chloride, the main research area is purine preparation antiinflammatory activity mol docking pharmacokinetic study; xanthine preparation antiinflammatory activity mol docking pharmacokinetic study.

In this work, novel blood-brain barrier (BBB)-permeable derivatives, e.g., I as potential P2X7 antagonists were designed and synthesized. They comprise purine or xanthine cores linked to an aryl group through different short spacers. Compounds were tested in YO-PRO-1 uptake assays and intracellular calcium dynamics in a human P2X7-expressing HEK293 cell line, two-electrode voltage-clamp in Xenopus laevis oocytes, and in interleukin 1β release assays in mouse peritoneal macrophages. BBB permeability was assessed by parallel artificial membrane permeability assays and P-glycoprotein ATPase activity. Dichloroarylpurinylethanones featured a certain P2X7 blockade, being compound (2-(6-chloro-9H-purin-9-yl)-1-(2,4-dichlorophenyl)ethan-1-one) (I), named ITH15004, the most potent, selective, and BBB-permeable antagonist. Compound I can be considered as a first non-nucleotide purine hit for future drug optimizations.

Journal of Medicinal Chemistry published new progress about Anti-inflammatory agents. 7079-48-3 belongs to class chlorides-buliding-blocks, name is 4-Fluoro-2-methylbenzene-1-sulfonyl chloride, and the molecular formula is C7H6ClFO2S, Application of 4-Fluoro-2-methylbenzene-1-sulfonyl chloride.

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

Emam, Soha H. published the artcileDesign and synthesis of methoxyphenyl- and coumarin-based chalcone derivatives as anti-inflammatory agents by inhibition of NO production and down-regulation of NF-κB in LPS-induced RAW264.7 macrophage cells, Product Details of C13H9ClO2, the main research area is aryloxy methoxyaryl chalcone aryloxyaryloxopropenyl coumarin preparation antiinflammatory activity; structure methoxyarylaryloxychalcone aryloxyaryloxopropenylchalcone antiinflammatory activity; inhibition nitric oxide release macrophage methoxyarylaryloxychalcone aryloxyaryloxopropenylchalcone; mol docking methoxyarylaryloxychalcone IKKbeta; Anti-inflammatory; Chalcones; LPS-induced RAW264.7 macrophages; Molecular docking; Nitric oxide inhibition; Nuclear factor kappa B.

Exaggerated inflammatory responses may cause serious and debilitating diseases such as acute lung injury and rheumatoid arthritis. Two series of chalcone derivatives were prepared as anti-inflammatory agents. (Aryloxy)methoxychalcones and (aryloxyaryl)oxopropenylcoumarins were synthesized and compared for their inhibition of COX-2 enzyme and nitric oxide production suppression. Methoxylated phenyl-based chalcones showed better inhibition to COX-2 enzyme and nitric oxide suppression than the coumarin-based chalcones. Among the 18 synthesized chalcone derivatives, I exhibited the highest anti-inflammatory activity by inhibition of nitric oxide concentration in LPS-induced RAW264.7 macrophages (IC50 = 11.2μM). I showed suppression of iNOS and COX-2 enzymes and depressed the expression of NF-κB and phosphorylated IκB in LPS-stimulated macrophages. Finally, mol. docking studies suggested the inhibition of IKKβ as a mechanism of action and highlighted the importance of hydrophobic interactions with I.

Bioorganic Chemistry published new progress about Anti-inflammatory agents. 61343-99-5 belongs to class chlorides-buliding-blocks, name is 4-(4-Chlorophenoxy)benzaldehyde, and the molecular formula is C13H9ClO2, Product Details of C13H9ClO2.

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

Laha, Joydev K. published the artcileScope of Successive C-H Functionalizations of the Methyl Group in 3-Picolines: Intramolecular Carbonylation of Arenes to the Metal-Free Synthesis of 4-Azafluorenones, HPLC of Formula: 480438-56-0, the main research area is picoline aryl oxidant intramol carbonylation; azafluorenone preparation.

A transition-metal-free, t-BuOOH mediated intramol. carbonylation of arenes in 2-aryl-3-picolines via oxidative C-H functionalizations of the Me group has been developed, providing an expedient synthesis of 4-azafluorenones I [R = 7-MeO, 7-OCF3, 6,7-Cl2, 6-Cl-7-OPr-i, 7,8-(OMe)2, etc] . Distinct from the current literature wherein methylarenes have been used as acylating agents, 2-aryl-3-picolines in this study are transformed into aldehydes, which give 4-azafluorenones upon rapid intramol. acylation. The study demonstrates the first example of intramol. carbonylation of arenes utilizing a Me group as latent carbonyl functionality.

Organic Letters published new progress about C-H bond activation (oxidative). 480438-56-0 belongs to class chlorides-buliding-blocks, name is 3-Chloro-4-isopropoxyphenylboronic acid, and the molecular formula is C9H12BClO3, HPLC of Formula: 480438-56-0.

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

Gu, Jiali published the artcileRational design of esterase BioH with enhanced enantioselectivity towards methyl (S)-o-chloromandelate, COA of Formula: C9H9ClO3, the main research area is rational design esterase BioH enantioselectivity methyl chloromandelate.

Me (R)-o-chloromandelate (R-CMM) is an intermediate for the platelet aggregation inhibitor clopidogrel. Its preparation through enzymic resolution of the corresponding ester has been hindered by the lack of an enzyme with satisfying enantioselectivity and activity. In the present work, we aimed to improve the enzymic enantioselectivity towards Me (S)-o-chloromandelate (S-CMM) by rational design, using esterase BioH as a model enzyme. Based on the differences in the binding mode of S- and R-enantiomers at the active cavity of the enzyme, the steric and electronic interactions between the key amino acids of BioH and the enantiomers were finely tuned. The enantioselectivity of esterase BioH towards S-CMM was improved from 3.3 (the wild type) to 73.4 (L123V/L181A/L207F). Synergistic interaction was observed between point mutations, and insight into the source of enzymic enantioselectivity was gained by mol. dynamics simulations. The results can provide a reference for the enzyme design of other enzymes towards S-CMM for the enhancement of enantioselectivity.

Applied Microbiology and Biotechnology published new progress about Enzyme functional sites, active. 32345-60-1 belongs to class chlorides-buliding-blocks, name is (S)-Methyl 2-(2-chlorophenyl)-2-hydroxyacetate, and the molecular formula is C9H9ClO3, COA of Formula: C9H9ClO3.

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

Fuller, Ray W. published the artcileNorepinephrine N-methyltransferase inhibition by benzamidines, phenylacetamidines, benzylguanidines, and phenylethylguanidines, HPLC of Formula: 50292-25-6, the main research area is norepinephrine methyltransferase inhibitor amidine; guanidine aryl methyltransferase inhibitor.

Mono- and dichloro derivatives of 21 title compounds and 18 benzylamines, α-methylbenzylamines, and amphetamines were studied as inhibitors of norepinephrine N-methyltransferase (EC 2.1.1.28) [9037-68-7]. The 2 most effective inhibitors in vitro were 2,3-dichlorobenzamidine-HCl (I-HCl) [55154-87-5] and 3,4-dichlorophenylacetamidine (II) [55154-91-1] with pI50 values of 5.55 and 5.36, resp. I and II are reversible inhibitors and competitive with norepinephrine in vitro, but are not effective in blocking enzyme activity in vivo in rats.

Journal of Medicinal Chemistry published new progress about Structure-activity relationship. 50292-25-6 belongs to class chlorides-buliding-blocks, name is 3,4-Dichlorobenzene-1-carboximidamide hydrochloride, and the molecular formula is C7H7Cl3N2, HPLC of Formula: 50292-25-6.

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

Xu, Rui published the artcileDiscovery of spirocyclic sulfonamides as potent Akt inhibitors with exquisite selectivity against PKA, HPLC of Formula: 7079-48-3, the main research area is spirocyclic sulfonamide preparation Akt inhibitor SAR.

We describe the design and synthesis of novel bicyclic spiro sulfonamides, e.g. I, as potent Akt inhibitors. Through structure-based rational design, we have successfully improved PKA selectivity of previously disclosed spirochromanes. Representative compounds showed favorable Akt potency while exhibiting up to 1000-fold selectivity against PKA.

Bioorganic & Medicinal Chemistry Letters published new progress about Structure-activity relationship. 7079-48-3 belongs to class chlorides-buliding-blocks, name is 4-Fluoro-2-methylbenzene-1-sulfonyl chloride, and the molecular formula is C7H6ClFO2S, HPLC of Formula: 7079-48-3.

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

Speri, Enrico published the artcileCinnamonitrile Adjuvants Restore Susceptibility to β-Lactams against Methicillin-Resistant Staphylococcus aureus, Synthetic Route of 61343-99-5, the main research area is preparation cinnamonitrile adjuvant beta lactam MRSA infection.

β-Lactams are used routinely to treat Staphylococcus aureus infections. However, the emergence of methicillin-resistant S. aureus (MRSA) renders them clin. precarious. We describe a class of cinnamonitrile adjuvants that restore the activity of oxacillin (a penicillin member of the β-lactams) against MRSA. The lead adjuvants were tested against six important strains of MRSA, one vancomycin-intermediate S. aureus (VISA) strain, and one linezolid-resistant S. aureus strain. Five compounds out of 84 total compounds showed broad potentiation. At 8 μM (E)-3-(5-(3,4-dichlorobenzyl)-2-(trifluoromethoxy)phenyl)-2-(methylsulfonyl)acrylonitrile (26) potentiated oxacillin with a >4000-fold reduction of its MIC (from 256 to 0.06 mg·L-1). This class of adjuvants holds promise for reversal of the resistance phenotype of MRSA.

ACS Medicinal Chemistry Letters published new progress about Antibacterial agent resistance. 61343-99-5 belongs to class chlorides-buliding-blocks, name is 4-(4-Chlorophenoxy)benzaldehyde, and the molecular formula is C13H9ClO2, Synthetic Route of 61343-99-5.

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