Category: 29124-57-0

Henry, Sean P.; Fernandez, Thomas J.; Anand, Jessica P.; Griggs, Nicholas W.; Traynor, John R.; Mosberg, Henry I. published the artcile< Structural Simplification of a Tetrahydroquinoline-Core Peptidomimetic μ-Opioid Receptor (MOR) Agonist/δ-Opioid Receptor (DOR) Antagonist Produces Improved Metabolic Stability>, Computed Properties of 29124-57-0, the main research area is tetrahydroquinoline core peptidomimetic MOR DOR antagonist metabolic stability.

We have previously reported a series of μ-opioid receptor (MOR) agonist/δ-opioid receptor (DOR) antagonist ligands to serve as potential nonaddictive opioid analgesics. These ligands have been shown to be active in vivo, do not manifest withdrawal syndromes or reward behavior in conditioned-place preference assays in mice, and do not produce dependence. Although these attributes are promising, these analogs exhibit poor metabolic stability in mouse liver microsomes, likely due to the central tetrahydroquinoline scaffold in this series. As such, a structure-activity relationship (SAR) campaign was pursued to improve their metabolic stability. This resulted in a shift from our original bicyclic tetrahydroquinoline core to a monocyclic benzylic-core system. By eliminating one of the rings in this scaffold and exploring the SAR of this new core, two promising analogs were discovered. These analogs (5l and 5m) had potency and efficacy values at MOR better or comparable to morphine, retained their DOR-antagonist properties, and showed a 10-fold improvement in metabolic stability.

Journal of Medicinal Chemistry published new progress about Analgesia. 29124-57-0 belongs to class bromides-buliding-blocks, and the molecular formula is C7H6BrNO, Computed Properties of 29124-57-0.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Hu, Di; Pi, Chao; Hu, Wei; Han, Xiliang; Wu, Yangjie; Cui, Xiuling published the artcile< Ru(III)-catalyzed construction of variously substituted quinolines from 2-aminoaromatic aldehydes (ketones) and isoxazoles: Isoxazoles as cyclization reagent and cyano sources>, Electric Literature of 29124-57-0, the main research area is aminoarom carbonyl compound isoxazole ruthenium catalyst cyclization; cyanoquinoline preparation green chem.

A Ru(III)-catalyzed annulation reaction of 2-aminoarom. aldehydes (ketones) and isoxazoles to afford diverse 3-cyanoquinolines was developed. Notably, isoxazole acted as a cyclization reagent and nontoxic cyano source via N-O bond cleavage and fragmentation. Variously substituted (especially 6- or 7-substituted) quinolines could be easily afforded. This procedure featured wide functional group compatibility, efficiency and avoiding toxic cyano source. Meanwhile, this protocol could be successfully applied to scale-up synthesis. Further chem. transformations of 3-cyanoquinoline could give some valuable skeletons, demonstrating its potential in synthetic application.

Chinese Chemical Letters published new progress about Aromatic amines Role: RCT (Reactant), RACT (Reactant or Reagent). 29124-57-0 belongs to class bromides-buliding-blocks, and the molecular formula is C7H6BrNO, Electric Literature of 29124-57-0.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Gopalsamy, Ariamala; Aulabaugh, Ann E.; Barakat, Amey; Beaumont, Kevin C.; Cabral, Shawn; Canterbury, Daniel P.; Casimiro-Garcia, Agustin; Chang, Jeanne S.; Chen, Ming Z.; Choi, Chulho; Dow, Robert L.; Fadeyi, Olugbeminiyi O.; Feng, Xidong; France, Scott P.; Howard, Roger M.; Janz, Jay M.; Jasti, Jayasankar; Jasuja, Reema; Jones, Lyn H.; King-Ahmad, Amanda; Knee, Kelly M.; Kohrt, Jeffrey T.; Limberakis, Chris; Liras, Spiros; Martinez, Carlos A.; McClure, Kim F.; Narayanan, Arjun; Narula, Jatin; Novak, Jonathan J.; O’Connell, Thomas N.; Parikh, Mihir D.; Piotrowski, David W.; Plotnikova, Olga; Robinson, Ralph P.; Sahasrabudhe, Parag V.; Sharma, Raman; Thuma, Benjamin A.; Vasa, Dipy; Wei, Liuqing; Wenzel, A. Zane; Withka, Jane M.; Xiao, Jun; Yayla, Hatice G. published the artcile< PF-07059013: A Noncovalent Modulator of Hemoglobin for Treatment of Sickle Cell Disease>, Recommanded Product: 2-Amino-5-bromobenzaldehyde, the main research area is pf07059013 noncovalent Hb modulator sickle cell disease.

Sickle cell disease (SCD) is a genetic disorder caused by a single point mutation (β6 Glu → Val) on the β-chain of adult Hb (HbA) that results in sickled Hb (HbS). In the deoxygenated state, polymerization of HbS leads to sickling of red blood cells (RBC). Several downstream consequences of polymerization and RBC sickling include vaso-occlusion, hemolytic anemia, and stroke. We report the design of a noncovalent modulator of HbS, clin. candidate PF-07059013 (23). The seminal hit mol. was discovered by virtual screening and confirmed through a series of biochem. and biophys. studies. After a significant optimization effort, we arrived at 23, a compound that specifically binds to Hb with nanomolar affinity and displays strong partitioning into RBCs. In a 2-wk multiple dose study using Townes SCD mice, 23 showed a 37.8% (±9.0%) reduction in sickling compared to vehicle treated mice. 23 (PF-07059013) has advanced to phase 1 clin. trials.

Journal of Medicinal Chemistry published new progress about Crystal structure. 29124-57-0 belongs to class bromides-buliding-blocks, and the molecular formula is C7H6BrNO, Recommanded Product: 2-Amino-5-bromobenzaldehyde.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Darrah, Kristie; Wang, Ting; Cook, Ian; Cacace, Mary; Deiters, Alexander; Leyh, Thomas S. published the artcile< Allosteres to regulate neurotransmitter sulfonation>, Formula: C7H6BrNO, the main research area is SULT1A3 allosteric inhibitor catecholamine sulfonation; SULT1A3; allosteric regulation; allostery; catecholamine; dopamine; enzyme inhibitor; enzyme kinetics; enzyme mechanism; enzyme structure; epinephrine; inhibition; mechanism; neurotransmitter; norepinephrine; nuclear magnetic resonance (NMR); serotonin; spin label; sulfotransferase.

Catecholamine neurotransmitter levels in the synapses of the brain shape human disposition – cognitive flexibility, aggression, depression, and reward seeking – and manipulating these levels is a major objective of the pharmaceutical industry. Certain neurotransmitters are extensively sulfonated and inactivated by human sulfotransferase 1A3 (SULT1A3). To our knowledge, sulfonation as a therapeutic means of regulating transmitter activity has not been explored. Here, we describe the discovery of a SULT1A3 allosteric site that can be used to inhibit the enzyme. The structure of the new site is determined using spin-label-triangulation NMR. The site forms a cleft at the edge of a conserved ∼30-residue active-site cap that must open and close during the catalytic cycle. Allosteres anchor into the site via π-stacking interactions with two residues that sandwich the planar core of the allostere and inhibit the enzyme through cap-stabilizing interactions with substituents attached to the core. Changes in cap free energy were calculated ab initio as a function of core substituents and used to design and synthesize a series of inhibitors intended to progressively stabilize the cap and slow turnover. The inhibitors bound tightly (34 nm to 7.4μm) and exhibited progressive inhibition. The cap-stabilizing effects of the inhibitors were exptl. determined and agreed remarkably well with the theor. predictions. These studies establish a reliable heuristic for the design of SULT1A3 allosteric inhibitors and demonstrate that the free-energy changes of a small, dynamic loop that is critical for SULT substrate selection and turnover can be calculated accurately.

Journal of Biological Chemistry published new progress about Allosterism. 29124-57-0 belongs to class bromides-buliding-blocks, and the molecular formula is C7H6BrNO, Formula: C7H6BrNO.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Sun, Shuang-Shuang; Mo, Zu-Yu; Chen, Yan-Yan; Xu, Yan-Li published the artcile< Synthesis of Selenyl-Substituted Quinoline Derivatives via Substrate-Controlled Three-Component Domino Reactions>, Computed Properties of 29124-57-0, the main research area is cyclohexanedione aminobenzaldehyde diselenide tandem three component selenylation; selenyl dihydroacridinone preparation; alkanedione aminobenzaldehyde diselenide tandem three component selenylation; diselenoacetyl quinoline preparation.

A simple and efficient method for the preparation of selenyl-substituted quinoline derivatives through a Csp3 selenylation of in-situ generated 3-acetyl quinolines was developed. This protocol was easy to handle, scalable and good functional group tolerant, providing a rapid method to 3-selenoacetyl quinoline and 3-diselenoacetyl quinoline derivatives

Journal of Organic Chemistry published new progress about Acridines Role: PRP (Properties), SPN (Synthetic Preparation), PREP (Preparation). 29124-57-0 belongs to class bromides-buliding-blocks, and the molecular formula is C7H6BrNO, Computed Properties of 29124-57-0.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Song, Jing-Ru; Li, Na; Li, Dian-Peng published the artcile< Synthesis and anti-proliferation activity of Mogrol derivatives bearing quinoline and triazole moieties>, Related Products of 29124-57-0, the main research area is Mogrol quinolinyl triazolyl synthesis antitumor agent; Lung cancer; Mogrol; Quinoline; Structural modification; Triazole.

A series of novel derivatives based on Mogrol were designed and synthesized in attempt to improve anti-lung cancer activity. The cytotoxicity against human lung cancer cells including A549 and NCI-H460 were performed by Cell Counting Kit-8 (CCK8) assay in vitro. The screening result showed that compound 8f exhibited the strongest activity with an IC50 value of 4.47μM against A549 cell, and could induce the cell apoptosis in a dose-dependent manner and arrest cell cycle at G0/G1 phase. Besides, compound 8f displayed anti-proliferation effect on A549 cell through inhibiting phosphorylation of signal transducer and activator of transcription 3 (STAT3). Furthermore, compared with Mogrol, compound 10a significantly improved the cytotoxicity against NCI-H460 with the IC50 value of 17.13μM. The research stimulated the development of potential therapeutic agent for lung cancer from the natural Mogrol.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 29124-57-0 belongs to class bromides-buliding-blocks, and the molecular formula is C7H6BrNO, Related Products of 29124-57-0.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Sun, Huai-Ri; Zhao, Qingyang; Yang, Hui; Yang, Sen; Gou, Bo-Bo; Chen, Jie; Zhou, Ling published the artcile< Chiral Phosphoric-Acid-Catalyzed Cascade Prins Cyclization>, Electric Literature of 29124-57-0, the main research area is chiral phosphoric acid catalyst cascade Prins cyclization; trans fused pyrano furo tetrahydroquinoline stereoselective preparation; stereoselective cascade Prins cyclization quinone methide aminobenzaldehyde.

Asym. Prins cyclization of in situ generated quinone methides and o-aminobenzaldehyde has been developed with chiral phosphoric acid as an efficient catalyst. This unconventional method provides a facile access to diverse functionalized trans-fused pyrano-/furo-tetrahydroquinoline derivatives in excellent yield and with excellent diastereo- and enantioselectivities (up to 99% yield and 99% ee). Mechanistic studies suggested that the three adjacent tertiary stereocenters were constructed through the sequential formation of C-O, C-C, and C-N bonds.

Organic Letters published new progress about Diastereoselective synthesis. 29124-57-0 belongs to class bromides-buliding-blocks, and the molecular formula is C7H6BrNO, Electric Literature of 29124-57-0.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Whitmarsh-Everiss, Thomas; Olsen, Asger Hegelund; Laraia, Luca published the artcile< Identification of Inhibitors of Cholesterol Transport Proteins Through the Synthesis of a Diverse, Sterol-Inspired Compound Collection>, Name: 2-Amino-5-bromobenzaldehyde, the main research area is cholesterol transport protein inhibitor sterol synthesis; cholesterol-transport proteins; inhibitors; library synthesis; natural products.

Cholesterol transport proteins regulate a vast array of cellular processes including lipid metabolism, vesicular and non-vesicular trafficking, organelle contact sites, and autophagy. Despite their undoubted importance, the identification of selective modulators of this class of proteins has been challenging due to the structural similarities in the cholesterol-binding site. Herein we report a general strategy for the identification of selective inhibitors of cholesterol transport proteins via the synthesis of a diverse sterol-inspired compound collection. Fusion of a primary sterol fragment to an array of secondary privileged scaffolds led to the identification of potent and selective inhibitors of the cholesterol transport protein Aster-C, which displayed a surprising preference for the unnatural-sterol AB-ring stereochem. and new inhibitors of Aster-A. We propose that this strategy can and should be applied to any therapeutically relevant sterol-binding protein.

Angewandte Chemie, International Edition published new progress about Cell membrane. 29124-57-0 belongs to class bromides-buliding-blocks, and the molecular formula is C7H6BrNO, Name: 2-Amino-5-bromobenzaldehyde.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Cook, Ian; Cacace, Mary; Wang, Ting; Darrah, Kristie; Deiters, Alexander; Leyh, Thomas S. published the artcile< Small-molecule control of neurotransmitter sulfonation>, COA of Formula: C7H6BrNO, the main research area is dopamine metabolite neurotransmitter sulfonation; SULT1A3; allosteric; catecholamine; human mammary epithelial cells; inhibitor; molecular dynamics; neurotransmitter; structure activity relationship; sulfotransferase.

Controlling unmodified serotonin levels in brain synapses is a primary objective when treating major depressive disorder-a disease that afflicts ∼20% of the world′s population. Roughly 60% of patients respond poorly to first-line treatments and thus new therapeutic strategies are sought. To this end, we have constructed isoform-specific inhibitors of the human cytosolic sulfotransferase 1A3 (SULT1A3)-the isoform responsible for sulfonating ∼80% of the serotonin in the extracellular brain fluid. The inhibitor design includes a core ring structure, which anchors the inhibitor into a SULT1A3-specific binding pocket located outside the active site, and a side chain crafted to act as a latch to inhibit turnover by fastening down the SULT1A3 active-site cap. The inhibitors are allosteric, they bind with nanomolar affinity and are highly specific for the 1A3 isoform. The cap-stabilizing effects of the latch can be accurately calculated and are predicted to extend throughout the cap and into the surrounding protein. A free-energy correlation demonstrates that the percent inhibition at saturating inhibitor varies linearly with cap stabilization – the correlation is linear because the rate-limiting step of the catalytic cycle, nucleotide release, scales linearly with the fraction of enzyme in the cap-open form. Inhibitor efficacy in cultured cells was studied using a human mammary epithelial cell line that expresses SULT1A3 at levels comparable with those found in neurons. The inhibitors perform similarly in ex vivo and in vitro studies; consequently, SULT1A3 turnover can now be potently suppressed in an isoform-specific manner in human cells.

Journal of Biological Chemistry published new progress about Allosterism. 29124-57-0 belongs to class bromides-buliding-blocks, and the molecular formula is C7H6BrNO, COA of Formula: C7H6BrNO.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary

Zhou, Zhenghong; Hu, Kangfei; Wang, Jiawei; Li, Zhibin; Zhang, Yan; Zha, Zhenggen; Wang, Zhiyong published the artcile< Electrosynthesis of Quinazolines and Quinazolinones via an Anodic Direct Oxidation C(sp3)-H Amination/C-N Cleavage of Tertiary Amine in Aqueous Medium>, Application of C7H6BrNO, the main research area is quinazoline quinazolinone electrochem preparation green chem; tertiary amine carbonyl aniline anodic oxidation amination cleavage.

An electrochem. synthesis for quinazolines and quinazolinones was developed via a C(sp3)-H amination/C-N cleavage by virtue of the anodic oxidation The reaction can be carried out in aqueous media under mild conditions to afford the desired products with high yields. The reaction mechanism was proposed after detailed investigation.

ACS Omega published new progress about Amination. 29124-57-0 belongs to class bromides-buliding-blocks, and the molecular formula is C7H6BrNO, Application of C7H6BrNO.

Referemce:
Bromide – Wikipedia,
bromide – Wiktionary