Category: 343338-28-3

Link, John O. published the artcileClinical targeting of HIV capsid protein with a long-acting small molecule, COA of Formula: C4H11NOS, the main research area is HIV infection capsid protein antiviral GS6207 viral replication cycle.

Abstract: Oral antiretroviral agents provide life-saving treatments for millions of people living with HIV, and can prevent new infections via pre-exposure prophylaxis1-5. However, some people living with HIV who are heavily treatment-experienced have limited or no treatment options, owing to multidrug resistance6. In addition, suboptimal adherence to oral daily regimens can neg. affect the outcome of treatment-which contributes to virol. failure, resistance generation and viral transmission-as well as of pre-exposure prophylaxis, leading to new infections1,2,4,7-9. Long-acting agents from new antiretroviral classes can provide much-needed treatment options for people living with HIV who are heavily treatment-experienced, and addnl. can improve adherence10. Here we describe GS-6207, a small mol. that disrupts the functions of HIV capsid protein and is amenable to long-acting therapy owing to its high potency, low in vivo systemic clearance and slow release kinetics from the s.c. injection site. Drawing on X-ray crystallog. information, we designed GS-6207 to bind tightly at a conserved interface between capsid protein monomers, where it interferes with capsid-protein-mediated interactions between proteins that are essential for multiple phases of the viral replication cycle. GS-6207 exhibits antiviral activity at picomolar concentrations against all subtypes of HIV-1 that we tested, and shows high synergy and no cross-resistance with approved antiretroviral drugs. In phase-1 clin. studies, monotherapy with a single s.c. dose of GS-6207 (450 mg) resulted in a mean log10-transformed reduction of plasma viral load of 2.2 after 9 days, and showed sustained plasma exposure at antivirally active concentrations for more than 6 mo. These results provide clin. validation for therapies that target the functions of HIV capsid protein, and demonstrate the potential of GS-6207 as a long-acting agent to treat or prevent infection with HIV.

Nature (London, United Kingdom) published new progress about Antiviral agents. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, COA of Formula: C4H11NOS.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Turdi, Huji published the artcileScreening Hit to Clinical Candidate: Discovery of BMS-963272, a Potent, Selective MGAT2 Inhibitor for the Treatment of Metabolic Disorders, SDS of cas: 343338-28-3, the main research area is MGAT2 inhibitor metabolic disorder aryl dihydropyridinone.

MGAT2 inhibition is a potential therapeutic approach for the treatment of metabolic disorders. High-throughput screening of the BMS internal compound collection identified the aryl dihydropyridinone compound 1 (hMGAT2 IC50 = 175 nM) as a hit. Compound 1 had moderate potency against human MGAT2, was inactive vs mouse MGAT2 and had poor microsomal metabolic stability. A novel chem. route was developed to synthesize aryl dihydropyridinone analogs to explore structure-activity relationship around this hit, leading to the discovery of potent and selective MGAT2 inhibitors 21f, 21s, and 28e that are stable to liver microsomal metabolism After triaging out 21f due to its inferior in vivo potency, pharmacokinetics, and structure-based liabilities and tetrazole 28e due to its inferior channel liability profile, 21s (BMS-963272) was selected as the clin. candidate following demonstration of on-target weight loss efficacy in the diet-induced obese mouse model and an acceptable safety and tolerability profile in multiple preclin. species.

Journal of Medicinal Chemistry published new progress about Body weight loss. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, SDS of cas: 343338-28-3.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Lundrigan, Travis published the artcileEnantioselective Imine Reduction Catalyzed by Phosphenium Ions, Recommanded Product: (S)-2-Methylpropane-2-sulfinamide, the main research area is diazophosphenium triflate cation preparation reduction catalyst; enantioselective imine reduction aryl heteroaryl pyrrolidine piperidine.

The first use of phosphenium cations in asym. catalysis is reported. A diazaphosphenium triflate, prepared in two or three steps on a multigram scale from com. available materials, catalyzes the hydroboration or hydrosilylation of cyclic imines with enantiomeric ratios of up to 97:3. Catalyst loadings are as low as 0.2 mol %. Twenty-two aryl/heteroaryl pyrrolidines and piperidines were prepared using this method. Imines containing functional groups such as thiophenes or pyridyl rings that can challenge transition-metal catalysts were reduced employing these systems.

Journal of the American Chemical Society published new progress about Crystal structure. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, Recommanded Product: (S)-2-Methylpropane-2-sulfinamide.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Xin, Bo-Tao published the artcileStructure-based design of inhibitors selective for human proteasome β2c or β2i subunits, Safety of (S)-2-Methylpropane-2-sulfinamide, the main research area is proteasome beta 2c 2i subunit inhibitor crystal structure.

Subunit-selective proteasome inhibitors are valuable tools to assess the biol. and medicinal relevance of individual proteasome active sites. Whereas the inhibitors for the β1c, β1i, β5c, and β5i subunits exploit the differences in the substrate-binding channels identified by X-ray crystallog., compounds selectively targeting β2c or β2i could not yet be rationally designed because of the high structural similarity of these two subunits. Here, we report the development, chem. synthesis, and biol. screening of a compound library that led to the identification of the β2c- and β2i-selective compounds LU-002c (4 (I); IC50 β2c: 8 nM, IC50 β2i/β2c: 40-fold) and LU-002i (5 (II); IC50 β2i: 220 nM, IC50 β2c/β2i: 45-fold), resp. Co-crystal structures with β2 humanized yeast proteasomes visualize protein-ligand interactions crucial for subunit specificity. Altogether, organic syntheses, activity-based protein profiling, yeast mutagenesis, and structural biol. allowed us to decipher significant differences of β2 substrate-binding channels and to complete the set of subunit-selective proteasome inhibitors.

Journal of Medicinal Chemistry published new progress about Crystal structure. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, Safety of (S)-2-Methylpropane-2-sulfinamide.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Ladduwahetty, Tammy published the artcileIdentification of a Potent, Selective, and Brain-Penetrant Rho Kinase Inhibitor and its Activity in a Mouse Model of Huntington’s Disease, Application of (S)-2-Methylpropane-2-sulfinamide, the main research area is piperazine analog preparation Rho kinase inhibitor SAR docking pharmacokinetics.

The Rho kinase (ROCK) pathway is implicated in the pathogenesis of several conditions, including neurol. diseases. In Huntington’s disease (HD), ROCK is implicated in mutant huntingtin (HTT) aggregation and neurotoxicity, and members of the ROCK pathway are increased in HD mouse models and patients. To validate this mode of action as a potential treatment for HD, a potent, selective, central nervous system (CNS)-penetrant ROCK inhibitor was sought. Identifying a compound that could be dosed orally in mice with selectivity against other AGC kinases, including protein kinase G (PKG), whose inhibition could potentially activate the ROCK pathway, was paramount for the program. The optimization of published ligands to identify a novel series of ROCK inhibitors based on a piperazine core was demonstrated. Morphing of the early series developed inhouse by scaffold hopping enabled the identification of a compound exhibiting high potency and desired selectivity and demonstrating a robust pharmacodynamic (PD) effect by the inhibition of ROCK-mediated substrate (MYPT1) phosphorylation after oral dosing.

Journal of Medicinal Chemistry published new progress about Molecular docking. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, Application of (S)-2-Methylpropane-2-sulfinamide.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Cao, Hengyi published the artcileDiscovery of new small molecule inhibitors targeting isocitrate dehydrogenase 1 (IDH1) with blood-brain barrier penetration, Formula: C4H11NOS, the main research area is glioblastoma antitumor pharmacokinetics isocitrate dehydrogenase 1 blood brain barrier; Acute myeloid leukemia; Blood-brain barrier; Cancer therapy; Glioblastoma; Isocitrate dehydrogenase 1; Small molecule inhibitors.

Isocitrate dehydrogenase 1 (IDH1), which catalyzes the conversion of isocitrate to α-ketoglutarate, is one of key enzymes in the tricarboxylic acid cycle (TCA). Hotspot mutation at Arg132 in IDH1 that alters the function of IDH1 by further converting the α-ketoglutarate(α-KG) to 2-hydroxyglutarate (2-HG) have been identified in a variety of cancers. Because the IDH1 mutations occur in a significant portion of gliomas and glioblastomas, it is important that IDH1 inhibitors have to be brain penetrant to treat IDH1-mutant brain tumors. Here we report the efforts to design and synthesize a novel serial of mutant IDH1 inhibitors with improved activity and the blood-brain barrier (BBB) penetration. We show that compound 5, (R)-4-((S)-1-fluoroethyl)-3-(2-(((S)-1-(7-(trifluoromethyl)4,5-dihydroimidazo[1,5-a]quinolin-3-yl)ethyl)amino)pyrimidin-4-yl)oxazolidin-2-one [2379528-08-0], exhibits good brain exposure and potent 2-HG inhibition in a HT1080-derived mouse xenograft model, which makes it a potential preclin. candidate to treat IDH1-mutant brain tumors.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, Formula: C4H11NOS.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Li, Sizhe published the artcileStereospecific Synthesis of Glycoside Mimics Through Migita-Kosugi-Stille Cross-Coupling Reactions of Chemically and Configurationally Stable 1-C-Tributylstannyl Iminosugars, Name: (S)-2-Methylpropane-2-sulfinamide, the main research area is iminosugar glycoside mimic stereospecific synthesis; Migita Kosugi Stille coupling configurational stable tributylstannyl iminosugar.

A process for the de novo synthesis of imino-C-glycosides is described. The methodol. is based on the reaction of 1-C-stannylated iminosugars with various electrophiles under the conditions of Migita-Kosugi-Stille cross-couplings, which gives 1-C-substituted iminosugar derivatives in a stereoretentive process. The required iminoglycosyl stannanes are obtained by way of the highly stereoselective addition of tributylstannyllithium to (SR)- or (SS)-N-tert-butanesulfinyl glycosylamines, followed by an activation cyclization sequence. Most interestingly, the methodol. is tunable: the configuration of the tin adduct is controlled exclusively by the tert-butanesulfinyl auxiliary, thus giving access after ring formation to ‘α’-configured or ‘β’-configured iminoglycosyl stannanes. With the subsequent stereoretentive C-C bond-forming process, the methodol. allows the synthesis of pseudo anomers of imino-C-glycosyl compounds in a controlled fashion.

Advanced Synthesis & Catalysis published new progress about Addition reaction. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, Name: (S)-2-Methylpropane-2-sulfinamide.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Welsh, Erin N. published the artcileShort syntheses of 1-substituted dibenzothiophene derivatives, Application of (S)-2-Methylpropane-2-sulfinamide, the main research area is dibenzothiophene preparation.

A simple one-pot preparation of 1-lithiodibenzothiophene from com. materials via a cascade of two benzyne additions and conversion to several derivatives I (R = I, CHO, CN, C(O)CF3, etc.) by addition of electrophiles (N,N-dimethylformamide, benzaldehyde, 1-propanal, etc.) was demonstrated. A chiral amine containing the 1-dibenzothiophenes motif II (R1 = H, (S)-S(O)C(CH3)3; R2 = Me, Et) was also prepared This work avoids the use of precious metals or tert-butyllithium and is much shorter and more convenient than existing routes to 1-substituted dibenzothiophenes I.

Organic & Biomolecular Chemistry published new progress about Addition reaction. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, Application of (S)-2-Methylpropane-2-sulfinamide.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

McClymont, Kyle S. published the artcileTotal Synthesis of (-)-Maximiscin, Computed Properties of 343338-28-3, the main research area is maximiscin enantioselective total synthesis.

A short, enantioselective synthesis of (-)-maximiscin (I), a structurally intriguing metabolite of mixed biosynthetic origin, is reported. A retrosynthetic anal. predicated on maximizing ideality and efficiency led to several unusual disconnections and tactics. Formation of the central highly oxidized pyridone ring through a convergent coupling at the end of the synthesis simplified the route considerably. The requisite building blocks could be prepared from feedstock materials (derived from shikimate and mesitylene). Strategies rooted in hidden symmetry recognition, C-H functionalization, and radical retrosynthesis played key roles in developing this concise route.

Journal of the American Chemical Society published new progress about C-H bond activation. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, Computed Properties of 343338-28-3.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Mackey, Pamela published the artcileStereoselective Installation of Five Contiguous Stereogenic Centers in a Double Aldol-Tishchenko Cascade and Evaluation of the Key Transition State through DFT Calculation, Related Products of amides-buliding-blocks, the main research area is stereoselective double Aldol Tishchenko cascade transition state analysis.

The stereoselective formation of 5 contiguous chiral centers in a single pot reaction is demonstrated using an aldol, aldol-Tishchenko reaction of N-tert-Bu sulfinimines. One diastereoisomer (from 32 possibilities) predominates, and a series of cyclic and acyclic 3-amino-1,5-diol derivatives are synthesized in good yields (up to 80%) and excellent diastereoselectivities (up to >98:2 dr). Investigations support two reversible aldol steps, and multiple intermediates which are funnelled through a remarkably selective, irreversible, Tishchenko reduction, in a Curtin-Hammett phenomenon. DFT calculations using a disolvated (THF) model reveal the factors controlling stereoselectivity in the final irreversible Tishchenko step.

Organic Letters published new progress about Activation energy. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, Related Products of amides-buliding-blocks.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics