Tag: M.W=100-150

Zheng, Bin published the artcileStereoselective synthesis of a tubulysin core for antibody-drug conjugate studies, Computed Properties of 343338-28-3, the main research area is tripeptide enantioselective synthesis tubulysin core antibody drug conjugate; peptide coupling amidation hydrosilation sulfinimine steric effect.

An expeditious synthesis of an advanced tripeptide intermediate en route to a tubulysin antibody-drug conjugate payload is described. The efficient formation of an N-Pr tertiary amide required tailoring the amine component to reduce steric demand. Addnl., double activation of the carboxylate was required via an aluminum-Lewis acid coupled activated ester strategy to enable the formation of the highly congested amide bond with superior retention of stereochem. integrity. Other permutations of reactant structure and reagents met with failure. The realization of this key direct bond construction enabled a convergent solution-phase synthesis of the unnatural tubulysin tripeptide in a highly convergent manner from three simple building blocks in eight steps and 22.4% overall yield utilizing only a single silica gel chromatog. purification

Organic Process Research & Development published new progress about Amidation. 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

Goswami, Prithwish published the artcileEfficient access to general α-tertiary amines via water-accelerated organocatalytic multicomponent allylation, Quality Control of 343338-28-3, the main research area is tertiary amine preparation; ketone allyl boronic acid ester benzhydrazide multicomponent allylation organocatalyst; ketoester allyl boronic acid ester benzhydrazide multicomponent allylation organocatalyst; allyl boronic acid ester ketoester amine multicomponent allylation organocatalyst.

A tetrasubstituted carbon atom connected by three sp3 or sp2-carbons with single nitrogen, i.e., the α-tertiary amines I [R = n-Pr, CH2CO2Et, Ph, etc.; R1 = Me, Et, n-Pr, etc.], was an essential structure of diverse naturally occurring alkaloids and pharmaceuticals. The synthetic approach toward ATA structures was intricate, therefore, a straightforward catalytic method had remained a substantial challenge. Herein, an efficient water-accelerated organocatalytic allylation to directly access ATA incorporating homoallylic amine structures I by exploiting readily accessible general ketones/keto esters as useful starting material along with allyl boronic acid esters and benzhydrazide/amines. The synergistic action of a hydrophobic Bronsted acid in combination with a squaramide hydrogen-bonding donor under aqueous condition enabled the facile formation of the desired moiety I. The developed exceptionally mild but powerful system facilitated a broad substrate scope and enabled efficient multi-gram scalability.

Nature Communications published new progress about Allylation. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, Quality Control of 343338-28-3.

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

McKerrall, Steven J. published the artcileStructure- and Ligand-Based Discovery of Chromane Arylsulfonamide Nav1.7 Inhibitors for the Treatment of Chronic Pain, Quality Control of 343338-28-3, the main research area is pain analgesic chromane arylsulfonamide sodium channel crystal structure pharmacokinetics.

Using structure- and ligand-based design principles, a novel series of piperidyl chromane arylsulfonamide Nav1.7 inhibitors was discovered. Early optimization focused on improvement of potency through refinement of the low energy ligand conformation and mitigation of high in vivo clearance. An in vitro hepatotoxicity hazard was identified and resolved through optimization of lipophilicity and LLE to arrive at GNE-616 (24(I)), a highly potent, metabolically stable, subtype selective inhibitor of Nav1.7. I showed a robust PK/PD response in a Nav1.7 dependent mouse model and site-directed mutagenesis was used to identify residues critical for the isoform selectivity profile of I.

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

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

Brown, Alan D. published the artcileThe discovery and optimization of benzimidazoles as selective NaV1.8 blockers for the treatment of pain, HPLC of Formula: 343338-28-3, the main research area is benzimidazole derivative preparation sodium channel blocker pain; Benzimidazole; Inflammatory pain; Na(V)1.8; Neuropathic pain; PF-06305591; SCN10A; Voltage gated sodium channel.

The voltage gated sodium channel NaV1.8 has been postulated to play a key role in the transmission of pain signals. Core hopping from our previously reported phenylimidazole leads has allowed the identification of a novel series of benzimidazole NaV1.8 blockers. Subsequent optimization allowed the identification of compound 9, PF-06305591, as a potent, highly selective blocker with an excellent preclin. in vitro ADME and safety profile.

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

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

Zhao, Guodong published the artcileSynthesis of 2-Arylpiperidines via Pd-Catalyzed Arylation of Aza-Achmatowicz Rearrangement Products with Arylboronic Acids, COA of Formula: C4H11NOS, the main research area is arylpiperidine synthesis palladium catalyzed arylation aza Achmatowicz arylboronic acid.

The first Pd-catalyzed arylation of aza-Achmatowicz rearrangement products with arylboronic acids is achieved, providing versatile 2-aryldihydropyridinones for facile synthesis of highly functionalized 2-arylpiperidines. Key to this arylation is the use of non-phosphine-ligand palladium precatalyst. The substrate scope is demonstrated with >26 examples, and the utility of 2-aryldihydropyridinones is illustrated by the synthesis of a small collection of 2-arylpiperidines with substituents or functional groups at any carbon (C2-C6) as well as two NK1 receptor antagonists (+)-CP-999,94 and (+)-L-733,060.

Organic Letters published new progress about Acetylation. 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

Chen, Wen published the artcileTotal synthesis of (-)-vindoline, Name: (S)-2-Methylpropane-2-sulfinamide, the main research area is vindoline synthesis.

In this full paper, a stereocontrolled strategy for the total synthesis of (-)-vindoline is described. This synthetic route features: (1) rapid construction of the stereochem. center at C19 through a highly diastereoselective vinylogous Mannich addition; (2) tandem Heathcock/aza-Prins cyclization to install rings C and E in vindoline; (3) oxidative transformation of β-ketoester to enone; (4) stereoselective inversion of C4 stereochem. with triphenylphosphine and carbon tetrabromide followed by Bronsted acid.

Tetrahedron published new progress about Cyclization. 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

Kempson, James published the artcileSynthesis Optimization, Scale-Up, and Catalyst Screening Efforts toward the MGAT2 Clinical Candidate, BMS-963272, Safety of (S)-2-Methylpropane-2-sulfinamide, the main research area is tetrazolyltolyl trifluorobutoxyphenyl trifluoromethyl dihydropyridinone enantioselective preparation.

This paper describes the efficient scale-up synthesis of 1 (BMS-963272) which relies upon a highly selective Mannich-type alkylation strategy to stereospecifically install a quaternary carbon center. An intramol. cyclization reaction was also used to form the aryl dihydropyridone (ADHP) core. The optimized route was demonstrated to provide more than 100 g of active pharmaceutical ingredient for preclin. toxicol. evaluation. A catalyst screening effort was also discussed as part of a complimentary convergent approach which will facilitate a more expedient assessment of back-up mols. bearing aryl diversity at the C4-position of the ADHP core.

Organic Process Research & Development published new progress about Cyclization. 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

Li, Qigang published the artcileCopper-Catalyzed Enantioselective Ring-Opening of Cyclic Diaryliodoniums and O-Alkylhydroxylamines, Application of (S)-2-Methylpropane-2-sulfinamide, the main research area is cyclic diaryliodonium alkylhydroxylamine copper catalyst enantioselective ring opening atropisomer; hydroxyamino iodobiaryl stereoselective preparation.

A preparation of 2-hydroxyamino-2′-iodobiaryls via the Cu-catalyzed enantioselective ring-opening reaction of cyclic diaryliodonium salts with O-alkylhydroxylamines is reported. 3,5-Di(tert-butyl)phenyl bis(oxazoline) was found to be the optimal ligand, and up to 99% ee values were achieved. The use of CaO as the base dramatically improved the yields and inhibited the side reactions. Finally, synthetic applications of these hydroxylamines were briefly demonstrated.

Organic Letters published new progress about Atropisomers. 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

Brownsey, Duncan K. published the artcileIdentification of ligand linkage vectors for the development of p300/CBP degraders, HPLC of Formula: 343338-28-3, the main research area is protein CBP degrader development ligand linkage vector.

To develop new degrader mols. from an existing protein ligand a linkage vector must be identified and then joined with a suitable E3 ligase without disrupting binding to the resp. targets. This is typically achieved through empirically evaluating the degradation efficacy of a series of synthetic degraders. Our strategy for determining optimal linkage sites utilizes biotinylated protein ligands, linked via potential conjugation sites of an inhibitor to confirm whether target protein is maintained after forming a conjugate. This method provides low-cost, qual. evidence that the addition of a linker moiety at a specific position can be tolerated, guiding further optimization. We demonstrate the application of this method through the exploration of linkage vectors on A-485, a known ligand of p300/CBP, and found a conjugation site through a urea moiety. Pomalidomide was then conjugated through this site with several different linkers and cell viability and degradation were assessed for this library using a myeloma cell line, MM1. S. Compound 18i, with a PEG4 linker, was found to be the most effective p300 degrader and linker length greater than 10 atoms afforded enhanced degradation

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

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

Kazmierski, Wieslaw M. published the artcileDNA-Encoded Library Technology-Based Discovery, Lead Optimization, and Prodrug Strategy toward Structurally Unique Indoleamine 2,3-Dioxygenase-1 (IDO1) Inhibitors, Quality Control of 343338-28-3, the main research area is DNA library discovery prodrug indoleamine dioxygenase inhibitor immunomodulator.

We report the discovery of a novel indoleamine 2,3-dioxygenase-1 (IDO1) inhibitor class through the affinity selection of a previously unreported indole-based DNA-encoded library (DEL). The DEL exemplar, spiro-chromane 1, had moderate IDO1 potency but high in vivo clearance. Series optimization quickly afforded a potent, low in vivo clearance lead 11. Although amorphous 11 was highly bio-available, crystalline 11 was poorly soluble and suffered disappointingly low bio-availability because of solubility-limited absorption. A prodrug approach was deployed and proved effective in discovering the highly bio-available phosphonooxymethyl 31, which rapidly converted to 11 in vivo. Obtaining crystalline 31 proved problematic, however; thus salt screening was performed in an attempt to circumvent this obstacle and successfully delivered greatly soluble and bio-available crystalline tris-salt 32. IDO1 inhibitor 32 is characterized by a low calculated human dose, best-in-class potential, and an unusual inhibition mode by binding the IDO1 heme-free (apo) form.

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

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