109523-13-9

Usage

Chemical Properties

White to off-white powder

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 80875-98-5 (2S,3aS,7aS)-perhydroindole-2-carboxylic acid 
• 960529-90-2 benzyl (2S,3aS,7aS)-N-(tert-butoxycarbonyl)octahydroindole-2-carboxylate 
• 16851-56-2 indolin-2-yl carboxylic acid 
• 80828-13-3 (+/-)-(2S,3aS,7aS)-octahydroindole-2-carboxylic acid 
• 192436-84-3 methyl (2S,3aS,7aS)-octahydro-1H-indole-2-carboxylate 
• 82717-91-7 (+/-)-benzyl (2S,3aS,7aS)-octahydroindole-2-carboxylate p-toluenesulfonic acid salt 
• 365973-21-3 (2S,3aS,7aS)-octahydroindole-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester 

Downstream Products

• 945405-64-1 C₃₀H₃₈N₄O₅ 
• 365973-26-8 (2S,3aS,7aR)-7a-Allyl-octahydro-indole-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester 
• 365973-27-9 (2S,3aS,7aR)-7a-Allyl-octahydro-indole-1,2-dicarboxylic acid 1-benzyl ester 
• 365973-29-1 (2S,3aS,7aR)-7a-(2-oxoethyl)-octahydroindole-1,2-dicarboxylic acid 1-benzyl ester 2-tert-butyl ester 
• 365973-28-0 (2S,3aS,7aR)-7a-allyl-octahydroindole-1,2-dicarboxylic acid 1-benzyl ester 2-tert-butyl ester 
• 365973-31-5 (2S,3aS,7aR)-7a-[3-(N-benzyloxycarbonyl-N'-tert-butoxycarbonylamino)-3-methoxycarbonyl-allyl]-octahydroindole-1,2-dicarboxylic acid 1-benzyl ester 2-tert-butyl ester 
• 1029280-07-6 C₄₂H₅₈N₄O₆ 
• 1029280-09-8 C₄₂H₅₈N₄O₆ 
• 1415120-51-2 (2S,3aS,7aS)-tert-butyl 2-((2-amino-4-bromophenyl)carbamoyl)octahydro-1H-indole-1-carboxylate 
• 1415119-50-4 (2S,3aS,7aS)-tert-butyl 2-((2-amino-5-bromophenyl)carbamoyl)octahydro-1H-indole-1-carboxylate 

Relevant academic research and scientific papers

Discovery, Optimization, and Evaluation of Quinazolinone Derivatives with Novel Linkers as Orally Efficacious Phosphoinositide-3-Kinase Delta Inhibitors for Treatment of Inflammatory Diseases

Guided by molecular docking, a commonly used open-chain linker was cyclized into a five-membered pyrrolidine to lock the overall conformation of the propeller-shaped molecule. Different substituents were introduced into the pyrrolidine moiety to block oxidative metabolism. Surprisingly, it was found that a small methyl substituent could be used to alleviate the oxidative metabolism of pyrrolidine while maintaining or enhancing potency, which could be described as a "magic methyl". Further optimization around the "3rd blade"of the propeller led to identification of a series of potent and selective PI3Kδinhibitors. Among them, compound 50 afforded an optimum balance of PK profiles and potency. Oral administration of 50 attenuated the arthritis severity in a dose-dependent manner in a collagen-induced arthritis model without obvious toxicity. Furthermore, 50 demonstrated excellent pharmacokinetic properties with high bioavailability, suggesting that 50 might be an acceptable candidate for treatment of inflammatory diseases.

Asymmetric Synthesis of α,β-Epoxy-?-lactams through Tandem Darzens/Hemiaminalization Reaction

A catalytic asymmetric tandem Darzens/hemiaminalization reaction of glyoxals with α-bromo-β-esteramides or α-bromo-β-ketoamide was accomplished in the presence of a chiral N,N′-dioxide/Yb(III) complex. Various chiral α,β-epoxy-?-lactams were obtained in moderate to good yields with excellent diastereo- and enantioselectivities. The versatility of the transformation is illustrated in the formal synthesis of berkeleyamide D.

Promotion of the collagen triple helix in a hydrophobic environment

In contrast to many other water-soluble peptide arrangements, the formation of a triple helix in collagen proceeds inside out: polar glycyl residues form the interior, whereas nonpolar prolyl side chains constitute the exterior. In our work, we decided to exploit this aspect of the peptide architecture in order to create hyperstable collagen mimicking peptides (CMPs). The key element of this study is the environment. Given that the peptide assembles in a nonpolar medium, the collapse of the polar peptide backbone into the triple helix should become more favorable. Following this idea, we prepared CMPs based on hydrophobic proline analogues. The synthesis was performed by a combination of liquid- and solid-phase approaches: first, hexapeptides were prepared in solution, and then these were launched into conventional Fmoc-based peptide synthesis on a solid support. The resulting peptides showed an excellent signal of the triple helix in the model nonpolar solvent (octanol) according to circular dichroism observations. In a study of a series of oligomers, we found that the minimal length of the peptides required for triple helical assembly is substantially lower compared to water-soluble CMPs. Our results suggest further explorations of the CMPs in hydrophobic media; in particular, we highlight the suggestion that collagen could be converted into a membrane protein.

Development of a Commercial Process for Odalasvir

Odalasvir is a selective inhibitor of hepatitis C virus NS5A protein, a key target for combination therapies. This paper describes the chemical process development for the synthesis of this active pharmaceutical ingredient and the improvements that were achieved over the medicinal chemistry route. Optimization of all of the reaction conditions and crystallizations resulted in higher throughput and a highly improved process mass intensity. The process is robust and has been scaled up to ～100 kg batches without issues.

Amide Iridium Complexes As Catalysts for Transfer Hydrogenation Reduction of N-sulfonylimine

Sulfonamide moieties widely exist in natural products, biologically active substance, and pharmaceuticals. Here, an efficient water-soluble amide iridium complexes-catalyzed transfer hydrogenation reduction of N-sulfonylimine is developed, which can be carried out under environmentally friendly conditions, affording a series of sulfonamide compounds in excellent yields (96-98%). In comparison with organic solvents, water is shown to be critical for a high catalytic transfer hydrogenation reduction in which the catalyst loading can be as low as 0.001 mol %. These amide iridium complexes are easy to synthesize, one structure of which was determined by single-crystal X-ray diffraction. This protocol gives an operationally simple, practical, and environmentally friendly strategy for synthesis of sulfonamide compounds.

Synthetic method for catalyzing imine to be reduced into amine

The invention discloses a synthesis method for catalyzing imine to be reduced into amine, wherein the synthesis method is characterized by comprising the following steps: 1, sequentially putting a sulfonyl imine compound and a catalyst I into a reaction bottle according to a reaction molar ratio of 1:0.01 at normal temperature and normal pressure, adding formic acid and a triethylamine solution according to a volume ratio of 5:2, and reacting in a solvent for 1-15 minutes to obtain a reaction product; and 2, after the reaction in the step 1 is finished, sequentially and slowly adding water and ethyl acetate into an obtained reaction product, sufficiently stirring, standing for layering, extracting a separated water layer by using ethyl acetate, combining an extract of ethyl acetate with a separated organic layer, washing by using saturated edible salt water, and drying by using anhydrous sodium sulfate, evaporating to remove the ethyl acetate solvent to obtain a crude product, and separating and purifying by silica gel column chromatography to obtain the amine compound.

Substituted quinazoline -4 - ketone compound as well as preparation method and application thereof

The invention relates to a substituted quinazoline -4 - ketone compound and a preparation method and application thereof, and belongs to the field of chemical medicines. The invention provides a compound shown I. A pharmaceutically acceptable salt, a stereoisomer or a solvate thereof. The invention further provides a preparation method and application of the compound. Biological experiments show that the compound has good inhibitory activity on PI3K. , The compound has good inhibitory activity on multiple tumor cell proliferation, wherein certain compounds exhibit better anti-proliferative activity than CAL-101 and IPI-145. The compound disclosed by the invention also has a good anti-inflammatory effect.

COMPOUNDS, COMPOSITIONS AND METHODS FOR SYNTHESIS

The present disclosure, among other things, provides technologies for synthesis, including reagents and methods for stereoselective synthesis. In some embodiments, the present disclosure provides compounds useful as chiral auxiliaries. In some embodiments, the present disclosure provides reagents and methods for oligonucleotide synthesis. In some embodiments, the present disclosure provides reagents and methods for chirally controlled preparation of oligonucleotides. In some embodiments, technologies of the present disclosure are particularly useful for constructing challenging internucleotidic linkages, providing high yields and stereoselectivity.

ODALASVIR POLYMORPHS AND METHODS OF MANUFACTURE THEREOF

The invention provides Odalasvir polymorphs, hydrates, and solvates that exhibit advantageous properties, including purity, useful for the preparation of a therapeutic formulation.

Hepatitis C virus inhibitors, and pharmaceutical compositions and application thereof

The invention provides hepatitis C virus inhibitors, and pharmaceutical compositions and an application thereof, wherein the hepatitis C virus inhibitors are compounds represented by the formula (I), or crystal forms, pharmaceutically acceptable salts, hydrates or solvates thereof. The compounds have better inhibitory activity of a hepatitis C virus protein NS5A, have better pharmacodynamic/pharmacokinetic properties, have good applicability and high safety, can be used for preparing drugs for treatment of hepatitis C virus infection, and have good prospects for market development.