106904-10-3

Upstream product

• 288-88-0 1,2,4-Triazole 
• 53250-83-2 2-chloro-4-(methanesulfonyl)benzoic acid 
• 504-02-9 1,3-cylohexanedione 
• 1671-18-7 4-methylsulfonyl-1-methyl-2-chlorobenzene 

Downstream Products

• 214532-11-3 2-Chloro-4-methanesulfonyl-benzoic acid 1-methyl-2,2-dioxo-1,2-dihydro-2λ⁶-thieno[3,2-c][1,2]thiazin-4-yl ester 
• 99105-77-8 sulcotrione 
• 1169551-55-6 8-bromo-2-[2-chloro-4-(methylsulfonyl)phenyl][1]benzofuro[3,2-d]pyrimidin-4(3H)-one 
• 1258282-39-1 C₂₃H₁₆Cl₂N₂O₃S 
• 1258224-56-4 C₁₇H₁₄ClN₅O₃S 
• 1258224-57-5 C₁₇H₁₄ClN₅O₃S₂ 
• 1572922-59-8 C₁₉H₂₀Cl₂N₂O₅S 
• 1431662-55-3 C₂₂H₁₉Cl₂N₃O₅S 
• 1572922-71-4 C₂₂H₁₈Cl₂N₂O₄S 

Relevant academic research and scientific papers

Manufacturing Development and Genotoxic Impurity Control Strategy of the Hedgehog Pathway Inhibitor Vismodegib

The development work toward the robust and efficient manufacturing process to vismodegib, the active pharmaceutical ingredient (API) in Erivedge, is described. The optimization of the four-stage manufacturing process was designed to produce the API with the required critical quality attributes: (1) the selective catalytic hydrogenation reduction of the nitro compound 3 to the corresponding aniline 4 while minimizing the formation of potential genotoxic (mutagenic) impurities; (2) the control of the polymorphic phase and multipoint specification for particle size distribution.

Design, synthesis, herbicidal activity, in vivo enzyme activity evaluation and molecular docking study of acylthiourea derivatives as novel acetohydroxyacid synthase inhibitor

In order to develop novel herbicides, a series of novel acylthiourea derivatives containing methylsulfone were synthesized and characterized by melting point, elemental analysis, infrared spectroscopy, mass spectrometry and 1H NMR spectroscopy. Furthermore, the preliminary herbicidal activity of title compounds was determined against Echinochloa crusgal, Polypogon fugax, Digitaria adscendens, Brassica napus, Amaranthus retroflexus and Abutilon theophrasti. The results of the petri dish experiments showed that a small part of title compounds had a good inhibitory effect on Digitaria adscendens and Brassica napus. The results of the greenhouse herbicidal activity experiments indicated that the compounds 4p, 4 w and 4x exhibited more high herbicidal activity against Brassica napus and Digitaria adscendens than the commercial herbicide bensulfuron-methyl. Moreover, except for compound 4i, all test compounds performed well in crop safety evaluation. Next, acetohydroxyacid synthase (AHAS) enzyme activity experiments were carried out, and the results showed that compound 4x had the highest inhibition rate reaching 89.12%. Finally, in order to screen AHAS inhibitor, molecular docking was performed by using AHAS protein and target ligand molecules 4a-4x. The results of molecular docking were similar to bioassay experiments. Compound 4p, 4w and 4x were considered potential AHAS inhibitors.

Discovery of [1,2,4]triazolo[4,3-a]pyridines as potent Smoothened inhibitors targeting the Hedgehog pathway with improved antitumor activity in vivo

Triple-negative breast cancer (TNBC), a subset of breast cancers, have poorer survival than other breast cancer types. Recent studies have demonstrated that the abnormal Hedgehog (Hh) pathway is activated in TNBC and that these treatment-resistant cancers are sensitive to inhibition of the Hh pathway. Smoothened (Smo) protein is a vital constituent in Hh signaling and an attractive drug target. Vismodegib (VIS) is one of the most widely studied Smo inhibitors. But the clinical application of Smo inhibitors is limited to adult patients with BCC and AML, with many side effects. Therefore, it's necessary to develop novel Smo inhibitor with better profiles. Twenty [1,2,4]triazolo[4,3-a]pyridines were designed, synthesized and screened as Smo inhibitors. Four of these novel compounds showed directly bound to Smo protein with stronger binding affinity than VIS. The new compounds showed broad anti-proliferative activity against cancer cell lines in vitro, especially triple-negative breast cancer cells. Mechanistic studies demonstrated that TPB15 markedly induced cell cycle arrest and apoptosis in MDA-MB-468 cells. TPB15 blocked Smo translocation into the cilia and reduced Smo protein and mRNA expression. Furthermore, the expression of the downstream regulatory factor glioma-associated oncogene 1 (Gli1) was significantly inhibited. Finally, TPB15 demonstrated greater anti-tumor activity in our animal models than VIS with lower toxicity. Hence, these results support further optimization of this novel scaffold to develop improved Smo antagonists.

Pyrazole compound, salt and uses thereof,

The invention discloses a pyrazole compound and a salt thereof, wherein the structural formula of the pyrazole compound is represented by a formula (I). According to the invention, the pyrazole compound has good prevention and control effect on various gr

Rh(III)-Catalyzed C-H Amidation of Arenes with N-Methoxyamide as an Amidating Reagent

The Rh(III)-catalyzed amidation of C(sp2)-H bonds has been reported by employing the N-methoxyamide as a novel amino source. An excellent level of functional group tolerance can be achieved when N-methoxyamide derivatives are used as the amidating reagents. Importantly, several known bioactive compounds such as Aminalon, Pregabalin, Gabapentin, and Probenecid can be transformed to effective amidating reagents, as a way to facilitate the development of new bioactive molecules.

Design, synthesis and biological evaluation of deuterated Vismodegib for improving pharmacokinetic properties

Vismodegib is an oral and high selective hedgehog (Hh) inhibitor used for the treatment of basal cell carcinoma (BCC). In this work, analogs of Vismodegib with deuterium-for-hydrogen replacement at certain metabolically active sites were prepared and found to have a better pharmacokinetic properties in mice. In particular, deuterated compound SKLB-C2211 obviously altered the blood circulation behavior compared to its prototype, which was demonstrated by significantly prolonged blood circulation half-life time (t1/2) and increased AUC0→∞. These results suggested SKLB-C2211 had the potential to be a long-acting inhibitor against Hh signaling pathway, and laid the foundation for the further research of its druggability.

3 - [4 - (methyl sulfonyl) - 2-chlorobenzoyl] bicyclo [3.2.1] - 2,4- octadione method for the synthesis of (by machine translation)

3 - [4 - (methyl sulfonyl) - 2-chlorobenzoyl] bicyclo [3.2.1]-octane -2,4-dione are synthetic intermediates of the herbicide, the present invention discloses a synthetic 3 - [4 - (methyl sulfonyl) - 2-chlorobenzoyl] bicyclo [3.2.1]-octane -2,4-dione metho

Vismodegib and wherein the intermediate preparation method

The invention provides a preparation method for vismodegib and an intermediate of vismodegib, in other words, a preparation method for 2-chloro-N-(4-chloro-3-(pyridin-2-yl)-phenyl)-4-(methylsulfonyl)benzamide and the intermediate. The method comprises: ta

Method for preparing Vismodegib

The invention provides a preparation method for vismodegib, and in other words, a preparation method for 2-chloro-N-(4-chloro-3-(pyridin-2-yl)-phenyl)-4-(methylsulfonyl)benzamide. The method comprises: firstly preparing an intermediate 2-(3-nitrophenyl)py

2-substituent-4-methyl-sulfonyl-α, α, α-trichloro toluene and its preparation method and application

The invention discloses 2-substituent-4-methylsulfonyl-alpha,alpha,alpha-trichlorotoluene having a structure represented by formula (IV), and a preparation method and an application thereof. The preparation method comprises the following steps: adding 2-substituent-4-methylsulfonyltoluene having a structure represented by formula (II), an inert organic solvent and an acid binding agent into an autoclave, introducing chlorine, closing the autoclave, heating to 20-150DEG C for a reaction at 0.1-2MPa for 4-40h, and post-processing the obtained reaction solution after the reaction to obtain the above product (IV). The above compound (IV) can be used for synthesizing a triketone herbicide key intermediate 2-substituent-4-methylsulfonylbenzoyl chloride represented by formula (I). Compared with present 2-substituent-4-methylsulfonylbenzoyl chloride synthesis methods, the method has the advantages of short process route, few three wastes, low cost and the like.