940-63-6

Upstream product

• 589-18-4 4-Methylbenzyl alcohol 
• 17356-08-0 thiourea 
• 104-82-5 4-Methylbenzyl chloride 

Downstream Products

• 1071654-23-3 (4-methylphenyl)methanesulfonyl azide 
• 1417156-26-3 N-allyl-N-(4-methoxyphenyl)-1-(4-methylphenyl)methanesulfonamide 
• 1417156-22-9 N-allyl-1-(4-methylphenyl)-N-phenylmethanesulfonamide 
• 1417156-53-6 1-(4-methylphenyl)-2-thia-3-azabicyclo[3.1.0]hexane 2,2-dioxide 
• 1417156-40-1 3-(4-methoxyphenyl)-1-(4-methylphenyl)-2-thia-3-azabicyclo[3.1.0]hexane 2,2-dioxide 
• 1417156-35-4 1-(2-methylphenyl)-3-phenyl-2-thia-3-azabicyclo[3.1.0]hexane 2,2-dioxide 
• 51419-59-1 4-methylbenzylsulfonyl chloride 
• 680221-21-0 5-chloro-3-(4-methylbenzyl)thio-1,2,4-thiadiazole 

Relevant academic research and scientific papers

Design, synthesis and biological evaluation of novel N-sulfonylamidine-based derivatives as c-Met inhibitors via Cu-catalyzed three-component reaction

In our continuing efforts to develop novel c-Met inhibitors as potential anticancer candidates, a series of new N-sulfonylamidine derivatives were designed, synthesized via Cu-catalyzed multicomponent reaction (MCR) as the key step, and evaluated for their in vitro biological activities against c-Met kinase and four cancer cell lines (A549, HT-29, MKN-45 and MDA-MB-231). Most of the target compounds showed moderate to significant potency at both the enzyme-based and cell-based assay and possessed selectivity for A549 and HT-29 cancer cell lines. The preliminary SAR studies demonstrated that compound 26af (c-Met IC50 = 2.89 nM) was the most promising compound compared with the positive foretinib, which exhibited the remarkable antiproliferative activities, with IC50 values ranging from 0.28 to 0.72 μM. Mechanistic studies of 26af showed the anticancer activity was closely related to the blocking phosphorylation of c-Met, leading to cell cycle arresting at G2/M phase and apoptosis of A549 cells by a concentration-dependent manner. The promising compound 26af was further identified as a relatively selective inhibitor of c-Met kinase, which also possessed an acceptable safety profile and favorable pharmacokinetic properties in BALB/c mouse. The favorable drug-likeness of 26af suggested that N-sulfonylamidines may be used as a promising scaffold for antitumor drug development. Additionally, the docking study and molecular dynamics simulations of 26af revealed a common mode of interaction with the binding site of c-Met. These positive results indicated that compound 26af is a potential anti-cancer candidate for clinical trials, and deserves further development as a selective c-Met inhibitor.

Optimization of P2Y12 Antagonist Ethyl 6-(4-((Benzylsulfonyl)carbamoyl)piperidin-1-yl)-5-cyano-2-methylnicotinate (AZD1283) Led to the Discovery of an Oral Antiplatelet Agent with Improved Druglike Properties

P2Y12 antagonists are widely used as antiplatelet agents for the prevention and treatment of arterial thrombosis. Based on the scaffold of a known P2Y12 antagonist AZD1283, a series of novel bicyclic pyridine derivatives were designed and synthesized. The cyclization of the ester substituent on the pyridine ring to the ortho-methyl group led to lactone analogues of AZD1283 that showed significantly enhanced metabolic stability in subsequent structure-pharmacokinetic relationship studies. The metabolic stability was further enhanced by adding a 4-methyl substituent to the piperidinyl moiety. Compound 58l displayed potent inhibition of platelet aggregation in vitro as well as antithrombotic efficacy in a rat ferric chloride model. Moreover, 58l showed a safety profile that was superior to what was observed for clopidogrel in a rat tail-bleeding model. These results support the further evaluation of compound 58l as a promising drug candidate.

Novel and highly efficient synthesis of 3-(alkyl/benzylthio)-9b-hydroxy-1H-imidazo[5,1-a]isoindole-1,5(9bH)-dione derivatives

The oxidation of 3a,8a-dihydroxy-2-(alkyl/benzylthio)indeno[1,2-d]imidazol-8(3H)-ones to give the corresponding 3-(alkyl/benzylthio)-9b-hydroxy-1H-imidazo[5,1-a]isoindole-1,5(9bH)-dione derivatives in good to excellent yields at room temperature using two oxidants, periodic acid in aqueous ethanol and lead(IV) acetate in acetic acid, has been reported.

Tert -Butyl Hypochlorite Mediated Oxidative Chlorination of S -Alkylisothiourea Salts: Synthesis of Sulfonyl Chlorides

Under neutral conditions, a variety of S-alkylisothiourea salts were smoothly converted into the corresponding sulfonyl chlorides through tert-butyl chlorite mediated oxidative chlorination in good to excellent yields after simple purification. In addition to the environmental and procedural advantages of this method, the neutral conditions potentially make it applicable to substrates that bear acid-sensitive functional groups. For example, the Cbz-protected 2-aminoethanesulfonyl chloride could be synthesized in moderate to good yields under the current neutral conditions, and the acid-sensitive Cbz-protecting group was not affected.

Clean and economic synthesis of alkanesulfonyl chlorides from S-alkyl isothiourea salts via bleach oxidative chlorosulfonation

A simple procedure for clean and economic synthesis of alkanesulfonyl chlorides via bleach-mediated oxidative chlorosulfonation of S-alkyl isothiourea salts is disclosed. This procedure is environment- and worker-friendly with the advantages of readily accessible materials and reagents, simple and safe operations, easy purification without chromatography, and affords high yields of up to 99%.

Convenient and environment-friendly synthesis of sulfonyl chlorides from S -alkylisothiourea salts via N-chlorosuccinimide chlorosulfonation

A convenient, practical, and environmentally friendly method for the synthesis of sulfonyl chlorides has been developed. Structurally diverse sulfonyl chlorides were synthesized in moderate to excellent yields from S-alkylisothiourea salts, which can be easily prepared from readily accessible alkyl halides or mesylates and inexpensive thiourea, via N-chlorosuccinimide chlorosulfonation. In large-scale syntheses, the byproduct succinimide from 'waste water' can be conveniently converted into the starting reagent N-chlorosuccinimide with sodium hypochlorite (bleach) to make the method sustainable. Georg Thieme Verlag Stuttgart, New York.

Simple synthesis of sulfonyl chlorides from thiol precursors and derivatives by NaClO2-mediated oxidative chlorosulfonation

A simple method to synthesize diverse sulfonyl chlorides through NaClO 2-mediated oxidative chlorosulfonation of S-alkyl isothiourea salts is presented. The approach features safe operation, environmental friendliness, convenient purification procedures, and delivers high yields of up to 96%. The procedure is also applicable to substrates such as thiols, disulfides, thioacetates, and xanthates. It is a versatile and convenient method for the synthesis of various sulfonyl chlorides from different thiol precursors and derivatives. Georg Thieme Verlag Stuttgart, New York.

INHIBITION OF CELL PROLIFERATION

The disclosed modulators of Rb:Raf-1 interactions are potent, selective disruptors of Rb:Raf-1 binding, with IC50 values ranging from 80 nM to 500 nM. Further, these compounds are surprisingly effective in inhibiting a wide variety of cancer cells, including osteosarcoma, epithelial lung carcinoma, non small cell lung carcinoma, three different pancreatic cancer cell lines, two different glioblastoma cell lines, metastatic breast cancer, melanoma, and prostate cancer. Moreover, the disclosed compounds effectively disrupt angiogenesis and significantly inhibited tumors in nude mice derived from human epithelial lung carcinoma tumors. Accordingly, the disclosed compounds, pharmaceutical compositions comprising the compounds, methods of inhibiting cell proliferation, methods of treating subjects with cancer, and methods of preparing the disclosed compounds are provided.

Thiodialkylenyl-5-bistetrazoles and Thiouronium Salts as Potential Slow Acting Anticancer Agents

A series of Thiodialkylenyl-5-bistetrazoles and Thiouronium salts have been synthesised.The above compounds in comparison with thiodiglycollic and thiodipropionic acids and thiophene-2,5-bisdimethylenylthiouronium dichloride are expected to have prolonged anticancer effect in vivo.