226396-71-0

Usage

Usage

Building block in organic synthesis

Applications

Manufacturing of pharmaceuticals, agrochemicals, and other fine chemicals

Reactivity

Versatile, compatible with a wide range of chemical reactions

Structural feature

Methyl ester group allows for easy manipulation of the molecule's structure

Unique property

Fluorobenzenesulfonyl group provides unique properties beneficial for the development of new chemical entities.

Upstream product

• 67-56-1 methanol 
• 383-38-0 p-fluorophenylsulphonylacetic acid 
• 226396-70-9 (4-fluoro-phenylsulfanyl)-acetic acid methyl ester 
• 1765-93-1 4-fluoroboronic acid 
• 96-32-2 bromoacetic acid methyl ester 
• 824-80-6 sodium 4-fluorobenzenesulfinate 
• 105-39-5 chloroacetic acid ethyl ester 
• 68-12-2 N,N-dimethyl-formamide 
• 96-34-4 methyl chloroacetate 
• 349-88-2 4-Fluorobenzenesulfonyl chloride 
• 371-42-6 4-Fluorothiophenol 
• 369-51-7 4-fluorobenzenesulfinic acid 

Downstream Products

• 226396-72-1 4-(4-fluoro-benzenesulfonyl)-tetrahydro-pyran-4-carboxylic acid methyl ester 
• 1093735-62-6 7-chloro-4-(4-chlorophenyl)-3-((4-fluorophenyl)sulfonyl)quinoline 

Relevant academic research and scientific papers

Synthesis of Sulfones via Ru(II)-Catalyzed Sulfination of Boronic Acids

Ruthenium(II) complexes catalyze the insertion of sulfur dioxide into (het)aryl and alkenyl boronic acids. The transmetalation-sulfination process proceeds with DABSO in the presence of 5 mol % RuCl2(PPh3)3 in methanol at 100 °C. The intermediate sulfinate salt can be quenched with various electrophiles such as alkyl halides, epoxides, Michael acceptors, and λ3-iodanes in moderate to good yields. The reported sulfone synthesis can be performed either as a direct one-pot or one-pot two-step procedure depending on the reactivity of the electrophile.

Discovery and Preclinical Characterization of 3-((4-(4-Chlorophenyl)-7-fluoroquinoline-3-yl)sulfonyl)benzonitrile, a Novel Non-acetylenic Metabotropic Glutamate Receptor 5 (mGluR5) Negative Allosteric Modulator for Psychiatric Indications

Negative allosteric modulators (NAM) of metabotropic glutamate receptor 5 (mGluR5) have been implicated as a potential pharmacotherapy for a number of psychiatric diseases, including anxiety and depression. Most of the mGluR5 NAM clinical candidates can be characterized by the central acetylenic moiety that connects the terminal pharmacophores. Identification of a sulfoquinoline hit via high throughput screening (HTS) followed by optimization provided a 4-phenyl-3-aryl-sulfoquinoline lead compound with the minimal pharmacophore. Optimization of the core and aryl appendages was performed by scanning and matrix libraries synthesized by the multiple parallel synthesis approach. Biological evaluation of matrix libraries provided a number of potent, metabolically stable, and in vivo active compounds. One of these compounds, 25 showed high efficacy and safety in preclinical in vivo models; this allowed its nomination as a novel, nonacetylenic mGluR5 NAM clinical candidate. Compound 25 was advanced to first-in-man trials for the treatment of psychiatric conditions.

Discovery of 4-amino-3-arylsulfoquinolines, a novel non-acetylenic chemotype of metabotropic glutamate 5 (mGlu5) receptor negative allosteric modulators

Negative allosteric modulators of metabotropic glutamate receptor 5 (mGlu5) showed efficacy in a number of animal models of different CNS diseases including anxiety and depression. Virtually all of the compounds which reached the clinic belong to the same chemotype having an acetylenic linker that connects (hetero)cyclic moieties. Searching for new chemotypes we identified a morpholino-sulfoquinoline derivative (1) by screening our corporate compound deck. The HTS hit showed reasonable affinity and selectivity towards mGlu5 receptors, however, its inferior metabolic stability prevented its testing in?vivo. In a chemical program we aimed to improve the affinity, physicochemical properties and metabolic stability exploring three regions of the hit. Systematic variation of different amines at position 4 (region I) led to the identification of 4-methyl-piperidinyl analogues. Substituents of the quinoline core (region II) and the phenylsulfonyl moiety (region III) were mapped by parallel synthesis. Evaluation of both morpholino- and 4-methyl-piperidinyl-sulfoquinoline libraries of about 270 derivatives revealed beneficial substituent combinations in regions II and III. Blood levels of optimized 4-methyl-piperidinyl-sulfoquinolines, however, were still insufficient for robust in?vivo efficacy. Finally, introducing 4-hydoxymethyl-piperidinyl substituent to region I resulted in new sulfoquinolines with greatly improved solubility and reasonable affinity coupled with affordable metabolic stability. The most promising analogues (24 and 25) showed high blood levels and demonstrated significant efficacy in the experimental model of anxiety.

Synthesis and structure-activity relationships of β- and α-piperidine sulfone hydroxamic acid matrix metalloproteinase inhibitors with oral antitumor efficacy

α-Piperidine-β-sulfone hydroxamate derivatives were explored that are potent for matrix metalloproteinases (MMP)-2, -9, and -13 and are sparing of MMP-1. The investigation of the β-sulfones subsequently led to the discovery of hitherto unknown α-sulfone h

TETRAHYDROCARBAZOLES AND DERIVATIVES

The present invention relates to compounds of the formula (I) wherein R1, R2, R3, R4, R5, X1, X2, X3, X4, n, and k are defined in the description and claims, and pharmaceutically acceptable salts and/or pharmaceutically acceptable esters thereof. The compounds are useful for in the treatment and prophylaxis of diseases which are modulated by LXRα and/or LXR? agonists, including increased lipid and cholesterol levels, particularly low HDL-cholesterol, high LDL-cholesterol, atherosclerotic diseases, diabetes, particularly non-insulin dependent diabetes mellitus, metabolic syndrome, dyslipidemia, Alzheimer's disease, sepsis, inflammatory diseases such as colitis, pancreatitis, cholestasis/fibrosis of the liver, and diseases that have an inflammatory component such as Alzheimer's disease or impaired/improvable cognitive function.

Aromatic sulfone hydroxamates and their use as protease inhibitors

This invention is directed to aromatic sulfone hydroxamates (also known as “aromatic sulfone hydroxamic acids”) and salts thereof that, inter alia, inhibit matrix metalloproteinase (also known as “matrix metalloprotease” or “MMP”) activity and/or aggrecanase activity. This invention also is directed to a prevention or treatment method that comprises administering such a compound or salt in an MMP-inhibiting and/or aggrecanase-inhibiting effective amount to an animal, particularly a mammal having (or disposed to having) a pathological condition associated with MMP and/or aggrecanase activity.

Discovery of Small-Molecule Inhibitors of the ATPase Activity of Human Papillomavirus E1 Helicase

The Boehringer Ingelheim compound collection was screened for inhibitors of the ATPase activity of human papillomavirus E1 helicase to develop antiviral agents that inhibit human papillomavirus (HPV) DNA replication. This screen led to the discovery of (biphenyl-4-sulfonyl)acetic acid 1, which inhibits the ATPase activity of HPV type 6 E1 helicase with a low micromolar IC50 value. A hit-to-lead exercise rapidly converted 1 into a low nanomolar lead series.

Applicability of Hammett Equation to Kinetics of Acid-catalysed Esterification of meta- and para-Substituted Phenylmercaptoacetic and Phenylsulphonylacetic Acids with Methanol

Rate constants have been determined for the acid-catalysed esterification of meta- and para-substituted phenylmercaptoacetic and phenylsulphonylacetic acids with methanol using hydrogen chloride as catalyst.The lower reactivities of phenylmercaptoacetic acids compared to those of the corresponding phenoxyacetic acids are discussed.