78066-30-5

Upstream product

• 105-39-5 chloroacetic acid ethyl ester 
• 15946-37-9 sodium 3-chlorobenzenesulfinate 
• 68-12-2 N,N-dimethyl-formamide 
• 63503-60-6 3-chlorophenylboronic acid 
• 96-32-2 bromoacetic acid methyl ester 
• 67-56-1 methanol 
• 3938-05-4 3-Chlor-phenylsulfonylessigsaeure 

Downstream Products

• 865706-12-3 C₁₄H₁₅ClO₅S 
• 865705-90-4 C₁₅H₁₇ClO₅S 

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 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.

SULFONYL-QUINOLINE DERIVATIVES

New mGluRl and mGluR5 receptor subtype preferring ligands of formula: (I) and/or salts and/or hydrates and/or solvates thereof, to the processes and intermediates for their preparation, to pharmaceutical compositions containing these compounds and to thei

QUINOLINE DERIVATIVES USEFUL IN THE TREATMENT OF MGLUR5 RECEPTOR-MEDIATED DISORDERS

Compounds of formula (I): and/or enantiomers and/or racemates and/or diastereomers and/or pharmaceutically acceptable salts thereof formed with acids or bases, to the process for their preparation, to the intermediates of the preparation process, to the p

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.

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.