125488-16-6

Upstream product

• 110-89-4 piperidine 
• 3884-33-1 2-chloro-4-(p-bromophenyl)-thiazole 
• 4540-33-4 piperdinium acetate 
• 65679-14-3 1-(4-bromophenyl)-2-thiocyanatoethanone 
• 14294-09-8 piperidine-1-carbothioamide 
• 99-73-0 para-bromophenacyl bromide 

Relevant academic research and scientific papers

Synthesis and structure-activity relationship of aminoarylthiazole derivatives as correctors of the chloride transport defect in cystic fibrosis

Abstract The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel present in the membrane of epithelial cells. Mutations affecting the CFTR gene cause cystic fibrosis (CF), a multi-organ severe disease. The most common CF mutation, F508del, impairs the processing and activity (gating) of CFTR protein. Other mutations, like G551D, only cause a gating defect. Processing and gating defects can be targeted by small molecules called generically correctors and potentiators, respectively. Aminoarylthiazoles (AATs) represent an interesting class of compounds that includes molecules with dual activity, as correctors and potentiators. With the aim to improve the activity profile of AATs, we have now designed and synthesized a library of novel compounds in order to establish an initial SAR that may provide indications about the chemical groups that are beneficial or detrimental for rescue activity. The new compounds were tested as correctors and potentiators in CFBE41o-expressing F508del-CFTR using a functional assay. A dual active compound, AAT-4a, characterized by improved efficacy and marked synergy when combined with the corrector VX-809 has been identified. Moreover, by computational methods, a possible binding site for AATs in nucleotide binding domain NBD1 has been detected. These results will direct the synthesis of new analogues with possibly improved activity.

Discovery, synthesis, and biological evaluation of novel SMN protein modulators

Spinal muscular atrophy (SMA) is an autosomal recessive disorder affecting the expression or function of survival motor neuron protein (SMN) due to the homozygous deletion or rare point mutations in the survival motor neuron gene 1 (SMN1). The human genome includes a second nearly identical gene called SMN2 that is retained in SMA. SMN2 transcripts undergo alternative splicing with reduced levels of SMN. Up-regulation of SMN2 expression, modification of its splicing, or inhibition of proteolysis of the truncated protein derived from SMN2 have been discussed as potential therapeutic strategies for SMA. In this manuscript, we detail the discovery of a series of arylpiperidines as novel modulators of SMN protein. Systematic hit-to-lead efforts significantly improved potency and efficacy of the series in the primary and orthogonal assays. Structure-property relationships including microsomal stability, cell permeability, and in vivo pharmacokinetics (PK) studies were also investigated. We anticipate that a lead candidate chosen from this series may serve as a useful probe for exploring the therapeutic benefits of SMN protein up-regulation in SMA animal models and a starting point for clinical development.

ARYLTHIAZOLYL PIPERIDINES AND RELATED COMPOUNDS AS MODULATORS OF SURVIVAL MOTOR NEURON (SMN) PROTEIN PRODUCTION

Aryl substituted thiazol-2-yl-piperidines and related compounds useful as modulators of survival motor neuron (SMN) protein production are provided herein. Without being bound to any particular theory it is believed the aryl substituted thiazol-2-yl-piper

Synthesis and Characterization of 1,3-Bis-(2-dialkylamino-5-thiazolyl)-Substituted Squaraines and Their 2-(Dialkylamino)thiazole Precursors

By condensation of squaric acid (1) with 2-(dialkylamino)-substituted thiazoles 8 a novel type of heterocyclic-substituted squaraines of the general structure 9 was prepared in moderate yield mostly.The squaraines 9 obtained are sparingly soluble in the most organic solvents and exhibit, in these solvents, narrow absorption bands in the visible range at about 620-700 nm.In dispersed form, the absorption bands of the squaraines 9 are, however, broadened and shifted into the NIR region at about 900 nm.These unique properties of the new squaraines 9 suggest the use of these dyes as spectral sensitizers for laser-driven data recording or data storage media. - Key Words: Squaraines/ Squaric acid/ Thiazoles/ Sensitizers

Substituted 2-Aminothiazoles from α-Thiocyanato-acetophenones and Dialkylamines

α-Thiocyanato-acetophenones 1 react with dialkylammonium salts of weak acids (acetates, propionates, benzoates) to give 2-dialkylamino-4-aryl-thiazoles 4.As reaction medium aliphatic alcohols (methanol, ethanol), dipolar-aprotic solvents (acetonitrile, di