61858-38-6

Upstream product

• 186581-53-3 diazomethane 
• 618-51-9 3-Iodobenzoic acid 
• 1711-10-0 3-iodobenzoyl chloride 
• 80-11-5 N-methyl-N-nitrosotoluene-p-sulfonamide 
• 14452-30-3 3'-iodoacetophenone 

Downstream Products

• 1037183-81-5 2-amino-5-(3-iodophenyl)imidazole-1-carboxylic acid tert-butyl ester 
• 382153-04-0 diethyl(3-iodobenzyl)amine 
• 70522-49-5 N-(3-Iodphenacyl)cyclopropylamin 

Relevant academic research and scientific papers

Redesigning of the cap conformation and symmetry of the diphenylethyne core to yield highly potent pan-genotypic NS5A inhibitors with high potency and high resistance barrier

Herein, we report the discovery of several NS5A inhibitors with potency against HCV genotype 1b in the picomolar range. Compounds (15, 33) were of extremely high potency against HCV genotype 1b (EC50 ≈ 1 pM), improved activity against genotype 3a (GT 3a) and good metabolic stability. We studied the impact of changing the cap conformation relative to the diphenylethyne core and/or compound symmetry on both potency and metabolic stability. The analogs obtained exhibited improved potency against HCV genotypes 1a, 1b, 3a and 4a compared to the clinically approved candidate daclatasvir with EC50 values in the low picomolar range and SI50s > 7 orders of magnitude. Compound 15, a symmetrically m-, m’-substituted diphenyl ethyne analog, was 150-fold more potent than daclatasvir against GT 3a, while compound 33, an asymmetrically m-, p-substituted diphenyl ethyne analog, was 35-fold more potent than daclatasvir against GT 3a. In addition, compound 15 exhibited a higher resistance barrier than daclatasvir against genotype 1b.

Identification of Thiazoyl Guanidine Derivatives as Novel Antifungal Agents Inhibiting Ergosterol Biosynthesis for Treatment of Invasive Fungal Infections

Invasive fungal infections (IFIs) are fatal infections, but treatment options are limited. The clinical efficacies of existing drugs are unsatisfactory because of side effects, drug-drug interaction, unfavorable pharmacokinetic profiles, and emerging drug-resistant fungi. Therefore, the development of antifungal drugs with a new mechanism is an urgent issue. Herein, we report novel aryl guanidine antifungal agents, which inhibit a novel target enzyme in the ergosterol biosynthesis pathway. Structure-activity relationship development and property optimization by reducing lipophilicity led to the discovery of 6h , which showed potent antifungal activity againstAspergillus fumigatusin the presence of serum, improved metabolic stability, and PK properties. In the murine systemicA. fumigatusinfection model, 6h exhibited antifungal efficacy equivalent to voriconazole ( 1e ). Furthermore, owing to the inhibition of a novel target in the ergosterol biosynthesis pathway, 6h showed antifungal activity against azole-resistantA. fumigatus.

Synthesis and preliminary biological evaluation of radiolabeled 5-BDBD analogs as new candidate PET radioligands for P2X4 receptor

P2X4 receptor has become an interesting molecular target for treatment and PET imaging of neuroinflammation and associated brain diseases such as Alzheimer's disease. This study reports the first design, synthesis, radiolabeling and biological evaluation

α-Ketothioamide Derivatives: A Promising Tool to Interrogate Phosphoglycerate Dehydrogenase (PHGDH)

Given the putative role of PHGDH in cancer, development of inhibitors is required to explore its function. In this context, we established and validated a straightforward enzymatic assay suitable for high-throughput screening and we identified inhibitors with similar chemical scaffolds. Through a convergent pharmacophore approach, we synthesized α-ketothioamides that exhibit interesting in vitro PHGDH inhibition and encouraging cellular results. These novel probes may be used to understand the emerging biology of this metabolic target.

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.

P2X4 RECEPTOR MODULATING COMPOUNDS

Provided herein are P2X4 receptor modulating compounds, methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. The compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, including but not limited to, chronic pain, neuropathy, inflammatory diseases and central nervous system disorders.

P2X4 RECEPTOR MODULATING COMPOUNDS AND METHODS OF USE THEREOF

Provided herein are P2X4 receptor modulating compounds, methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. The compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, including but not limited to, chronic pain, neuropathy, inflammatory diseases and central nervous system disorders.

Silver(I)-Catalyzed conia-ene reaction: Synthesis of 3-pyrrolines via a 5-endo-dig cyclization

A novel method has been developed for the synthesis of 3-pyrrolines from β-ketopropargylamines via a 5-endo-dig carbocyclization. This transformation involves a silver-catalyzed Conia-ene type reaction tolerating broad substrate scope with good to excellent yields. Furthermore, this methodology has been extended for the construction of 2-substituted pyrroles under base-mediated conditions. Copyright

INHIBITION OF BACTERIAL BIOFILMS WITH IMIDAZOLE-PHENYL DERIVATIVES

Disclosure is provided for imidazole-phenyl derivative compounds that prevent, remove and/or inhibit the formation of biofilms, compositions comprising these compounds, devices comprising these compounds, and methods of using the same.

Synthesis of a 2-aminoimidazole library for antibiofilm screening utilizing the sonogashira reaction

(Chemical Equation Presented) The divergent synthesis of a 21-member library composed of 2-aminoimidazole compounds for evaluation as novel antibiofilm molecules is presented. The Sonogashira reaction was employed with three regioisomeric aryl iodides and 11 different alkynes to generate variously substituted diverse ring systems. Good to excellent yields (80-97%) for the reaction were obtained, and the products provide adequate handles for further manipulation into more advanced analogues.