マリアアザミ

Cu-Catalyzed Electerophilic Amination

Oxime Benzoate Can DoI t!

 

 

An efficient copper-catalyzed electrophilic amination of benzoxazoles with O-benzoyl hydroxylamines is described, employing CuCl catalyst, PPh₃ ligand, and LiO^tBu base.

This simple air-stable copper catalysis enables the preparation of various 2-aminobenzoxazole derivatives at room temperature in good yields.

Protonated DBU Can Catalyze Cyclization

 

 

Protonated 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) as a catalyst for cascade addition/cyclization of 2-alkynylaniline and carbon disulfide has been described.

This process provides a convenient route for synthesis of a variety of benzo[d][1,3]thiazine-2(4H)-thiones in high yields with high regio- and stereoselectivity at room temperature without metal.

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Benzothiazole From Weinreb Amide

 

One pot synthesis of 2-substituted benzimidazoles/benzothiazoles through condensation is followed by cyclization of Weinreb amide with o-diaminoarene or o-aminothiophenol is reported.

 

 

In the presence of boron trifluoride etherate in 1,4-dioxane solvent, a high yield (75–94%) was achieved within 60 min.

 

Weinreb amide shows high selectivity in the reaction, even in presence of other active functional groups such as carboxyl, halogen, cyano, and methoxy.

 

 

 

 

 

N-(substituted benzothiazol-2-yl)amides as anticonvulsant and neuroprotective

Design, synthesis and evaluation of N-(substituted benzothiazol-2-yl)amides as anticonvulsant and neuroprotective

 

 

 

 

 

 

A series of N-(substituted benzothiazol-2-yl)amide derivatives 2a–h and 4a–h were synthesized by the EDC coupling reactions of substituted-benzothiazol-2-amine with 4-oxo-4-phenylbutanoic acid/2-benzoyl benzoic acid and evaluated for their anticonvulsant and neuroprotective effect.


 N-(6-methoxybenzothiazol-2-yl)-4-oxo-4-phenylbutanamide (2f) emerged as the most effective anticonvulsant with median doses of 40.96 mg/kg (MES ED₅₀), 85.16 mg/kg (scPTZ ED₅₀) and 347.6 mg/kg (TD₅₀).


Furthermore, compound 2f displayed promising neuroprotective effect by lowering the levels of MDA and LDH; therefore, it represents a potential lead in search for safer and effective anticonvulsants having neuroprotective effects.

Indole-N-glucoside, TA-1887 As a Sodium Glucose Cotransporter 2 Inhibitor

 

Abstract

 

 

 

Inhibition of the renal sodium glucose cotransporter (SGLT) increases urinary glucose excretion (UGE) and thus reduces blood glucose levels during hyperglycemia.

 

To explore the potential of new antihyperglycemic agents, we synthesized and determined the human SGLT2 (hSGLT2) inhibitory potential of novel substituted 3-benzylindole-N-glucosides 6.

 

Optimization of 6 resulted in the discovery of 3-(4-cyclopropylbenzyl)-4-fluoroindole-N-glucoside 6a-4 (TA-1887), a highly potent and selective hSGLT2 inhibitor, with pronounced antihyperglycemic effects in high-fat diet-fed KK (HF-KK) mice.

 

Our results suggest the potential of indole-N-glucosides as novel antihyperglycemic agents through inhibition of renal SGLT2.

Keywords:

Type 2 diabetes; sodium glucose cotransporter 2 inhibitor; urinary glucose excretion; indole-N-glucoside; TA-1887; antihyperglycemic effect

 

 

 

Rhodanine Class of Compounds as Inhibitors of Protein Reductase

Enoyl acyl carrier protein (ACP) reductase, one of the enzymes of the type II fatty acid biosynthesis pathway, has been established as a promising target for the development of new drugs for malaria.

Here we present the discovery of a rhodanine (2-thioxothiazolidin-4-one) class of compounds as inhibitors of this enzyme using a combined approach of rational selection of compounds for screening, analogue search, docking studies, and lead optimization.

The most potent inhibitor exhibits an IC₅₀ of 35.6 nM against Plasmodium falciparum enoyl ACP reductase (PfENR) and inhibits growth of the parasite in red blood cell cultures at an IC₅₀ value of 750 nM.


Many more compounds of this class were found to inhibit PfENR at low nanomolar to low micromolar concentrations, expanding the scope for developing new antimalarial drugs. The structure−activity relationship of these rhodanine compounds is discussed.