28284-05-1

Antimicrobial peptides (AMPs) are a key component of the human immune system. Synthetic AMP mimics represent a novel strategy to counteract the increasing incidence of antimicrobial resistance. Here, we describe the synthesis of novel glyoxamide derivativ

Tuberculosis (TB) is one of the leading causes of death worldwide. The emergence of multi-drug resistant strains of Mycobacterium tuberculosis (Mtb) and TB-HIV co-infection are major public health challenges. The anti-TB drugs of first choice were developed more than 4 decades ago and present several adverse effects, making the treatment of TB even more complicated and the development of new chemotherapeutics for this disease imperative. In this work, we synthesized two series of new acylhydrazides and evaluated their activity against different strains of Mtb. Derivatives of isoniazid (INH) showed important anti-Mtb activity, some being more potent than all anti-TB drugs of first choice. Moreover, three compounds proved to be more potent than INH against resistant Mtb. The Ames test showed favorable results for two of these substances compared to INH, one of which presented expressly lower toxicity to HepG2 cells than that of INH. This result shows that this compound has the potential to overcome one of the main adverse effects of this drug.

Using ligand-based design strategy, a set of isatin-3-carbohydrazones was designed, synthesized and evaluated for dual fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) inhibition properties. Compound 5-chloro-N′-(5-chloro-2-oxoindolin-3-ylidene)-2-hydroxybenzohydrazide (13 b) emerged as a potent MAGL inhibitor with nanomolar activity (IC50=3.33 nM), while compound 5-chloro-N′-(1-(4-fluorobenzyl)-2-oxoindolin-3-ylidene)-2-hydroxybenzohydrazide (13 j) was the most potent selective FAAH inhibitor (IC50=37 nM). Compound 5-chloro-N′-(6-chloro-2-oxoindolin-3-ylidene)-2-hydroxybenzohydrazide (13 c) showed dual FAAH-MAGL inhibitory activity with an IC50 of 31 and 29 nM respectively. Enzyme kinetics studies revealed that the isatin-based carbohydrazones are reversible inhibitors for both FAAH and MAGL. Further, blood-brain permeability assay confirmed that the lead compounds (13 b, 13 c, 13 g, 13 m and 13 q) are suitable as CNS candidates. Molecular dynamics simulation studies revealed the putative binding modes and key interactions of lead inhibitors within the enzyme active sites. The lead dual FAAH-MAGL inhibitor 13 c showed significant antioxidant activity and neuroprotection in the cell-based cytotoxicity assay. In summary, the study yielded three potent FAAH/MAGL inhibitor compounds (13 b, 13 c and 13 j) with acceptable pharmacokinetic profile and thus can be considered as promising candidates for treating neurological and mood disorders.

Isatin derivatives, and methods of using isatin and isatin derivatives as photoinitiators, are described.

Implication of carbonic anhydrases (CAs) in many physiological functions made them attractive therapeutic targets. Herein, we report the synthesis of three series of benzenesulfonamide-based compounds (5a-e, 9a-e and 10a-e) as potential ligands to four of

New multipurpose arylation/acylation/transamination reagents, N-acylisatins, have been developed by selective ‘inside-outside’ C?N bond cleavage under different catalytic conditions. As activated amides, N-acylisatins undergo Rh-catalyzed C?H arylation and Pd-catalyzed acylation by cleavage outside the C?N bond, and the desired biaryls and diaryl ketones were obtained in good to excellent yields. Generally, the combination of N-acylisatins with amines leads to a ring-opening reaction and formation of transamination products in a predictable manner through inside C?N bond cleavage. Interestingly, treatment of N-acylisatins with amines lead to unexpected outer-ring transamination products when CsF is added, which shows that CsF can favor the outside C?N bond cleavage path. Notably, this work presents a new strategy for multiple chemical transformations of a single amide to achieve various products by selective C?N bond cleavage. (Figure presented.).

The instant invention relates to compounds of formula I wherein: R is selected from H, Me or Cl, and R′ is selected from: H, NH2, NHCOCH3 NHCOCF3 or NHCOCH2Cl. The invention further provides a process for obtaining the compounds of formula I and their use.

The first example of an intramolecular decarboxylative acylation reaction for the synthesis of 4H-benzoxazin-4-one derivatives has been described. The silver-mediated reaction has a broad substrate scope and provides a mild and rapid approach to the corre

A series of N-aroylated isatins 1-15 was synthesized and evaluated for their antiglycation activity. All compounds showed a varying degree of glycation inhibitory activity with IC50 values between 18.01 ± 0.05-693.7 ± 3.0 μM, when compared with the standard (aminoguanidine) having an IC50 = 268.7 ± 12.4 μM. Compound 1 was found to be the most active member of this series with an IC50 = 18.01 ± 0.05 μM. Compound 10 showed an IC50 = 72.5 ± 0.09 μM, whereas compound 7 has an IC50 = 80.18 ± 0.07 μM. Compounds 3, 9, and 13 showed IC50 values 170.2 ± 0.62, 117.91 ± 2.9, 171.3 ± 0.79 μM, respectively. Rest of the compounds along with parent isatin were found to be inactive. The structures of all the synthetic compounds were deduced by spectroscopic analysis.

A range of secondary 2-amidophenylglyoxylamides self-assemble by intermolecular hydrogen bonding between the secondary amide proton and the 2-amidophenyl carbonyl oxygen atom.

While commercial isatins were practically inactive against the target proteases, thiosemicarbazone derivatives were found to be active. The most active compound from the series displayed an inhibitory IC50 value of 1 μM against rhodesain. One thiosemicarbazone was found to be active against all three proteases with inhibitory IC50 values of 10 μM or less. A combination of N-benzylation and appropriate substitution on the aromatic portion of the isatin scaffold was generally found to be beneficial especially against cruzain for ketone inhibitors.

N-acylsatins can be directly converted in high yields to N-alkylindoles by reduction, at room temperature, with freshly prepared BH3*THF complex.This reduction represents an alternative method for the preparation of N-alkylindoles with long-chain alkyl groups, especially those with halogens within the carbon chain.

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