Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Identification of N-(2-Phenoxyethyl)imidazo[1,2-a]pyridine-3-carboxamides as New Antituberculosis Agents.

ABSTRACT: A series of imidazo[1,2-a]pyridine carboxamides (IPAs) bearing an N-(2-phenoxyethyl) moiety was designed and synthesized as new antitubercular agents. Seven 2,6-dimethyl IPAs demonstrated excellent in vitro activity (MIC: 0.025-0.054 ?g/mL) against the drug susceptive H37Rv strain and two clinically isolated multidrug-resistant Mycobacterium tuberculosisstrains. Compound 10j displayed acceptable safety and pharmacokinetic properties, opening a new direction for further development.

SUBMITTER: Wu Z

PROVIDER: S-EPMC5150680 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Identification of N-(2-Phenoxyethyl)imidazo[1,2-a]pyridine-3-carboxamides as New Antituberculosis Agents.

Wu Zhaoyang Z Lu Yu Y Li Linhu L Zhao Rui R Wang Bin B Lv Kai K Liu Mingliang M You Xuefu X

ACS medicinal chemistry letters 20161011 12

A series of imidazo[1,2-a]pyridine carboxamides (IPAs) bearing an N-(2-phenoxyethyl) moiety was designed and synthesized as new antitubercular agents. Seven 2,6-dimethyl IPAs demonstrated excellent in vitro activity (MIC: 0.025-0.054 μg/mL) against the drug susceptive H37Rv strain and two clinically isolated multidrug-resistant Mycobacterium tuberculosisstrains. Compound 10j displayed acceptable safety and pharmacokinetic properties, opening a new direction for ...[more]

PMID: 27994751

Similar Datasets

Advent of Imidazo[1,2-a]pyridine-3-carboxamides with Potent Multi- and Extended Drug Resistant Antituberculosis Activity.

Project description:A set of nine 2,7-dimethylimidazo[1,2-a]pyridine-3-carboxamides and one 2,6-dimethylimidazo[1,2-a]pyrimidine-3-carboxamide were synthesized. The compounds were evaluated for their in vitro anti-tuberculosis activity versus replicating, non-replicating, multi- and extensive drug resistant Mtb strains. The MIC(90) values of seven of these agents were ≤ 1 μM against the various tuberculosis strains tested. A representative compound of this class (1) was screened against seven non-tubercular strains as well as other non-mycobacteria organisms and demonstrated remarkable microbe selectivity. A transcriptional profiling experiment of Mtb treated with compound 1 was performed to give a preliminary indication of the mode of action. Lastly, the in vivo ADME properties of compounds 1, 3, 4, and 6 were assessed. The 2,7-dimethylimidazo[1,2-a]pyridine-3-carboxamides are a drug-like and synthetically accessible class of anti-TB agents that have excellent selective potency against multi- and extensive drug resistant TB and encouraging pharmacokinetics.

| S-EPMC3117668 | biostudies-literature

Imidazo[1,2-a]Pyridine-3-Carboxamides Are Active Antimicrobial Agents against Mycobacterium avium Infection In Vivo.

Project description:A panel of six imidazo[1,2-a]pyridine-3-carboxamides (IAPs) were shown to have low-micromolar activity against Mycobacterium avium strains. Compound ND-10885 (compound 2) showed significant activity in the lung, spleen, and liver in a mouse M. avium infection model. A combined regimen consisting of ND-10885 (compound 2) and rifampin was additive in its anti-M. avium activity in the lung. Our data indicate that IAPs represent a new class of antibiotics that are active against M. avium and could potentially serve as an effective addition to a combined treatment regimen.

| S-EPMC4958206 | biostudies-other

Identification of novel imidazo[1,2-a]pyridine inhibitors targeting M. tuberculosis QcrB.

Project description:Mycobacterium tuberculosis is a major human pathogen and the causative agent for the pulmonary disease, tuberculosis (TB). Current treatment programs to combat TB are under threat due to the emergence of multi-drug and extensively-drug resistant TB. Through the use of high throughput whole cell screening of an extensive compound library a number of imidazo[1,2-a]pyridine (IP) compounds were obtained as potent lead molecules active against M. tuberculosis and Mycobacterium bovis BCG. The IP inhibitors (1-4) demonstrated minimum inhibitory concentrations (MICs) in the range of 0.03 to 5 µM against a panel of M. tuberculosis strains. M. bovis BCG spontaneous resistant mutants were generated against IP 1, 3, and 4 at 5× MIC and subsequent whole genome sequencing identified a single nucleotide polymorphism (937)ACC>(937)GCC (T313A) in qcrB, which encodes the b subunit of the electron transport ubiquinol cytochrome C reductase. This mutation also conferred cross-resistance against IP 1, 3 and 4 demonstrating a common target. Gene dosage experiments confirmed M. bovis BCG QcrB as the target where over-expression in M. bovis BCG led to an increase in MIC from 0.5 to >8 µM for IP 3. An acute murine model of TB infection established bacteriostatic activity of the IP series, which await further detailed characterization.

| S-EPMC3534098 | biostudies-literature

2-Phenyl-imidazo[1,2-a]pyridine-3-carbaldehyde.

Project description:In the title compound, C(14)H(10)N(2)O, the dihedral angle between the imidazo[1,2-a]pyridine and phenyl rings is 28.61 (4)° The mol-ecules are connected into broad chains parallel to the a axis by weak C-H⋯O and C-H⋯N hydrogen bonds. The linking of the ribbons is provided by π-π stacking inter-actions between neighbouring pyridine rings, with a centroid-centroid distance of 3.7187 (7) Å.

| S-EPMC2961188 | biostudies-literature

4-Arylthieno[2,3-b]pyridine-2-carboxamides Are a New Class of Antiplasmodial Agents.

Project description:Malaria causes hundreds of thousands of deaths every year, making it one of the most dangerous infectious diseases worldwide. Because the pathogens have developed resistance against most of the established anti-malarial drugs, new antiplasmodial agents are urgently needed. In analogy to similar antiplasmodial ketones, 4-arylthieno[2,3-b]pyridine-2-carboxamides were synthesized by Thorpe-Ziegler reactions. In contrast to the related ketones, these carboxamides are only weak inhibitors of the plasmodial enzyme PfGSK-3 but the compounds nevertheless show strong antiparasitic activity. The most potent representatives inhibit the pathogens with IC50 values in the two-digit nanomolar range and exhibit high selectivity indices (>100).

| S-EPMC7397174 | biostudies-literature

Scaffold-switching: an exploration of 5,6-fused bicyclic heteroaromatics systems to afford antituberculosis activity akin to the imidazo[1,2-a]pyridine-3-carboxylates.

Project description:A set of 5,6-fused bicyclic heteroaromatic scaffolds were investigated for their in vitro anti-tubercular activity versus replicating and non-replicating strains of Mycobacterium tuberculosis (Mtb) in an attempt to find an alternative scaffold to the imidazo[1,2-a]pyridine and imidazo[1,2-a]pyrimidines that were previously shown to have potent activity against replicating and drug resistant Mtb. The five new bicyclic heteroaromatic scaffolds explored in this study include a 2,6-dimethylimidazo[1,2-b]pyridazine-3-carboxamide (7), a 2,6-dimethyl-1H-indole-3-carboxamide (8), a 6-methyl-1H-indazole-3-carboxamide (9), a 7-methyl-[1,2,4]triazolo[4,3-a]pyridine-3-carboxamide (10), and a 5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carboxamide (11). Additionally, imidazo[1,2-a]pyridines isomers (2 and 12) and a homologous imidazo[1,2-a]pyrimidine isomer (6) were prepared and compared. Compounds 2 and 6 were found to be the most potent against H37Rv Mtb (MIC's of 0.1 μM and 1.3 μM) and were inactive (MIC >128 μM) against Staphylococcus aureus, Escherichia coli and Candida albicans. Against other non-tubercular mycobacteria strains, compounds 2 and 6 had activity against Mycobacterium avium (16 and 122 μM, respectively), Mycobacterium kansasii (4 and 19 μM, respectively), Mycobacterium bovis BCG (1 and 8 μM, respectively) while all the other scaffolds were inactive (>128 μM).

| S-EPMC4096046 | biostudies-literature

Identification of Pyrazolo[1,5-a]pyridine-3-carboxamide Diaryl Derivatives as Drug Resistant Antituberculosis Agents.

Project description:A series of pyrazolo[1,5-a]pyridine-3-carboxamide (PPA) derivatives bearing diaryl side chain was designed and synthesized as new antituberculosis agents, aiming to improve the efficacy toward drug resistant Mycobacterium tuberculosis (Mtb) strains. Most of the substituted diphenyl and heterodiaryl PPAs exhibited excellent in vitro potency against the drug susceptive H37Rv strain (MIC < 0.002-0.381 μg/mL) and drug resistant Mtb strains (INH-resistant (rINH), MIC < 0.002-0.465 μg/mL; RMP-resistant (rRMP), MIC < 0.002-0.004 μg/mL). Noticeably, some compounds also showed very low cytotoxicity against Vero cells. Further, compound 6j displayed good pharmacokinetic profiles with oral bioavailability (F) of 41% and significantly reduced the bacterial burden in an autoluminescent H37Ra infected mouse model.

| S-EPMC6421536 | biostudies-literature

Ethyl 5-methyl-imidazo[1,2-a]pyridine-2-carboxyl-ate.

Project description:The title compound, C(11)H(12)N(2)O(2), was synthesized from the reaction of 6-methyl-pyridin-2-amine and ethyl 3-bromo-2-oxopropionate. In the mol-ecular structure, the six- and five-membered rings are individually almost planar with r.m.s. deviations of 0.003 and 0.002?Å, respectively. The two rings are almost coplanar, the dihedral angle between their planes being 1.4?(3)°. Inter-molecular C-H?O and C-H?N hydrogen bonds are present in the crystal structure.

| S-EPMC3007311 | biostudies-literature

Imidazo[1,2-a]pyridine-based peptidomimetics as inhibitors of Akt.

Project description:We report the design, synthesis, and biological evaluation of imidazopyridine-based peptidomimetics based on the substrate consensus sequence of Akt, an AGC family serine/threonine kinase hyperactivated in over 50% of human tumors. Our ligand-based approach led to the identification of novel substrate mimetic inhibitors of Akt1 featuring an unnatural extended dipeptide surrogate. Compound 11 inhibits Akt isoforms in the sub-micromolar range and exhibits improved proteolytic stability relative to a parent pentapeptide.

| S-EPMC4176526 | biostudies-literature

2-(Ethyl-sulfin-yl)imidazo[1,2-a]pyridine-3-sulfonamide.

Project description:The supra-molecular structure of the title compound, C(9)H(11)N(3)O(3)S(2), is defined by two inter-molecular hydrogen bonds. Pairs of N-H⋯N hydrogen bonds link the mol-ecules into centrosymmetric dimers and N-H⋯O hydrogen bonds link the dimers into a tubular chain structure running parallel to the a axis.

| S-EPMC3344477 | biostudies-literature