2549-19-1Relevant academic research and scientific papers
Synthesis and biological evaluation of new imidazo[1,2-a]pyridine derivatives designed as mefloquine analogues.
Lima, Patricia C,Avery, Mitchell A,Tekwani, Babu L,de Alves, Helio M,Barreiro, Eliezer J,Fraga, Carlos A M
, p. 825 - 832 (2002)
This paper describes the synthesis and the in vitro antimalarial profile of two new imidazo[1,2-a]pyridine derivatives 4HCl and 13HCl, structurally proposed as mefloquine (1) analogues, by exploring bioisosterism and molecular simplification tools. The synthetic route employed to access the title compounds used, as starting material, the previously described ethyl 2-methylimidazo[1,2-aJpyridine-3-carboxylate derivative (5). These novel heterocyclic derivatives 4HCl and 13HCl presented modest antimalarial activity against the W-2 and D-6 clones of Plasmodium falciparum as well as inhibitors of in vitro heme polymerization compared to mefloquine.
Structural modification of zolpidem led to potent antimicrobial activity in imidazo[1,2-: A] pyridine/pyrimidine-1,2,3-triazoles
Reddyrajula, Rajkumar,Dalimba, Udaya Kumar
, p. 16281 - 16299 (2019/11/03)
Ambien (zolpidem), an imidazo[1,2-a]pyridine derivative, is a commercial drug to treat insomnia which also possesses antitubercular activity against Mycobacterium tuberculosis H37Rv. In this paper, we describe the synthesis of three diverse lead series of imidazo[1,2-a]pyridine/pyrimidine-1,2,3-triazoles (IPTs) which are designed by specific structural modifications of zolpidem. Most of the IPTs exhibited remarkable in vitro antitubercular activity with an MIC of 1.56 μg mL-1, which is two-fold higher than the MIC of zolpidem. Further, the synthesized IPTs displayed moderate inhibitory activity against several bacterial and fungal strains as well, and also showed an acceptable safety profile as verified through in vitro cytotoxicity assessment against Vero cells. In addition, the potent IPTs exhibited promising binding interactions within the active site of the InhA enzyme. An interesting correlation between the in vitro inhibitory activity and the binding mode was observed: most of the potent molecules (MIC = 1.56 μg mL-1) interact through a H-bond with the Tyr 158 residue of the target enzyme. These efforts toward the structural modification of zolpidem could be helpful for further optimization of the IPT core to develop new anti-TB drugs.
NBS mediated protocol for the synthesis of N-bridged fused heterocycles in water
Bhagat, Saket B.,Telvekar, Vikas N.
supporting information, p. 3662 - 3666 (2017/08/23)
A facile and environmental friendly protocol for the synthesis of N-bridged fused bicyclic compounds such as imidazo[1,2-a]pyridines, imidazo[1,2-a]pyrimidines, and imidazo[2,1-b]thiazole, from commercially available starting materials has been developed.
2-Aminopyridines as an α-Bromination Shuttle in a Transition Metal-Free One-Pot Synthesis of Imidazo[1,2-a]pyridines
Roslan, Irwan Iskandar,Ng, Kian-Hong,Chuah, Gaik-Khuan,Jaenicke, Stephan
supporting information, p. 364 - 369 (2016/04/26)
A wide range of imidazo[1,2-a]pyridines are accessible from cheap and readily available 2-aminopyridines and 1,3-dicarbonyl compounds using a unique CBrCl3/2-aminopyridine system for bromination at the α-carbon. 2-Aminopyridine is not only the substrate but also acts as a bromination shuttle, transferring the bromine atom from CBrCl3 to the α-carbon of the 1,3-dicarbonyl. The reaction mechanism involves a series of reversible steps, including an addition reaction with cyclic transition state, to form a bromo-hemiaminal intermediate. Isolated yields of up to 97% were obtained under mild conditions and at short reaction times in this transition metal-free, one-pot synthesis.
CBr4 Mediated Oxidative C-N Bond Formation: Applied in the Synthesis of Imidazo[1,2-α]pyridines and Imidazo[1,2-α]pyrimidines
Huo, Congde,Tang, Jing,Xie, Haisheng,Wang, Yajun,Dong, Jie
supporting information, p. 1016 - 1019 (2016/03/15)
The carbon tetrabromide mediated oxidative carbon-nitrogen bond formation of 2-aminopyridines or 2-aminopyrimidines with β-keto esters or 1,3-diones, leading to a variety of complex imidazo[1,2-α]pyridines or imidazo[1,2-α]pyrimidines, is reported. The re
Microwave-assisted synthesis and photophysical studies of novel fluorescent N-acylhydrazone and semicarbazone-7-OH-coumarin dyes
Pereira, Thiago Moreira,Vitório, Felipe,Amaral, Ronaldo Costa,Zanoni, Kassio Papi Silva,Murakami Iha, Neyde Yukie,Kümmerle, Arthur Eugen
, p. 8846 - 8854 (2016/10/11)
A microwave-assisted synthesis of novel N-acylhydrazone and semicacarbazone-7-hidroxy-coumarins derivatives, starting from 3-acetyl-7-hydroxy-2H-chromen-2-one, is described. This optimized protocol led to higher yields and considerable reduction in reaction time from ～24 to ～1 hour. Aqueous solutions of these compounds showed bright blue to cyan emission and maximum quantum yields of 0.244. The stereoelectronic effects of the attached groups led to modulation of the spectral characteristics by favoring syn or anti amide conformers. The synthesized compounds showed pH dependent luminescence and a strong batochromic shift up to 65 nm in a low polarity medium (methanol) due to a better stabilization of the syn-conformer promoting this redshifted emission. These characteristics can be exploited for designing new luminescent probes for pH as well as polar microenvironments.
Identification and development of 2-methylimidazo[1,2-a]pyridine-3- carboxamides as Mycobacterium tuberculosis pantothenate synthetase inhibitors
Samala, Ganesh,Nallangi, Radhika,Devi, Parthiban Brindha,Saxena, Shalini,Yadav, Renu,Sridevi, Jonnalagadda Padma,Yogeeswari, Perumal,Sriram, Dharmarajan
, p. 4223 - 4232 (2014/08/18)
In the present study, we used crystal structure of mycobacterial pantothenate synthetase (PS) bound with 2-(2-(benzofuran-2-ylsulfonylcarbamoyl)- 5-methoxy-1H-indol-1-yl) acetic acid inhibitor for virtual screening of antitubercular compound database to identify new scaffolds. One of the identified lead was modified synthetically to obtain thirty novel analogues. These synthesized compounds were evaluated for Mycobacterium tuberculosis (MTB) PS inhibition study, in vitro antimycobacterial activities and cytotoxicity against RAW 264.7 cell line. Among the compounds tested, N′-(1-naphthoyl)- 2-methylimidazo[1,2-a]pyridine-3-carbohydrazide (5b) was found to be the most active compound with IC50 of 1.90 ± 0.12 μM against MTB PS, MIC of 4.53 μM against MTB with no cytotoxicity at 50 μM. The binding affinity of the most potent inhibitor 5b was further confirmed biophysically through differential scanning fluorimetry.
Lead optimization of a novel series of imidazo[1,2-a]pyridine amides leading to a clinical candidate (Q203) as a multi- and extensively-drug- resistant anti-tuberculosis agent
Kang, Sunhee,Kim, Ryang Yeo,Seo, Min Jung,Lee, Saeyeon,Kim, Young Mi,Seo, Mooyoung,Seo, Jeong Jea,Ko, Yoonae,Choi, Inhee,Jang, Jichan,Nam, Jiyoun,Park, Seijin,Kang, Hwankyu,Kim, Hyung Jun,Kim, Jungjun,Ahn, Sujin,Pethe, Kevin,Nam, Kiyean,No, Zaesung,Kim, Jaeseung
, p. 5293 - 5305 (2014/07/08)
A critical unmet clinical need to combat the global tuberculosis epidemic is the development of potent agents capable of reducing the time of multi-drug-resistant (MDR) and extensively-drug-resistant (XDR) tuberculosis therapy. In this paper, we report on the optimization of imidazo[1,2-a]pyridine amide (IPA) lead compound 1, which led to the design and synthesis of Q203 (50). We found that the amide linker with IPA core is very important for activity against Mycobacterium tuberculosis H37Rv. Linearity and lipophilicity of the amine part in the IPA series play a critical role in improving in vitro and in vivo efficacy and pharmacokinetic profile. The optimized IPAs 49 and 50 showed not only excellent oral bioavailability (80.2% and 90.7%, respectively) with high exposure of the area under curve (AUC) but also displayed significant colony-forming unit (CFU) reduction (1.52 and 3.13 log10 reduction at 10 mg/kg dosing level, respectively) in mouse lung.
A novel solvent-free approach to imidazole containing nitrogen-bridgehead heterocycles
Attanasi, Orazio A.,Bianchi, Luca,Campisi, Linda A.,Crescentini, Lucia De,Favi, Gianfranco,Mantellini, Fabio
supporting information, p. 3646 - 3649 (2013/08/23)
A very simple domino reaction under solvent-free conditions of various pyridine-like heterocycles with 1,2-diaza-1,3-dienes produces in good yields imidazo[1,2-a]pyridines, imidazo[1,2-a]quinolines, and imidazo[2,1-a] isoquinolines. The advantage of this one-pot transformation lies in the use of simple pyridine-like compounds without prefunctionalization of the starting heterocycles.
Design, synthesis, and pharmacological evaluation of N-acylhydrazones and novel conformationally constrained compounds as selective and potent orally active phosphodiesterase-4 inhibitors
Kümmerle, Arthur E.,Schmitt, Martine,Cardozo, Suzana V. S.,Lugnier, Claire,Villa, Pascal,Lopes, Alexandra B.,Romeiro, Nelilma C.,Justiniano, Hélène,Martins, Marco A.,Fraga, Carlos A. M.,Bourguignon, Jean-Jacques,Barreiro, Eliezer J.
, p. 7525 - 7545 (2012/11/06)
Among a small series of tested N-acylhydrazones (NAHs), the compound 8a was selected as a selective submicromolar phosphodiesterase-4 (PDE4) inhibitor associated with anti-TNF-α properties measured both in vitro and in vivo. The recognition pattern of compound 8a was elucidated through molecular modeling studies based on the knowledge of the 3D-structure of zardaverine, a PDE4 inhibitor resembling the structure of 8a, cocrystallized with the PDE4. Based on further conformational analysis dealing with N-methyl-NAHs, a quinazoline derivative (19) was designed as a conformationally constrained NAH analogue and showed similar in vitro pharmacological profile, compared with 8a. In addition 19 was found active when tested orally in LPS-evoked airway hyperreactivity and fully confirmed the working hypothesis supporting this work.
