Synthesis and Neurotropic Activity of New Pyrimido[4′,5′:4,5]Thieno[2,3-b]Quinoline Derivatives

Дабаева, В. В.; Bagdasaryan, M. R.; Noravyan, A. S.; Dzhagatspanyan, I. A.; Nazaryan, I. M.; Akopyan, A. G.

doi:10.1007/s11094-015-1334-5

Cited by 10 publications

(5 citation statements)

References 7 publications

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“…4-Aminoalkylamino derivatives of pyrido[3′,2′:4,5] thieno[3,2- d ]pyrimidine have been shown to interact with a number of molecular targets, including phosphodiesterase IV, and to have potential use in the treatment of asthma and chronic obstructive pulmonary disease ( 22 ; S. L. M. Pages and M. J. Taltavull, U.S. patent application, June 2006) and in the control of tumor necrosis factor alpha (TNF-α) release ( 23 ) and to have beta2 adrenoreceptor agonist activity ( 24 ). Additionally, diverse biological activities, such as anticonvulsant ( 25 – 27 ) and neurotropic ( 28 , 29 ) activities, have been ascribed to compounds similar to those presented here. To our knowledge, this is the first description of pyrido-thieno-pyrimidines as inhibitors of P-type ATPases.…”

Section: Discussionsupporting

confidence: 53%

Identification of Antifungal H ⁺ -ATPase Inhibitors with Effect on Plasma Membrane Potential

Kjellerup

Gordon²,

Cohrt³

et al. 2017

Antimicrob Agents Chemother

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The plasma membrane H+-ATPase (Pma1) is an essential fungal protein and a proposed target for new antifungal medications. The compounds in a small-molecule library containing ∼191,000 commercially available compounds were screened for their ability to inhibit Saccharomyces cerevisiae plasma membranes containing Pma1. The overall hit rate was 0.2%, corresponding to 407 compounds. These hit compounds were further evaluated for ATPase selectivity and broad-spectrum antifungal activity. Following this work, one Pma1 inhibitor series based on compound 14 and analogs was selected for further evaluation. This compound series was able to depolarize the membrane and inhibit extracellular acidification in intact fungal cells concomitantly with a significant increase in intracellular ATP levels. Collectively, we suggest that these effects may be a common feature of Pma1 inhibitors. Additionally, the work uncovered a dual mechanism for the previously identified cationic peptide BM2, revealing fungal membrane disruption, in addition to Pma1 inhibition. The methods presented here provide a solid platform for the evaluation of Pma1-specific inhibitors in a drug development setting. The present inhibitors could serve as a starting point for the development of new antifungal agents with a novel mode of action.

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Section: Discussionsupporting

confidence: 53%

Identification of Antifungal H ⁺ -ATPase Inhibitors with Effect on Plasma Membrane Potential

Kjellerup

Gordon²,

Cohrt³

et al. 2017

Antimicrob Agents Chemother

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“…136 -137 °C. 7 ). δ H (400 MHz, (CDCl 3 ) 1.79-1.90 (4H, m, H-6 and H-7), 2.76 (2H, t, J = 6.4 Hz, H-5), 2.93 (2H, t, J = 6.4 Hz, H-8), 7.63 (1H, s, H-4).…”

Section: -Chloro-5678-tetrahydroquinoline-3-carbonitrilementioning

confidence: 99%

“…SYNLETT0 9 3 6 -5 2 1 4 1 4 3 7 -2 0 9 6 © Georg Thieme Verlag Stuttgart • New York 2016, 27, 2811-2814 letter Chloroquinoline 1 was formed through the chlorination, using POCl 3 of 7, 11 itself formed following literature procedures from cyclohexanone 8. 1 Amination of chloride 1 with amines 2a,b was performed in DMSO with KF (2.4 equiv) at 120 °C overnight 12 to give coupled products 3a,b, respectively.…”

Section: Scheme 1 Retrosynthetic Plan Towards N-unsubstituted Thienopyridine Analoguesmentioning

confidence: 99%

Synthesis of 3-Amino-2-carboxamide Tetrahydropyrrolo[2,3-b]quinolines

Pilkington

Haverkate

Rensburg

et al. 2016

Synlett

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All reactions were carried out under a nitrogen atmosphere in dry, freshly distilled solvents unless otherwise noted. All NMR spectra were recorded on a Bruker Avance DRX 400 MHz spectrometer at ambient temperature. Chemical shifts are reported relative to the solvent peak of chloroform (δ 7.26 for 1 H and δ 77.0 for 13 C), DMSO (δ 2.50 for 1 H and δ 39.5 for 13 C), CD 3 OD (δ 3.31 for 1 H and δ 49.00 for 13 C), or acetone (δ 2.05 for 1 H and δ 29.8 for 13 C). 1 H NMR data is reported as position (δ), relative integral, multiplicity (s, singlet; d, doublet; t, triplet; td, triplet of doublets; dd, doublet of doublets; m, multiplet; br, broad peak), coupling constant (J, Hz), and the assignment of the atom. 13 C NMR data are reported as position (δ) and assignment of the atom. All NMR assignments were performed using HSQC and HMBC experiments. High-resolution mass spectroscopy (HRMS) was carried out by either chemical ionization (CI) or electrospray ionization (ESI) on a MicroTOF-Q mass spectrometer. Unless noted, chemical reagents were used as purchased. Experimental Procedures: 2-Azido-N-phenyl acetamide 6a To a solution of bromide 5a (0.80 g, 3.7 mmol) in DMSO (15 mL) under an atmosphere of nitrogen at room temperature was added NaN 3 (0.267 g, 4.1 mmol) and the reaction left to stir for 3 d. Water (30 mL) was then added and the product extracted with ether (3 x 30 mL). The combined organic layers were washed with water (2 x 30 mL) and brine (30 mL), dried (Na 2 SO 4) and the solvent removed in vacuo to give the desired azide 6a (0.658 g, quant.) as a

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“…A functionalization of substituents and a new ring addition to the thieno[2,3- b ]pyridine core system may be used to enhance and broaden the application of compounds. Thus, biological activities exhibited by ring-fused thienopyridines include antimicrobial and antiprotozoal, − antihistaminic, antiproliferative/anticancer, − anti-Alzheimer, anticonvulsant, and neurotropic − effects. Pyrido[3′,2′:4,5]thieno[3,2- d ]pyrimidines were reported as phosphodiesterase type 4 inhibitors, multitarget Ser/Thr kinase inhibitors, Cdc7 kinase inhibitors, and hepatic gluconeogenesis inhibitors …”

Section: Introductionmentioning

confidence: 99%

Unusual Oxidative Dimerization in the 3-Aminothieno[2,3-b]pyridine-2-carboxamide Series

et al. 2021

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Noncatalyzed, regio-and stereoselective hypochlorite oxidation of 3-aminothieno[2,3-b]pyridine-2-carboxamides is presented. Unexpectedly, the oxidation proceeded by different mechanistic pathways, and different products were formed, depending on the nature of solvents used. A possible mechanism, the structure of products, kinetics and dynamics of intramolecular processes, and biological activity of products are discussed.

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Synthesis and Neurotropic Activity of New Pyrimido[4′,5′:4,5]Thieno[2,3-b]Quinoline Derivatives

Cited by 10 publications

References 7 publications

Identification of Antifungal H ⁺ -ATPase Inhibitors with Effect on Plasma Membrane Potential

Identification of Antifungal H ⁺ -ATPase Inhibitors with Effect on Plasma Membrane Potential

Synthesis of 3-Amino-2-carboxamide Tetrahydropyrrolo[2,3-b]quinolines

Unusual Oxidative Dimerization in the 3-Aminothieno[2,3-b]pyridine-2-carboxamide Series

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Synthesis and Neurotropic Activity of New Pyrimido[4′,5′:4,5]Thieno[2,3-b]Quinoline Derivatives

Cited by 10 publications

References 7 publications

Identification of Antifungal H + -ATPase Inhibitors with Effect on Plasma Membrane Potential

Identification of Antifungal H + -ATPase Inhibitors with Effect on Plasma Membrane Potential

Synthesis of 3-Amino-2-carboxamide Tetrahydropyrrolo[2,3-b]quinolines

Unusual Oxidative Dimerization in the 3-Aminothieno[2,3-b]pyridine-2-carboxamide Series

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Identification of Antifungal H ⁺ -ATPase Inhibitors with Effect on Plasma Membrane Potential

Identification of Antifungal H ⁺ -ATPase Inhibitors with Effect on Plasma Membrane Potential