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Andrzej Stańczak - One of the best experts on this subject based on the ideXlab platform.

  • Cinnoline Scaffold—A Molecular Heart of Medicinal Chemistry?
    Molecules (Basel Switzerland), 2019
    Co-Authors: Marta Szumilak, Andrzej Stańczak
    Abstract:

    The Cinnoline nucleus is a very important bicyclic heterocycle that is used as the structural subunit of many compounds with interesting pharmaceutical properties. Cinnoline derivatives exhibit broad spectrum of pharmacological activities such as antibacterial, antifungal, antimalarial, anti-inflammatory, analgesic, anxiolytic and antitumor activities. Some of them are under evaluation in clinical trials. In the present review, we have compiled studies focused on the biological properties of Cinnoline derivatives conducted by many research groups worldwide between 2005 and 2019. Comprehensive and target oriented information clearly indicate that the development of Cinnoline based molecules constitute a significant contribution to the identification of lead compounds with optimized pharmacodynamic and pharmacokinetic properties.

  • Cinnoline scaffold a molecular heart of medicinal chemistry
    Molecules, 2019
    Co-Authors: Marta Szumilak, Andrzej Stańczak
    Abstract:

    The Cinnoline nucleus is a very important bicyclic heterocycle that is used as the structural subunit of many compounds with interesting pharmaceutical properties. Cinnoline derivatives exhibit broad spectrum of pharmacological activities such as antibacterial, antifungal, antimalarial, anti-inflammatory, analgesic, anxiolytic and antitumor activities. Some of them are under evaluation in clinical trials. In the present review, we have compiled studies focused on the biological properties of Cinnoline derivatives conducted by many research groups worldwide between 2005 and 2019. Comprehensive and target oriented information clearly indicate that the development of Cinnoline based molecules constitute a significant contribution to the identification of lead compounds with optimized pharmacodynamic and pharmacokinetic properties.

  • Synthesis and Biological Activity of Some 4‐Amino‐3‐Cinnolinecarboxylic Acid Derivatives. Part 5. Pyrimido[5,4‐c]Cinnolines and Triazepino[7,6‐c]Cinnoline.
    ChemInform, 2010
    Co-Authors: Andrzej Stańczak, Z. B. Ochocki, W. Pakulska
    Abstract:

    A series of substituted 3-aminopyrimido[5,4-c]Cinnolines 3, 7 was prepared. 6,7-Substituted 4-amino-3-Cinnolinecarboxylic acid 1 were condensed with acetic anhydride to give the respective 1,3-oxazino[5,4-c]Cinnolines 2. The obtained derivatives reacted with hydrazines and gave 3-aminopyrimido[5,4-c]Cinnolines. Reaction of the esters 5 with hydrazines produced hydrazides 6, which upon treatment with N,N-dimethylformamide dimethyl acetal gave 3-aminopyrimido[5,4-c]Cinnolines 7. Treatment of 6b with bromocyan produced 2-amino-3,4-dihydro-3,10-dimethyl-5 H-1,3,4-triazepino[7,6-c]cinnolin-5-on (8b). Some of the synthesized compounds were screened for their effect on the CNS.

  • Cinnoline Derivatives with Biological Activity
    ChemInform, 2007
    Co-Authors: Wieslawa Lewgowd, Andrzej Stańczak
    Abstract:

    Although Cinnoline belongs to a family of fairly well known heterocycles, the interest in the study of its derivatives continues. Cinnoline compounds demonstrate interesting bioactivity and many research papers have discussed the biological property, structure-activity relationship, and applications in medicinal science. Attention has been paid to the synthesis of heterocyclic compounds bearing a Cinnoline moiety, mainly because of the interest in their broad spectrum of pharmacological activities. This chronological work summarizes almost all synthetic papers and patents concerning the biological properties of 107 Cinnoline derivatives published over the last 50 years with 117 references.

  • Synthesis and biological activity of some 4-amino-3-Cinnolinecarboxylic acid derivatives. Part 5: Pyrimido[5,4-c]Cinnolines and triazepino[7,6-c]Cinnoline.
    Die Pharmazie, 1998
    Co-Authors: Andrzej Stańczak, Z. B. Ochocki, W. Pakulska
    Abstract:

    A series of substituted 3-aminopyrimido[5,4-c]Cinnolines 3, 7 was prepared. 6,7-Substituted 4-amino-3-Cinnolinecarboxylic acid 1 were condensed with acetic anhydride to give the respective 1,3-oxazino[5,4-c]Cinnolines 2. The obtained derivatives reacted with hydrazines and gave 3-aminopyrimido[5,4-c]Cinnolines. Reaction of the esters 5 with hydrazines produced hydrazides 6, which upon treatment with N,N-dimethylformamide dimethyl acetal gave 3-aminopyrimido[5,4-c]Cinnolines 7. Treatment of 6b with bromocyan produced 2-amino-3,4-dihydro-3,10-dimethyl-5 H-1,3,4-triazepino[7,6-c]cinnolin-5-on (8b). Some of the synthesized compounds were screened for their effect on the CNS.

Mark J Kurth - One of the best experts on this subject based on the ideXlab platform.

  • quinoxalino 2 3 c Cinnolines and their 5 n oxide alkoxylation of methyl substituted quinoxalino 2 3 c Cinnolines to acetals and orthoesters
    Journal of Organic Chemistry, 2011
    Co-Authors: Makhluf J Haddadin, Mirna Elkhatib, Tharallah A Shoker, Christine M Beavers, Marilyn M Olmstead, James C Fettinger, Kelli M Farber, Mark J Kurth
    Abstract:

    We report the alkoxylation of methyl-substituted quinoxalino[2,3-c]Cinnolines to give acetals and orthoesters in high yields. Routes to the precursors of this alkoxylation reaction as well as other quinoxalino[2,3-c]Cinnoline and their 5-oxide derivatives are reported. Most of these quinoxalino[2,3-c]Cinnolines were prepared by cyclization of the corresponding 2-amino-3-(2-nitrophenyl)quinoxaline, which, in turn, result from an unusual Beirut reaction from benzofurazan oxides plus 2-nitrobenzylcyanides. Mechanistic explanations for these intriguing reactions are presented.

Claudia Vergelli - One of the best experts on this subject based on the ideXlab platform.

  • Cinnoline derivatives as human neutrophil elastase inhibitors
    Journal of Enzyme Inhibition and Medicinal Chemistry, 2016
    Co-Authors: Maria Paola Giovannoni, Igor A. Schepetkin, Letizia Crocetti, Giovanna Ciciani, Agostino Cilibrizzi, Gabriella Guerrini, Andrei I. Khlebnikov, Mark T. Quinn, Claudia Vergelli
    Abstract:

    AbstractCompounds that can effectively inhibit the proteolytic activity of human neutrophil elastase (HNE) represent promising therapeutics for treatment of inflammatory diseases. We present here the synthesis, structure–activity relationship analysis, and biological evaluation of a new series of HNE inhibitors with a Cinnoline scaffold. These compounds exhibited HNE inhibitory activity but had lower potency compared to N-benzoylindazoles previously reported by us. On the other hand, they exhibited increased stability in aqueous solution. The most potent compound, 18a, had a good balance between HNE inhibitory activity (IC50 value = 56 nM) and chemical stability (t1/2 = 114 min). Analysis of reaction kinetics revealed that these Cinnoline derivatives were reversible competitive inhibitors of HNE. Furthermore, molecular docking studies of the active products into the HNE binding site revealed two types of HNE inhibitors: molecules with cinnolin-4(1H)-one scaffold, which were attacked by the HNE Ser195 hydr...

  • Cinnoline derivatives as human neutrophil elastase inhibitors
    2016
    Co-Authors: Maria Paola Giovannoni, Igor A. Schepetkin, Letizia Crocetti, Giovanna Ciciani, Agostino Cilibrizzi, Gabriella Guerrini, Andrei I. Khlebnikov, Mark T. Quinn, Claudia Vergelli
    Abstract:

    Compounds that can effectively inhibit the proteolytic activity of human neutrophil elastase (HNE) represent promising therapeutics for treatment of inflammatory diseases. We present here the synthesis, structure–activity relationship analysis, and biological evaluation of a new series of HNE inhibitors with a Cinnoline scaffold. These compounds exhibited HNE inhibitory activity but had lower potency compared to N-benzoylindazoles previously reported by us. On the other hand, they exhibited increased stability in aqueous solution. The most potent compound, 18a, had a good balance between HNE inhibitory activity (IC50 value = 56 nM) and chemical stability (t1/2 = 114 min). Analysis of reaction kinetics revealed that these Cinnoline derivatives were reversible competitive inhibitors of HNE. Furthermore, molecular docking studies of the active products into the HNE binding site revealed two types of HNE inhibitors: molecules with cinnolin-4(1H)-one scaffold, which were attacked by the HNE Ser195 hydroxyl group at the amido moiety, and Cinnoline derivatives containing an ester function at C-4, which is the point of attack of Ser195.

W. Pakulska - One of the best experts on this subject based on the ideXlab platform.

Aijun Lin - One of the best experts on this subject based on the ideXlab platform.