Structure-activity studies of 20-deoxo-20-amino derivatives of tylosin-related macrolides.

Continuing our research in the field of new heterocyclic compounds, herein we report on the synthesis and antitumor activity of new amino derivatives of pyrido[3’,2’:4,5](furo)thieno[3,2-d]pyrimidines as well as of two new heterocyclic systems: furo[2–e]imidazo[1,2-c]pyrimidine and furo[2,3-e]pyrimido[1,2-c]pyrimidine. Thus, by refluxing the 8-chloro derivatives of pyrido[3’,2’:4,5]thieno(furo)[3,2-d]pyrimidines with various amines, the relevant pyrido[3’,2’:4,5]thieno(furo)[3,2-d]pyrimidin-8-amines were obtained. Further, the cyclization of some amines under the action of phosphorus oxychloride led to the formation of new heterorings: imidazo[1,2-c]pyrimidine and pyrimido[1,2-c]pyrimidine. The possible antitumor activity of the newly synthesized compounds was evaluated in vitro. The biological tests evidenced that some of them showed pronounced antitumor activity. A study of the structure–activity relationships revealed that the compound activity depended mostly on the nature of the amine fragments. A docking analysis was also performed for the most active compounds.

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ChemInform Abstract: Amino Derivatives of Phenyl Alkyl Thiophene as Inhibitors of Bone Resorption. Structure-Activity Relationship.

ChemInform ◽

10.1002/chin.199852177 ◽

2010 ◽

Vol 29 (52) ◽

pp. no-no

Author(s):

M. WIERZBICKI ◽

M.-F. BOUSSARD ◽

F. SAUVEUR ◽

G. KIRSCH ◽

M. SABATINI ◽

...

Keyword(s):

Bone Resorption ◽

Structure Activity Relationship ◽

Activity Relationship ◽

Structure Activity ◽

Amino Derivatives ◽

Derivatives Of

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Synthesis, Docking Studies into CDK-2 and Anticancer Activity of New Derivatives Based Pyrimidine Scaffold and Their Derived Glycosides

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557519666190312165717 ◽

2019 ◽

Vol 19 (13) ◽

pp. 1093-1110 ◽

Cited By ~ 5

Author(s):

Adel A.H. Abdel Rahman ◽

Ibrahim F. Nassar ◽

Amira K.F. Shaban ◽

Dina S. EL-Kady ◽

Hanem M. Awad ◽

...

Keyword(s):

Anticancer Activity ◽

Human Liver ◽

Docking Studies ◽

Cyclin Dependent Kinase ◽

Binding Interaction ◽

Enzyme Active Site ◽

Human Liver Cancer ◽

Amino Derivatives ◽

Activity Behavior ◽

Derivatives Of

Background & Objective:New diaryl-substituted pyrimidinedione compounds, their thioxo derivatives as well as their bicyclic thiazole compounds were synthesized and characterized.Methods:The glycosylamino derivatives of the synthesized disubstituted derivatives of the pyrimidine scaffold were also prepared via reaction of the N3-amino derivatives with a number of monosaccharides followed by acetylation.Results:The anticancer activity of the synthesized compounds was studied against human liver cancer (HepG2) and RPE-1cell lines. Compounds 2a, 2b, 3a and 12 showed potent activities with IC50 results comparable to that of doxorubicin.Conclusion:Docking investigations into Cyclin-dependent kinase 2 (CDK-2) enzyme, a potential target for cancer medication, were also reported showing the possible binding interaction into the enzyme active site to support their activity behavior.

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Therapeutic Journey of 5-Pyrazolones as a Versatile Scaffold: A Review

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557521999210101224058 ◽

2021 ◽

Vol 21 ◽

Author(s):

Ravinder Sharma ◽

Pooja A. Chawla ◽

Viney Chawla ◽

Rajeev Verma ◽

Nandita Nawal ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Protease Inhibitor ◽

Medicinal Chemistry ◽

Membered Ring ◽

Present Review ◽

Biological Profile ◽

3C Protease ◽

Structure Activity ◽

Derivatives Of ◽

Heterocyclic Moiety

Abstract: A sizeable proportion of currently marketed drugs come from heterocycles. The heterocyclic moiety 5-pyrazolone is well known five membered ring containing nitrogen. Derivatives of this wonder nucleus have exhibited activities as diverse as antimicrobial, anti-inflammatory, analgesic, antidepressant, anticonvulsant, antidiabetic, antihyperlipidemic, antiviral, antitubercular, antioxidant, anticancer and antiviral including action against severe acute respiratory syndrome (SARS) or 3C protease inhibitor. A number of drugs based on this motif have already made it to the market. Standard texts and literature on medicinal chemistry cite different approaches for the synthesis of 5-pyrazolones. The present review provides an insight view to 5-pyrazolone synthesis, their biological profile and structure activity relationship studies.

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Structure-Activity Relationship and Antimicrobial Evaluation of N-Phenylpyrazole Curcumin Derivatives

Current Bioactive Compounds ◽

10.2174/1573407215666190124115010 ◽

2020 ◽

Vol 16 (4) ◽

pp. 481-488

Author(s):

Heli Sanghvi ◽

Satyendra Mishra

Keyword(s):

Antibacterial Activity ◽

Gram Negative Bacteria ◽

Pyrazole Derivatives ◽

Gram Positive ◽

Gram Negative ◽

E Coli ◽

Curcumin Derivatives ◽

Structure Activity ◽

Electron Donating Groups ◽

Derivatives Of

Background: Curcumin, one of the most important pharmacologically significant natural products, has gained significant consideration among scientists for decades since its multipharmacological activities. 1, 3-Dicarbonyl moiety of curcumin was found to be accountable for the rapid degradation of curcumin molecule. The aim of present work is to replace 1, 3-dicarbonyl moiety of curcumin by pyrazole and phenylpyrazole derivatives with a view to improving its stability and to investigate the role of substitution in N-phenylpyrazole curcumin on its antibacterial activity against both Gram-positive as well as Gram-negative bacteria. Methods: Pyrazole derivatives of curcumin were prepared by heating curcumin with phenyhydrazine/ substituted phenyhydrazine derivatives in AcOH. The residue was purified by silica gel column chromatography. Structures of purified compounds were confirmed by 1H NMR and Mass spectroscopy. The synthesized compounds were evaluated for their antibacterial activity by the microdilution broth susceptibility test method against gram positive (S. aureus) and gram negative (E. coli). Results: Effects of substitution in N-phenylpyrazole curcumin derivatives against S. aureus and E. coli were studied. The most active N-(3-Nitrophenylpyrazole) curcumin (12) exhibits twenty-fold more potency against S. aureus (MIC: 10μg/mL)) and N-(2-Fluoroophenylpyrazole) curcumin (5) fivefold more potency against E. coli (MIC; 50 μg/mL) than N-phenylpyrazole curcumin (4). Whereas, a remarkable decline in anti-bacterial activity against S. aureus and E. coli was observed when electron donating groups were incorporated in N-phenylpyrazole curcumin (4). Comparative studies of synthesized compounds suggest the effects of electron withdrawing and electron donating groups on unsubstituted phenylpyrazole curcumin (4). Conclusion: The structure-activity relationship (SAR) results indicated that the electron withdrawing and electron donating at N-phenylpyrazole curcumin played key roles for their bacterial inhibitory effects. The results of the antibacterial evaluation showed that the synthesized pyrazole derivatives of curcumin displayed moderate to very high activity in S. aureus. In conclusion, the series of novel curcumin derivatives were designed, synthesized and tested for their antibacterial activities against S. aureus and E. coli. Among them, N-(3-Nitrophenylpyrazole curcumin; 12) was most active against S. aureus (Gram-positive) and N-(2-Fluoroophenylpyrazole) curcumin (5) against E. coli (Gram-negative) bacteria.

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Thermal cyclocondensations of 3-N(4- and 5-benzimidazolyl and benztriazolyl)amino derivatives of 2-propenoic acid

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19872918 ◽

1987 ◽

Vol 52 (12) ◽

pp. 2918-2925 ◽

Cited By ~ 10

Author(s):

Viktor Milata ◽

Dušan Ilavský

Keyword(s):

Uv Spectra ◽

Propenoic Acid ◽

Amino Derivatives ◽

Derivatives Of ◽

C Nmr ◽

Ir And Uv Spectra

The cyclization of 3-N(4- and 5-benzimidazolyl and benztriazolyl)amino-2-cyano- and 2-ethoxycarbonyl-2-propenoate esters Ia, b-IVa, b under the conditions of the Gould-Jacobs reaction leads to angularly ring-fused substituted imidazo or triazolo[4,5-f] (V, VI) and [4,5-h] (VII, VIII) quinolines, respectively. The esters Vb-VIIIb have been transformed into the corresponding chloroderivatives Vc-VIIIc. 3-N(5-Benzimidazolyl and 5-benztriazolyl)amino-2-cyano-2-propenenitriles are cyclized in the presence of aluminium(III) chloride to give the aminoquinolines Vd, VId. The structure of the products has been characterized by their 1H, 13C NMR, IR, and UV spectra.

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