1980 Award in medicinal chemistry. Medicinal chemistry and dynamic structure-activity analysis in the discovery of drugs acting at histamine H2 receptors

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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A Structure–Activity Analysis of Biased Agonism at the Dopamine D2 Receptor

Journal of Medicinal Chemistry ◽

10.1021/jm401318w ◽

2013 ◽

Vol 56 (22) ◽

pp. 9199-9221 ◽

Cited By ~ 63

Author(s):

Jeremy Shonberg ◽

Carmen Klein Herenbrink ◽

Laura López ◽

Arthur Christopoulos ◽

Peter J. Scammells ◽

...

Keyword(s):

Dopamine D2 Receptor ◽

D2 Receptor ◽

Activity Analysis ◽

Biased Agonism ◽

Dopamine D2 ◽

Structure Activity

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Clinanthus microstephium , an Amaryllidaceae Species with Cholinesterase Inhibitor Alkaloids: Structure−Activity Analysis of Haemanthamine Skeleton Derivatives

Chemistry & Biodiversity ◽

10.1002/cbdv.201800662 ◽

2019 ◽

Vol 16 (5) ◽

pp. e1800662

Author(s):

Tonino G. Adessi ◽

José L. Borioni ◽

Natalia B. Pigni ◽

Jaume Bastida ◽

Valeria Cavallaro ◽

...

Keyword(s):

Cholinesterase Inhibitor ◽

Activity Analysis ◽

Structure Activity

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Synthesis, Antiprotozoal Activity, and Cheminformatic Analysis of 2-Phenyl-2H-Indazole Derivatives

Molecules ◽

10.3390/molecules26082145 ◽

2021 ◽

Vol 26 (8) ◽

pp. 2145

Author(s):

Karen Rodríguez-Villar ◽

Lilián Yépez-Mulia ◽

Miguel Cortés-Gines ◽

Jacobo David Aguilera-Perdomo ◽

Edgar A. Quintana-Salazar ◽

...

Keyword(s):

Phenyl Ring ◽

Medicinal Chemistry ◽

Structural Features ◽

Pharmacological Properties ◽

Antiprotozoal Activity ◽

One Pot ◽

Biological Assays ◽

Structure Activity Relationships ◽

Structure Activity ◽

Synthetic Methodologies

Indazole is an important scaffold in medicinal chemistry. At present, the progress on synthetic methodologies has allowed the preparation of several new indazole derivatives with interesting pharmacological properties. Particularly, the antiprotozoal activity of indazole derivatives have been recently reported. Herein, a series of 22 indazole derivatives was synthesized and studied as antiprotozoals. The 2-phenyl-2H-indazole scaffold was accessed by a one-pot procedure, which includes a combination of ultrasound synthesis under neat conditions as well as Cadogan’s cyclization. Moreover, some compounds were derivatized to have an appropriate set to provide structure-activity relationships (SAR) information. Whereas the antiprotozoal activity of six of these compounds against E. histolytica, G. intestinalis, and T. vaginalis had been previously reported, the activity of the additional 16 compounds was evaluated against these same protozoa. The biological assays revealed structural features that favor the antiprotozoal activity against the three protozoans tested, e.g., electron withdrawing groups at the 2-phenyl ring. It is important to mention that the indazole derivatives possess strong antiprotozoal activity and are also characterized by a continuous SAR.

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