scholarly journals The Discovery of Novel Selective D1 Dopaminergic Agonists: A-68930, A-77636, A-86929, and ABT-413

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Yvonne Connolly Martin
Keyword(s):  
Medicinal Chemistry ◽  
Partial Agonist ◽  
Skf 38393 ◽  
The Novel ◽  
Bioactive Conformation ◽  
Dopaminergic Agonists ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
A 68930

The novel selective D1 dopaminergic full agonists A-68930, A-77636 were discovered by the synthesis of molecules to probe the bioactive conformation of the partial agonist SKF-38393, by the use of this information to add D1 affinity and selectivity to a screening hit, and by traditional medicinal chemistry exploration of structure-activity relationships. The subsequent design of A-86929 and ABT-413 capitalized on these results, recently disclosed agonists, and traditional medicinal chemistry.

scholarly journals Bicyclic Basic Merbarone Analogues as Antiproliferative Agents

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 557
Author(s):  
Andrea Spallarossa ◽  
Matteo Lusardi ◽  
Chiara Caneva ◽  
Aldo Profumo ◽  
Camillo Rosano ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Side Chain ◽  
The Novel ◽  
Bioactive Conformation ◽  
Pyrimidine Derivatives ◽  
Topoisomerase Iiα ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Step Procedure ◽  
Pyrimidine Moiety

Pyrimido-pyrimidine derivatives have been developed as rigid merbarone analogues. In a previous study, these compounds showed potent antiproliferative activity and efficiently inhibited topoisomerase IIα. To further extend the structure–activity relationships on pyrimido-pyrimidines, a novel series of analogues was synthesized by a two-step procedure. Analogues 3–6 bear small alky groups at positions 1 and 3 of the pyrimido-pyrimidine scaffold whereas at position 6a (4-chloro)phenyl substituent was inserted. The basic side chains introduced at position 7 were selected on the basis of the previously developed structure–activity relationships. The antiproliferative activity of the novel compounds proved to be affected by both the nature of the basic side chain and the substituents on the pyrimido-pyrimidine moiety. Derivatives 5d and 5e were identified as the most promising molecules still showing reduced antiproliferative activity in comparison with the previously prepared pyrimido-pyrimidine analogues. In topoisomerase IIα-5d docking complex, the ligand would poorly interact with the enzyme and assume a different orientation in comparison with 1d bioactive conformation.

scholarly journals Synthesis and structure-activity relationships of the novel isothiobarbamine analogues with lowered basicity

2020 ◽  
Author(s):  
I. A. Novakov ◽  
L. L. Brunilina ◽  
V. V. Chapurkin ◽  
M. B. Nawrozkij ◽  
D. S. Sheikin ◽  
...  
Keyword(s):  
The Novel ◽  
Structure Activity Relationships ◽  
Structure Activity

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

Molecules ◽  
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.

scholarly journals Advances in indoleamine 2,3-dioxygenase 1 medicinal chemistry

MedChemComm ◽  
2017 ◽  
Vol 8 (7) ◽  
pp. 1378-1392 ◽  
Author(s):  
Alice Coletti ◽  
Francesco Antonio Greco ◽  
Daniela Dolciami ◽  
Emidio Camaioni ◽  
Roccaldo Sardella ◽  
...  
Keyword(s):  
Structure Function ◽  
Medicinal Chemistry ◽  
Next Generation ◽  
Structure Activity Relationships ◽  
Indoleamine 2,3 Dioxygenase ◽  
Structure Activity

Structure–function relationships of IDO1 and structure–activity relationships of inhibitors are discussed with an outlook on next generation IDO1 ligand.

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