Cytostatic 6-Arylpurine Nucleosides III. Synthesis and Structure-Activity Relationship Study in Cytostatic Activity of 6-Aryl-, 6-Hetaryl- and 6-Benzylpurine Ribonucleosides

2001 ◽  
Vol 66 (3) ◽  
pp. 483-499 ◽  
Author(s):  
Michal Hocek ◽  
Antonín Holý ◽  
Ivan Votruba ◽  
Hana Dvořáková
Keyword(s):  
Cross Coupling ◽  
Structure Activity Relationship ◽  
Cytostatic Activity ◽  
Activity Relationship ◽  
Coupling Reactions ◽  
Arylboronic Acids ◽  
Cross Coupling Reactions ◽  
Structure Activity ◽  
Relationship Study

A series of fifteen 6-aryl-, 6-hetaryl- and 6-benzylpurine ribonucleosides has been prepared by Pd-catalyzed cross-coupling reactions of 6-chloro-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)- purine with arylboronic acids, hetarylzinc halides, hetarylstannanes or benzylzinc halides followed by deprotection. Structure-activity relationship study revealed that besides 6-(4-substituted phenyl)purine nucleosides, also some 6-hetaryl- and 6-benzylpurine ribonucleosides possess considerable cytostatic activity.

Inhibition of Functionalized 1,3-Dienes against Trypanosoma cruzi

2005 ◽  
Vol 60 (5-6) ◽  
pp. 415-420
Author(s):  
Aivlé Cabrera ◽  
Diana Henríquez ◽  
Thamara Bustos ◽  
Julio Herrera ◽  
Neudo Urdaneta
Keyword(s):  
Trypanosoma Cruzi ◽  
Cross Coupling ◽  
Vero Cells ◽  
Structure Activity Relationship ◽  
Palladium Complexes ◽  
Activity Relationship ◽  
Coupling Reactions ◽  
Cross Coupling Reactions ◽  
Structure Activity ◽  
Diphenyltetrazolium Bromide

Six functionalized 1,3-dienes were synthesized using cross-coupling reactions, catalyzed by palladium complexes, between alkenylboronic acids and α-bromo-α,β-unsaturated carbonylic compounds. Their cytotoxicity against epimastigotes of Trypanosoma cruzi and fibroblastic Vero cells was evaluated, using concentrations ranging from 100 μm to 2.5 mм in experiments with three incubation times (4, 8 and 16 h). These tests were performed using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] colorimetric bioassays and its further reduction to formazan, according to the viability of the parasites and cells. With the exception of (5E,6E)-5-benzylidene-2-methylundec-6-en-4-one, all compounds were cytotoxic to both Trypanosoma cruzi and Vero cells, however differential values of IC50 were observed for two of these compounds. A possible structure-activity relationship is discussed.

C–H activation enables a rapid structure–activity relationship study of arylcyclopropyl amines for potent and selective LSD1 inhibitors

2016 ◽  
Vol 14 (36) ◽  
pp. 8576-8585 ◽  
Author(s):  
Shin Miyamura ◽  
Misaho Araki ◽  
Yosuke Ota ◽  
Yukihiro Itoh ◽  
Shusuke Yasuda ◽  
...  
Keyword(s):  
Cross Coupling ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Structure Activity ◽  
Relationship Study ◽  
Coupling Sequence

Potent and selective LSD1 inhibitors were synthesized rapidly by a C–H borylation and cross-coupling sequence.

Synthesis of Acyclic Nucleotide Analogues Derived from 2-Amino-6-C-substituted Purines via Cross-Coupling Reactions of 2-Amino-9-{2-[(diisopropoxyphosphoryl)methoxy]ethyl}-6-halopurines with Diverse Organometallic Reagents

2000 ◽  
Vol 65 (8) ◽  
pp. 1357-1373 ◽  
Author(s):  
Michal Česnek ◽  
Michal Hocek ◽  
Antonín Holý
Keyword(s):  
Ion Exchange ◽  
Cross Coupling ◽  
Ion Exchange Chromatography ◽  
Exchange Chromatography ◽  
Cytostatic Activity ◽  
Coupling Reactions ◽  
Nucleotide Analogues ◽  
Organometallic Reagents ◽  
Arylboronic Acids ◽  
Cross Coupling Reactions

Cross-coupling reactions of 2-amino-6-chloro-9-{2-[(diisopropoxyphosphoryl)methoxy]ethyl}purine (1) and 2-amino-9-{2-[(diisopropoxyphosphoryl)methoxy]ethyl}-6-iodopurine (2) with diverse types of organometallic reagents have been studied. Arylboronic acids reacted with 1 to give the corresponding 2-amino-6-arylpurines 3a-3d in good yields. Analogously, trialkylaluminium reagents were used for the preparation of 6-alkyl-2-aminopurines 3k and 3l from 1. Hetarylzinc halides and hetarylstannanes required the use of 2-amino-6-iodopurine 2 to give the corresponding 2-amino-6-hetarylpurines 3e-3j in fair to good yields. A CuI/KF mediated coupling of perfluoroalkylsilanes with 2 afforded the 2-amino-6-perfluoroalkylpurines 3m and 3n in moderate yields. Cleavage of the esters 3 with bromo(trimethyl)silane gave the target free phosphonates 4 that were purified by ion- exchange chromatography. The title compounds were tested on antiviral and cytostatic activity.

Cytostatic 6-Arylpurine Nucleosides II. Synthesis of Sugar-Modified Derivatives: 9-(2-Deoxy-β-D-erythro-pentofuranosyl)-, 9-(5-Deoxy-β-D-ribofuranosyl)- and 9-(2,3-Dihydroxypropyl)-6-phenylpurines

2000 ◽  
Vol 65 (11) ◽  
pp. 1683-1697 ◽  
Author(s):  
Michal Hocek ◽  
Antonín Holý ◽  
Ivan Votruba ◽  
Hana Dvořáková
Keyword(s):  
Cross Coupling ◽  
Cytostatic Activity ◽  
Coupling Reactions ◽  
Cross Coupling Reactions ◽  
Highly Active ◽  
Phenylboronic Acids

9-(2-Deoxy-β-D-erythro-pentofuranosyl)-6-(4-substituted phenyl)purines, 9-(5-deoxy-β-D-ribofuranosyl)-6-(4-substituted phenyl)purines and 9-(2,3-dihydroxypropyl)-6-(4-substituted phenyl)purines were prepared by the Suzuki-Miyaura cross-coupling reactions of the corresponding protected 9-substituted 6-chloropurines with substituted phenylboronic acids followed by MeONa mediated deprotection. In contrast to the highly active 6-phenylpurine ribonucleosides, the title compounds did not show any considerable cytostatic activity.

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