17433-19-1Relevant articles and documents
Conformation of N,N′-bis(3-pyridylformyl)piperazine and spontaneous formation of a saturated quadruple stranded metallohelicate
Sahoo, Himansu Sekhar,Chand, Dillip Kumar
, p. 7223 - 7225 (2010)
Ligand N,N′-bis(3-pyridylformyl)piperazine, L1, exists in syn and anti conformers in solution state almost in equal proportion. Formation of a saturated quadruple stranded helicate is observed when Pd(NO 3)2 is reacted with ligand L1. In the complexed form the ligand exists in a flattened boat conformation with anti form.
Synthesis and biological evaluation of heteroaryldiamides and heteroaryldiamines as cytotoxic agents, apoptosis inducers and caspase-3 activators
Echeverria, Mikel,Mendivil, Beatriz,Cordeu, Lucia,Cubedo, Elena,Garcia-Foncillas, Jesus,Font, Maria,Sanmartin, Carmen,Palop, Juan Antonio
, p. 182 - 192 (2007/10/03)
The work described here involved the synthesis and biological evaluation of new heteroaryldiamides and heteroaryldiamines. A new general model in which the structures can be adjusted has been applied in this study. Three different structural units can be distinguished: a central nucleus and two symmetric terminal units. The central element is either an aliphatic chain of varying length and flexibility, piperazine, or a polyamine nucleus. However, the terminal units are pyridine, quinoline, indole, benzene or pyrido[2,3-d] pyrimidine with different substituents. The antitumoural activities of the compounds were evaluated in vitro by examining their cytotoxic effects against human breast, colon, and bladder cancer cell lines. Compounds that showed cytotoxic activity were subjected to both apoptosis and caspase-3 assays. With regard to selectivity, the cytotoxicity was also determined in cell cultures of two nontumoural lines. The most promising compounds are 4c, 5c and 7, which are amino-pyridinium, quinolyl-N-oxide, and pyridyl derivatives, respectively, and these reveal a significant in vitro cytotoxicity in at least two of the three cell lines tested. These compounds induced apoptosis and also produced a rapid dose-dependent increase in the caspase-3 level in HT-29 cells. Other encouraging profiles were found, such as those presented by 1k and 8d, which are cytotoxic and apoptotic but do not provoke an increase in the level of caspase-3, or those presented by 2f, 3c and 4a, which are slightly cytotoxic but do not show any other significant activity. The different types of behaviour of each compound are not necessarily parallel in the three cell lines tested.
Design and synthesis of piperidine-3-carboxamides as human platelet aggregation inhibitors
Zheng,Salgia,Thompson,Dillingham,Bond,Feng,Prasad,Gollamudi
, p. 180 - 188 (2007/10/02)
A detailed structure-activity analysis was carried out using eight 1- alkyl(aralkyl)nipecotamides (type 5), 33 bis-nipecotamidoalkanes and aralkanes (type 6), and 7 N,N'-bis(nipecotoyl)-piperazines (type 7) as inhibitors of human platelet aggregation. Steric factors played an important role in determining the activity of type 5 compounds possessing an appropriate degree of hydrophobic character. Types 6 and 7 compounds were more potent than the corresponding type 5 molecules. Hydrophobic character appeared to influence the activity of type 6 compounds. A 3-substituent on the piperidine ring was necessary for antiplatelet activity; the substituent should be preferably an amide with its C attached directly to the ring. 3,5- Disubstitution and 2-substitution led to a decline in activity. Optimal activity was attained when the two nipecotoyl ring N atoms were connected by an aralkyl group, and separated by ~7 ?. It is suggested that van der Waals forces and π interactions may govern the inhibitor-platelet interaction. The most potent type 6 inhibitor was α,α'-bis[3-(N-ethyl-N- butylcarbamoyl)piperidino]-p-xylene (6i). The most potent type 5 compound was 1-decyl-3-(N,N-diethylcarbamoyl)piperidine (5a). Any substitution on the piperazine ring of type 7 compounds led to a decline in activity, the most active analog being N,N'-bis(1-decylnipecotoyl)piperazine (7a). It is suggested that nipecotamides interact with anionic platelet sites located 7 ? from each other and connected by a hydrophobic well.
