1026273-07-3Relevant academic research and scientific papers
Synthesis, biological activity and conformational study of 1,4- benzoxazine derivatives as potassium channel modulators
Caliendo, Giuseppe,Grieco, Paolo,Perissutti, Elisa,Santagada, Vincenzo,Santini, Antonello,Albrizio, Stefania,Fattorusso, Caterina,Pinto, Aldo,Sorrentino, Raffaella
, p. 957 - 967 (1998)
With the aim of discovering new molecules with K+-channel activating properties, we have synthesized derivatives of cromakalim (CRK), an important molecule which shows specific affinity towards K+ channels, by replacing the benzopyrane ring of this reference compound with a 1,4-benzoxazine moiety. A different number of substituents showing a good discrimination between hydrophobic and electronic properties have been inserted at the 6-position of the 1,4-benzoxazine ring. We describe here the synthesis and discuss the solid state conformation of these new molecules. When tested on rat aorta ring precontracted with phenylephrine, two compounds (2c and 2d) showed a concentration-dependent relaxation similar to that measured for cromakalim but less potent than this reference drug.
Synthesis by microwave irradiation of a substituted benzoxazine parallel library with preferential relaxant activity for guinea pig trachealis
Caliendo, Giuseppe,Perissutti, Elisa,Santagada, Vincenzo,Fiorino, Ferdinando,Severino, Beatrice,Cirillo, Donatella,D'Emmanuele Di Villa Bianca, Roberta,Lippolis, Laura,Pinto, Aldo,Sorrentino, Raffaella
, p. 815 - 826 (2007/10/03)
An efficient, facile, and practical parallel combinatorial synthesis of substituted-benzoxazines under microwave irradiation was described. The procedure involved the use of a microwave oven especially designed for organic synthesis suitable for parallel synthesis of solution libraries. A demonstration 19-membered library of substituted N,N-dimethyl- and N-methyl-benzoxazine amide derivatives, structurally related to the potassium channel opener cromakalim, was generated by both conventional and microwave procedures, achieving a reduction from 7 h to 30-36 min in library generation time for the microwave approach. All the synthesized compounds were tested using the in vitro models of rat aorta and guinea pig trachea rings pre-contracted with phenylephrine and carbachol, respectively. All N,N-dimethyl amide derivatives showed a relaxant activity higher on guinea pig trachea rings than on rat aorta rings.
Synthesis and vasorelaxant activity of new 1,4-benzoxazine derivatives potassium channel openers
Caliendo, Giuseppe,Perissutti, Elisa,Santagada, Vincenzo,Fiorino, Ferdinando,Severino, Beatrice,Di Villa Bianca, Roberta d'Emmanuele,Lippolis, Laura,Pinto, Aldo,Sorrentino, Raffaella
, p. 2663 - 2669 (2007/10/03)
As part of a search for new potassium channel openers, the synthesis and vasorelaxant activity of new 1,4-benzoxazine derivatives derived from transformation of the benzopyran skeleton of cromakalim were described. Several new 1,4-benzoxazine derivatives were provided with significant vasorelaxant activity with an overall pharmacological behavior similar to CRK (1f, 1i, 2d, 2e, 2f and 2i).
