Synthesis by microwave irradiation of a substituted benzoxazine parallel library with preferential relaxant activity for guinea pig trachealis.
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.
Caliendo
Giuseppe
G
Dipartimento di Chimica Farmaceutica e Tossicologica, Università di Napoli Federico II, Via D. Montesano 49, 80131 Naples, Italy. caliendo@unina.it
Perissutti
Elisa
E
Santagada
Vincenzo
V
Fiorino
Ferdinando
F
Severino
Beatrice
B
Cirillo
Donatella
D
di Villa Bianca
Roberta d'Emmanuele
Rd
Lippolis
Laura
L
Pinto
Aldo
A
Sorrentino
Raffaella
R
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D048588:Benzoxazines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000528:radiation effects*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008872:Microwaves; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D048588:Benzoxazines