Synthesis and structure-activity relationships of vasicine analogues as bronchodilatory agents

Article abstract of DOI:10.1007/s00044-006-0141-7

The series of vasicine (1) analogues, an alkaloid from Adhatoda vasica Nees., were synthesized with changes in A, B or C rings. Compounds 3-19 were evaluated for in vitro bronchodilatory activity using isolated guinea pig tracheal chain. Compounds 3-8 were also synthesized in good yields using microwave-mediated synthesis under solvent free conditions. Compounds 5 and 8 with seven-member C ring were more active than etofylline and caused 100% relaxation of both the histamine and acetylcholine pre-contracted guinea pig tracheal chain. The structure-activity relationship studies showed that the quinazoline and oxo functionalities were essential for activity. The compounds without C ring and instead having aliphatic and phenyl substitutions in B ring showed relaxation against histamine pre-contracted tracheal chain only, 2-methyl substituted analogues, 12 and 13, being most active with 100% relaxation effect. Birkhaeuser Boston 2006.

Full text of DOI:10.1007/s00044-006-0141-7

Med Chem Res 14:6 (2005) 347–368
௠ Birkha¨user Boston 2006
DOI: 10.1007/s00044-006-0141-7

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Received:
10-14-05
Accepted:
5-15-06
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