Synthesis and bronchodilatory activity of some nitrogen bridgehead compounds.
A series of tricyclic nitrogen bridgehead compounds 7-22 have been synthesised and evaluated for their in vitro bronchodilatory activity using isolated guinea pig tracheal chain, precontracted with acetylcholine. The relaxant effect of 2,3,4,5-tetrahydroazepino[2,1-b]-8,9-dimethoxyquinazolin-11(1H)-one (7) (DPJ-386) was greater than that of theophylline, aminophylline and quinazoline derivative 3, which lacks methoxy groups at positions 8 and 9. Various nitrogen containing functionalities such as benzylamino, acetamido, benzamido and phthalimido were also introduced at 9 position of 3. This resulted in loss of relaxation activity in precontracted guinea pig tracheal chain. These results show that the better relaxation property possessed by compound 7 hydrochloride is due to methoxy groups at 8 and 9 positions.
Jindal
Dharam Paul
DP
University Institute of Pharmaceutical Sciences (formerly Department of Pharmaceutical Sciences), Panjab University, Chandigarh 160 014, India. dharampjindal@yahoo.co.in
Bhatti
Ravinder Singh
RS
Ahlawat
Seema
S
Gupta
Ranju
R
D000109:Acetylcholine; D000818:Animals; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D009584:Nitrogen / Q000737:chemistry*; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects*
C470127:2,3,4,5-tetrahydroazepino(2,1-b)-8,9-dimethoxyquinazolin-11(1H)-one; D001952:Bridged-Ring Compounds; D001993:Bronchodilator Agents; D011799:Quinazolines; D009584:Nitrogen; D000109:Acetylcholine