Design, synthesis and evaluation of racemic 1-(4-hydroxyphenyl)-2-[3-(substituted phenoxy)-2-hydroxy-1-propyl]amino-1-propanol hydrochlorides as novel uterine relaxants.
Novel 1-(4-hydroxyphenyl)-2-[3-(substituted phenoxy)-2-hydroxy-1-propyl]amino-1-propanol hydrochlorides were designed based on the pharmacophore for potent uterine relaxant activity and by utilizing the principles of structural hybridization. The designed molecules were synthesized as racemates by a novel route and were evaluated for uterine relaxant activity in vitro on isolated rat uterus and in vivo in pregnant rats. Their cAMP-releasing potential was studied using rat uterus tissue homogenates by the cAMP [(3)H] assay, and cardiac stimulant potential was evaluated on isolated guinea pig right atrium. All compounds exhibited potent uterine relaxant activity in vitro and produced a significant delay in the onset of labour in pregnant rats; their cAMP-releasing potential was slightly less, while their cardiac stimulant potential was insignificant as compared to isoxsuprine hydrochloride.
Viswanathan
C L
CL
Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai 400 098, India. chelakara_viswanathan@yahoo.com
Kodgule
M M
MM
Chaudhari
A S
AS
D000433:1-Propanol / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D002316:Cardiotonic Agents / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D015195:Drug Design; D005260:Female; D007556:Isoxsuprine / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D014599:Uterus / Q000187:drug effects* / Q000502:physiology
D002316:Cardiotonic Agents; D000433:1-Propanol; D000242:Cyclic AMP; D007556:Isoxsuprine