title: Synthesis, beta-adrenergic blocking activity and beta-receptor binding affinities of 1-substituted-3-(2-isopropyl-5-methyl-phenoxy)-propan-2-ol oxalates.
abstract: The compounds 1-isopropylamino-3-(2-isopropyl-5-methyl-phenoxy)-propan-2-ol oxalate (5) and 1-tert-butylamino-3-(2-isopropyl-5-methyl-phenoxy)-propan-2-ol oxalate (6) were synthesized from thymol (1), a naturally occurring agent in Thymus vulgaris L. Pharmacological evaluation of 5 and 6 were carried out using mouse ECG and isolated rat uterus models. Pretreatment of 5 (100 microg/kg, i.v.) and 6 (50 microg/kg, i.v.) antagonized isoprenaline (2 microg/kg, i.v.) induced tachycardia, similar to that of atenolol (CAS 29122-68-7, 20 microg/kg, i.v.) pretreatment in mouse ECG experiments as measured by R-R interval. Pretreatment of 5 and 6 blocked isoprenaline and adrenaline induced relaxation of isolated rat uterus (unprimed). Also the compounds 5 and 6 were subjected to in vitro beta1- and beta2-adrenergic receptor binding assay using turkey erythrocyte membrane (beta1) and lung homogenate of rats (beta2). Both 5 and 6 showed beta-adrenergic receptor affinity comparable with that of propranolol (propranolol hydrochloride, CAS 318-98-9) with out selectivity to any one beta-adrenergic receptor. These results suggest that both the compounds possess non-selective beta-adrenergic blocking activity, with the tert-butyl derivative 6 being more active than the isopropyl derivative 5.
authors.affiliation: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India. dharampjindal@yahoo.co.in
authors.forename: Dharam Paul
authors.initials: DP
authors.lastname: Jindal
authors.forename: Mohane S
authors.initials: MS
authors.lastname: Coumar
authors.forename: K
authors.initials: K
authors.lastname: Nandakumar
authors.forename: Subhash Laxmanrao
authors.initials: SL
authors.lastname: Bodhankar
authors.forename: Prasad Gopal
authors.initials: PG
authors.lastname: Purohit
authors.forename: Kakasaheb Ramoo
authors.initials: KR
authors.lastname: Mahadik
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Bruni
authors.forename: Elga
authors.initials: E
authors.lastname: Collavoli
authors.forename: Paola
authors.initials: P
authors.lastname: Massarelli
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001667:Binding, Competitive; D004562:Electrocardiography / Q000187:drug effects; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D010070:Oxalates / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D020005:Propanols / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D013943:Thymol / Q000737:chemistry; D046930:Thymus Plant / Q000737:chemistry; D014599:Uterus / Q000187:drug effects
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D010070:Oxalates; D020005:Propanols; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D013943:Thymol; D001262:Atenolol; D007545:Isoproterenol