Synthesis, β-adrenergic blocking activity and β-receptor binding affinities of 1-substituted-3-(2-isopropyl-5-methyl-phenoxy)-propan-2-ol oxalates

Dharam Paul Jindal, Mohane S. Coumar, K. Nandakumar, Subhash Laxmanrao Bodhankar, Prasad Gopal Purohit, Kakasaheb Ramoo Mahadik, Giancarlo Bruni, Elga Collavoli, Paola Massarelli

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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 μg/kg, i.v.) and 6 (50 μg/kg, i.v.) antagonized isoprenaline (2 μg/kg, i.v.) induced tachycardia, similar to that of atenolol (CAS 29122-68-7, 20 μg/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 β1- and β2-adrenergic receptor binding assay using turkey erythrocyte membrane (β1) and lung homogenate of rats (β2). Both 5 and 6 showed β-adrenergic receptor affinity comparable with that of propranolol (propranolol hydrochloride, CAS 318-98-9) with out selectivity to any one β-adrenergic receptor. These results suggest that both the compounds possess non-selective β-adrenergic blocking activity, with the tert-butyl derivative 6 being more active than the isopropyl derivative 5.

Original languageEnglish
Pages (from-to)557-562
Number of pages6
JournalFarmaco
Volume58
Issue number8
DOIs
Publication statusPublished - 01-08-2003

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Oxalates
Adrenergic Agents
Adrenergic Receptors
Rats
Electrocardiography
Isoproterenol
Propranolol
Uterus
Thymus Plant
Derivatives
Thymol
Thymus
Atenolol
Erythrocyte Membrane
Tachycardia
Epinephrine
Assays
Pharmacology
Membranes
Lung

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science
  • Drug Discovery

Cite this

Jindal, Dharam Paul ; Coumar, Mohane S. ; Nandakumar, K. ; Bodhankar, Subhash Laxmanrao ; Purohit, Prasad Gopal ; Mahadik, Kakasaheb Ramoo ; Bruni, Giancarlo ; Collavoli, Elga ; Massarelli, Paola. / Synthesis, β-adrenergic blocking activity and β-receptor binding affinities of 1-substituted-3-(2-isopropyl-5-methyl-phenoxy)-propan-2-ol oxalates. In: Farmaco. 2003 ; Vol. 58, No. 8. pp. 557-562.
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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 μg/kg, i.v.) and 6 (50 μg/kg, i.v.) antagonized isoprenaline (2 μg/kg, i.v.) induced tachycardia, similar to that of atenolol (CAS 29122-68-7, 20 μg/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 β1- and β2-adrenergic receptor binding assay using turkey erythrocyte membrane (β1) and lung homogenate of rats (β2). Both 5 and 6 showed β-adrenergic receptor affinity comparable with that of propranolol (propranolol hydrochloride, CAS 318-98-9) with out selectivity to any one β-adrenergic receptor. These results suggest that both the compounds possess non-selective β-adrenergic blocking activity, with the tert-butyl derivative 6 being more active than the isopropyl derivative 5.",
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Jindal, DP, Coumar, MS, Nandakumar, K, Bodhankar, SL, Purohit, PG, Mahadik, KR, Bruni, G, Collavoli, E & Massarelli, P 2003, 'Synthesis, β-adrenergic blocking activity and β-receptor binding affinities of 1-substituted-3-(2-isopropyl-5-methyl-phenoxy)-propan-2-ol oxalates', Farmaco, vol. 58, no. 8, pp. 557-562. https://doi.org/10.1016/S0014-827X(03)00083-1

Synthesis, β-adrenergic blocking activity and β-receptor binding affinities of 1-substituted-3-(2-isopropyl-5-methyl-phenoxy)-propan-2-ol oxalates. / Jindal, Dharam Paul; Coumar, Mohane S.; Nandakumar, K.; Bodhankar, Subhash Laxmanrao; Purohit, Prasad Gopal; Mahadik, Kakasaheb Ramoo; Bruni, Giancarlo; Collavoli, Elga; Massarelli, Paola.

In: Farmaco, Vol. 58, No. 8, 01.08.2003, p. 557-562.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Synthesis, β-adrenergic blocking activity and β-receptor binding affinities of 1-substituted-3-(2-isopropyl-5-methyl-phenoxy)-propan-2-ol oxalates

AU - Jindal, Dharam Paul

AU - Coumar, Mohane S.

AU - Nandakumar, K.

AU - Bodhankar, Subhash Laxmanrao

AU - Purohit, Prasad Gopal

AU - Mahadik, Kakasaheb Ramoo

AU - Bruni, Giancarlo

AU - Collavoli, Elga

AU - Massarelli, Paola

PY - 2003/8/1

Y1 - 2003/8/1

N2 - 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 μg/kg, i.v.) and 6 (50 μg/kg, i.v.) antagonized isoprenaline (2 μg/kg, i.v.) induced tachycardia, similar to that of atenolol (CAS 29122-68-7, 20 μg/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 β1- and β2-adrenergic receptor binding assay using turkey erythrocyte membrane (β1) and lung homogenate of rats (β2). Both 5 and 6 showed β-adrenergic receptor affinity comparable with that of propranolol (propranolol hydrochloride, CAS 318-98-9) with out selectivity to any one β-adrenergic receptor. These results suggest that both the compounds possess non-selective β-adrenergic blocking activity, with the tert-butyl derivative 6 being more active than the isopropyl derivative 5.

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