Please use this identifier to cite or link to this item: http://nopr.niscair.res.in/handle/123456789/9138
Title: Synthesis of 4-(benzamide)-and 4- (phthalimide)-substituted phenoxypropanolamines and their <img src='/image/spc_char/beta.gif' border=0><sub>1</sub>-, <img src='/image/spc_char/beta.gif' border=0><sub>2</sub>-adrenergic receptor binding studies
Authors: Jindal, Dharam Paul
Singh, Babita
Coumar, Mohane Selvaraj
Keywords: Phenoxypropanolamines
isoindoline
adrenergic receptor
4-benzamide
4-phthalimide
Issue Date: Jul-2005
Publisher: CSIR
Series/Report no.: <b>Int</b>.<b>Cl</b>.<b><sup>7</sup> C 07 D</b>
Abstract: <i style="">N</i>-[4-(2-Hydroxy-3-isopropylaminopropoxy)phenyl]-1-oxo-isoindoline <b style="">3</b> possess a cardioselective <img src='/image/spc_char/beta.gif' border=0>-adrenergic receptor binding affinity. Herein we attempted to synthesize the unreduced compound <i style="">N</i>-[4-(2-hydroxy-3-isopropyl­aminopropoxy)phenyl]phthalimide <b style="">4</b>. But, reaction of <i style="">N</i>-[4-(2,3-epoxypropoxy)phenyl]phthalimide <b style="">10</b> with isopropyl­amine opened the phthalimide ring to give <i style="">N</i>-[4-(2-hydroxy-3-isopropylaminopropoxy)phenyl]-2-isopropylcarbamoylbenzamide <b style="">12</b> instead of <b style="">4 </b>as expected. While treatment of <b style="">10</b> with <i style="">tert</i>-butylamine gives <i style="">N</i>-[4-(3-<i style="">tert</i>-butylamino-2-hydroxy­pro­poxy)phenyl]phthalimide <b style="">15</b>. Further, reaction of <b style="">15</b> with isopropylamine opened the phthalimide ring to yield <i style="">N</i>-[4-(3-<i style="">tert</i>-butylamino-2-hydroxypropoxy)phenyl]-2-isopropylcarbamoylbenzamide <b style="">16</b>. Also, reaction of <i style="">N</i>-[4-(2,3-epoxy­pro­poxy)­phenyl]-5,6-dimethoxyphthalimide <b style="">11</b> with isopropylamine affords the phthalimide ring opened analogue <i style="">N</i>-[4-(2-hydroxy-3-isopropylaminopropoxy)phenyl]-2-isopropylcarbamoyl-5,6-dimethoxybenzamide<b style=""> 13</b>. Compounds <b style="">12</b>, <b style="">13</b>, <b style="">15 </b>and <b style="">16 </b>have been tested for their <i style="">in vitro</i> <img src='/image/spc_char/beta.gif' border=0><sub>1</sub>- and <img src='/image/spc_char/beta.gif' border=0><sub>2</sub>-adrenergic receptor binding affinity using turkey erythrocyte membrane (<img src='/image/spc_char/beta.gif' border=0><sub>1</sub>) and lung homogenate of rats (<img src='/image/spc_char/beta.gif' border=0><sub>2</sub>). The percentage inhibition of [<sup>3</sup>H]DHA binding to both <img src='/image/spc_char/beta.gif' border=0><sub>1</sub>- and <img src='/image/spc_char/beta.gif' border=0><sub>2</sub>-adrenergic receptors are compared with that of the standard non-selective <img src='/image/spc_char/beta.gif' border=0>-adrenergic blocking agent propranolol <b style="">1</b> and selective agent atenolol. All the tested compounds exhibit binding affinity to <img src='/image/spc_char/beta.gif' border=0><sub>1</sub>-adrenergic receptors at the tested concentration [10<sup>-5</sup> M] and most of them (<b style="">12</b>, <b style="">15</b>, <b style="">16</b>) exhibit cardioselectivity (selectivity ratio > 1). The dimethoxy analogue <b style="">13 </b>shows selectivity towards <img src='/image/spc_char/beta.gif' border=0><sub>2</sub>-adrenergic receptor (selectivity ratio < 1).
Description: 1441-1445
URI: http://hdl.handle.net/123456789/9138
ISSN: 0975-0983(Online); 0376-4699(Print)
Appears in Collections:IJC-B Vol.44B(07) [July 2005]

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