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Indian Journal of Chemistry -Section B (IJC-B) >
IJC-B Vol.44B [2005] >
IJC-B Vol.44B(07) [July 2005] >
| Title: | Synthesis of 4-(benzamide)-and 4- (phthalimide)-substituted phenoxypropanolamines and their  1-, 2-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 |
| IPC Code: | Int.Cl.7 C 07 D |
| Abstract: | N-[4-(2-Hydroxy-3-isopropylaminopropoxy)phenyl]-1-oxo-isoindoline 3 possess a cardioselective -adrenergic receptor binding affinity. Herein we attempted to
synthesize the unreduced compound N-[4-(2-hydroxy-3-isopropylaminopropoxy)phenyl]phthalimide
4. But, reaction of N-[4-(2,3-epoxypropoxy)phenyl]phthalimide
10 with isopropylamine opened the
phthalimide ring to give N-[4-(2-hydroxy-3-isopropylaminopropoxy)phenyl]-2-isopropylcarbamoylbenzamide
12 instead of 4 as expected. While treatment of 10 with tert-butylamine
gives N-[4-(3-tert-butylamino-2-hydroxypropoxy)phenyl]phthalimide 15. Further, reaction of 15 with isopropylamine opened the
phthalimide ring to yield N-[4-(3-tert-butylamino-2-hydroxypropoxy)phenyl]-2-isopropylcarbamoylbenzamide
16. Also, reaction of N-[4-(2,3-epoxypropoxy)phenyl]-5,6-dimethoxyphthalimide
11 with isopropylamine affords the
phthalimide ring opened analogue N-[4-(2-hydroxy-3-isopropylaminopropoxy)phenyl]-2-isopropylcarbamoyl-5,6-dimethoxybenzamide 13. Compounds 12, 13, 15 and 16 have been tested for their in
vitro 1-
and 2-adrenergic
receptor binding affinity using turkey erythrocyte membrane (1) and lung homogenate of rats (2). The percentage inhibition of [3H]DHA
binding to both 1-
and 2-adrenergic
receptors are compared with that of the standard non-selective -adrenergic blocking agent propranolol 1 and selective agent atenolol. All the tested compounds exhibit
binding affinity to 1-adrenergic receptors at the tested concentration [10-5
M] and most of them (12, 15, 16) exhibit cardioselectivity (selectivity ratio > 1). The dimethoxy analogue 13
shows selectivity towards 2-adrenergic receptor (selectivity ratio < 1). |
| Page(s): | 1441-1445 |
| ISSN: | 0975-0983(Online); 0376-4699(Print) |
| Source: | IJC-B Vol.44B(07) [July 2005]
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