N-[4-(2-Hydroxy-3-isopropylaminopropoxy)phenyl-l-oxo-isoindoline 3 possess a cardioselective beta-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]plithalimide 10 with isopropylamine opened the phthalimide ring to give N-[4-(2-hydroxy-3-isopropylaminopeopoxy)phenyll-2-isopropylcarbamoylbenzainide 12 instead of 4 as expected. While treatment of 10 with tert-buitylamine gives N-[4-(3-tert-butylamino-2-hydroxypropoxy)phenyllphthalimide 15. Further, reaction of 15 with isopropylamine opened the phtlialimide ring to yield N-[4-(3-tertbutylamino-2-hydroxypropoxy)phenyl]-2-isopropylearbainoylbenzamide 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-hydroxy3-isopropylaminopropoxy)phenyl]-2-isopropylcarbamoyl-5,6-dimethoxybeiizamide 13. Compounds 12, 13, 15 and 16 have been tested for their in vitro beta(1)- and beta(2)-adrenergic receptor binding affinity using turkey erythrocyte-membrane (01) and lung homogenate of rats (beta(2)). The percentage inhibition of [H-3]DHA binding to both beta(1)-and beta(2)-adrenergic receptors are compared with that of the standard non-selective beta-adrenergic blocking agent propranolol 1 and selective agent atenolol. All the tested compounds exhibit binding affinity to PI-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 beta(2)-adrenergic receptor (selectivity ratio < 1).

Jindal, D.P., Singh, B., Coumar, M.S., Bruni, G., & Massarelli, P. (2005). Synthesis of 4-(benzamide)- and 4-(phthalimide)-substituted phenoxypropanolamines and their beta1, beta2-adrenergic receptors binding studies. INDIAN JOURNAL OF CHEMISTRY. SECTION B, ORGANIC CHEMISTRY, INCLUDING MEDICAL CHEMISTRY, 44(7), 1441-1445.

Synthesis of 4-(benzamide)- and 4-(phthalimide)-substituted phenoxypropanolamines and their beta1, beta2-adrenergic receptors binding studies

BRUNI, GIANCARLO;MASSARELLI, PAOLA
2005

Abstract

N-[4-(2-Hydroxy-3-isopropylaminopropoxy)phenyl-l-oxo-isoindoline 3 possess a cardioselective beta-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]plithalimide 10 with isopropylamine opened the phthalimide ring to give N-[4-(2-hydroxy-3-isopropylaminopeopoxy)phenyll-2-isopropylcarbamoylbenzainide 12 instead of 4 as expected. While treatment of 10 with tert-buitylamine gives N-[4-(3-tert-butylamino-2-hydroxypropoxy)phenyllphthalimide 15. Further, reaction of 15 with isopropylamine opened the phtlialimide ring to yield N-[4-(3-tertbutylamino-2-hydroxypropoxy)phenyl]-2-isopropylearbainoylbenzamide 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-hydroxy3-isopropylaminopropoxy)phenyl]-2-isopropylcarbamoyl-5,6-dimethoxybeiizamide 13. Compounds 12, 13, 15 and 16 have been tested for their in vitro beta(1)- and beta(2)-adrenergic receptor binding affinity using turkey erythrocyte-membrane (01) and lung homogenate of rats (beta(2)). The percentage inhibition of [H-3]DHA binding to both beta(1)-and beta(2)-adrenergic receptors are compared with that of the standard non-selective beta-adrenergic blocking agent propranolol 1 and selective agent atenolol. All the tested compounds exhibit binding affinity to PI-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 beta(2)-adrenergic receptor (selectivity ratio < 1).
Jindal, D.P., Singh, B., Coumar, M.S., Bruni, G., & Massarelli, P. (2005). Synthesis of 4-(benzamide)- and 4-(phthalimide)-substituted phenoxypropanolamines and their beta1, beta2-adrenergic receptors binding studies. INDIAN JOURNAL OF CHEMISTRY. SECTION B, ORGANIC CHEMISTRY, INCLUDING MEDICAL CHEMISTRY, 44(7), 1441-1445.
File in questo prodotto:
File Dimensione Formato  
IJCB 2005, 44B(7) 1441-1445.pdf

non disponibili

Tipologia: Post-print
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 55.89 kB
Formato Adobe PDF
55.89 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11365/34664
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo