Abstract:
:Several analogues of cirazoline (2), a selective alpha1-adrenoreceptor agonist, were prepared and their pharmacological profiles studied. Although at the alpha1-adrenoreceptor all the compounds displayed a significant agonist activity, at the alpha2-adrenoreceptor they showed either agonist or antagonist activity depending on the nature of the phenyl substituent. The qualitative structure-activity relationship led us to the conclusion that the oxygen atom in the side-chain is essential for alpha1-agonist activity, while the cyclopropyl ring is not, and may be replaced by several groups. Of the groups studied, isopropoxy appears to be the best. Instead, the same substitution (i.e., isopropoxy for the cyclopropyl ring) at alpha2-adrenoreceptors causes a reversal of activity. On the other hand, the cyclopropyl ring seems to be important for alpha1-selectivity. Compound 20 is the most potent alpha1-agonist of the series, being equiactive with cirazoline on rat vas deferens and in pithed rat.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Pigini M,Quaglia W,Gentili F,Marucci G,Cantalamessa F,Franchini S,Sorbi C,Brasili Ldoi
10.1016/s0968-0896(00)00030-4subject
Has Abstractpub_date
2000-05-01 00:00:00pages
883-8issue
5eissn
0968-0896issn
1464-3391pii
S0968-0896(00)00030-4journal_volume
8pub_type
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