Abstract:
:A series of N-aryl heteroarylisopropanolamines in which an indole or a 3-arylpyrrole moiety was linked to an aryl group through an isopropanolamine linker, were designed and synthesized as potential anti-HIV-1-PR agents. Series was tested for their ability in blocking PR activity. As a rule, indole derivatives of class 1 exhibited more potency than pyrrole analogues of class 2 while tert-butylamide substituents increased anti-PR potency. In fact, bis tert-butylamide 1e showed the highest activity with IC(50)=25 microM. Even if not very potent, a simple class of anti-PR agents, with a facile synthetic pathway was discovered. QSAR studies on isopropanolamines 1 and 2 were performed in comparison with diarylbutanols, a new class of non peptidic anti-PR agents, recently discovered by Agouron Pharmaceuticals. QSAR and CoMFA models based on 30 diarylbutanols used as a training set were developed. The obtained models were used to investigate the binding mode of the newly synthesized derivatives 1 and 2. The results of this study suggest that N-aryl heteroarylisopropanolamines bind to the PR active site similarly to the diarylbutanols of Agouron.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Di Santo R,Costi R,Artico M,Massa S,Ragno R,Marshall GR,La Colla Pdoi
10.1016/s0968-0896(02)00119-0subject
Has Abstractpub_date
2002-08-01 00:00:00pages
2511-26issue
8eissn
0968-0896issn
1464-3391pii
S0968089602001190journal_volume
10pub_type
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