Document Detail


Computer-aided structure-affinity relationships in a set of piperazine and 3,8-diazabicyclo[3.2.1]octane derivatives binding to the mu-opioid receptor.
MedLine Citation:
PMID:  8294946     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Molecular modeling studies were carried out on a set of piperazine and 3,8-diazabicyclo[3.2.1]octane derivatives with the aim to highlight the main factors modulating their affinity for the mu-opioid receptor. Structure-affinity relationships were developed with the aid of molecular mechanics and semiempirical quantum-mechanics methods. According to our proposed pharmacodynamic model, the binding to the mu-receptor is promoted by the following physico-chemical features: the presence of hydrocarbon fragments on the nitrogen ring frame capable of interacting with one of two hypothesized hydrophobic receptor pockets; a 'correct' orientation of an N-propionyl side chain so as to avoid a sterically hindered region of the receptor; the possibility of accepting a hydrogen bond from a receptor site complementary to the morphine phenol oxygen.
Authors:
D Barlocco; G Cignarella; G Greco; E Novellino
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of computer-aided molecular design     Volume:  7     ISSN:  0920-654X     ISO Abbreviation:  J. Comput. Aided Mol. Des.     Publication Date:  1993 Oct 
Date Detail:
Created Date:  1994-02-28     Completed Date:  1994-02-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8710425     Medline TA:  J Comput Aided Mol Des     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  557-71     Citation Subset:  IM    
Affiliation:
Istituto Chimico Farmaceutico e Tossicologico, Università degli Studi di Milan, Italy.
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MeSH Terms
Descriptor/Qualifier:
Bicyclo Compounds / chemistry,  metabolism*
Computer Simulation*
Models, Chemical
Models, Molecular*
Molecular Conformation
Piperazines / chemistry,  metabolism*
Quantum Theory
Receptors, Opioid, delta / metabolism
Receptors, Opioid, mu / metabolism*
Structure-Activity Relationship
Thermodynamics
Chemical
Reg. No./Substance:
0/Bicyclo Compounds; 0/Piperazines; 0/Receptors, Opioid, delta; 0/Receptors, Opioid, mu

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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