FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1985237260> ?p ?o ?g. }

• W1985237260 endingPage "1093" @default.
• W1985237260 startingPage "1085" @default.
• W1985237260 abstract "In a continuing effort to further characterize the role of the dopamine transporter in the pharmacological effects of cocaine, a series of chiral and achiral N-substituted analogues of 3alpha-[bis(4'-fluorophenyl)methoxy]tropane (5) has been prepared as potential selective dopamine transporter ligands. These novel compounds displaced [(3)H]WIN 35,428 binding from the dopamine transporter in rat caudate putamen with K(i) values ranging from 13. 9 to 477 nM. Previously, it was reported that 5 demonstrated a significantly higher affinity for the dopamine transporter than the parent drug, 3alpha-(diphenylmethoxy)tropane (3; benztropine). However, 5 remained nonselective over muscarinic m(1) receptors (dopamine transporter, K(i) = 11.8 nM; m(1), K(i) = 11.6 nM) which could potentially confound the interpretation of behavioral data, for this compound and other members of this series. Thus, significant effort has been directed toward developing analogues that retain high affinity at the dopamine transporter but have decreased affinity at muscarinic sites. Recently, it was discovered that by replacing the N-methyl group of 5 with the phenyl-n-butyl substituent (6) retention of high binding affinity at the dopamine transporter (K(i) = 8.51 nM) while decreasing affinity at muscarinic receptors (K(i) = 576 nM) was achieved, resulting in 68-fold selectivity. In the present series, a further improvement in the selectivity for the dopamine transporter was accomplished, with the chiral analogue (S)-N-(2-amino-3-methyl-n-butyl)-3alpha-[bis(4'-fluorophenyl)metho xy] tropane (10b) showing a 136-fold selectivity for the dopamine transporter versus muscarinic m(1) receptors (K(i) = 29.5 nM versus K(i) = 4020 nM, respectively). In addition, a comparative molecular field analysis (CoMFA) model was derived to correlate the binding affinities of all the N-substituted 3alpha-[bis(4'-fluorophenyl)methoxy]tropane analogues that we have prepared with their 3D-structural features. The best model (q(2) = 0. 746) was used to accurately predict binding affinities of compounds in the training set and in a test set. The CoMFA coefficient contour plot for this model, which provides a visual representation of the chemical environment of the binding domain of the dopamine transporter, can now be used to design and/or predict the binding affinities of novel drugs within this class of dopamine uptake inhibitors." @default.
• W1985237260 created "2016-06-24" @default.
• W1985237260 creator A5004899629 @default.
• W1985237260 creator A5017374112 @default.
• W1985237260 creator A5026011651 @default.
• W1985237260 creator A5046256096 @default.
• W1985237260 creator A5061926206 @default.
• W1985237260 creator A5067428741 @default.
• W1985237260 creator A5067751090 @default.
• W1985237260 date "2000-02-25" @default.
• W1985237260 modified "2023-10-16" @default.
• W1985237260 title "Highly Selective Chiral N-Substituted 3α-[Bis(4‘-fluorophenyl)methoxy]tropane Analogues for the Dopamine Transporter: Synthesis and Comparative Molecular Field Analysis" @default.
• W1985237260 cites W1877347825 @default.
• W1985237260 cites W1964094660 @default.
• W1985237260 cites W1980014219 @default.
• W1985237260 cites W1991442236 @default.
• W1985237260 cites W1999331154 @default.
• W1985237260 cites W2007604257 @default.
• W1985237260 cites W2016487214 @default.
• W1985237260 cites W2020024663 @default.
• W1985237260 cites W2035054874 @default.
• W1985237260 cites W2042578245 @default.
• W1985237260 cites W2047597821 @default.
• W1985237260 cites W2057109001 @default.
• W1985237260 cites W2063465857 @default.
• W1985237260 cites W2072059583 @default.
• W1985237260 cites W2082450996 @default.
• W1985237260 cites W2083674889 @default.
• W1985237260 cites W2951803564 @default.
• W1985237260 cites W2952607276 @default.
• W1985237260 cites W4247426437 @default.
• W1985237260 doi "https://doi.org/10.1021/jm990265s" @default.
• W1985237260 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10737741" @default.
• W1985237260 hasPublicationYear "2000" @default.
• W1985237260 type Work @default.
• W1985237260 sameAs 1985237260 @default.
• W1985237260 citedByCount "42" @default.
• W1985237260 countsByYear W19852372602014 @default.
• W1985237260 countsByYear W19852372602015 @default.
• W1985237260 countsByYear W19852372602016 @default.
• W1985237260 countsByYear W19852372602018 @default.
• W1985237260 countsByYear W19852372602020 @default.
• W1985237260 countsByYear W19852372602021 @default.
• W1985237260 countsByYear W19852372602022 @default.
• W1985237260 crossrefType "journal-article" @default.
• W1985237260 hasAuthorship W1985237260A5004899629 @default.
• W1985237260 hasAuthorship W1985237260A5017374112 @default.
• W1985237260 hasAuthorship W1985237260A5026011651 @default.
• W1985237260 hasAuthorship W1985237260A5046256096 @default.
• W1985237260 hasAuthorship W1985237260A5061926206 @default.
• W1985237260 hasAuthorship W1985237260A5067428741 @default.
• W1985237260 hasAuthorship W1985237260A5067751090 @default.
• W1985237260 hasConcept C104317684 @default.
• W1985237260 hasConcept C134018914 @default.
• W1985237260 hasConcept C149011108 @default.
• W1985237260 hasConcept C170493617 @default.
• W1985237260 hasConcept C185592680 @default.
• W1985237260 hasConcept C2776552330 @default.
• W1985237260 hasConcept C2776755682 @default.
• W1985237260 hasConcept C2776995303 @default.
• W1985237260 hasConcept C2908949072 @default.
• W1985237260 hasConcept C2909816965 @default.
• W1985237260 hasConcept C2910393698 @default.
• W1985237260 hasConcept C513476851 @default.
• W1985237260 hasConcept C55493867 @default.
• W1985237260 hasConcept C71240020 @default.
• W1985237260 hasConcept C86803240 @default.
• W1985237260 hasConceptScore W1985237260C104317684 @default.
• W1985237260 hasConceptScore W1985237260C134018914 @default.
• W1985237260 hasConceptScore W1985237260C149011108 @default.
• W1985237260 hasConceptScore W1985237260C170493617 @default.
• W1985237260 hasConceptScore W1985237260C185592680 @default.
• W1985237260 hasConceptScore W1985237260C2776552330 @default.
• W1985237260 hasConceptScore W1985237260C2776755682 @default.
• W1985237260 hasConceptScore W1985237260C2776995303 @default.
• W1985237260 hasConceptScore W1985237260C2908949072 @default.
• W1985237260 hasConceptScore W1985237260C2909816965 @default.
• W1985237260 hasConceptScore W1985237260C2910393698 @default.
• W1985237260 hasConceptScore W1985237260C513476851 @default.
• W1985237260 hasConceptScore W1985237260C55493867 @default.
• W1985237260 hasConceptScore W1985237260C71240020 @default.
• W1985237260 hasConceptScore W1985237260C86803240 @default.
• W1985237260 hasIssue "6" @default.
• W1985237260 hasLocation W19852372601 @default.
• W1985237260 hasLocation W19852372602 @default.
• W1985237260 hasOpenAccess W1985237260 @default.
• W1985237260 hasPrimaryLocation W19852372601 @default.
• W1985237260 hasRelatedWork W1877347825 @default.
• W1985237260 hasRelatedWork W1969780406 @default.
• W1985237260 hasRelatedWork W1981915089 @default.
• W1985237260 hasRelatedWork W1988962265 @default.
• W1985237260 hasRelatedWork W2002711099 @default.
• W1985237260 hasRelatedWork W2019313771 @default.
• W1985237260 hasRelatedWork W2019647316 @default.
• W1985237260 hasRelatedWork W2039116048 @default.
• W1985237260 hasRelatedWork W2144847650 @default.
• W1985237260 hasRelatedWork W2163903441 @default.
• W1985237260 hasVolume "43" @default.

• next