Literature DB >> 24630561

Evaluation of structural effects on 5-HT(2A) receptor antagonism by aporphines: identification of a new aporphine with 5-HT(2A) antagonist activity.

Shashikanth Ponnala1, Junior Gonzales2, Nirav Kapadia2, Hernan A Navarro3, Wayne W Harding4.   

Abstract

A set of aporphine analogs related to nantenine was evaluated for antagonist activity at 5-HT2A and α1A adrenergic receptors. With regards to 5-HT2A receptor antagonism, a C2 allyl group is detrimental to activity. The chiral center of nantenine is not important for 5-HT2A antagonist activity, however the N6 nitrogen atom is a critical feature for 5-HT2A antagonism. Compound 12b was the most potent 5-HT2A aporphine antagonist identified in this study and has similar potency to previously identified aporphine antagonists 2 and 3. The ring A and N6 modifications examined were detrimental to α1A antagonism. A slight eutomeric preference for the R enantiomer of nantenine was observed in relation to α1A antagonism.
Copyright © 2014 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  5-HT(2A); Antagonist; Aporphine; Nantenine; Structure–activity relationship (SAR); α(1A)

Mesh：

Substances：

Year:  2014        PMID： 24630561      PMCID： PMC4022183          DOI： 10.1016/j.bmcl.2014.02.066

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  32 in total

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Authors:  Stevan Pecic; Pooja Makkar; Sandeep Chaudhary; Boojala V Reddy; Hernan A Navarro; Wayne W Harding
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3.  10-substituted 11-oxygenated (R)-aporphines: synthesis, pharmacology, and modeling of 5-HT1A receptor interactions.

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Review 4.  Atypical antipsychotic agents: a critical review.

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5.  New aporphinoid 5-HT2A and α1A antagonists via structural manipulations of nantenine.

Authors:  Sandeep Chaudhary; Shashikanth Ponnala; Onica Legendre; Junior A Gonzales; Hernán A Navarro; Wayne W Harding
Journal:  Bioorg Med Chem       Date:  2011-08-18       Impact factor: 3.641

6.  Microwave-Assisted Direct Biaryl Coupling: First Application to the Synthesis of Aporphines.

Authors:  Sandeep Chaudhary; Stevan Pecic; Onica Legendre; Wayne W Harding
Journal:  Tetrahedron Lett       Date:  2009-05-20       Impact factor: 2.415

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Journal:  J Med Chem       Date:  2008-02-06       Impact factor: 7.446
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  6 in total

1.  Synthesis and evaluation of aporphine analogs containing C1 allyl isosteres at the h5-HT(2A) receptor.

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Journal:  Bioorg Med Chem Lett       Date:  2015-10-09       Impact factor: 2.823

2.  Identification of C10 nitrogen-containing aporphines with dopamine D1 versus D5 receptor selectivity.

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Journal:  Bioorg Med Chem Lett       Date:  2015-07-11       Impact factor: 2.823

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5.  Synthesis and evaluation of nuciferine and roemerine enantiomers as 5-HT2 and α1 receptor antagonists.

Authors:  Hui Li Heng; Chin Fei Chee; Sek Peng Chin; Yifan Ouyang; Hao Wang; Michael J C Buckle; Deron R Herr; Ian C Paterson; Stephen W Doughty; Noorsaadah Abd Rahman; Lip Yong Chung
Journal:  Medchemcomm       Date:  2018-02-26       Impact factor: 3.597

6.  Pharmacological profiling an abundantly expressed schistosome serotonergic GPCR identifies nuciferine as a potent antagonist.

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  6 in total

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