Literature DB >> 25699143

Evaluation and synthesis of polar aryl- and heteroaryl spiroazetidine-piperidine acetamides as ghrelin inverse agonists.

Suvi T M Orr1, Ramsay Beveridge2, Samit K Bhattacharya3, Kimberly O Cameron3, Steven Coffey2, Dilinie Fernando2, David Hepworth3, Margaret V Jackson4, Vishal Khot2, Rachel Kosa5, Kimberly Lapham5, Paula M Loria6, Kim F McClure3, Jigna Patel7, Colin Rose3, James Saenz7, Ingrid A Stock6, Gregory Storer2, Maria von Volkenburg4, Derek Vrieze2, Guoqiang Wang2, Jun Xiao2, Yingxin Zhang2.   

Abstract

Several polar heteroaromatic acetic acids and their piperidine amides were synthesized and evaluated as ghrelin or type 1a growth hormone secretagogue receptor (GHS-R1a) inverse agonists. Efforts to improve pharmacokinetic and safety profile was achieved by modulating physicochemical properties and, more specifically, emphasizing increased polarity of our chemical series. ortho-Carboxamide containing compounds provided optimal physicochemical, pharmacologic, and safety profile. pH-dependent chemical stability was also assessed with our series.

Entities:  

Keywords:  Heteroaryl acetic acid; carboxamide; ghrelin; growth hormone secretagogue receptor 1a; spiroazetidine-piperidine; type 2 diabetes

Year:  2014        PMID： 25699143      PMCID： PMC4329598          DOI： 10.1021/ml500414n

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  30 in total

1.  Discovery of a new class of ghrelin receptor antagonists.

Authors:  Jeffrey T Mihalic; Yong-Jae Kim; Mike Lizarzaburu; Xiaoqi Chen; Jeff Deignan; Malgorzata Wanska; Ming Yu; Jiasheng Fu; Xi Chen; Alex Zhang; Richard Connors; Lingming Liang; Michelle Lindstrom; Ji Ma; Liang Tang; Kang Dai; Leping Li
Journal:  Bioorg Med Chem Lett       Date:  2012-01-14       Impact factor: 2.823

Review 2.  Structural modifications that alter the P-glycoprotein efflux properties of compounds.

Authors:  Stephen A Hitchcock
Journal:  J Med Chem       Date:  2012-04-16       Impact factor: 7.446

3.  Discovery of tetralin carboxamide growth hormone secretagogue receptor antagonists via scaffold manipulation.

Authors:  Hongyu Zhao; Zhili Xin; Gang Liu; Verlyn G Schaefer; H Douglas Falls; Wiweka Kaszubska; Christine A Collins; Hing L Sham
Journal:  J Med Chem       Date:  2004-12-30       Impact factor: 7.446

4.  Synthesis and pharmacological in vitro and in vivo evaluations of novel triazole derivatives as ligands of the ghrelin receptor. 1.

Authors:  Luc Demange; Damien Boeglin; Aline Moulin; Delphine Mousseaux; Joanne Ryan; Gilbert Bergé; Didier Gagne; Annie Heitz; Daniel Perrissoud; Vittorio Locatelli; Antonio Torsello; Jean-Claude Galleyrand; Jean-Alain Fehrentz; Jean Martinez
Journal:  J Med Chem       Date:  2007-03-22       Impact factor: 7.446

5.  Identification of potent, selective, CNS-targeted inverse agonists of the ghrelin receptor.

Authors:  Kim F McClure; Margaret Jackson; Kimberly O Cameron; Daniel W Kung; David A Perry; Suvi T M Orr; Yingxin Zhang; Jeffrey Kohrt; Meihua Tu; Hua Gao; Dilinie Fernando; Ryan Jones; Noe Erasga; Guoqiang Wang; Jana Polivkova; Wenhua Jiao; Roger Swartz; Hirokazu Ueno; Samit K Bhattacharya; Ingrid A Stock; Sam Varma; Victoria Bagdasarian; Sylvie Perez; Dawn Kelly-Sullivan; Ruduan Wang; Jimmy Kong; Peter Cornelius; Laura Michael; Eunsun Lee; Ann Janssen; Stefanus J Steyn; Kimberly Lapham; Theunis Goosen
Journal:  Bioorg Med Chem Lett       Date:  2013-07-30       Impact factor: 2.823

Review 6.  Structure, regulation and function of ghrelin.

Authors:  Takahiro Sato; Yuki Nakamura; Yuki Shiimura; Hideko Ohgusu; Kenji Kangawa; Masayasu Kojima
Journal:  J Biochem       Date:  2011-10-31       Impact factor: 3.387

7.  Discovery and pharmacological evaluation of growth hormone secretagogue receptor antagonists.

Authors:  Zhili Xin; Michael D Serby; Hongyu Zhao; Christi Kosogof; Bruce G Szczepankiewicz; Mei Liu; Bo Liu; Charles W Hutchins; Kathy A Sarris; Ethan D Hoff; H Douglas Falls; Chun W Lin; Christopher A Ogiela; Christine A Collins; Michael E Brune; Eugene N Bush; Brian A Droz; Thomas A Fey; Victoria E Knourek-Segel; Robin Shapiro; Peer B Jacobson; David W A Beno; Teresa M Turner; Hing L Sham; Gang Liu
Journal:  J Med Chem       Date:  2006-07-27       Impact factor: 7.446

8.  Ghrelin is a growth-hormone-releasing acylated peptide from stomach.

Authors:  M Kojima; H Hosoda; Y Date; M Nakazato; H Matsuo; K Kangawa
Journal:  Nature       Date:  1999-12-09       Impact factor: 49.962

9.  Identification of spirocyclic piperidine-azetidine inverse agonists of the ghrelin receptor.

Authors:  Daniel W Kung; Steven B Coffey; Ryan M Jones; Shawn Cabral; Wenhua Jiao; Michael Fichtner; Philip A Carpino; Colin R Rose; Richard F Hank; Michael G Lopaze; Roger Swartz; Hou Tommy Chen; Zachary Hendsch; Bruce Posner; Christopher F Wielis; Brian Manning; Jeffrey Dubins; Ingrid A Stock; Sam Varma; Mary Campbell; Demetria DeBartola; Rachel Kosa-Maines; Stefanus J Steyn; Kim F McClure
Journal:  Bioorg Med Chem Lett       Date:  2012-05-17       Impact factor: 2.823

10.  Pyrazolinone-piperidine dipeptide growth hormone secretagogues (GHSs). Discovery of capromorelin.

Authors:  Philip A Carpino; Bruce A Lefker; Steven M Toler; Lydia C Pan; John R Hadcock; Ewell R Cook; Joseph N DiBrino; Anthony M Campeta; Shari L DeNinno; Kristin L Chidsey-Frink; William A Hada; John Inthavongsay; F Michael Mangano; Michelle A Mullins; David F Nickerson; Oicheng Ng; Christine M Pirie; John A Ragan; Colin R Rose; David A Tess; Ann S Wright; Li Yu; Michael P Zawistoski; Paul A DaSilva-Jardine; Theresa C Wilson; David D Thompson
Journal:  Bioorg Med Chem       Date:  2003-02-20       Impact factor: 3.641
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  3 in total

Review 1.  Advances in the Development of Nonpeptide Small Molecules Targeting Ghrelin Receptor.

Authors:  Gianfabio Giorgioni; Fabio Del Bello; Wilma Quaglia; Luca Botticelli; Carlo Cifani; E Micioni Di Bonaventura; M V Micioni Di Bonaventura; Alessandro Piergentili
Journal:  J Med Chem       Date:  2022-02-14       Impact factor: 7.446

2.  Prediction of Lipophilicity and Pharmacokinetics of Chloroacetamides by Chemometric Approach.

Authors:  Gyöngyi Vastag; Suzana Apostolov; Borko Matijević
Journal:  Iran J Pharm Res       Date:  2018       Impact factor: 1.696

3.  Organocatalytic Access to Enantioenriched Spirooxindole-Based 4-Methyleneazetidines.

Authors:  Giulia Rainoldi; Matteo Faltracco; Claudia Spatti; Alessandra Silvani; Giordano Lesma
Journal:  Molecules       Date:  2017-11-21       Impact factor: 4.411
  3 in total

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