Literature DB >> 16480874

Ketopiperazine-based renin inhibitors: optimization of the "C" ring.

Daniel D Holsworth1, Cuiman Cai, Xue-Min Cheng, Wayne L Cody, Dennis M Downing, Noe Erasga, Chitase Lee, Noel A Powell, Jeremy J Edmunds, Michael Stier, Mehran Jalaie, Erli Zhang, Pat McConnell, Michael J Ryan, John Bryant, Tingsheng Li, Aparna Kasani, Eric Hall, Rajendra Subedi, Mohammad Rahim, Samarendra Maiti.   

Abstract

A systematic investigation of the S3 sub-pocket activity requirements was conducted. It was observed that linear and sterically small side chain substituents are preferred in the S3 sub-pocket for optimal renin inhibition. Polar groups in the S3-sub-pocket were not well tolerated and caused a reduction in renin inhibitory activity. Further, compounds with clog P's < or = 3 demonstrated a dramatic reduction in CYP3A4 inhibitory activity.

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Year:  2006        PMID： 16480874     DOI： 10.1016/j.bmcl.2006.01.084

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


  5 in total

1.  Exploring the pH-Dependent Structure-Dynamics-Function Relationship of Human Renin.

Authors:  Shuhua Ma; Jack A Henderson; Jana Shen
Journal:  J Chem Inf Model       Date:  2020-12-23       Impact factor: 4.956

2.  Design, synthesis and biological evaluation of renin inhibitors guided by simulated annealing of chemical potential simulations.

Authors:  Ian S Cloudsdale; John K Dickson; Thomas E Barta; Brian S Grella; Emilie D Smith; John L Kulp; Frank Guarnieri; John L Kulp
Journal:  Bioorg Med Chem       Date:  2017-05-19       Impact factor: 3.641

3.  Structure-based design of substituted piperidines as a new class of highly efficacious oral direct Renin inhibitors.

Authors:  Takeru Ehara; Osamu Irie; Takatoshi Kosaka; Takanori Kanazawa; Werner Breitenstein; Philipp Grosche; Nils Ostermann; Masaki Suzuki; Shimpei Kawakami; Kazuhide Konishi; Yuko Hitomi; Atsushi Toyao; Hiroki Gunji; Frederic Cumin; Nikolaus Schiering; Trixie Wagner; Dean F Rigel; Randy L Webb; Jürgen Maibaum; Fumiaki Yokokawa
Journal:  ACS Med Chem Lett       Date:  2014-04-21       Impact factor: 4.345

Review 4.  Recent syntheses of 1,2,3,4-tetrahydroquinolines, 2,3-dihydro-4(1H)-quinolinones and 4(1H)-quinolinones using domino reactions.

Authors:  Baskar Nammalwar; Richard A Bunce
Journal:  Molecules       Date:  2013-12-24       Impact factor: 4.411

Review 5.  Decades-old renin inhibitors are still struggling to find a niche in antihypertensive therapy. A fleeting look at the old and the promising new molecules.

Authors:  Krishnappa Ramya; Ramalingam Suresh; Honnavalli Yogish Kumar; B R Prashantha Kumar; N B Sridhara Murthy
Journal:  Bioorg Med Chem       Date:  2020-03-28       Impact factor: 3.641
  5 in total

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