Literature DB >> 27994738

Sulfonamides as Selective NaV1.7 Inhibitors: Optimizing Potency and Pharmacokinetics to Enable in Vivo Target Engagement.

Isaac E Marx1, Thomas A Dineen1, Jessica Able1, Christiane Bode1, Howard Bregman1, Margaret Chu-Moyer1, Erin F DiMauro1, Bingfan Du1, Robert S Foti1, Robert T Fremeau1, Hua Gao1, Hakan Gunaydin1, Brian E Hall1, Liyue Huang1, Thomas Kornecook1, Charles R Kreiman1, Daniel S La1, Joseph Ligutti1, Min-Hwa Jasmine Lin1, Dong Liu1, Jeff S McDermott1, Bryan D Moyer1, Emily A Peterson1, Jonathan T Roberts1, Paul Rose1, Jean Wang1, Beth D Youngblood1, Violeta Yu1, Matthew M Weiss1.   

Abstract

Human genetic evidence has identified the voltage-gated sodium channel NaV1.7 as an attractive target for the treatment of pain. We initially identified naphthalene sulfonamide 3 as a potent and selective inhibitor of NaV1.7. Optimization to reduce biliary clearance by balancing hydrophilicity and hydrophobicity (Log D) while maintaining NaV1.7 potency led to the identification of quinazoline 16 (AM-2099). Compound 16 demonstrated a favorable pharmacokinetic profile in rat and dog and demonstrated dose-dependent reduction of histamine-induced scratching bouts in a mouse behavioral model following oral dosing.

Entities:  

Keywords:  NaV1.5; NaV1.7; Sodium channel; histamine scratching model; pain

Year:  2016        PMID： 27994738      PMCID： PMC5150675          DOI： 10.1021/acsmedchemlett.6b00243

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


  13 in total

1.  Use of uptake intrinsic clearance from attached rat hepatocytes to predict hepatic clearance for poorly permeable compounds.

Authors:  Liyue Huang; April Chen; John Roberts; Brett Janosky; Xuhai Be; Loren Berry; Min-Hwa Jasmine Lin
Journal:  Xenobiotica       Date:  2012-03-22       Impact factor: 1.908

Review 2.  Voltage-Gated Sodium Channels: Structure, Function, Pharmacology, and Clinical Indications.

Authors:  Manuel de Lera Ruiz; Richard L Kraus
Journal:  J Med Chem       Date:  2015-05-14       Impact factor: 7.446

3.  Lipophilicity in drug discovery.

Authors:  Michael J Waring
Journal:  Expert Opin Drug Discov       Date:  2010-03       Impact factor: 6.098

Review 4.  Medicinal chemistry design principles for liver targeting through OATP transporters.

Authors:  Meihua Tu; Alan M Mathiowetz; Jeffrey A Pfefferkorn; Kimberly O Cameron; Robert L Dow; John Litchfield; Li Di; Bo Feng; Spiros Liras
Journal:  Curr Top Med Chem       Date:  2013       Impact factor: 3.295

5.  The discovery of benzenesulfonamide-based potent and selective inhibitors of voltage-gated sodium channel Na(v)1.7.

Authors:  Shaoyi Sun; Qi Jia; Alla Y Zenova; Mikhail Chafeev; Zaihui Zhang; Sophia Lin; Rainbow Kwan; Mike E Grimwood; Sultan Chowdhury; Clint Young; Charles J Cohen; Renata M Oballa
Journal:  Bioorg Med Chem Lett       Date:  2014-08-14       Impact factor: 2.823

6.  Discovery of Aryl Sulfonamides as Isoform-Selective Inhibitors of NaV1.7 with Efficacy in Rodent Pain Models.

Authors:  Thilo Focken; Shifeng Liu; Navjot Chahal; Maxim Dauphinais; Michael E Grimwood; Sultan Chowdhury; Ivan Hemeon; Paul Bichler; David Bogucki; Matthew Waldbrook; Girish Bankar; Luis E Sojo; Clint Young; Sophia Lin; Noah Shuart; Rainbow Kwan; Jodie Pang; Jae H Chang; Brian S Safina; Daniel P Sutherlin; J P Johnson; Christoph M Dehnhardt; Tarek S Mansour; Renata M Oballa; Charles J Cohen; C Lee Robinette
Journal:  ACS Med Chem Lett       Date:  2016-01-19       Impact factor: 4.345

Review 7.  From genes to pain: Na v 1.7 and human pain disorders.

Authors:  Sulayman D Dib-Hajj; Theodore R Cummins; Joel A Black; Stephen G Waxman
Journal:  Trends Neurosci       Date:  2007-10-22       Impact factor: 13.837

8.  Paroxysmal itch caused by gain-of-function Nav1.7 mutation.

Authors:  Grazia Devigili; Roberto Eleopra; Tiziana Pierro; Raffaella Lombardi; Sara Rinaldo; Christian Lettieri; Catharina G Faber; Ingemar S J Merkies; Stephen G Waxman; Giuseppe Lauria
Journal:  Pain       Date:  2014-05-10       Impact factor: 6.961

9.  Cardiac Safety Implications of hNav1.5 Blockade and a Framework for Pre-Clinical Evaluation.

Authors:  Gül Erdemli; Albert M Kim; Haisong Ju; Clayton Springer; Robert C Penland; Peter K Hoffmann
Journal:  Front Pharmacol       Date:  2012-01-26       Impact factor: 5.810

10.  Global Nav1.7 knockout mice recapitulate the phenotype of human congenital indifference to pain.

Authors:  Jacinthe Gingras; Sarah Smith; David J Matson; Danielle Johnson; Kim Nye; Lauren Couture; Elma Feric; Ruoyuan Yin; Bryan D Moyer; Matthew L Peterson; James B Rottman; Rudolph J Beiler; Annika B Malmberg; Stefan I McDonough
Journal:  PLoS One       Date:  2014-09-04       Impact factor: 3.240
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  4 in total

1.  Discovery and hit-to-lead evaluation of piperazine amides as selective, state-dependent NaV1.7 inhibitors.

Authors:  Brian A Sparling; S Yi; J Able; H Bregman; Erin F DiMauro; R S Foti; H Gao; A Guzman-Perez; H Huang; M Jarosh; T Kornecook; J Ligutti; B C Milgram; B D Moyer; B Youngblood; V L Yu; M M Weiss
Journal:  Medchemcomm       Date:  2016-12-02       Impact factor: 3.597

Review 2.  Inhibition of NaV1.7: the possibility of ideal analgesics.

Authors:  Yutaka Kitano; Tsuyoshi Shinozuka
Journal:  RSC Med Chem       Date:  2022-08-01

3.  FGF13 Is Required for Histamine-Induced Itch Sensation by Interaction with NaV1.7.

Authors:  Fei Dong; Haixiang Shi; Liu Yang; Huaqing Xue; Manyi Wei; Yan-Qing Zhong; Lan Bao; Xu Zhang
Journal:  J Neurosci       Date:  2020-11-10       Impact factor: 6.167

4.  Chemical Synthesis, Proper Folding, Nav Channel Selectivity Profile and Analgesic Properties of the Spider Peptide Phlotoxin 1.

Authors:  Sébastien Nicolas; Claude Zoukimian; Frank Bosmans; Jérôme Montnach; Sylvie Diochot; Eva Cuypers; Stephan De Waard; Rémy Béroud; Dietrich Mebs; David Craik; Didier Boturyn; Michel Lazdunski; Jan Tytgat; Michel De Waard
Journal:  Toxins (Basel)       Date:  2019-06-21       Impact factor: 4.546
  4 in total

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