Design, synthesis, and evaluation of 3,5-disubstituted 7-azaindoles as Trk inhibitors with anticancer and antiangiogenic activities

Journal of Medicinal Chemistry
Seunghee HongSungwoo Hong

Abstract

Tropomyosin-related kinase A (TrkA) is considered a promising target in the development of a therapeutic treatment of cancer and pain. In this study, we designed and synthesized a series of novel 7-azaindole-based Trk kinase inhibitors through the structure-based design strategy. By varying the functional groups at the 3 and 5 positions of a 7-azaindole scaffold, we studied the structure-activity relationships (SAR) profiles and identified a series of potent Trk inhibitors. Representative derivatives showed desirable activity in cellular proliferation and apoptosis assays. Moreover, these inhibitors exhibited noteworthy antiangiogenic activity.

References

Jun 12, 2001·Current Opinion in Neurobiology·A Patapoutian, L F Reichardt
Mar 27, 2003·Progress in Neuro-psychopharmacology & Biological Psychiatry·Paula C Ashe, Mark D Berry
Mar 12, 2004·Bioorganic & Medicinal Chemistry Letters·Edgar R WoodKaren Lackey
Jun 1, 2005·Cancer Letters·Alexander SchrammAngelika Eggert
Dec 7, 2007·Bioorganic & Medicinal Chemistry Letters·Soong-Hoon KimPing Chen
Jan 18, 2008·Cancer Research·Eric AdriaenssensHubert Hondermarck
May 30, 2008·Bioorganic & Medicinal Chemistry Letters·Rabindranath TripathyJohn P Mallamo
Jul 24, 2008·Journal of Medicinal Chemistry·Tao WangDingwei Yu
May 7, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Garrett M BrodeurAudrey E Evans
May 16, 2009·Expert Opinion on Therapeutic Patents·Tao WangMichelle L Lamb
Apr 23, 2010·Chemistry, an Asian Journal·Dong Jae BaekSanghee Kim
Jun 24, 2010·Molecular Cancer·Rodrigue RomonXuefen Le Bourhis
Nov 12, 2010·Bioorganic & Medicinal Chemistry Letters·Seunghee HongSungwoo Hong
Dec 15, 2010·Molecular and Cellular Neurosciences·Katsuya NakamuraCarol J Thiele
Feb 16, 2011·Journal of Medicinal Chemistry·Qi SunBlake R Peterson

❮ Previous
Next ❯

Citations

Nov 6, 2013·Journal of Medicinal Chemistry·Stéphanie GourdainRobert H Dodd
Dec 3, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jean-Yves MérourSylvain Routier
Jul 4, 2012·Cytokine & Growth Factor Reviews·Hubert Hondermarck
Sep 26, 2012·British Journal of Pharmacology·Renaud PrudentLaurence Lafanechère
Mar 21, 2016·European Journal of Medicinal Chemistry·Suresh NarvaVenkata Gowri Chandra Sekhar Kondapalli
Jun 20, 2016·European Journal of Medicinal Chemistry·Jaana Tammiku-TaulMati Karelson
Jul 14, 2016·The Journal of Organic Chemistry·Aniket MishraIndubhusan Deb
Jan 10, 2017·Expert Opinion on Therapeutic Patents·Mohammed I El-Gamal, Hanan S Anbar
Jan 18, 2017·Bioorganic & Medicinal Chemistry Letters·Clémence FeneyrollesAbdelaziz Yasri
Jun 17, 2015·Chemical Communications : Chem Comm·Yechan Kim, Sungwoo Hong
Jun 23, 2016·Chemical Communications : Chem Comm·Ciaran P SeathAllan J B Watson
Nov 11, 2016·Beilstein Journal of Organic Chemistry·Kirsty L WilsonAllan J B Watson
May 5, 2018·Organic & Biomolecular Chemistry·Changduo PanJin-Tao Yu
Jan 15, 2021·Organic & Biomolecular Chemistry·Jidan LiuZhao-Qing Liu
Mar 2, 2021·Acta Pharmaceutica Sinica. B·Tingting JiangLiang Ouyang
Nov 1, 2013·Organic Letters·Prakash KannaboinaParthasarathi Das
Feb 18, 2015·The Journal of Organic Chemistry·Cécile CroixMarie-Claude Viaud-Massuard
Aug 25, 2017·ACS Medicinal Chemistry Letters·Chengbin YangYaming Zhou
Jul 9, 2014·Journal of Medicinal Chemistry·Soyoung LeeSungwoo Hong
Aug 11, 2018·Journal of Medicinal Chemistry·Anna CzarnaUlli Rothweiler
Oct 27, 2017·The Journal of Organic Chemistry·Aniket MishraIndubhusan Deb

❮ Previous
Next ❯

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis