Literature DB >> 29456793

Synthesis of Novel Tetrahydroisoquinoline CXCR4 Antagonists with Rigidified Side-Chains.

Edgars Jecs1, Eric J Miller1, Robert J Wilson1, Huy H Nguyen1, Yesim A Tahirovic1, Brook M Katzman1, Valarie M Truax1, Michelle B Kim1, Katie M Kuo1, Tao Wang2, Chi S Sum2, Mary E Cvijic2, Gretchen M Schroeder2, Lawrence J Wilson1, Dennis C Liotta1.   

Abstract

A structure-activity relationship study of potent TIQ15-derived CXCR4 antagonists is reported. In this investigation, the TIQ15 side-chain was constrained to improve its drug properties. The cyclohexylamino congener 15a was found to be a potent CXCR4 inhibitor (IC50 = 33 nM in CXCL12-mediated Ca2+ flux) with enhanced stability in liver microsomes and reduced inhibition of CYP450 (2D6). The improved CXCR4 antagonist 15a has potential therapeutic application as a single agent or combinatory anticancer therapy.

Entities:  

Year:  2017        PMID： 29456793      PMCID： PMC5807867          DOI： 10.1021/acsmedchemlett.7b00406

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


  26 in total

1.  Synthesis and SAR of novel CXCR4 antagonists that are potent inhibitors of T tropic (X4) HIV-1 replication.

Authors:  Renato Skerlj; Gary Bridger; Ernie McEachern; Curtis Harwig; Chris Smith; Trevor Wilson; Duane Veale; Helen Yee; Jason Crawford; Krystyna Skupinska; Rossana Wauthy; Wen Yang; Yongbao Zhu; David Bogucki; Maria Di Fluri; Jonathon Langille; Dana Huskens; Erik De Clercq; Dominique Schols
Journal:  Bioorg Med Chem Lett       Date:  2010-11-06       Impact factor: 2.823

Review 2.  Understanding CYP2D6 interactions.

Authors:  Marcel J de Groot; Florian Wakenhut; Gavin Whitlock; Ruth Hyland
Journal:  Drug Discov Today       Date:  2009-07-26       Impact factor: 7.851

3.  The alpha-chemokine, stromal cell-derived factor-1alpha, binds to the transmembrane G-protein-coupled CXCR-4 receptor and activates multiple signal transduction pathways.

Authors:  R K Ganju; S A Brubaker; J Meyer; P Dutt; Y Yang; S Qin; W Newman; J E Groopman
Journal:  J Biol Chem       Date:  1998-09-04       Impact factor: 5.157

4.  CXCL12/CXCR4 blockade induces multimodal antitumor effects that prolong survival in an immunocompetent mouse model of ovarian cancer.

Authors:  Elda Righi; Satoshi Kashiwagi; Jianping Yuan; Michael Santosuosso; Pierre Leblanc; Rachel Ingraham; Benjamin Forbes; Beth Edelblute; Brian Collette; Deyin Xing; Magdalena Kowalski; Maria Cristina Mingari; Fabrizio Vianello; Michael Birrer; Sandra Orsulic; Glenn Dranoff; Mark C Poznansky
Journal:  Cancer Res       Date:  2011-07-08       Impact factor: 12.701

5.  Blockade of CXCR4 in oral squamous cell carcinoma inhibits lymph node metastases.

Authors:  Daisuke Uchida; Tomitaro Onoue; Nobuyuki Kuribayashi; Yoshifumi Tomizuka; Tetsuya Tamatani; Hirokazu Nagai; Youji Miyamoto
Journal:  Eur J Cancer       Date:  2010-10-19       Impact factor: 9.162

6.  Discovery of tetrahydroisoquinoline-based CXCR4 antagonists.

Authors:  Valarie M Truax; Huanyu Zhao; Brooke M Katzman; Anthony R Prosser; Ana A Alcaraz; Manohar T Saindane; Randy B Howard; Deborah Culver; Richard F Arrendale; Prahbakar R Gruddanti; Taylor J Evers; Michael G Natchus; James P Snyder; Dennis C Liotta; Lawrence J Wilson
Journal:  ACS Med Chem Lett       Date:  2013-09-05       Impact factor: 4.345

7.  Chemokine receptor CXCR4 expression is correlated with VEGF expression and poor survival in soft-tissue sarcoma.

Authors:  Yoshinao Oda; Naomi Tateishi; Hiroshi Matono; Suguru Matsuura; Hidetaka Yamamaoto; Sadafumi Tamiya; Ryohei Yokoyama; Shuichi Matsuda; Yukihide Iwamoto; Masazumi Tsuneyoshi
Journal:  Int J Cancer       Date:  2009-04-15       Impact factor: 7.396

Review 8.  The chemokine system, and its CCR5 and CXCR4 receptors, as potential targets for personalized therapy in cancer.

Authors:  Polina Weitzenfeld; Adit Ben-Baruch
Journal:  Cancer Lett       Date:  2013-10-18       Impact factor: 8.679

9.  Inhibition of CXCR4 in CML cells disrupts their interaction with the bone marrow microenvironment and sensitizes them to nilotinib.

Authors:  E Weisberg; A K Azab; P W Manley; A L Kung; A L Christie; R Bronson; I M Ghobrial; J D Griffin
Journal:  Leukemia       Date:  2011-12-20       Impact factor: 11.528

10.  CXCR4 inhibitors could benefit to HER2 but not to triple-negative breast cancer patients.

Authors:  S Lefort; A Thuleau; Y Kieffer; P Sirven; I Bieche; E Marangoni; A Vincent-Salomon; F Mechta-Grigoriou
Journal:  Oncogene       Date:  2016-09-26       Impact factor: 9.867
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  4 in total

1.  ONO-8430506: A Novel Autotaxin Inhibitor That Enhances the Antitumor Effect of Paclitaxel in a Breast Cancer Model.

Authors:  Yuzo Iwaki; Akira Ohhata; Shingo Nakatani; Katsuya Hisaichi; Yasuyuki Okabe; Atsushi Hiramatsu; Toshihide Watanabe; Shingo Yamamoto; Taihei Nishiyama; Juta Kobayashi; Yasuo Hirooka; Hideki Moriguchi; Tatsuo Maeda; Makoto Katoh; Yuka Komichi; Hiroto Ota; Naoya Matsumura; Masahiro Okada; Tetsuya Sugiyama; Hiroshi Saga; Akira Imagawa
Journal:  ACS Med Chem Lett       Date:  2020-05-14       Impact factor: 4.345

2.  Discovery of N-Alkyl Piperazine Side Chain Based CXCR4 Antagonists with Improved Drug-like Properties.

Authors:  Yesim A Tahirovic; Valarie M Truax; Robert J Wilson; Edgars Jecs; Huy H Nguyen; Eric J Miller; Michelle B Kim; Katie M Kuo; Tao Wang; Chi S Sum; Mary E Cvijic; Gretchen M Schroeder; Lawrence J Wilson; Dennis C Liotta
Journal:  ACS Med Chem Lett       Date:  2018-04-09       Impact factor: 4.345

3.  Amino-Heterocycle Tetrahydroisoquinoline CXCR4 Antagonists with Improved ADME Profiles via Late-Stage Buchwald Couplings.

Authors:  Huy H Nguyen; Yesim A Tahirovic; Valarie M Truax; Robert J Wilson; Edgars Jecs; Eric J Miller; Michelle B Kim; Nicholas S Akins; Lingjie Xu; Yi Jiang; Tao Wang; Chi S Sum; Mary E Cvijic; Gretchen M Schroeder; Lawrence J Wilson; Dennis C Liotta
Journal:  ACS Med Chem Lett       Date:  2021-10-04       Impact factor: 4.632

Review 4.  At the Bench: Pre-clinical evidence for multiple functions of CXCR4 in cancer.

Authors:  Gary D Luker; Jinming Yang; Ann Richmond; Stefania Scala; Claudio Festuccia; Margret Schottelius; Hans-Jürgen Wester; Johann Zimmermann
Journal:  J Leukoc Biol       Date:  2020-10-26       Impact factor: 4.962
  4 in total

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