Literature DB >> 26819673

Tetrahydroisoquinoline Phenols: Selective Estrogen Receptor Downregulator Antagonists with Oral Bioavailability in Rat.

James S Scott1, Andrew Bailey1, Robert D M Davies1, Sébastien L Degorce1, Philip A MacFaul1, Helen Gingell1, Thomas Moss1, Richard A Norman1, Jennifer H Pink1, Alfred A Rabow1, Bryan Roberts1, Peter D Smith1.   

Abstract

A series of tetrahydroisoquinoline phenols was modified to give an estrogen receptor downregulator-antagonist profile. Optimization around the core, alkyl side chain, and pendant aryl ring resulted in compounds with subnanomolar levels of potency. The phenol functionality was shown to be required to achieve highly potent compounds, but unusually this was compatible with obtaining high oral bioavailabilities in rat.

Entities:  

Keywords:  Estrogen receptor; antagonist; bioavailable; downregulator; phenol; tetrahydroisoquinoline

Year:  2015        PMID： 26819673      PMCID： PMC4716595          DOI： 10.1021/acsmedchemlett.5b00413

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


  12 in total

1.  Estrogen receptor modulators: identification and structure-activity relationships of potent ERalpha-selective tetrahydroisoquinoline ligands.

Authors:  Johanne Renaud; Serge François Bischoff; Thomas Buhl; Philipp Floersheim; Brigitte Fournier; Christine Halleux; Joerg Kallen; Hansjoerg Keller; Jean-Marc Schlaeppi; Wilhelm Stark
Journal:  J Med Chem       Date:  2003-07-03       Impact factor: 7.446

2.  Tetrahydroisoquinolines as subtype selective estrogen agonists/antagonists.

Authors:  Richard Chesworth; Michael P Zawistoski; Bruce A Lefker; Kimberly O Cameron; Robert F Day; F Michael Mangano; Robert L Rosati; Stacy Colella; Donna N Petersen; Amy Brault; Bihong Lu; Lydia C Pan; Pia Perry; Oicheng Ng; Tessa A Castleberry; Thomas A Owen; Thomas A Brown; David D Thompson; Paul DaSilva-Jardine
Journal:  Bioorg Med Chem Lett       Date:  2004-06-07       Impact factor: 2.823

3.  Identification of GDC-0810 (ARN-810), an Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) that Demonstrates Robust Activity in Tamoxifen-Resistant Breast Cancer Xenografts.

Authors:  Andiliy Lai; Mehmet Kahraman; Steven Govek; Johnny Nagasawa; Celine Bonnefous; Jackie Julien; Karensa Douglas; John Sensintaffar; Nhin Lu; Kyoung-Jin Lee; Anna Aparicio; Josh Kaufman; Jing Qian; Gang Shao; Rene Prudente; Michael J Moon; James D Joseph; Beatrice Darimont; Daniel Brigham; Kate Grillot; Richard Heyman; Peter J Rix; Jeffrey H Hager; Nicholas D Smith
Journal:  J Med Chem       Date:  2015-05-22       Impact factor: 7.446

4.  Optimisation and validation of a medium-throughput electrophysiology-based hERG assay using IonWorks HT.

Authors:  M H Bridgland-Taylor; A C Hargreaves; A Easter; A Orme; D C Henthorn; M Ding; A M Davis; B G Small; C G Heapy; N Abi-Gerges; F Persson; I Jacobson; M Sullivan; N Albertson; T G Hammond; E Sullivan; J-P Valentin; C E Pollard
Journal:  J Pharmacol Toxicol Methods       Date:  2006-03-06       Impact factor: 1.950

5.  Reactive metabolite trapping screens and potential pitfalls: bioactivation of a homomorpholine and formation of an unstable thiazolidine adduct.

Authors:  Eva M Lenz; Scott Martin; Ralf Schmidt; Pierre-Emmanuel Morin; Robin Smith; Daniel J Weston; Malken Bayrakdarian
Journal:  Chem Res Toxicol       Date:  2014-06-05       Impact factor: 3.739

6.  Discovery and preclinical pharmacology of a novel, potent, nonsteroidal estrogen receptor agonist/antagonist, CP-336156, a diaryltetrahydronaphthalene.

Authors:  R L Rosati; P Da Silva Jardine; K O Cameron; D D Thompson; H Z Ke; S M Toler; T A Brown; L C Pan; C F Ebbinghaus; A R Reinhold; N C Elliott; B N Newhouse; C M Tjoa; P M Sweetnam; M J Cole; M W Arriola; J W Gauthier; D T Crawford; D F Nickerson; C M Pirie; H Qi; H A Simmons; G T Tkalcevic
Journal:  J Med Chem       Date:  1998-07-30       Impact factor: 7.446

7.  Investigation of (E)-3-[4-(2-Oxo-3-aryl-chromen-4-yl)oxyphenyl]acrylic Acids as Oral Selective Estrogen Receptor Down-Regulators.

Authors:  Sébastien L Degorce; Andrew Bailey; Rowena Callis; Chris De Savi; Richard Ducray; Gillian Lamont; Philip MacFaul; Mickael Maudet; Scott Martin; Rémy Morgentin; Richard A Norman; Aurélien Peru; Jennifer H Pink; Patrick A Plé; Bryan Roberts; James S Scott
Journal:  J Med Chem       Date:  2015-04-01       Impact factor: 7.446

8.  A Screening Assay Cascade to Identify and Characterize Novel Selective Estrogen Receptor Downregulators (SERDs).

Authors:  Rowena Callis; Alfred Rabow; Michael Tonge; Robert Bradbury; Mairi Challinor; Karen Roberts; Karen Jones; Graeme Walker
Journal:  J Biomol Screen       Date:  2015-04-07

Review 9.  Tamoxifen: a most unlikely pioneering medicine.

Authors:  V Craig Jordan
Journal:  Nat Rev Drug Discov       Date:  2003-03       Impact factor: 84.694

10.  Optimization of a Novel Binding Motif to (E)-3-(3,5-Difluoro-4-((1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylic Acid (AZD9496), a Potent and Orally Bioavailable Selective Estrogen Receptor Downregulator and Antagonist.

Authors:  Chris De Savi; Robert H Bradbury; Alfred A Rabow; Richard A Norman; Camila de Almeida; David M Andrews; Peter Ballard; David Buttar; Rowena J Callis; Gordon S Currie; Jon O Curwen; Chris D Davies; Craig S Donald; Lyman J L Feron; Helen Gingell; Steven C Glossop; Barry R Hayter; Syeed Hussain; Galith Karoutchi; Scott G Lamont; Philip MacFaul; Thomas A Moss; Stuart E Pearson; Michael Tonge; Graeme E Walker; Hazel M Weir; Zena Wilson
Journal:  J Med Chem       Date:  2015-10-07       Impact factor: 7.446
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  8 in total

Review 1.  Targeted Protein Degradation by Small Molecules.

Authors:  Daniel P Bondeson; Craig M Crews
Journal:  Annu Rev Pharmacol Toxicol       Date:  2016-10-12       Impact factor: 13.820

2.  Novel Selective Estrogen Receptor Downregulators (SERDs) Developed against Treatment-Resistant Breast Cancer.

Authors:  Rui Xiong; Jiong Zhao; Lauren M Gutgesell; Yueting Wang; Sue Lee; Bhargava Karumudi; Huiping Zhao; Yunlong Lu; Debra A Tonetti; Gregory R J Thatcher
Journal:  J Med Chem       Date:  2017-02-10       Impact factor: 7.446

Review 3.  Recent progress in selective estrogen receptor downregulators (SERDs) for the treatment of breast cancer.

Authors:  Irshad Ahmad; Shimy Mathew; Sofia Rahman
Journal:  RSC Med Chem       Date:  2020-03-06

4.  Human Estrogen Receptor Alpha Antagonists, Part 3: 3-D Pharmacophore and 3-D QSAR Guided Brefeldin A Hit-to-Lead Optimization toward New Breast Cancer Suppressants.

Authors:  Nezrina Kurtanović; Nevena Tomašević; Sanja Matić; Elenora Proia; Manuela Sabatino; Lorenzo Antonini; Milan Mladenović; Rino Ragno
Journal:  Molecules       Date:  2022-04-28       Impact factor: 4.927

5.  Biomimetic Phosphate-Catalyzed Pictet-Spengler Reaction for the Synthesis of 1,1'-Disubstituted and Spiro-Tetrahydroisoquinoline Alkaloids.

Authors:  Jianxiong Zhao; Daniel Méndez-Sánchez; John M Ward; Helen C Hailes
Journal:  J Org Chem       Date:  2019-05-31       Impact factor: 4.354

6.  Wenshenyang recipe treats infertility through hormonal regulation and inflammatory responses revealed by transcriptome analysis and network pharmacology.

Authors:  Lan Xie; Shuai Zhao; Xiaoling Zhang; Wenting Huang; Liansheng Qiao; Delin Zhan; Chengmei Ma; Wei Gong; Honglei Dang; Hua Lu
Journal:  Front Pharmacol       Date:  2022-08-08       Impact factor: 5.988

Review 7.  Next-Generation Drugs and Probes for Chromatin Biology: From Targeted Protein Degradation to Phase Separation.

Authors:  Katerina Cermakova; H Courtney Hodges
Journal:  Molecules       Date:  2018-08-06       Impact factor: 4.411

8.  Alangium longiflorum Merr. Leaf Extract Induces Apoptosis in A549 Lung Cancer Cells with Minimal NFκB Transcriptional Activation.

Authors:  Cielo Mae D Marquez; Jerremiah G Garcia; Jessica G Antonio; Sonia D Jacinto; Michael C Velarde
Journal:  Asian Pac J Cancer Prev       Date:  2020-08-01
  8 in total

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