5FQT

Selective estrogen receptor downregulator antagonists: Tetrahydroisoquinoline phenols 4.

Summary for 5FQT

• Entry DOI: 10.2210/pdb5fqt/pdb
• Related: 5FQP 5FQR 5FQS 5FQV
• Descriptor: ESTROGEN RECEPTOR ALPHA, (E)-3-[4-(6-hydroxy-2-isobutyl-5-methyl-3,4-dihydro-1H-isoquinolin-1-yl)phenyl]prop-2-enoic acid (3 entities in total)
• Functional Keywords: signaling protein, breast cancer, estrogen receptor downregulator, fulvestrant, thiq, nuclear hormone receptor
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 28623.58

Authors

Scott, J.S.,Bailey, A.,Davies, R.D.M.,Degorce, S.L.,MacFaul, P.A.,Gingell, H.,Moss, T.,Norman, R.A.,Pink, J.H.,Rabow, A.A.,Roberts, B.,Smith, P.D. (deposition date: 2015-12-14, release date: 2016-02-10, Last modification date: 2024-05-08)

Primary citation

Scott, J.S.,Bailey, A.,Davies, R.D.,Degorce, S.L.,MacFaul, P.A.,Gingell, H.,Moss, T.,Norman, R.A.,Pink, J.H.,Rabow, A.A.,Roberts, B.,Smith, P.D.
Tetrahydroisoquinoline Phenols: Selective Estrogen Receptor Downregulator Antagonists with Oral Bioavailability in Rat.
Acs Med.Chem.Lett., 7:94-, 2016

PubMed 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.

PubMed: 26819673
DOI: 10.1021/ACSMEDCHEMLETT.5B00413

Experimental method

X-RAY DIFFRACTION (1.99 Å)