학술논문
A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light.
Document Type
Academic Journal
Author
Gómez-Santacana X; Division of Medicinal Chemistry, Amsterdam Institute for Molecules Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, 1081 HZ, Amsterdam, The Netherlands.; present address: Institute of Functional Genomics, Université de Montpellier, Unité 5302 CNRS and Unité U1191, INSERM, 34090 Montpellier, France.; de Munnik SM; Division of Medicinal Chemistry, Amsterdam Institute for Molecules Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, 1081 HZ, Amsterdam, The Netherlands.; Mocking TAM; Division of Medicinal Chemistry, Amsterdam Institute for Molecules Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, 1081 HZ, Amsterdam, The Netherlands.; Hauwert NJ; Division of Medicinal Chemistry, Amsterdam Institute for Molecules Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, 1081 HZ, Amsterdam, The Netherlands.; Sun S; Division of Medicinal Chemistry, Amsterdam Institute for Molecules Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, 1081 HZ, Amsterdam, The Netherlands.; Vijayachandran P; Division of Medicinal Chemistry, Amsterdam Institute for Molecules Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, 1081 HZ, Amsterdam, The Netherlands.; de Esch IJP; Division of Medicinal Chemistry, Amsterdam Institute for Molecules Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, 1081 HZ, Amsterdam, The Netherlands.; Vischer HF; Division of Medicinal Chemistry, Amsterdam Institute for Molecules Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, 1081 HZ, Amsterdam, The Netherlands.; Wijtmans M; Division of Medicinal Chemistry, Amsterdam Institute for Molecules Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, 1081 HZ, Amsterdam, The Netherlands.; Leurs R; Division of Medicinal Chemistry, Amsterdam Institute for Molecules Medicines and Systems (AIMMS), Vrije Universiteit Amsterdam, 1081 HZ, Amsterdam, The Netherlands.
Source
Publisher: Beilstein-Institut Country of Publication: Germany NLM ID: 101250746 Publication Model: eCollection Cited Medium: Print ISSN: 1860-5397 (Print) Linking ISSN: 18605397 NLM ISO Abbreviation: Beilstein J Org Chem Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
1860-5397
Abstract
We report a detailed structure-activity relationship for the scaffold of VUF16216, a compound we have previously communicated as a small-molecule efficacy photoswitch for the peptidergic chemokine GPCR CXCR3. A series of photoswitchable azobenzene ligands was prepared through various synthetic strategies and multistep syntheses. Photochemical and pharmacological properties were used to guide the design iterations. Investigations of positional and substituent effects reveal that halogen substituents on the ortho -position of the outer ring are preferred for conferring partial agonism on the cis form of the ligands. This effect could be expanded by an electron-donating group on the para -position of the central ring. A variety of efficacy differences between the trans and cis forms emerges from these compounds. Tool compounds VUF15888 ( 4d ) and VUF16620 ( 6e ) represent more subtle efficacy switches, while VUF16216 ( 6f ) displays the largest efficacy switch, from antagonism to full agonism. The compound class disclosed here can aid in new photopharmacology studies of CXCR3 signaling.
(Copyright © 2019, Gómez-Santacana et al.; licensee Beilstein-Institut.)
(Copyright © 2019, Gómez-Santacana et al.; licensee Beilstein-Institut.)